An antioxidant is a molecule capable of inhibiting the oxidation of other molecules. Oxidation is a chemical reaction that transfers electrons from a substance to an oxidizing agent. Oxidation reactions can produce free radicals. In turn, these radicals can start chain reactions that damage cells. Antioxidants terminate these chain reactions by removing free radical intermediates, and inhibit other oxidation reactions. They do this by being oxidized themselves, so antioxidants are often reducing agents such as thiols, ascorbic acid or polyphenols.[1]

Although oxidation reactions are crucial for life, they can also be damaging; hence, plants and animals maintain complex systems of multiple types of antioxidants, such as glutathione, vitamin C, and vitamin E as well as enzymes such as catalase, superoxide dismutase and various peroxidases. Low levels of antioxidants, or inhibition of the antioxidant enzymes, cause oxidative stress and may damage or kill cells.

As oxidative stress might be an important part of many human diseases, the use of antioxidants in pharmacology is intensively studied, particularly as treatments for stroke and neurodegenerative diseases. However, it is unknown whether oxidative stress is the cause or the consequence of disease.

Antioxidants are widely used as ingredients in dietary supplements in the hope of maintaining health and preventing diseases such as cancer, coronary heart disease and even altitude sickness. Although initial studies suggested that antioxidant supplements might promote health, later large clinical trials did not detect any benefit and suggested instead that excess supplementation may be harmful.[2][3] In addition to these uses of natural antioxidants in medicine, these compounds have many industrial uses, such as preservatives in food and cosmetics and preventing the degradation of rubber and gasoline.

Haematinics

Blood-tonics, blood-restoratives, analeptic tonics. These are generally remedies which improve the quality

of the blood; but the name blood-tonics or haematinics is generally applied specially to such remedies as

increase the quantity of red blood-corpuscles and haemoglobin in the blood. The quality of the blood

depends upon a number of conditions: upon the amount and nature of the food ingested, on the digestion,

on the formation and excretion of the various products of tissue-change, and more especially on the

formation and destruction of the red blood-corpuscles themselves.

The red blood-corpuscles are probably formed in the spleen, the medulla of bones, the liver, and possibly

other parts of the body, from leucocytes which lose their nucleus, take up haema-globin, and alter their

form to that of the red corpuscles.

The red corpuscles are probably destroyed, at least to a great extent, in the liver, and probably also in the

spleen. The colouring matter of bile contains a quantity of iron, and appears to be formed from

haemoglobin.

An abnormal condition of the liver, by leading to excessive destruction of blood-corpuscles, may therefore

be an important cause of anaemia. The corpuscles contain albuminous matters as well as haemoglobin,

and deficiency of albumen in the blood will lead to anaemia. Thus, in cases of Bright's disease, the loss of

albumen through the kidneys tends to produce anaemia, and this must be combated by lessening the

loss, if possible, as well as by supplying albumen.

The blood-corpuscles also contain fat, and deficiency of fatty food will tend to produce anaemia. Cod-liver

oil, on the other hand, which is an easily assimilated form of fat, is a powerful haematinic. In anaemia

there is a deficiency of iron in the blood, and chalybeate preparations are among the most powerful of all

haematinics.

One well-marked disease due to imperfect nutrition is scurvy. In it there is not only a deficiency of red

blood-corpuscles, but a tendency to extravasation. Its pathology is not definitely made out, and it has

been supposed to be due to a deficiency of salts of potassium in the blood, but it is much more likely that

it is due to increase in the chlorides, and especially chloride of sodium, either absolutely or relatively to

the carbonates.

Excess of chloride of sodium causes the blood-corpuscles to pass out of the vessels (p. 63), and

potassium salts alone, or beef-tea, which contains them, do not cure scurvy; but it is removed by fresh

vegetables or by lime-juice.

 

GENERAL DEBILITY

MEANING

General debility refers to the lack of strength and energy in people. This refers to general

weakness and the inability to perform day-to-day functions smoothly.

SIGNS & SYMPTOMS

Weakness is the most common symptom. The person feels weak but has no concrete measurable loss of strength. There may be total body weakness or the weakness may be localized to certain areas like a limb, a side of the body etc.

CAUSES

Various causes can lead to general debility.

Shortage or lack of food is one of the most common reasons for general debility. If a

person doesn't eat properly he or she may develop general debility.

Rigorous work might also lead to lack of strength in the human body.

General debility is also caused by mental stress.

Having a cough and cold very often makes a person weak, resulting in lack of strength.

Convalescence is the gradual recovery of health and strength after illness. It refers to the later stage of an infectious disease or illness when the patient recovers and returns to normal, but may continue to be a source of infection even if feeling better. In this sense, "recovery" can be considered a synonymous term.

Convalescent Care Facilities are sometimes recognized by the abbreviation CCF.

Methylcobalamin

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Jump to: navigation, search

Methylcobalamin

Systematic (IUPAC) name

carbanide; cobalt(3+);

[5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-

(hydroxymethyl)oxolan-3-yl]

1-[3-[(4Z,9Z,14Z)-2,13,18-tris(2-amino-2-oxoethyl)

-7,12,17-tris(3-amino-3-oxopropyl)

-3,5,8,8,13,15,18,19-octamethyl-2,7,12,17-tetrahydro

-1H-corrin-21-id-3-yl]propanoylamino]

propan-2-yl phosphate

Identifiers

CAS number 13422-55-4

ATC code B03 BA05

PubChem CID 6436232

Chemical data

Formula C63H91Co N 13O14P

Mol. mass 1344.40 g/mol

Therapeutic considerations

Pregnancy cat. ?

Legal status

Routes oral,subliungal,injection.

Methylcobalamin is a cobalamin (MeCbl or MeB12) used in the treatment of peripheral neuropathy, diabetic neuropathy, and as a preliminary treatment for Amyotrophic lateral sclerosis. It is a form of vitamin B12 and differs from cyanocobalamin in that the cyanide is replaced by a methyl group.[1]

This vitamer is one of two active coenzymes used by B12-dependent enzymes in the body, and is specifically the B12 form used by 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR), also known as methionine synthase. Methylcobalamin is notable for being one of the few examples in nature of a bona fide organometallic bond.

It is produced preferentially by some species of bacteria. If these come into contact with heavy metals in the environment, these may become methylated forms of the metal which, in the case of methylmercury, is highly toxic.[2]

Methylcobalamin has been studied in conjunction with sleep-wake rhythm disorders, where it appears to yield benefits, but at a low or inconsistent level.[3]

It is used in treating diseases of vitamin B12 deficiency (such as pernicious anemia), or diseases of effective B12 deficiency, such as vitamin B12 metabolic pathway pathologies.

One study suggests that once absorbed, methylcobalamin may be retained in the body better than cyanocobalamin.[4]

Methylcobalamin is another name for Vitamin B12, a substance found naturally in meat, milk and fish. Because Vitamin B12 is important to nervous system to functioning and the process of blood cell formation, people with deficiencies of the vitamin are

commonly treated with B12 Methylcobalamin supplements; however, these supplements pose a risk for side effects in some patients.

Types of Side Effects

1. Possible side effects of Methylcobalamin include itching and diarrhea or loose stools. Patients who use skin creams for psoriasis that contain B12 are more likely to develop itching than those using oral supplements to treat a vitamin deficiency, according to RxList.

Allergic Reactions

2. Though uncommon, some people develop allergic reactions to Methylcobalamin, causing shortness of breath , hives, wheezing, chest pain and swelling of the face or extremities, according to the Physicians Desktop Reference. Because allergic reactions have the potential to develop into life-threatening conditions like shock, seek emergency medical attention if you develop any allergy symptoms while taking Methylcobalamin.

Risks

3. Rarely, Methylcobalamin causes the formation of blood clots, leading to life-threatening events like pulmonary embolisms, stroke and heart attacks, cautions RxList.

Drug Interactions

4. Because the antibacterial drug Chloramphenicol interferes with the action of B12 supplements, avoid use of Methylcobalamin if you are given a prescription for the antibiotic.

Considerations

5. Although Methylcobalamin has no known adverse effects on fetal development, discuss with your doctor what dosage you should be taking if you are pregnant. If you have a medical history of blood clots, Leber's Disease, anemia or any disorder that causes an excessive amount of blood cells like polycythemia vera, it may not be safe for you to take B12 supplements due to possible side effects.

Read more: Methylcobalamin Side Effects | eHow.com http://www.ehow.com/facts_5534755_methylcobalamin-side-effects.html#ixzz0vWqo5NHj

Methylcobalamin is the coenzyme form of vitamin B-12, which means your body can use it without requiring extra steps to transform it into a usable substance. Methylcobalamin is used to

treat a number of diseases and deficiencies, and there are multiple benefits that come with taking methylcobalamin.

Sleep Problems According to mend.net, methylcobalamin can help with sleep problems, specifically sleep-wake rhythm disorders. These sleep-wake rhythm disorders include advanced sleep phase syndrome and delayed sleep phase syndrome. Methylcobalamin helps replenish the brain's neurotransmitters when the neurotransmitters are being produced by amino acids in the brain. Considering that sleep disorders can have a number of extremely serious effects--such as weight gain, weight loss , and diminished problem solving skills--methylcobalamin is an important supplement to take if you are suffering from sleep problems.

Vitamin B Deficiency Taking methylcobalamin can also help if you have a vitamin B deficiency disorder. Since methylcobalamin can be instantly used by your body instead of having to convert it into a more usable form, you can feel the effects of it more quickly than other vitamin B forms. Some of the symptoms of vitamin B deficiency that methylcobalamin can help alleviate include--but are not limited to--the following: tiredness, decreased mental capacity, memory loss and memory problems, inability to concentrate, irritability, depression, sores in the corner of your mouth, shortness of breath , and a sharp stabbing pain in the palm of your hands.

Anemia Methylcobalamin can also help with the effects of anemia. Anemia is a decrease in the number of normal red blood cells or a decrease in the normal amount of hemoglobin found in your blood. Anemia can range from mild to severe. Some of the symptoms of severe anemia include: fainting, chest pain, angina, and a heart attack. Some of the symptoms of milder anemia include fatigue, dizziness, muscular weakness, and a feeling of coldness. Taking methylcobalamin has been shown to help with the symptoms of anemia.

Read more: Methylcobalamin Benefits | eHow.com http://www.ehow.com/list_6363623_methylcobalamin-benefits.html#ixzz0vWr18rIK

Cyanocobalamin, more commonly known as vitamin B-12, is commonly used to fight fatigue, encourage weight loss and improve overall health. According to natural supplement specialist Dr. Ray Sahelian of Los Angeles, "Methylcobalamin is the methylated form of cobalamin." Dr. Sahelian believes both forms of the B-12 vitamin are effective and useful.

Uses

1. Production of red blood cells is dependent on vitamin B-12. Injections, sublingual use (dissolving under the tongue) or oral doses of the vitamin are used to treat anemia, vitamin malabsorption, fatigue and boost the immune system . Both methylcobalamin and

cyanocobalamin are effective in treating conditions that have resulted in low B-12 absorption.

Origin

2. There are four naturally occurring cobalamines in nature and animals. There are methyl-, cyano-, hydroxy- and adenosyl-. Occurring in small amounts naturally, cyanocobalamin is manufactured in a lab and is the commonly prescribed form of B-12 vitamin.

Forms

3. Taking methylcobalamin or cyanocobalamin as an injection, sublingual or orally are all effective methods according to Dr. Sahelian. Given in large doses, due to the known problems with absorption, he says patients still get the amount needed even with low absorption rates. The Food and Drug Administration's recommended daily amount of B-12 in the United States is 6 micrograms daily.

Features

4. Methylcobalamin has "metabolic and therapeutic" applications according to Dr. Sahelian. He notes methylcobalamin helps in the formation of S-adenosylmethionine (SAM-e), a popular mood-altering compound. Chronic Fatigue Symdrome and Fibromyalgia patients have also reported an increase in health with the use of B-12. Elevated body temperature is a side effect of methylcobalamin. Cyanocobalamin is carried by more pharmacies.

Symptoms

5. Talk with your doctor about testing your B-12 levels and prescribing methylcobalamin and cyanocobalamin if the following symptoms are bothering you: fatigue, insomnia, fuzzy thoughts and memory loss, tingling in the hands or feet, ringing in the ear, headaches, dizziness or loss of balance

Bell's palsy or idiopathic facial paralysis[1]is a dysfunction of cranial nerve VII (the facial nerve) that results in inability to control facial muscles on the affected side. Several conditions can cause a facial paralysis, e.g., brain tumor, stroke, and Lyme disease. However, if no specific cause can be identified, the condition is known as Bell's palsy. Named after Scottish anatomist Charles Bell, who first described it, Bell's palsy is the most common acute mononeuropathy (disease involving only one nerve) and is the most common cause of acute facial nerve paralysis.

Bell's palsy is defined as an idiopathic unilateral facial nerve paralysis, usually self-limiting. The trademark is rapid onset of partial or complete palsy, usually in a single day. It can occur bilaterally resulting in total facial paralysis in around 1% of cases. [2]

It is thought that an inflammatory condition leads to swelling of the facial nerve. The nerve travels through the skull in a narrow bone canal beneath the ear. Nerve swelling and compression in the narrow bone canal are thought to lead to nerve inhibition, damage or death. No readily identifiable cause for Bell's palsy has been found.

Corticosteroids have been found to improve outcomes while anti-viral drugs have not. Early treatment is necessary for steroids to be effective. Most people recover spontaneously and achieve near-normal to normal functions. Many show signs of improvement as early as 10 days after the onset, even without treatment.

Often the eye in the affected side cannot be closed. The eye must be protected from drying up, or the cornea may be permanently damaged resulting in impaired vision. In some cases denture wearers experience some discomfort.

Contents[show]

[edit] Signs and symptoms

Facial nerve: the facial nerve's nuclei are in the brainstem (they are represented in the diagram as a „θ“). Orange: nerves coming from the left hemisphere of the brain. Yellow: nerves coming from the right hemisphere of the brain. Note that the forehead muscles receive innervation from both hemispheres of the brain (represented in yellow and orange).

Bell's palsy is characterized by facial drooping on the affected half, due to malfunction of the facial nerve (VII cranial nerve), which controls the muscles of the face. Facial palsy is typified by inability to control movement in the facial muscles. The paralysis is of the infranuclear/lower motor neuron type.

The facial nerves control a number of functions, such as blinking and closing the eyes, smiling, frowning, lacrimation, and salivation. They also innervate the stapedial (stapes) muscles of the middle ear and carry taste sensations from the anterior two thirds of the tongue.

Clinicians should determine whether the forehead muscles are spared. Due to an anatomical peculiarity, forehead muscles receive innervation from both sides of the brain. The forehead can therefore still be wrinkled by a patient whose facial palsy is caused by a problem in one of the hemispheres of the brain (central facial palsy). If the problem resides in the facial nerve itself (peripheral palsy) all nerve signals are lost on the ipsilateral (same side of the lesion) half side of the face, including to the forehead (contralateral forehead still wrinkles).

One disease that may be difficult to exclude in the differential diagnosis is involvement of the facial nerve in infections with the herpes zoster virus. The major differences in this condition are the presence of small blisters, or vesicles, on the external ear and hearing disturbances, but these findings may occasionally be lacking (zoster sine herpete).

Lyme disease may produce the typical palsy, and may be easily diagnosed by looking for Lyme-specific antibodies in the blood. In endemic areas Lyme disease may be the most common cause of facial palsy.

The degree of nerve damage can be assessed using the House-Brackmann score.

Although defined as a mononeuritis (involving only one nerve), patients diagnosed with Bell’s palsy may have "myriad neurological symptoms" including "facial tingling, moderate or severe headache/neck pain, memory problems, balance problems, ipsilateral limb paresthesias, ipsilateral limb weakness, and a sense of clumsiness" that are "unexplained by facial nerve dysfunction".[3] This is yet an enigmatic facet of this condition.

[edit] Cause

Some viruses are thought to establish a persistent (or latent) infection without symptoms, e.g. the Zoster virus of the face[4] and Epstein-Barr viruses, both of the herpes family. Reactivation of an existing (dormant) viral infection has been suggested[5] as cause behind the acute Bell's palsy. Studies[6] suggest that this new activation could be preceded by trauma, environmental factors, and metabolic or emotional disorders, thus suggesting that stress - emotional stress, environmental stress (e.g. cold), physical stress (e.g. trauma) - in short, a host of different conditions, may trigger reactivation.

[edit] Pathology

Anatomy of the face.

It is thought that as a result of inflammation of the facial nerve, pressure is produced on the nerve where it exits the skull within its bony canal, blocking the transmission of neural signals or damaging the nerve. Patients with facial palsy for which an underlying cause can be found are not considered to have Bell's palsy per se. Possible causes include tumor, meningitis, stroke, diabetes mellitus, head trauma and inflammatory diseases of the cranial nerves (sarcoidosis, brucellosis, etc.). In these conditions, the neurologic findings are rarely restricted to the facial nerve. Babies can be born with facial palsy[7]. In a few cases, bilateral facial palsy has been associated with acute HIV infection.

In some research[8] the herpes simplex virus type 1 (HSV-1) was identified in a majority of cases diagnosed as Bell's palsy. This has given hope for anti-inflammatory and anti-viral drug therapy (prednisone and acyclovir). Other research[5] however, identifies HSV-1 in only 31 cases (18 percent), herpes zoster (zoster sine herpete) in 45 cases (26 percent) in a total of 176 cases clinically diagnosed as Bell's Palsy. That infection with herpes simplex virus should play a major role in cases diagnosed as Bell's palsy therefore remains a hypothesis that requires further research.

In addition, the herpes simplex virus type 1 (HSV-1) infection is associated with demyelination of nerves. This nerve damage mechanism is different from the above mentioned - that oedema, swelling and compression of the nerve in the narrow bone canal is responsible for nerve damage. Demyelination may not even be directly caused by the virus, but by an unknown immune system response. The quote below captures this hypothesis and the implication for other types of treatment:

It is also possible that HSV-1 replication itself is not responsible for the damage to the facial nerves and that inhibition of HSV-1 replication by acyclovir does not prevent the progression of nerve dysfunction. Because the demyelination of facial nerves caused by HSV-1 reactivation, via an unknown immune response, is implicated in the pathogenesis of HSV-1-induced facial palsy, a new strategy of treatment to inhibit such an immune reaction may be also effective.[5]

[edit] Diagnosis

Bell's palsy is a diagnosis of exclusion; by elimination of other reasonable possibilities. Therefore, by definition, no specific cause can be ascertained. Bell's palsy is commonly referred to as idiopathic or cryptogenic, meaning that it is due to unknown causes. Being a residual diagnostic category, the Bell's Palsy diagnosis likely spans different conditions that our current level of medical knowledge cannot distinguish. This may inject fundamental uncertainty into the discussion below of etiology, treatment options, recovery patterns etc. See also the section below on Other symptoms. Studies[3] show that a large number of patients (45%) are not referred to a specialist, which suggests that Bell’s palsy is considered by physicians to be a straightforward diagnosis that is easy to manage. A significant number of cases are misdiagnosed (ibid.). This is unsurprising from a diagnosis of exclusion, which depends on a thorough investigation.

[edit] Treatment

In patients presenting with incomplete facial palsy, where the prognosis for recovery is very good, treatment may be unnecessary. Patients presenting with complete paralysis, marked by an inability to close the eyes and mouth on the involved side, are usually treated. Early treatment (within 3 days after the onset) is necessary for therapy to be effective.[9] Steroids have been shown to be effective at improving recovery while antivirals have not.

[edit] Steroids

Corticosteroid such as prednisone significantly improves recovery at 6 months and are thus recommended.[10]

[edit] Antivirals

Antivirals (such as acyclovir) are ineffective in improving recovery from Bell's palsy beyond steroids alone.[11] They were however commonly prescribed due to a theoretical link between Bell's palsy and the herpes simplex and varicella zoster virus.[12]

[edit] Complementary therapy

The efficacy of acupuncture remains unknown because the available studies are of low quality (poor primary study design or inadequate reporting practices).[13]

[edit] Prognosis

Even without any treatment, Bell's palsy tends to carry a good prognosis. In a 1982 study, when no treatment was available, of 1,011 patients, 85% showed first signs of recovery within 3 weeks after onset. For the other 15%, recovery occurred 3–6 months later. After a follow-up of at least 1 year or until restoration, complete recovery had occurred in more than two thirds (71%) of all patients. Recovery was judged moderate in 12% and poor in only 4% of patients.[14] Another study found that incomplete palsies disappear entirely, nearly always in the course of one month.

The patients who regain movement within the first two weeks nearly always remit entirely. When remission does not occur until the third week or later, a significantly greater part of the patients develop sequelae.[15] A third study found a better prognosis for young patients, aged below 10 years old, while the patients over 61 years old presented a worse prognosis.[6]

Major complications of the condition are chronic loss of taste (ageusia), chronic facial spasm and corneal infections. To prevent the latter, the eyes may be protected by covers, or taped shut during sleep and for rest periods, and tear-like eye drops or eye ointments may be recommended, especially for cases with complete paralysis. Where the eye does not close completely, the blink reflex is also affected, and care must be taken to protect the eye from injury.

Another complication can occur in case of incomplete or erroneous regeneration of the damaged facial nerve. The nerve can be thought of as a bundle of smaller individual nerve connections that branch out to their proper destinations. During regrowth, nerves are generally able to track the original path to the right destination - but some nerves may sidetrack leading to a condition known as synkinesis. For instance, regrowth of nerves controlling muscles attached to the eye may sidetrack and also regrow connections reaching the muscles of the mouth. In this way, movement of one also affects the other. For example, when the person closes the eye, the corner of the mouth lifts involuntarily.

In addition, around 6%[citation needed] of patients exhibit crocodile tear syndrome, also called gustatolacrimal reflex or Bogorad’s Syndrome, on recovery, where they will shed tears while eating. This is thought to be due to faulty regeneration of the facial nerve, a branch of which controls the lacrimal and salivary glands. Gustatorial sweating can also occur.

[edit] Epidemiology

The annual incidence of Bell's palsy is about 20 per 100,000 population, and the incidence increases with age.[16] Bell’s palsy affects about 40,000 people in the United States every year. It affects approximately 1 person in 65 during a lifetime.[citation needed] Familial inheritance has been found in 4–14% of cases.[17] Bell's Palsy is three times more likely to strike pregnant women than non-pregnant women.[18] It is also considered to be four times more likely to occur in diabetics than the general population.[19]

A range of annual incidence rates have been reported in the literature: 15,[17] 24,[20] and 25-53[3] (all rates per 100,000 population per year). Bell’s palsy is not a reportable disease, and there are no established registries for patients with this diagnosis, which complicates precise estimation.

Diabetic neuropathies are neuropathic disorders that are associated with diabetes mellitus. These conditions are thought to result from diabetic microvascular injury involving small blood vessels that supply nerves (vasa nervorum) in addition to macrovascular conditions that can culminate in diabetic neuropathy. Relatively common conditions which may be associated with diabetic neuropathy include third nerve palsy; mononeuropathy; mononeuropathy multiplex; diabetic amyotrophy; a painful polyneuropathy; autonomic neuropathy; and thoracoabdominal neuropathy.

Contents[show]

[edit] Signs and symptoms

Diabetic neuropathy affects all peripheral nerves: pain fibers, motor neurons, autonomic nerves. It therefore necessarily can affect all organs and systems since all are innervated. There are several distinct syndromes based on the organ systems and members affected, but these are by no means exclusive. A patient can have sensorimotor and autonomic neuropathy or any other combination. Symptoms vary depending on the nerve(s) affected and may include symptoms other than those listed. Symptoms usually develop gradually over years.

Symptoms may include:

Numbness and tingling of extremities Dysesthesia (decreased or loss of sensation to a body part) Diarrhea Erectile dysfunction Urinary incontinence (loss of bladder control) Impotence Facial, mouth and eyelid drooping Vision changes Dizziness Muscle weakness Difficulty swallowing Speech impairment Fasciculation (muscle contractions) Anorgasmia Burning or electric pain

Neuropathy Overview

Peripheral neuropathy is a general term referring to disorders of peripheral nerves. The peripheral nervous system is made up of the nerves that branch out of the spinal cord to all parts of the body.

Questions to Ask Your Doctor about Neuropathy(Free Handout)

Peripheral nerve cells have three main parts: cell body, axons, and dendrites (nerve/muscle junctions). Any part of the nerve can be affected, but damage to axons is most common. The axon transmits signals from nerve cell to nerve cell or muscle. Most axons are surrounded by a substance called myelin, which facilitates signal transmission.

Peripheral neuropathy can be associated with poor nutrition, a number of diseases (including diabetes), and pressure or trauma. Many people suffer from the disorder without ever identifying the cause.

Types of Neuropathy

Peripheral neuropathy can be broadly categorized by the type of nerve that has been damaged. The peripheral nervous system is made up of three types of nerves:

Questions to Ask Your Doctor about Neuropathy(Free Handout)

motor nerves (responsible for voluntary movement)

sensory nerves (responsible for sensing temperature, pain, touch, and limb positioning); including large and small fibers

autonomic nerves (responsible for involuntary functions such as breathing, blood pressure, sexual function, digestion)

Peripheral neuropathy also can be classified by where it occurs in the body. Nerve damage that occurs in one area of the body is called mononeuropathy, in many areas, polyneuropathy. When the disorder occurs in the same places on both sides of the body, the condition is called symmetric neuropathy.

Neuropathy Signs and Symptoms

Symptoms of neuropathy depend on the type of nerve(s) affected (e.g., motor, sensory, autonomic) and where the nerve is located in the body. One or more types of nerve may be damaged.

Questions to Ask Your Doctor about Neuropathy(Free Handout)

Muscle weakness, cramps, and spasms are associated with motor nerve damage. In some cases, neuropathy can cause a loss of balance and coordination.

Sensory nerve damage can produce tingling, numbness, and pain. Pain associated with sensory nerve damage is variously described as:

Sensation of wearing an invisible "glove" or "sock"

Burning, freezing, or electric-like

Extreme sensitivity to touch

If the autonomic nerves are damaged, involuntary functions may be affected. Symptoms that can result from this type of damage include abnormal blood pressure and heart rate, reduced ability to perspire, constipation, bladder dysfunction (e.g., incontinence), and sexual dysfunction.

Hyperhomocysteinemia

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Hyperhomocysteinemia

Classification and external resources

Homocysteine

DiseasesDB 29853

eMedicine neuro/578

Hyperhomocysteinemia is a medical condition characterized by an abnormally large level of homocysteine in the blood.

As a consequence of the biochemical reactions in which homocysteine is involved, deficiencies of the vitamins folic acid, pyridoxine (B6), or B12 can lead to high homocysteine levels.[1] Supplementation with pyridoxine, folic acid, B12 or trimethylglycine (betaine) reduces the concentration of homocysteine in the bloodstream.[2]

Hyperhomocysteinaemia is a disease which increases risk of other artery or vein diseases.

Hyperhomocysteinaemia usually occurs in people with at least one defective gene, which affects the breakdown of homocysteine. There are two common gene defects in the population. The first

gene codes for an enzyme. This gene is known as Methylenetetrahydrofolate reductase or MTHFR. The second common defective gene is methioninesynthetase or MS.[citation needed]

Hyperhomocysteinaemia is a high level of homocysteine in human blood. A high level of homocysteine makes a person more prone to have blood clots which may result in heart attacks and strokes. Hyperhomocysteinaemia also damages the linings of veins and arteries which prevents build up of blood clots. Hyperhomocysteinaemia is a risk factor for Coronary artery disease. Coronary artery disease is when plaque builds up inside the coronary arteries. These arteries supply the heart with blood.

People who are most likely to get hyperhomocysteinaemia are with two defective genes and having a diet low in Folate and vitamin B6 and B12. The effect upon these people is greater than the people with only one defective gene.[citation needed]

Hyperhomocysteinaemia is linked to an increased risk of blood clots, heart attacks and strokes. It can cause miscarriage, pre-eclampsia and other birth defects in pregnant women.

The best way to prevent hyperhomocysteinaemia is to eat foods which contain B6, B12, and folate such as potato, greens, beans and fish. The only natural sources of B12 are from animal products.

However, it is difficult to show that reducing your homocysteine levels will improve your health. In a study designed to see if lowering homocysteine will reduce heart ("vascular") and kidney problems, the results were just the opposite. [3] Patients with diabetes and known kidney disease ("diabetic nephropathy") were given commonly used doses of B vitamins: folic acid (2.5 mg/d), vitamin B6 (25 mg/d), and vitamin B12 (1 mg/d). Diabetics usually have elevated homocysteine levels and a higher risk for heart attacks and strokes, so they make an ideal population to study homocysteine's effects on human health. Taking B vitamins did reduce homocysteine, as expected, but unfortunately doubled the patient's risk of serious vascular complications (heart attack, stroke, death) and worsened their kidney function.

What Is It??     HOMOCYSTEINE

Homocysteine is an amino acid important in metabolism.  In the past, a markedly elevated homocysteine level has been associated with a higher risk of forming blood clots and vascular disease.  However, it is only recent that mild hyperhomocysteinemia has been associated with these complications.

As compared to the general population, persons with hyperhomocysteinemia have a 6.8 time greater risk of peripheral arterial disease, 2.5 time greater risk of stroke, and 2 time greater risk of heart disease.  The risk of mild

hyperhomocysteinemia may be as important as the risk associated with increased cholesterol or smoking history.

 

How Do You Get It??

Mild elevations of homocysteine in the body can be inherited.  This commonly occurs in up to 50% of persons from North America.  However, elevated homocysteine may also be related to a diet low in Vitamin B12 or Folic Acid.  The combination of an inherited syndrome and the dietary deficiency may increase the risk of developing blood clots or vascular disease.

 

Who Knows If They Have It??

People with recurrent blood clots or problems with vascular disease that have no other explanation may be tested for the presence of hyperhomocysteinemia.   A genetic test for one of the inherited defects, an abnormal MTHFR, is  available.

A  study was published evaluating whether the gene defect alone is a risk factor for recurrent blood clots.  This very large well done study demonstrated that the presence of this gene abnormality alone does NOT increase the risk of recurrent blood clots.  Therefore testing is controversial and guidelines will probably be revised in the future.

 

What Should You Do About It??

To treat hyperhomocysteinemia, vitamin supplements have been given in order to try to lower the level.  This can be done by taking a combination of Vitamin B6, B12, and Folic Acid.

However, recent data demonstrate that although you can lower the homocysteine level with B supplements, this has not improved the risk of recurrent blood clots or coronary disease.  Therefore use of vitamin supplementation is not recommended.

 Therefore, treatment with blood thinners may be needed. 

Axon

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For other uses, see Axon (disambiguation).

Structure of a typical neuron

Neuron

Dendrite

Soma

Axon

Nucleus

Node ofRanvier

Axon terminal

Schwann cell

Myelin sheath

An axon is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neuron's cell body or soma.

An axon is one of two types of protoplasmic protrusions that extrude from the cell body of a neuron, the other type being dendrites. Axons are distinguished from dendrites by several features, including shape (dendrites often taper while axons usually maintain a constant radius), length (dendrites are restricted to a small region around the cell body while axons can be much longer), and function (dendrites usually receive signals while axons usually transmit them). All of these rules have exceptions, however.

Some types of neurons have no axon—these are called amacrine cells, and transmit signals from their dendrites. No neuron ever has more than one axon; however in invertebrates such as insects the axon sometimes consists of several regions that function more or less independently of each other. Most axons branch, in some cases very profusely.

Axons make contact with other cells—usually other neurons but sometimes muscle or gland cells—at junctions called synapses. At a synapse, the membrane of the axon closely adjoins the membrane of the target cell, and special molecular structures serve to transmit electrical or electrochemical signals across the gap. Some synaptic junctions appear partway along an axon as it extends—these are called en passant ("in passing") synapses. Other synapses appear as terminals at the ends of axonal branches. A single axon, with all its branches taken together, can innervate multiple parts of the brain and generate thousands of synaptic terminals.

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[edit] Anatomy

Axons are in effect the primary transmission lines of the nervous system, and as bundles they help make up nerves. Individual axons are microscopic in diameter (typically about 1μm across), but may be up to several feet in length. The longest axons in the human body, for example, are those of the sciatic nerve, which run from the base of the spine to the big toe of each foot. These single-cell fibers of the sciatic nerve may extend a meter or even longer.[1]

In vertebrates, the axons of many neurons are sheathed in myelin, which is formed by either of two types of glial cells: Schwann cells ensheathing peripheral neurons and oligodendrocytes insulating those of the central nervous system. Along myelinated nerve fibers, gaps in the sheath known as nodes of Ranvier occur at evenly-spaced intervals. The myelination enables an especially rapid mode of electrical impulse propagation called saltation. The demyelination of axons is what causes the multitude of neurological symptoms found in the disease Multiple

Sclerosis. The axons of some neurons branch to form axon collaterals, that can be divided into a number of smaller branches called telodendria. Along these the bifurcated impulse travels simultaneously to signal more than one other cell.

[edit] Initial Segment

The initial segment of the axon is unmyelinated and is thought to be the usual site of action potential intiation.[2] The density of voltage-gated sodium channels is much higher here than is found in the adjacent cell body, excepting the axon hillock.[3]

[edit] Nodes of RanvierMain article: Nodes of Ranvier

Nodes of Ranvier are unmyelinated segments of the axon where action potentials are amplified and transmitted down the axon.

[edit] Physiology

The physiology can be described by the Hodgkin-Huxley Model, extended to vertebrates in Frankenhaeuser-Huxley equations. Peripheral nerve fibers can be classified based on axonal conduction velocity, mylenation, fiber size etc. For example, there are slow-conducting unmyelinated C fibers and faster-conducting myelinated Aδ fibers. More complex mathematical modeling continues to be done today. There are several types of sensory- as well as motorfibers. Other fibers not mentioned in table are e.g. fibers of the autonomic nervous system

[edit] Motor

Lower motor neurons have two kind of fibers:

Motor fiber types

TypeErlanger-Gasser

ClassificationDiameter Myelin Conduction velocity Associated muscle fibers

α Aα 13-20 µm Yes 80-120 m/s Extrafusal muscle fibers

γ Aγ 5-8 µm Yes 4-24 m/s[4][5] Intrafusal muscle fibers

[edit] Sensory

Different sensory receptors are innervated by different types of nerve fibers. Proprioceptors are innervated by type Ia, Ib and II sensory fibers, mechanoreceptors by type II and III sensory fibers and nociceptors and thermoreceptors by type III and IV sensory fibers.

Sensory fiber types

TypeErlanger-Gasser

ClassificationDiameter Myelin Conduction velocity Associated sensory receptors

Ia Aα 13-20 µm Yes 80-120 m/s Primary receptors of muscle spindle

Ib Aα 13-20 µm Yes 80-120 m/s Golgi tendon organ

II Aβ 6-12 µm Yes 33-75 m/sSecondary receptors of muscle spindleAll cutaneous mechanoreceptors

III Aδ 1-5 µm Thin 3-30 m/sFree nerve endings of touch and pressureNociceptors of neospinothalamic tractCold thermoreceptors

IV C 0.2-1.5 µm No 0.5-2.0 m/sNociceptors of paleospinothalamic tractWarmth receptors

[edit] Autonomic

Autonomic nervous system have two kind of peripheral fibers:

Motor fiber types

TypeErlanger-Gasser

ClassificationDiameter Myelin[6] Conduction velocity

preganglionic fibers B 1-5 µm Yes 3-15 m/s

postganglionic fibers C 0.2-1.5 µm No 0.5-2.0 m/s

[edit] Growth and development

Axon of 9 day old mouse with growth cone visible.

Growing axons move through their environment via the growth cone, which is at the tip of the axon. The growth cone has a broad sheet like extension called lamellipodia which contain protrusions called filopodia. The filopodia are the mechanism by which the entire process adheres to surfaces and explores the surrounding environment. Actin plays a major role in the mobility of this system. Environments with high levels of cell adhesion molecules or CAM's create an ideal environment for axonal growth. This seems to provide a "sticky" surface for axons to grow along. Examples of CAM's specific to neural systems include N-CAM, neuroglial CAM or NgCAM, TAG-1, MAG, and DCC, all of which are part of the immunoglobulin superfamily. Another set of molecules called extracellular matrix adhesion molecules also provide a sticky substrate for axons to grow along. Examples of these molecules include laminin, fibronectin, tenascin, and perlecan. Some of these are surface bound to cells and thus act as short range attractants or repellents. Others are difusible ligands and thus can have long range effects.

Cells called guidepost cells assist in the guidance of neuronal axon growth. These cells are typically other, sometimes immature, neurons.

[edit] History

Some of the first intracellular recordings in a nervous system were made in the late 1930s by K. Cole and H. Curtis. Alan Hodgkin and Andrew Huxley also employed the squid giant axon (1939) and by 1952 they had obtained a full quantitative description of the ionic basis of the action potential, leading the formulation of the Hodgkin-Huxley Model. Hodgkin and Huxley were awarded jointly the Nobel Prize for this work in 1963. The formulas detailing axonal conductance were extended to vertebrates in the Frankenhaeuser-Huxley equations. Erlanger and Gasser earlier developed the classification system for peripheral[7] nerve fibers, based on axonal conduction velocity, myelination, fiber size etc. Even recently our understanding of the biochemical basis for action potential propagation has advanced, and now includes many details about individual ion channels.

[edit] InjuryMain article: Nerve injury

In order of degree of severity, injury to a nerve can be described as neuropraxia, axonotmesis, or neurotmesis. Concussion is considered a mild form of diffuse axonal injury [8].

Myelin

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Structure of a typical neuron

Myelin sheath

Dendrite

Soma

Axon

Nucleus

Node ofRanvier

Axon terminal

Schwann cell

Myelin sheath

Myelin is a dielectric (electrically insulating) material that forms a layer, the myelin sheath, usually around only the axon of a neuron. It is essential for the proper functioning of the nervous system. Myelin is an outgrowth of a glial cell. Schwann cells supply the myelin for peripheral neurons, whereas oligodendrocytes, specifically of the interfascicular type, myelinate the axons of the central nervous system. Myelin is considered a defining characteristic of the (gnathostome) vertebrates, but it has also arisen by parallel evolution in some invertebrates.[1] Myelin was discovered in 1854 by Rudolf Virchow.[2]

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[edit] Composition of myelin

Myelin made by different cell types varies in chemical composition and configuration, but performs the same insulating function. Myelinated axons are white in appearance, hence the "white matter" of the brain.

Myelin is composed of about 80% lipid and about 20% protein. Some of the proteins that make up myelin are myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG), and proteolipid protein (PLP). Myelin is made up primarily of a glycolipid called galactocerebroside. The intertwining hydrocarbon chains of sphingomyelin serve to strengthen the myelin sheath.

[edit] Function of myelin layer

Transmission electron micrograph of a myelinated axon. Generated at the Electron Microscopy Facility at Trinity College, Hartford, CT.

The main purpose of a myelin layer (or sheath) is to increase the speed at which impulses propagate along the myelinated fiber. Along unmyelinated fibers, impulses move continuously as waves, but, in myelinated fibers, they hop or "propagate by saltation." Myelin increases electrical resistance across the cell membrane by a factor of 5,000 and decreases capacitance by a factor of 50.[citation needed] Thus, myelination helps prevent the electrical current from leaving the axon.

When a peripheral fiber is severed, the myelin sheath provides a track along which regrowth can occur. Unmyelinated fibers and myelinated axons of the mammalian central nervous system do not regenerate.

[edit] Demyelination and dysmyelinationFurther information: Demyelinating disease

Demyelination is the loss of the myelin sheath insulating the nerves, and is the hallmark of some neurodegenerative autoimmune diseases, including multiple sclerosis, acute disseminated encephalomyelitis, transverse myelitis, chronic inflammatory demyelinating polyneuropathy, Guillain-Barré Syndrome, central pontine myelinosis, inherited demyelinating diseases such as Leukodystrophy, and Charcot Marie Tooth. Sufferers of pernicious anaemia can also suffer nerve damage if the condition is not diagnosed quickly. Sub-acute combined degeneration of the spinal cord secondary to pernicious anaemia can lead to anything from slight peripheral nerve damage to severe damage to the central nervous system affecting speech, balance and cognitive awareness. When myelin degrades, conduction of signals along the nerve can be impaired or lost and the nerve eventually withers.

The immune system may play a role in demyelination associated with such diseases, including inflammation causing demyelination by overproduction of cytokines via upregulation of tumor necrosis factor (TNF)[3] or interferon.

Research to repair damaged myelin sheaths is ongoing. Techniques include surgically implanting oligodendrocyte precursor cells in the central nervous system and inducing myelin repair with certain antibodies. While there have been some encouraging results in mice (via stem cell transplantation), it is still unknown whether this technique can be effective in replacing myelin loss in humans.[4]

Dysmyelination is characterized by a defective structure and function of myelin sheaths; unlike demyelination, it does not produce lesions. Such defective sheaths often arise from genetic mutations affecting the biosynthesis and formation of myelin. The shiverer mouse represents one animal model of dysmyelination. Human diseases where dysmyelination has been implicated include leukodystrophies (Pelizaeus-Merzbacher disease, Canavan disease, phenylketonuria) and schizophrenia.[5][6][7]

[edit] Symptoms of demyelination

Demyelination (i.e., the destruction or loss of the myelin sheath) results in diverse symptoms determined by the functions of the affected neurons. It disrupts signals between the brain and other parts of the body; symptoms differ from patient to patient, and have different presentations upon clinical observation and in laboratory studies.

Typical symptoms include:

blurriness in the central visual field that affects only one eye; may be accompanied by pain upon eye movement;

double vision; odd sensation in legs, arms, chest, or face, such as tingling or numbness (neuropathy); weakness of arms or legs; cognitive disruption including speech impairment and memory loss; heat sensitivity (symptoms worsen, reappear upon exposure to heat such as a hot shower); loss of dexterity; difficulty coordinating movement or balance disorder; difficulty controlling bowel movements or urination; fatigue.

Nerve fibers

Function: conduction of action potential.

Myelinated nerve fibers

Function: rapid conduction of action potential.

Location: central nervous system (white matter), peripheral nervous system

Composition: rich in lipids

Nerve axon Myelin sheath (neurilemma, sheath of Schwann, oligodendrocytes) with nodes of Ranvier and

Schmidt-Lanterman clefts

Unmyelinated (bare) nerve fibers

Function: slow conduction of action potential.

Location: central nervous system (gray matter), peripheral nervous system (autonomic, visceral nervous system)

Nerve axon

Oligodendrocytes

Menorrhagia is an abnormally heavy and prolonged menstrual period at regular intervals. Causes may be due to abnormal blood clotting, disruption of normal hormonal regulation of periods or disorders of the endometrial lining of the uterus. Depending upon the cause, it may be associated with abnormally painful periods (dysmenorrhea).

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[edit] Definition

A normal menstrual cycle is 21–35 days in duration, with bleeding lasting an average of 5 days and total blood flow between 25 and 80 mL. A blood loss of greater than 80 ml or lasting longer than 7 days constitutes menorrhagia (also called hypermenorrhea). Some authors use menorrhagia exclusively when describing excessive quantity and hypermenorrhea for prolonged duration (although most use both terms interchangeably in the clinical setting). In practice this is not usually directly measured by patients or doctors. Menorrhagia also occurs at predictable and normal (usually about 28 days) intervals, distinguishing it from menometrorrhagia, which occurs at irregular and more frequent intervals. It is possible to estimate the amount of bleeding by the number of tampons or pads a woman uses during her period. As a guide a regular tampon fully soaked will hold about 5ml of blood. One may also have lighter cycles in volume, but blood flow may continue more than seven days thus constituting menorrhagia. An OB/GYN should still be consulted.

[edit] Cause

Usually no causative abnormality can be identified and treatment is directed at the symptom, rather than a specific mechanism. A brief overview of causes is given below, followed by a more formal medical list based on the nature of the menstrual cycle experienced.

[edit] Disorders of coagulation

With the shedding of an endometrial lining's blood vessels, normal coagulation process must occur to limit and eventually stop the blood flow. Blood disorders of platelets (such as ITP) or coagulation (such as von Willebrand disease) or use of anticoagulant medication (such as warfarin) are therefore possible causes, although a rare minority of cases. Platelet function studies pfa col/epi can also be used to ascertain platelet function abnormalities

[edit] Excessive build up in endometrial lining

Periods soon after the onset of menstruation in girls (the menarche) and just before menopause may in some women be particularly heavy. Hormonal disorders involving the ovaries-pituitary-hypothalamus (the 'ovarian endocrine axis') account for many cases, and hormonal-based treatments may regulate effectively.

The lining of the uterus builds up naturally under the hormonal effects of pregnancy, and an early spontaneous miscarriage may be mistaken for a heavier than normal period.

As women age and move towards menopause, ovulation is delayed and the remaining follicles in the ovaries become resistant to GnRH ( Gonadotropin releasing hormone )secreted by the hypothalamus gland in the brain. Either that or they don't develop an egg, and thus no

progesterone is produced. Without progesterone, the estrogen is "unopposed" and keeps building up the lining of the uterus.

During a woman's period, the endometrial lining which is normally shed never gets the signal to stop thickening. It keeps growing and sheds irregularly. Due to the extra thickness, the bleeding is unusually heavy. Less frequently in this age group, too little estrogen causes the irregular bleeding. Most cases of hemorrhagic are due to normal hormonal changes preceding menopause.

Irritation of the endometrium may result in increased blood flow, e.g. from infection (acute or chronic pelvic inflammatory disease) or the contraceptive intrauterine device (note the distinction from the IntraUterine System which is used to treat this condition).

Fibroids in the wall of the womb sometimes can cause increase menstrual loss if they protrude into the central cavity and so thereby increase endometrium's surface area.

Abnormalities of the endometrium such as adenomyosis (so called "internal endometriosis") where there is extension into the wall of the womb gives rise to enlarged tender uterus. Note, true endometriosis is a cause of pain (dysmenorrhoea) but usually not alteration in menstrual blood loss.

Endometrial carcinoma (cancer of the uterine lining) usually causes irregular bleeding, rather than the cyclical pattern of menorrhagia. Bleeding in between periods (intermenstrual bleeding or IMB) or after the menopause (post-menopausal bleeding or PMB) should always be considered suspicious.

[edit] Consideration by nature of the menstrual cycle

Excessive menses but normal cycle: o Painless:

Fibroids ( leiomyoma ) Ovarian endocrine disorder (dysfunctional uterine bleeding or DUB)(the most

common cause) Coagulation defects (rare) endometrial carcinoma endometrial polyp

o Painful: Pelvic inflammatory disease Endometriosis adenomyosis

Short cycle (<21 days) but normal menses (epimenorrhoea or polymenorrhoea). These are always anovulatory cycles due to hormonal disorders.

Short cycle and excessive menses (epimenorrhagia) due to ovarian dysfunction and may be secondary to blockage of blood vessels by tumours.

Excessive menses and long intervals. o Anovular ovarian disorder due to prolonged oestrogen production.

o This may occur following prolonged continuous courses of the combined oral contraceptive pill (e.g. where several packets are taken without a withdrawal gap in order to defer menstruation).

[edit] Differential Diagnosis

Pregnancy complications: o Ectopic pregnancy o Incomplete abortiono Miscarriage o Threatened abortion

Nonuterine bleeding: o Cervical ectropion/erosiono Cervical neoplasia/polypo Cervical or vaginal traumao Condylomatao Atrophic vaginitiso Foreign bodies

Pelvic inflammatory disease (PID): o Endometritiso Tuberculosis

Hypothyroidism

[edit] Risk Factors

Obesity Anovulation Estrogen administration (without progestogens) Prior treatment with progestational agents or oral contraceptives increases the risk of

endometrial atrophy, but decreases the risk of endometrial hyperplasia or neoplasia

[edit] ICD-9 codes

Classification of some causes

Cause ICD-9 code

Polyp of corpus uteri 621.0

Endometrial cystic hyperplasia 621.3

Other specified disorders of uterus, NEC 621.8

Excessive or frequent menstruation 626.2

Puberty bleeding 626.3

Irregular menstrual cycle 626.4

Metrorrhagia 626.6

Disorders of menstruation and other abnormal bleedingfrom female genital tract, other

626.8

Premenopausal menorrhagia 627.0

Postmenopausal bleeding 627.1

[edit] Diagnosis

Pelvic and rectal examination Pap smear Pelvic ultrasound scan is the first line diagnostic tool for identifying structural abnormalities.[1]

Endometrial biopsy to exclude endometrial cancer or atypical hyperplasia Hysteroscopy

[edit] Treatment

Where an underlying cause can be identified, treatment may be directed at this. Clearly heavy periods at menarche and menopause may settle spontaneously (the menarche being the start and menopause being the cessation of periods).

If the degree of bleeding is mild, all that may be sought by the woman is the reassurance that there is no sinister underlying cause. If anaemia occurs then iron tablets may be used to help restore normal hemoglobin levels.

The condition is often treated with hormones, particularly as dysfunctional uterine bleeding commonly occurs in the early and late menstrual years when contraception is also sought. Usually, oral combined contraceptive or progesterone only pills may be taken for a few months, but for longer-term treatment the alternatives of injected Depo Provera or the more recent progesterone releasing IntraUterine System (IUS) may be used. Fibroids may respond to hormonal treatment, and if they do not, then surgical removal may be required.

Tranexamic acid tablets that may reduce loss by up to 50%.[citation needed] This may be combined with hormonal medication previously mentioned. Anti-inflammatory medication like NSAIDs may also been used, but typically cause only a 30%[citation needed] reduction in flow.

A definitive treatment for menorrhagia is to perform hysterectomy (removal of the uterus). The risks of the procedure have been reduced with measures to reduce the risk of deep vein

thrombosis after surgery, and the switch from the front abdominal to vaginal approach greatly minimizing the discomfort and recuperation time for the patient; however extensive fibroids may make the womb too large for removal by the vaginal approach. Small fibroids may be dealt with by local removal (myomectomy). A further surgical technique is endometrial ablation (destruction) by the use of applied heat (thermoablation).

In the UK the use of hysterectomy for menorrhagia has been almost halved between 1989 and 2003[2]. This has a number of causes: better medical management, endometrial ablation and particularly the introduction of IUS[3][4] which may be inserted in the community and avoid the need for specialist referral; in one study up to 64% of women cancelled surgery[5].

[edit] Medications

These have been ranked by the UK's National Institute for Health and Clinical Excellence:[1]

First line o IntraUterine System insertion

Second Line o Tranexamic acid an antifibrinolytic agento Non-steroidal anti-inflammatory drugs (NSAIDs)o Combined oral contraceptive pills to prevent proliferation of the endometrium

Third line o Oral progestogen (e.g. norethisterone), to prevent proliferation of the endometriumo Injected progestogen (e.g. Depo provera)

Other options o Gonadotrophin-releasing hormone (GnRH) agonists (e.g. Goserelin)

[edit] Surgery

Dilation and curettage (D&C) is no longer performed for cases of simple menorrhagia, having a reserved role if a spontaneous abortion is incomplete

Endometrial ablation Uterine artery embolisation (UAE) Hysteroscopic myomectomy to remove fibroids over 3 cm in diameter Hysterectomy

[edit] Complications

Aside from the social distress of dealing with a prolonged and heavy period, over time the blood loss may prove to be greater than the body iron reserves or the rate of blood replenishment, leading to anemia. Symptoms attributable to the anemia may include shortness of breath, tiredness, weakness, tingling and numbness in fingers and toes, headaches, depression, becoming cold more easily, and poor concentration.

Prophylaxis: A measure taken for the prevention of a disease or condition.

For example, dental prophylaxis consists of removing plaque and cleaning the teeth to prevent cavities and gum disease.

The word "prophylaxis" is from the Greek and means "an advance guard."

The term prophylaxis refers to medical or public health measures taken in order to prevent disease or health problems, rather than to treat or cure an existing condition. Prophylaxis is also a way to stem an outbreak of disease, or minimize the symptoms of someone who has been exposed to a disease or virus.

Primary prophylaxis includes any measure that is taken to prevent disease before it occurs. A good example of this is having your teeth professionally cleaned by a dentist. The cleaning helps to prevent plaque, tooth decay, and gum disease. Secondary prophylaxis refers to procedures that help to prevent infection after exposure to a disease, or to ease symptoms associated with an illness or health condition. For example, if a health care worker is exposed to the HIV/AIDS virus, they will take an antiretroviral drug to help prevent them from contracting the disease.

Vaccinations are a good example of prophylaxis. Inoculations are used to ensure that the recipient does not contract a specific illness, therefore eliminating the possibility of a need for treatment later in life. On a larger scale, emergency preparedness is another form of prophylaxis. Since outbreaks can occur in disastrous situations, being prepared for such an event lessens the need for eventual treatment.

Condoms are referred to as prophylactics, because they prevent pregnancy and the spread of sexually transmitted diseases (STDs). Antibiotics are sometimes used as a prophylaxis when the patient has been exposed to a disease or substance such as anthrax, to lessen the symptoms or side effects from the exposure.

Anticoagulants are given to those who suffer from cardiovascular disease. Often these patients take a daily dose of acetylsalicylic acid in the form of over the counter drugs like Aspirin. The tablets help to thin the blood, thereby reducing the risk of blood clots that can cause heart attacks or stroke.

Any medical field you can think of makes use of prophylaxes. Plastic surgeons administer drugs to their patients to help prevent deep vein thrombosis (DVT), a potential risk with any cosmetic surgery. Radiation for cancer patients is considered prophylaxis. Even those who practice homeopathy and alternative medicine have various forms of prophylaxes that they use to treat patients with.

Prophylaxis can refer to an extensive regimen of drugs and medical procedures, or it can be as simple as using an antiseptic spray on a wound to speed healing and prevent infection.

Coronary disease (or coronary heart disease) refers to the failure of coronary circulation to supply adequate circulation to cardiac muscle and surrounding tissue. It is already the most common form of disease affecting the heart and an important cause of premature death in Europe, the Baltic states, Russia, North and South America, Australia and New Zealand. It has been predicted that all regions of the world will be affected by 2020.[1]

It is most commonly equated with atherosclerotic coronary artery disease, but coronary disease can be due to other causes, such as coronary vasospasm.[2] It is possible for the stenosis to be caused by the spasm.[3]

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[edit] Signs and symptoms

Coronary heart disease may be asymptomatic. If not, symptoms can include:

Chest heaviness Dyspnea Fatigue Chest pain Angina

Myocardial infarction is a complication of coronary disease. It is sometimes classified as a symptom.[4][5]

[edit] Causes

Coronary artery disease, the most common type of coronary disease, which has no clear etiology, has many risk factors, including smoking, radiotherapy to the chest, hypertension, diabetes, and hyperlipidemia.[6]

Also, having a Type A behavior pattern, a group of personality characteristics including time urgency and competitiveness, is linked to an increased risk of coronary disease. [7]

[edit] Treatment

[edit] Lifestyle changes

Lifestyle changes that may be useful in coronary disease include.

Weight control Smoking cessation Exercise

Healthy diet [8] A healthy diet would include the reduction of animal based foods and an increase in plant based foods.[9]

[edit] Medications to treat coronary disease

Cholesterol lowering medications, such as statins, are useful to decrease the amount of "bad" (LDL) cholesterol.[citation needed]

Nitroglycerin ACE inhibitors, which treat hypertension and may lower the risk of recurrent myocardial

infarction[citation needed]

Calcium channel blockers Aspirin [10]

[edit] Surgical intervention

Angioplasty Stents Coronary artery bypass [11] Heart Transplant

Osteoporosis

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Osteoporosis

Classification and external resources

Multiple osteoporotic wedge fractures demonstrated on a

lateral thoraco-lumbar spine X-ray

ICD-10 M 80. -M 82.

ICD-9 733.0

OMIM 166710

DiseasesDB 9385

MedlinePlus 000360

eMedicine med/1693 ped/1683 pmr/94 pmr/95

MeSH D010024

Osteoporosis is a disease of bones that leads to an increased risk of fracture. In osteoporosis the bone mineral density (BMD) is reduced, bone microarchitecture is disrupted, and the amount and variety of proteins in bone is altered. Osteoporosis is defined by the World Health Organization (WHO) in women as a bone mineral density 2.5 standard deviations below peak bone mass (20-

year-old healthy female average) as measured by DXA; the term "established osteoporosis" includes the presence of a fragility fracture.[1]

Osteoporosis is most common in women after menopause, when it is called postmenopausal osteoporosis, but may also develop in men, and may occur in anyone in the presence of particular hormonal disorders and other chronic diseases or as a result of medications, specifically glucocorticoids, when the disease is called steroid- or glucocorticoid-induced osteoporosis (SIOP or GIOP). Given its influence in the risk of fragility fracture, osteoporosis may significantly affect life expectancy and quality of life.

Disease of the parathyroid glands (hyperparathyroidism) is also a major cause of osteoporosis. Hyperparathyroidism should be high on the list of causes in any patient with severe osteoporosis, osteoporosis occurring at a young age, or osteoporosis in a male.

Over consumption of dietary protein is another often neglected cause of osteoporosis. The excess protein causes calcium to be taken from the bones and excreted in the urine.[2][3][4]

Osteoporosis can be prevented with lifestyle changes and sometimes medication; in people with osteoporosis, treatment may involve both. Lifestyle change includes exercise and preventing falls as well as reducing protein intake.[5][6] Medication includes calcium, vitamin D, bisphosphonates and several others. Fall-prevention advice includes exercise to tone deambulatory muscles, proprioception-improvement exercises; equilibrium therapies may be included. Exercise with its anabolic effect, may at the same time stop or reverse osteoporosis. Osteoporosis is a component of the frailty syndrome.

Contents[show]

[edit] Signs and symptoms

Osteoporosis itself has no specific symptoms; its main consequence is the increased risk of bone fractures. Osteoporotic fractures are those that occur in situations where healthy people would not normally break a bone; they are therefore regarded as fragility fractures. Typical fragility fractures occur in the vertebral column, rib, hip and wrist.

[edit] Fractures

The symptoms of a vertebral collapse ("compression fracture") are sudden back pain, often with radiculopathic pain (shooting pain due to nerve root compression) and rarely with spinal cord compression or cauda equina syndrome. Multiple vertebral fractures lead to a stooped posture, loss of height, and chronic pain with resultant reduction in mobility.[7]

Fractures of the long bones acutely impair mobility and may require surgery. Hip fracture, in particular, usually requires prompt surgery, as there are serious risks associated with a hip fracture, such as deep vein thrombosis and a pulmonary embolism, and increased mortality.

Fracture Risk Calculators assess the risk of fracture based upon several criteria, including BMD, age, smoking, alcohol usage, weight, and gender. Recognised calculators include FRAX[8] and Dubbo.

[edit] Falls risk

The increased risk of falling associated with aging leads to fractures of the wrist, spine and hip. The risk of falling, in turn, is increased by impaired eyesight due to any cause (e.g. glaucoma, macular degeneration), balance disorder, movement disorders (e.g. Parkinson's disease), dementia, and sarcopenia (age-related loss of skeletal muscle). Collapse (transient loss of postural tone with or without loss of consciousness) leads to a significant risk of falls; causes of syncope are manifold but may include cardiac arrhythmias (irregular heart beat), vasovagal syncope, orthostatic hypotension (abnormal drop in blood pressure on standing up) and seizures. Removal of obstacles and loose carpets in the living environment may substantially reduce falls. Those with previous falls, as well as those with a gait or balance disorder, are most at risk.[9]

[edit] Risk factors

Risk factors for osteoporotic fracture can be split between non-modifiable and (potentially) modifiable. In addition, there are specific diseases and disorders in which osteoporosis is a recognized complication. Medication use is theoretically modifiable, although in many cases the use of medication that increases osteoporosis risk is unavoidable.

[edit] Nonmodifiable

The most important risk factors for osteoporosis are advanced age (in both men and women) and female sex; oestrogen deficiency following menopause is correlated with a rapid reduction in bone mineral density, while in men a decrease in testosterone levels has a comparable (but less pronounced) effect. While osteoporosis occurs in people from all ethnic groups, European or Asian ancestry predisposes for osteoporosis.[10] Those with a family history of fracture or osteoporosis are at an increased risk; the heritability of the fracture as well as low bone mineral density are relatively high, ranging from 25 to 80 percent. There are at least 30 genes associated with the development of osteoporosis.[11] Those who have already had a fracture are at least twice as likely to have another fracture compared to someone of the same age and sex.[12]

[edit] Potentially modifiable

Excess alcohol—small amounts of alcohol do not increase osteoporosis risk and may even be beneficial, but chronic heavy drinking (alcohol intake greater than 3 units/day),[13] especially at a younger age, increases risk significantly.[14]

Vitamin D deficiency [15] —low circulating Vitamin D is common among the elderly worldwide.[16] Mild vitamin D insufficiency is associated with increased Parathyroid Hormone (PTH) production.[16] PTH increases bone resorption, leading to bone loss. A positive association exists between serum 1,25-dihydroxycholecalciferol levels and bone mineral density, while PTH is negatively associated with bone mineral density.[16]

Tobacco smoking —tobacco smoking inhibits the activity of osteoblasts, and is an independent risk factor for osteoporosis.[13][17] Smoking also results in increased breakdown of exogenous estrogen, lower body weight and earlier menopause, all of which contribute to lower bone mineral density.[16]

Malnutrition —nutrition has an important and complex role in maintenance of good bone. Identified risk factors include low dietary calcium and/or phosphorus, magnesium, zinc, boron, iron, fluoride, copper, vitamins A, K, E and C (and D where skin exposure to sunlight provides an inadequate supply). Excess sodium is a risk factor. High blood acidity may be diet-related, and is a known antagonist of bone.[18] Some have identified low protein intake as associated with lower peak bone mass during adolescence and lower bone mineral density in elderly populations.[16] Conversely, some have identified low protein intake as a positive factor, protein is among the causes of dietary acidity. Imbalance of omega 6 to omega 3 polyunsaturated fats is yet another identified risk factor.[1]

High protein diet—Research has found an association between diets high in animal protein and increased urinary calcium loss from the bones.[19][20][21]

Underweight /inactive—bone remodeling occurs in response to physical stress, and weight bearing exercise can increase peak bone mass achieved in adolescence.[16] In adults, physical activity helps maintain bone mass, and can increase it by 1 or 2%.[citation needed] Conversely, physical inactivity can lead to significant bone loss.[16] (Incidence of osteoporosis is lower in overweight people.)[22]

Excess physical activity—excessive exercise can lead to constant damage to the bones which can cause exhaustion of the structures as described above. There are numerous examples of marathon runners who developed severe osteoporosis later in life. In women, heavy exercise can lead to decreased estrogen levels, which predisposes to osteoporosis. In addition, intensive training without proper compensatory increased nutrition increases the risk.

Heavy metals —a strong association between cadmium, lead and bone disease has been established. Low level exposure to cadmium is associated with an increased loss of bone mineral density readily in both genders, leading to pain and increased risk of fractures, especially in the elderly and in females. Higher cadmium exposure results in osteomalacia (softening of the bone).[23]

Soft drinks—some studies indicate that soft drinks (many of which contain phosphoric acid) may increase risk of osteoporosis;[24] Others suggest soft drinks may displace calcium-containing drinks from the diet rather than directly causing osteoporosis.[25]

Caffeine —contrary to popular belief, there is no evidence linking caffeine to osteoporosis.[26]

[edit] Diseases and disorders

Many diseases and disorders have been associated with osteoporosis.[27] For some, the underlying mechanism influencing the bone metabolism is straight-forward, whereas for others the causes are multiple or unknown.

In general, immobilization causes bone loss (following the 'use it or lose it' rule). For example, localized osteoporosis can occur after prolonged immobilization of a fractured limb in a cast. This is also more common in active patients with a high bone turn-over (for example, athletes). Other examples include bone loss during space flight or in people who are bedridden or who use wheelchairs for various reasons.

Hypogonadal states can cause secondary osteoporosis. These include Turner syndrome, Klinefelter syndrome, Kallmann syndrome, anorexia nervosa, andropause,[28] hypothalamic amenorrhea or hyperprolactinemia.[28] In females, the effect of hypogonadism is mediated by estrogen deficiency. It can appear as early menopause (<45 years) or from prolonged premenopausal amenorrhea (>1 year). A bilateral oophorectomy (surgical removal of the ovaries) or a premature ovarian failure cause deficient estrogen production. In males, testosterone deficiency is the cause (for example, andropause or after surgical removal of the testes).

Endocrine disorders that can induce bone loss include Cushing's syndrome,[16] hyperparathyroidism,[16] thyrotoxicosis,[16] hypothyroidism, diabetes mellitus type 1 and 2,[29] acromegaly and adrenal insufficiency. In pregnancy and lactation, there can be a reversible bone loss.[27]

Malnutrition , parenteral nutrition [16] and malabsorption can lead to osteoporosis. Nutritional and gastrointestinal disorders that can predispose to osteoporosis include coeliac disease,[16] Crohn's disease, lactose intolerance, surgery[28] (after gastrectomy, intestinal bypass surgery or bowel resection) and severe liver disease (especially primary biliary cirrhosis).[28] Patients with bulimia can also develop osteoporosis. Those with an otherwise adequate calcium intake can develop osteoporosis due to the inability to absorb calcium and/or vitamin D. Other micro-nutrients such as vitamin K or vitamin B12 deficiency may also contribute.

Patients with rheumatologic disorders like rheumatoid arthritis,[28] ankylosing spondylitis,[28] systemic lupus erythematosus and polyarticular juvenile idiopathic arthritis are at increased risk of osteoporosis, either as part of their disease or because of other risk factors (notably corticosteroid therapy). Systemic diseases such as amyloidosis and sarcoidosis can also lead to osteoporosis.

Renal insufficiency can lead to osteodystrophy. Hematologic disorders linked to osteoporosis are multiple myeloma [28] and other monoclonal

gammopathies,[29] lymphoma and leukemia, mastocytosis,[28] hemophilia, sickle-cell disease and thalassemia.

Several inherited disorders have been linked to osteoporosis. These include osteogenesis imperfecta,[28] Marfan syndrome,[28] hemochromatosis,[16] hypophosphatasia, glycogen storage diseases, homocystinuria,[28] Ehlers-Danlos syndrome,[28] porphyria, Menkes' syndrome, epidermolysis bullosa and Gaucher's disease.

People with scoliosis of unknown cause also have a higher risk of osteoporosis. Bone loss can be a feature of complex regional pain syndrome. It is also more frequent in people with Parkinson's disease and chronic obstructive pulmonary disease.

[edit] Medication

Certain medications have been associated with an increase in osteoporosis risk; only steroids and anticonvulsants are classically associated, but evidence is emerging with regard to other drugs.

Steroid-induced osteoporosis (SIOP) arises due to use of glucocorticoids - analogous to Cushing's syndrome and involving mainly the axial skeleton. The synthetic glucocorticoid prescription drug prednisone is a main candidate after prolonged intake. Some professional guidelines recommend prophylaxis in patients who take the equivalent of more than 30 mg hydrocortisone (7.5 mg of prednisolone), especially when this is in excess of three months.[30] Alternate day use may not prevent this complication.[31]

Barbiturates , phenytoin and some other enzyme-inducing antiepileptics - these probably accelerate the metabolism of vitamin D.[32]

L-Thyroxine over-replacement may contribute to osteoporosis, in a similar fashion as thyrotoxicosis does.[27] This can be relevant in subclinical hypothyroidism.

Several drugs induce hypogonadism, for example aromatase inhibitors used in breast cancer, methotrexate and other anti-metabolite drugs, depot progesterone and gonadotropin-releasing hormone agonists.

Anticoagulants - long-term use of heparin is associated with a decrease in bone density,[33] and warfarin (and related coumarins) have been linked with an increased risk in osteoporotic fracture in long-term use.[34]

Proton pump inhibitors - these drugs inhibit the production of stomach acid; it is thought that this interferes with calcium absorption.[35] Chronic phosphate binding may also occur with aluminium-containing antacids.[27]

Thiazolidinediones (used for diabetes) - rosiglitazone and possibly pioglitazone, inhibitors of PPARγ, have been linked with an increased risk of osteoporosis and fracture.[36]

Chronic lithium therapy has been associated with osteoporosis.[27]

[edit] Pathogenesis

Osteoclast displaying many nuclei within its "foamy" cytoplasm

The underlying mechanism in all cases of osteoporosis is an imbalance between bone resorption and bone formation. In normal bone, there is constant matrix remodeling of bone; up to 10% of all bone mass may be undergoing remodeling at any point in time. The process takes place in bone multicellular units (BMUs) as first described by Frost in 1963.[37] Bone is resorbed by osteoclast cells (which derive from the bone marrow), after which new bone is deposited by osteoblast cells.[11]

The three main mechanisms by which osteoporosis develops are an inadequate peak bone mass (the skeleton develops insufficient mass and strength during growth), excessive bone resorption and inadequate formation of new bone during remodeling. An interplay of these three mechanisms underlies the development of fragile bone tissue.[11] Hormonal factors strongly determine the rate of bone resorption; lack of estrogen (e.g. as a result of menopause) increases bone resorption as well as decreasing the deposition of new bone that normally takes place in weight-bearing bones. The amount of estrogen needed to suppress this process is lower than that normally needed to stimulate the uterus and breast gland. The α-form of the estrogen receptor appears to be the most important in regulating bone turnover.[11] In addition to estrogen, calcium metabolism plays a significant role in bone turnover, and deficiency of calcium and vitamin D

leads to impaired bone deposition; in addition, the parathyroid glands react to low calcium levels by secreting parathyroid hormone (parathormone, PTH), which increases bone resorption to ensure sufficient calcium in the blood. The role of calcitonin, a hormone generated by the thyroid that increases bone deposition, is less clear and probably not as significant as that of PTH.[11]

Osteoblasts, several displaying a prominent Golgi apparatus, actively synthesizing osteoid containing two osteocytes.

The activation of osteoclasts is regulated by various molecular signals, of which RANKL (receptor activator for nuclear factor κB ligand) is one of best studied. This molecule is produced by osteoblasts and other cells (e.g. lymphocytes), and stimulates RANK (receptor activator of nuclear factor κB). Osteoprotegerin (OPG) binds RANKL before it has an opportunity to bind to RANK, and hence suppresses its ability to increase bone resorption. RANKL, RANK and OPG are closely related to tumor necrosis factor and its receptors. The role of the wnt signalling pathway is recognized but less well understood. Local production of eicosanoids and interleukins is thought to participate in the regulation of bone turnover, and excess or reduced production of these mediators may underlie the development of osteoporosis.[11]

Trabecular bone is the sponge-like bone in the ends of long bones and vertebrae. Cortical bone is the hard outer shell of bones and the middle of long bones. Because osteoblasts and osteoclasts inhabit the surface of bones, trabecular bone is more active, more subject to bone turnover, to remodeling. Not only is bone density decreased, but the microarchitecture of bone is disrupted. The weaker spicules of trabecular bone break ("microcracks"), and are replaced by weaker bone. Common osteoporotic fracture sites, the wrist, the hip and the spine, have a relatively high trabecular bone to cortical bone ratio. These areas rely on trabecular bone for strength, and therefore the intense remodeling causes these areas to degenerate most when the remodeling is imbalanced.[citation needed]

[edit] Diagnosis

A scanner used to measure bone density with dual-energy x-ray absorptiometry.

The diagnosis of osteoporosis can be made using conventional radiography and by measuring the bone mineral density (BMD).[38] The most popular method of measuring BMD is dual energy x-ray absorptiometry (DXA or DEXA). In addition to the detection of abnormal BMD, the diagnosis of osteoporosis requires investigations into potentially modifiable underlying causes; this may be done with blood tests. Depending on the likelihood of an underlying problem, investigations for cancer with metastasis to the bone, multiple myeloma, Cushing's disease and other above-mentioned causes may be performed.

[edit] Conventional radiography

Conventional radiography is useful, both by itself and in conjunction with CT or MRI, for detecting complications of osteopenia (reduced bone mass; pre-osteoporosis), such as fractures; for differential diagnosis of osteopenia; or for follow-up examinations in specific clinical settings, such as soft tissue calcifications, secondary hyperparathyroidism, or osteomalacia in renal osteodystrophy. However, radiography is relatively insensitive to detection of early disease and requires a substantial amount of bone loss (about 30%) to be apparent on x-ray images.

The main radiographic features of generalized osteoporosis are cortical thinning and increased radiolucency. Frequent complications of osteoporosis are vertebral fractures for which spinal radiography can help considerably in diagnosis and follow-up. Vertebral height measurements can objectively be made using plain-film x-rays by using several methods such as height loss together with area reduction, particularly when looking at vertical deformity in T4-L4, or by determining a spinal fracture index that takes into account the number of vertebrae involved.

Involvement of more than one vertebral bodies leads to kyphosis of the thoracic spine, obvious to the clinician as "dowager's hump."

[edit] Clinical decision rule

A number of clinical decision rules have been created to predict the risk of osteoporotic fractures. The QFracture score was developed in 2009 and is based on age, BMI, smoking status, alcohol use, rheumatoid arthritis, cardiovascular disease, type 2 diabetes, asthma, use of tricyclic antidepressants or corticosteroids, liver disease, and a history of falls in men. In women hormone replacement therapy, parental history of osteoporosis, gastrointestinal malabsorption, and menopausal symptoms are also taken into account.[39] A website is available to help apply this score.[40]

[edit] Dual energy X-ray absorptiometry

Dual energy X-ray absorptiometry (DXA, formerly DEXA) is considered the gold standard for the diagnosis of osteoporosis. Osteoporosis is diagnosed when the bone mineral density is less than or equal to 2.5 standard deviations below that of a young adult reference population. This is translated as a T-score. The World Health Organization has established the following diagnostic guidelines:[1][16]

T-score -1.0 or greater is "normal" T-score between -1.0 and -2.5 is "low bone mass" (or "osteopenia") T-score -2.5 or below is osteoporosis

When there has also been an osteoporotic fracture (also termed "low trauma-fracture" or "fragility fracture"), defined as one that occurs as a result of a fall from a standing height, the term "severe or established" osteoporosis is used.[1]

The International Society for Clinical Densitometry takes the position that a diagnosis of osteoporosis in men under 50 years of age should not be made on the basis of densitometric criteria alone. It also states that for pre-menopausal women, Z-scores (comparison with age group rather than peak bone mass) rather than T-scores should be used, and that the diagnosis of osteoporosis in such women also should not be made on the basis of densitometric criteria alone.[41]

[edit] Other measuring tools

Quantitative CT is different for DXA in that it gives separate estimates of BMD for trabecular and cortical bone as a true volumetric mineral density in mg/cm3. The technique can be performed at axial and peripheral sites, has sensitivity to changes over time, can analyze a whole area, and exclude irrelevant structures. Disadvantages are that it requires a high radiation dose, the scanners are expensive and large and are operator-dependent. The peripheral QCT has been developed to improve on the limitations of DXA and axial QCT.[42]

Quantitative ultrasound has many advantages in assessing osteoporosis. The modality is small, no ionizing radiation is involved, measurements can be made quickly and easily, and the cost of the device is low compared with DXA and QCT devices. The calcaneus is the most common skeletal site for quantitative ultrasound assessment because it has a high percentage of trabecular bone that is replaced more often than cortical bone, providing early evidence of metabolic change. Also, the calcaneus is fairly flat and parallel, reducing repositioning errors. The method can be applied to children, neonates, and preterm infants, just as well as to adults. Once microimaging tools to examine specific aspects of bone quality are developed, it is expected that quantitative ultrasound will be increasingly used in clinical practice.[43]

[edit] Screening

The U.S. Preventive Services Task Force (USPSTF) recommended in 2002 that all women 65 years of age or older should be screened with bone densitometry.[44] The Task Force recommends screening only those women ages 60 to 64 years of age who are at increased risk. The best risk factor for indicating increased risk is lower body weight (weight < 70 kg), with less evidence for smoking or family history. There was insufficient evidence to make recommendations about the optimal intervals for repeated screening and the appropriate age to stop screening. Clinical prediction rules are available to guide selection of women ages 60–64 for screening. The Osteoporosis Risk Assessment Instrument (ORAI) may be the most sensitive strategy[45]

Regarding the screening of men, a cost-analysis study suggests that screening may be "cost-effective for men with a self-reported prior fracture beginning at age 65 years and for men 80 years and older with no prior fracture".[46] Also cost-effective is the screening of adult men from middle age on to detect any significant decrease in testosterone levels, say, below 300.

[edit] Prevention

Methods to prevent osteoporosis include changes of lifestyle. However, there are medications that can be used for prevention as well. As a different concept there are osteoporosis ortheses which help to prevent spine fractures and support the building up of muscles. Fall prevention can help prevent osteoporosis complications.

[edit] Lifestyle

Lifestyle prevention of osteoporosis is in many aspects inversions from potentially modifiable risk factors. As tobacco smoking and unsafe alcohol intake have been linked with osteoporosis, smoking cessation and moderation of alcohol intake are commonly recommended in the prevention of osteoporosis. Many other risk factors, some modifiable and others non modifiable such as genetic may be involved in osteoporosis.[47]

Exercise

Achieving a higher peak bone mass through exercise and proper nutrition during adolescence is important for the prevention of osteoporosis. Exercise and nutrition throughout the rest of the life delays bone degeneration. Jogging, walking, or stair climbing at 70-90% of maximum effort

three times per week, along with 1,500 mg of calcium per day, increased bone density of the lumbar (lower) spine by 5% over nine months. Individuals already diagnosed with osteopenia or osteoporosis should discuss their exercise program with their physician to avoid fractures.[48]

Nutrition

Proper nutrition includes a diet sufficient in calcium and vitamin D. Patients at risk for osteoporosis (e.g. steroid use) are generally treated with vitamin D and calcium supplements and often with bisphosphonates. Vitamin D supplementation alone does not prevent fractures, and always needs to be combined with calcium.[49][50] Calcium supplements come in two forms: calcium carbonate and calcium citrate. Due to its lower cost, calcium carbonate is often the first choice, however it needs to be taken with food to maximize absorption. Calcium citrate is more expensive, but it is better absorbed than calcium carbonate and can be taken without food. In addition, patients who are taking proton pump inhibitors or H2 blockers do not absorb calcium carbonate well; calcium citrate is the supplement of choice in this population.[51] In renal disease, more active forms of Vitamin D such as cholecalciferol or (1,25-dihydroxycholecalciferol or calcitriol which is the main biologically active form of vitamin D) is used, as the kidney cannot adequately generate calcitriol from calcidiol (25-hydroxycholecalciferol) which is the storage form of vitamin D.In vitamin D assays, vitamin D2 (ergocalitrol) is not accurately measured, therefore vitamin D3 (cholecalciferol) is recommended for supplementation.[51]

High dietary protein intake increases calcium excretion in urine and has been linked to increased risk of fractures in research studies.[52] Other investigations have shown that protein is required for calcium absorption, but that excessive protein consumption inhibits this process. No interventional trials have been performed on dietary protein in the prevention and treatment of osteoporosis.[53]

[edit] Medication

Just as for treatment, bisphosphonate can be used in cases of very high risk. Other medicines prescribed for prevention of osteoporosis include raloxifene, a selective estrogen receptor modulator (SERM).

Estrogen replacement therapy remains a good treatment for prevention of osteoporosis but, at this time, is not recommended unless there are other indications for its use as well. There is uncertainty and controversy about whether estrogen should be recommended in women in the first decade after the menopause.

In hypogonadal men testosterone has been shown to give improvement in bone quantity and quality, but, as of 2008, there are no studies of the effects on fractures or in men with a normal testosterone level.[29]

[edit] Treatment

There are several medications used to treat osteoporosis, depending on gender. Medications themselves can be classified as antiresorptive or bone anabolic agents. Antiresorptive agents

work primarily by reducing bone resorption, while bone anabolic agents build bone rather than inhibit resorption. Lifestyle changes are an important aspect of treatment. A major problem is gaining long-term adherence to therapy from patients with osteoporosis. Fifty percent of patients do not take their medications and most discontinue within 1 year.[54]

[edit] Antiresorptive agents

Bisphosphonates

Bisphosphonates are the main pharmacological measures for treatment. However, newer drugs have appeared in the 1990s, such as teriparatide and strontium ranelate.In confirmed osteoporosis, bisphosphonate drugs are the first-line treatment in women. The most often prescribed bisphosphonates are presently sodium alendronate (Fosamax) 10 mg a day or 70 mg once a week, risedronate (Actonel) 5 mg a day or 35 mg once a week and/or ibandronate (Boniva) once a month.

A 2007 manufacturer-supported study suggested that in patients who had suffered a low-impact hip fracture, annual infusion of 5 mg zoledronic acid reduced risk of any fracture by 35% (from 13.9 to 8.6%), vertebral fracture risk from 3.8% to 1.7% and non-vertebral fracture risk from 10.7% to 7.6%. This study also found a mortality benefit: after 1.9 years, 9.6% of the study group (as opposed to 13.3% of the control group) had died of any cause, indicating a mortality benefit of 28%.[55] There are currently no studies which examine the efficacy or side-effects of zoledronic acid past the three-year period.[56]

Oral bisphosphonates are relatively poorly absorbed, and must therefore be taken on an empty stomach, with no food or drink to follow for the next 30 minutes. They are associated with inflammation of the esophagus (esophagitis) and are therefore sometimes poorly tolerated; weekly or monthly administration (depending on the preparation) decreases likelihood of esophagitis, and is now standard. Although intermittent dosing with the intravenous formulations such as zolendronate (zoledronic acid) avoids oral tolerance problems, these agents are implicated at higher rates in a rare but severe bone disease called osteonecrosis of the jaw.[57] For this reason, oral bisphosphonate therapy is probably to be preferred, and doctors now recommend that any needed remedial dental work be done before treatment begins.[58]

Estrogen analogs

Estrogen replacement therapy remains a good treatment for prevention of osteoporosis but, at this time, is not recommended unless there are other indications for its use as well. There is uncertainty and controversy about whether estrogen should be recommended in women in the first decade after the menopause.In hypogonadal men testosterone has been shown to give improvement in bone quantity and quality, but, as of 2008, there are no studies of the effects on fractures or in men with a normal testosterone level.[29]

Raloxifene

Selective Estrogen Receptor Modulators (SERMs) are a class of medications that act on the estrogen receptors throughout the body in a selective manner. Normally, bone mineral density (BMD) is tightly regulated by a balance between osteoblast and osteoclast activity in the trabecular bone. Estrogen has a major role in regulation of the bone formation-resorption equilibrium, as it stimulates osteoblast activity. Some SERMs such as raloxifene, act on the bone by slowing bone resorption by the osteoclasts.[59] Raloxifene has the added advantage of reducing the risk of invasive breast cancer.[60] SERMs have been proven effective in clinical trials.[61]

Calcitonin

Calcitonin works by directly inhibiting osteoclast activity via the calcitonin receptor. Calcitonin receptors have been identified on the surface of osteoclasts.[62] Calcitonin directly induces inhibition of osteoclastic bone resorption by affecting actin cytoskeleton which is needed for the osteoclastic activity.[63]

[edit] Bone anabolic agents

Teriparatide

Recently, teriparatide (Forteo, recombinant parathyroid hormone residues 1–34) has been shown to be effective in osteoporosis. It acts like parathyroid hormone and stimulates osteoblasts, thus increasing their activity. It is used mostly for patients with established osteoporosis (who have already fractured), have particularly low BMD or several risk factors for fracture or cannot tolerate the oral bisphosphonates. It is given as a daily injection with the use of a pen-type injection device. In some countries, Teriparatide is licensed to be used for treatment only if bisphosphonates have failed or are contraindicated. (In the US, this restriction has not been imposed by the FDA.) Patients with previous radiation therapy, or Paget's disease, or young patients, should avoid this medication.

Calcium salts

Calcium salts come as water insoluble and soluble formulations. Calcium carbonate is the primary water insoluble drug, while calcium citrate, lactate, and gluconate are water soluble. Calcium carbonate's absorption is improved in acidic conditions, while the water soluble salts are relatively unaffected by acidic conditions.

Sodium fluoride

Sodium fluoride treatment in patients with osteoporosis has been shown to cause skeletal changes such as pronounced bone density with increased number and thickness of trabeculae, cortical thickening, and partial obliteration of the medullary space.[64]

[edit] Other agents

RANKL inhibitors

Denosumab is a fully human monoclonal antibody that mimics the activity of osteoprotegerin. It binds to RANKL, thereby preventing RANKL from interacting with RANK and reducing its bone resorption. It was approved for use in the treatment of osteoporosis by the European Commission on May 28, 2010 and by the United States Food and Drug Administration on June 2, 2010.

Strontium ranelate

Oral strontium ranelate is an alternative oral treatment, belonging to a class of drugs called "dual action bone agents" (DABAs) by its manufacturer. It has proven efficacy, especially in the prevention of vertebral fracture.[65] In laboratory experiments, strontium ranelate was noted to stimulate the proliferation of osteoblasts, as well as inhibiting the proliferation of osteoclasts.Strontium ranelate is taken as a 2 g oral suspension daily, and is licenced for the treatment of osteoporosis to prevent vertebral and hip fracture. Strontium ranelate has side effect benefits over the bisphosphonates, as it does not cause any form of upper GI side effect, which is the most common cause for medication withdrawal in osteoporosis. In studies a small increase in the risk of venous thromboembolism was noted,[66] the cause for which has not been determined. This suggests it may be less suitable in patients at risk for thrombosis for different reasons. The uptake of (heavier) strontium in place of calcium into bone matrix results in a substantial and disproportionate increase in bone mineral density as measured on DXA scanning,[67] making further followup of bone density by this method harder to interpret for strontium treated patients. A correction algorithm has been devised.[68]

Although strontium ranelate is effective, it is not approved for use in the United States yet. However, strontium citrate is available in the US from several well-known vitamin manufacturers. Most researchers believe that strontium is safe and effective no matter what form it is used. The ranelate form is simply a device invented by the Servier company of France so that they could patent their version of strontium.[citation needed]

Strontium, no matter what the form, must be water-soluble and ionized in the stomach acid. Strontium is then protein-bound for transport from the intestinal tract into the blood stream. Unlike drugs like sodium alendronate (Fosamax), strontium doesn't inhibit bone recycling and, in fact, may produce stronger bones. Studies have shown that after five years alendronate may even cause bone loss, while strontium continues to build bone during lifetime use.[citation needed]

Strontium must not be taken with food or calcium-containing preparations as calcium competes with strontium during uptake. However, it is essential that calcium, magnesium, and vitamin D in therapeutic amounts must be taken daily, but not at the same time as strontium. Strontium should be taken on an empty stomach at night.[citation needed]

[edit] Nutrition

Calcium

Calcium is required to support bone growth, bone healing and maintain bone strength and is one aspect of treatment for osteoporosis. Recommendations for calcium intake vary depending country and age; for individuals at higher risk of osteoporosis (after fifty years of age) the amount recommended by US health agencies is 1,200 mg per day. Calcium supplements can be used to increase dietary intake, and absorption is optimized through taking in several small (500 mg or less) doses throughout the day.[69] The role of calcium in preventing and treating osteoporosis is unclear — some populations with extremely low calcium intake also have extremely low rates of bone fracture, and others with high rates of calcium intake through milk and milk products have higher rates of bone fracture. Other factors, such as protein, salt and vitamin D intake, exercise and exposure to sunlight, can all influence bone mineralization, making calcium intake one factor among many in the development of osteoporosis.[70] In the report of WHO (World Health Organization) in 2007, because calcium is consumed by an acid load with food, it influences osteoporosis.[71][72]

A meta-analysis of randomized controlled trials involving calcium and calcium plus vitamin D supported the use of high levels of calcium (1,200 mg or more) and vitamin D (800 IU or more), though outcomes varied depending on which measure was used to assess bone health (rates of fracture versus rates of bone loss).[73] The meta-analysis, along with another study, also supported much better outcomes for patients with high compliance to the treatment protocol.[74] In contrast, despite earlier reports in improved high density lipoprotein (HDL, "good cholesterol") in calcium supplementation, a possible increase in the rate of myocardial infarction (heart attack) was found in a study in New Zealand in which 1471 women participated. If confirmed, this would indicate that calcium supplementation in women otherwise at low risk of fracture may cause more harm than good.[75]

Vitamin D

Several studies have shown that a high intake of vitamin D reduces fractures in the elderly,[73][76] The Women's Health Initiative found that though calcium plus vitamin D did increase bone density by 1% but it did not affect hip fracture. It did increase formation of kidney stones by 17%.[77] This study has been criticised for using an inadequate dose of vitamin D (400 U) and for allowing the control arm to take supplemental vitamin D.

[edit] ExerciseMultiple studies have shown that aerobics, weight bearing, and resistance exercises can all maintain or increase BMD in postmenopausal women.[78] Many researchers have attempted to pinpoint which types of exercise are most effective at improving BMD and other metrics of bone quality, however results have varied. The BEST (Bone-Estrogen Strength Training) Project at the University of Arizona identified six specific weight training exercises that yielded the largest improvements in BMD; this project suggests squat, military press, lat pulldown, leg press, back extension, and seated row, with three weight training sessions a week of two sets of each exercise, alternating between moderate (6-8 reps at 70% of 1-rep max) and heavy (4-6 reps at 80% of 1-rep max).[79] One year of regular jumping exercises appears to increase the BMD and moment of inertia of the proximal tibia [80] in normal postmenopausal women. Treadmill walking, gymnastic training, stepping, jumping, endurance, and strength exercises all resulted in significant increases of L2-L4 BMD in osteopenic postmenopausal women.[81][82][83] Strength training elicited improvements specifically in distal radius and hip BMD.[84] Exercise combined with other pharmacological treatments such as hormone replacement therapy (HRT) has been shown to increases BMD more than HRT alone.[85]

Additional benefits for osteoporotic patients other than BMD increase include improvements in balance, gait, and a reduction in risk of falls.[86]

Definitions of Lrti on the Web:

While often used as a synonym for pneumonia, the rubric of lower respiratory tract infection can also be applied to other types of infection including lung abscess, acute bronchitis, and emphysema. Symptoms include shortness of breath, weakness, high fever, coughing and fatigue.

LRTI n. lower respiratory tract infection.

PID: Pelvic inflammatory disease (PID) is a general term that refers to infection of the fallopian tubes (tubes that carry eggs from the ovary to the womb) and of other internal reproductive organs in women. It is a common and serious complication of some sexually transmitted diseases (STDs). Inside the lower abdominal cavity, PID can damage the fallopian tubes and tissues in and near the uterus and ovaries. Untreated PID can lead to serious consequences including infertility, ectopic pregnancy, abscess formation, and chronic pelvic pain. 1

Pelvic Inflammatory Disease: Infection of the womb and fallopian tubes.

Pelvic Inflammatory Disease: Pelvic inflammatory disease (PID) is a general term that refers to infection of the fallopian tubes (tubes that carry eggs from the ovary to the womb) and of other internal reproductive organs in women. It is a common and serious complication of some sexually transmitted diseases (STDs). Inside the lower abdominal

cavity, PID can damage the fallopian tubes and tissues in and near the uterus and ovaries. Untreated PID can lead to serious consequences including infertility, ectopic pregnancy, abscess formation, and chronic pelvic pain. 1

Researching symptoms of Pelvic Inflammatory Disease: Further information about the symptoms of Pelvic Inflammatory Disease is available including a list of symptoms of Pelvic Inflammatory Disease, other diseases that might have similar symptoms in differential diagnosis of Pelvic Inflammatory Disease, or alternatively return to research other symptoms in the symptom center.

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Causes of Pelvic Inflammatory Disease: Research more detailed information about the causes of Pelvic Inflammatory Disease, other possibly hidden causes of Pelvic Inflammatory Disease, or other general information about Pelvic Inflammatory Disease.

Statistics and Pelvic Inflammatory Disease: Various sources and calculations are available in statistics about Pelvic Inflammatory Disease, prevalence and incidence statistics for Pelvic Inflammatory Disease, and you can also research other medical statistics in our statistics center.

Dyspepsia (from the Greek "δυς-" (Dys-) and "πέψη" (Pepse)), known as upset stomach or indigestion, refers to a condition of impaired digestion.[1] It is a medical condition characterized by chronic or recurrent pain in the upper abdomen, upper abdominal fullness and feeling full earlier than expected when eating.[2] It can be accompanied by bloating, belching, nausea, or heartburn. Dyspepsia is a common problem, and is frequently due to gastro-oesophageal reflux disease (GERD) or gastritis, but in a small minority may be the first symptom of peptic ulcer

disease (an ulcer of the stomach or duodenum) and occasionally cancer. Hence, unexplained newly-onset dyspepsia in people over 55 or the presence of other alarm symptoms may require further investigations.[3]

Contents[show]

[edit] Signs and symptoms

Please help improve this article by expanding it. Further information might be found on the talk page. (May 2008)

The characteristic symptoms of dyspepsia are upper abdominal pain, bloating, fullness and tenderness on palpation.[citation needed] Pain worsened by exertion and associated with nausea and perspiration may also indicate angina.[citation needed]

Occasionally dyspeptic symptoms are caused by medication, such as calcium antagonists (used for angina or high blood pressure), nitrates (used for angina), theophylline (used for chronic lung disease), bisphosphonates, corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDs, used as painkillers).[3]

The presence of gastrointestinal bleeding (vomit containing blood), difficulty swallowing, loss of appetite, unintentional weight loss, abdominal swelling and persistent vomiting are suggestive of peptic ulcer disease or malignancy, and would necessitate urgent investigations.[3]

[edit] Diagnosis

People under 55 years, without alarm symptoms, can be treated without investigation. People over 55 years with recent onset dyspepsia or those with alarm symptoms should be urgently investigated by upper gastrointestinal endoscopy. This will rule out peptic ulcer disease, medication-related ulceration, malignancy and other rarer causes.[3]

People under the age of 55 years with no alarm features do not need endoscopy but are considered for investigation for peptic ulcer disease caused by Helicobacter pylori infection. Investigation for H. pylori infection is usually performed when there is a moderate to high prevalence of this infection in the local community or the person with dyspepsia has other risk factors for H. pylori infection, related for example to ethnicity or immigration from a high-prevalence area. If infection is confirmed it can usually be eradicated by medication.

Medication-related dyspepsia is usually related to non-steroidal anti-inflammatory drugs (NSAIDs) and can be complicated by bleeding or ulceration with perforation of stomach wall.

[edit] Treatment

Functional and undifferentiated dyspepsia have similar treatments. Decisions around the use of drug therapy are difficult because trials included heartburn in the definition of dyspepsia. This led to the results favoring proton pump inhibitors (PPIs), which are effective for the treatment of heartburn. Traditional therapies used for this diagnosis include lifestyle modification, antacids, H2-receptor antagonists (H2-RAs), prokinetic agents, and antiflatulents. It has been noted that one of the most frustrating aspects of treating functional dyspepsia is that these traditional agents have been shown to have little or no efficacy.[4]

Antacids and sucralfate were found to be no better than placebo in a literature review.[5] H2-RAs have been shown to have marked benefit in poor quality trials (30% relative risk reduction[5]), but only a marginal benefit in good quality trials.[4] Prokinetic agents would empirically seem to work well since delayed gastric emptying is considered a major pathophysiological mechanism in functional dyspepsia.[4] They have been shown in a meta-analysis to produce a relative risk reduction of up to 50%, but the studies evaluated to come to this conclusion used the drug cisapride which has since been removed from the market (now only available as an investigational agent[6] due to serious adverse events such as torsades, and publication bias has been cited as a potential partial explanation for such a high benefit.[5] Modern prokinetic agents such as metoclopramide, erythromycin and tegaserod have little or no established efficacy and often result in substantial side effects.[5] Simethicone has been found to be of some value, as one trial suggests potential benefit over placebo and another shows equivalence with cisapride.[5] So, with the somewhat recent advent of the proton pump inhibitor (PPI) class of medications, the question of whether these new agents are superior to traditional therapy has arisen.

A 2002 systemic review of herbal products found that several herbs, including peppermint and caraway, have anti-dyspeptic effects for non-ulcer dyspepsia with "encouraging safety profiles".[7] A 2004 meta-analysis, pooling data from three double-blind placebo-controlled studies, found the multiple herbal extract Iberogast to be significantly more effective than placebo (p value = .001) at treating patients with functional dyspepsia through the targeting of multiple dyspeptic pathologies.[8] This German-made phytopharmaceutical was found to be equivalent to cisapride and significantly superior to metoclopramide at reducing the symptoms of functional dyspepsia over a four week period.[9][10] Retrospective surveillance of 40,961 children (12 years and under) found no serious side-effects.[11]

Currently, PPIs are, depending on the specific drug, FDA indicated for erosive esophagitis, gastroesophageal reflux disease (GERD), Zollinger-Ellison syndrome, eradication of H. pylori, duodenal and gastric ulcers, and NSAID-induced ulcer healing and prevention, but not functional dyspepsia. There are, however, evidence-based guidelines and literature that evaluate the use of PPIs for this indication. A helpful chart summarizing the major trials is available from the functional dyspepsia guidelines published in the World Journal of Gastroenterology in 2006.[4]

The CADET study was the first to compare a PPI (omeprazole 20mg daily) to both an H2-RA (ranitidine 150mg BID) as well as a prokinetic agent (cisapride 20mg BID) alongside placebo.[12] The study evaluated these agents in patients at 4 weeks and 6 months and noted that omeprazole had a significantly better response at 6 months (31%) than cisapride (13%) or placebo (14%) (p =

.001) while it was just above the cutoff for being statistically significantly better than ranitidine (21%) (p = .053). Omeprazole also showed a significant increase in quality of life scores over the other agents and placebo in all but one category measured (p = .01 to .05).

The ENCORE study, which was a follow-up of patients from the OPERA study, showed responders to omeprazole therapy had fewer clinic visits than non-responders (1.5 vs 2.0) over a three month period (p < .001).[13][14]

Zollinger–Ellison syndrome is a triad of gastric acid hypersecretion,severe peptic ulceration,non-beta cell islet tumor of pancreas(Gastrinoma). In this syndrome increased levels of the hormone gastrin are produced, causing the stomach to produce excess hydrochloric acid. Often the cause is a tumor (gastrinoma) of the duodenum or pancreas producing the hormone gastrin. Gastrin then causes an excessive production of acid which can lead to peptic ulcers in almost 95% of patients.

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[edit] Pathophysiology

Gastrin works on stomach parietal cells causing them to secrete more hydrogen ions into the stomach lumen. In addition, gastrin acts as a trophic factor for parietal cells, causing parietal cell hyperplasia. Thus there is an increase in the number of acid-secreting cells, and each of these cells produces acid at a higher rate. The increase in acidity contributes to the development of multiple peptic ulcers in the stomach and duodenum (small bowel).

[edit] Presentation

Patients with Zollinger–Ellison syndrome may experience abdominal pain and diarrhea. The diagnosis is also suspected in patients without symptoms who have severe ulceration of the stomach and small bowel, especially if they fail to respond to treatment.

Gastrinomas may occur as single tumors or as multiple, small tumors. About one-half to two-thirds of single gastrinomas are malignant tumors that most commonly spread to the liver and lymph nodes near the pancreas and small bowel. Nearly 25 percent of patients with gastrinomas have multiple tumors as part of a condition called multiple endocrine neoplasia type I (MEN I). MEN I patients have tumors in their pituitary gland and parathyroid glands in addition to tumors of the pancreas.

[edit] Symptoms

epigastric pain (stomach ache) diarrhea

melena Vomiting Weight loss

[edit] Diagnosis

Clinical suspicion of Zollinger–Ellison syndrome may be aroused when the above symptoms prove resistant to treatment, when the symptoms are especially suggestive of the syndrome, or endoscopy is suggestive. The diagnosis of Zollinger–Ellison syndrome is made by several laboratory tests and imaging studies.

Secretin stimulation test, which measures evoked gastrin levels Fasting gastrin levels, on at least three separate occasions[1]

Gastric acid secretion and pH

In addition, the source of the increased gastrin production must be discovered. This is either done using MRI or somatostatin receptor scintigraphy, the investigation of choice.[2]

[edit] Therapy

Proton pump inhibitors (such as omeprazole and lansoprazole) and histamine H2-receptor antagonists (such as famotidine and ranitidine) are used to slow down acid secretion. Cure is only possible if the tumors are surgically removed, or treated with chemotherapy. Octreotide can be used to alleviate symptoms.

[edit] History

This syndrome was first described in 1955 by Robert Zollinger and Edwin Ellison, surgeons at the Ohio State University.[

A hiatus hernia or hiatal hernia is the protrusion (or herniation) of the upper part of the stomach into the thorax through a tear or weakness in the diaphragm.

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[edit] Classification

Schematic Diagramm of different types of hiatus hernia. Green is the esophagus, Red is the diaphragma, blue is the HIS-angle. A is the normal anatomy, B is a pre-stage, C is a sliding hiatal hernia, and D is a paraesophageal type

There are two major kinds of hiatus hernia: [1]

The most common (95%) is the sliding hiatus hernia, where the gastroesophageal junction moves above the diaphragm together with some of the stomach.

The second kind is rolling (or paraesophageal) hiatus hernia, when a part of the stomach herniates through the esophageal hiatus and lies beside the esophagus, without movement of the gastroesophageal junction. It accounts for the remaining 5% of hiatus hernias. [2]

A third kind is also sometimes described, and is a combination of the first and second kinds.

[edit] Signs and symptoms

Hiatal Hernia has often been called the "great mimic" because its symptoms can resemble many disorders. For example, a person with this problem can experience dull pains in their chest, shortness of breath (caused by the hernia's effect on the diaphragm), and heart palpitations (due to irritation of the vagus nerve).

In most cases however, a hiatal hernia does not cause any symptoms. The pain and discomfort that a patient experiences is due to the reflux of gastric acid, air or bile. While there are several causes of acid reflux, it does happen more frequently in the presence of hiatal hernia.

[edit] Risk factors

The following are risk factors that can result in a hiatus hernia.

Increased pressure within the abdomen caused by: o Heavy lifting or bending overo Frequent or hard coughingo Hard sneezingo Pregnancy and deliveryo Violent vomiting o Straining with constipationo Obesity (extra weight pushes down on the abdomen increasing the pressure)o Use of the sitting position for defecation [3] (See epidemiology below)

Heredity Smoking Drug use , such as cocaine.[citation needed]

Stress Diaphragm weakness[citation needed]

[edit] Diagnosis

A large hiatus hernia on Xray marked by open arrows in contrast to the heart borders marked by closed arrows.

Upper GI endoscopy depicting hiatus hernia.

The diagnosis of a hiatus hernia is typically made through an upper GI series, endoscopy or High resolution manometry.

[edit] Treatment

In most cases, sufferers experience no discomfort and no treatment is required. However, when the hiatal hernia is large, or is of the paraesophageal type, it is likely to cause esophageal stricture and discomfort. Symptomatic patients should elevate the head of their beds and avoid lying down directly after meals until treatment is rendered. If the condition has been brought on by stress, stress reduction techniques may be prescribed, or if overweight, weight loss may be indicated. Medications that reduce the lower esophageal sphincter (or LES) pressure should be avoided. Antisecretory drugs like proton pump inhibitors and H2 receptor blockers can be used to reduce acid secretion.

Where hernia symptoms are severe and chronic acid reflux is involved, surgery is sometimes recommended, as chronic reflux can severely injure the esophagus and even lead to esophageal cancer.

The surgical procedure used is called Nissen fundoplication. In fundoplication, the gastric fundus (upper part) of the stomach is wrapped, or plicated, around the inferior part of the esophagus, preventing herniation of the stomach through the hiatus in the diaphragm and the reflux of gastric acid. The procedure is now commonly performed laparoscopically. With proper patient selection, laparoscopic fundoplication has low complication rates and a quick recovery.[4]

Complications include gas bloat syndrome, dysphagia (trouble swallowing), dumping syndrome, excessive scarring, and rarely, achalasia. The procedure sometimes fails over time, requiring a second surgery to make repairs.

[edit] Prognosis

A hiatus hernia per se does not cause any symptoms. The condition promotes reflux of gastric contents (via its direct and indirect actions on the anti-reflux mechanism) and thus is associated with gastroesophageal reflux disease (GERD). In this way a hiatus hernia is associated with all the potential consequences of GERD - heartburn, esophagitis, Barrett's esophagus and esophageal cancer. However the risk attributable to the hiatus hernia is difficult to quantify, and at most is low.[citation needed]

Besides discomfort from GERD and dysphagia, hiatal hernias can have severe consequences if not treated. While sliding hernias are primarily associated with gastroesophageal acid reflux, rolling hernias can strangulate a portion of the stomach above the diaphragm. This strangulation can result in esophageal or GI tract obstruction and the tissue can even become ischemic and necrose.

Another severe complication, although very rare, is a large herniation that can restrict the inflation of a lung, causing pain and breathing problems.

Most cases are asymptomatic.

[edit] Epidemiology

Incidence of hiatal hernias increases with age; approximately 60% of individuals aged 50 or older have a hiatal hernia.[5] Of these, 9% are symptomatic, depending on the competence of the lower esophageal sphincter (LES). 95% of these are "sliding" hiatus hernias, in which the LES protrudes above the diaphragm along with the stomach, and only 5% are the "rolling" type (paraesophageal), in which the LES remains stationary but the stomach protrudes above the diaphragm. People of all ages can get this condition, but it is more common in older people.

According to Dr. Denis Burkitt, "Hiatus hernia has its maximum prevalence in economically developed communities in North America and Western Europe....In contrast the disease is rare in situations typified by rural African communities."[3] Burkitt attributes the disease to insufficient dietary fiber and the use of the unnatural sitting position for defecation. Both factors create the need for straining at stool, increasing intraabdominal pressure and pushing the stomach through the esophageal hiatus in the diaphragm.[6]

Measurement of MIC

The minimum inhibitory concentration or MIC is defined as the minimum concentration of antibiotic which will inhibit the growth of the isolated microorganism . There are many ways to measure the MIC, including:

Broth dilution Agar dilution E-test

An example of the broth dilution test is shown below.

This figure shows a schematic of the broth dilution test. Bacteria are inoculated into tubes containing culture broth and varying concentrations of the antibiotic to be tested. The tubes are incubated to allow bacterial growth. The MIC is read as the lowest concentration of antibiotic which inhibited bacterial growth. In the above example, the MIC would be 8 micrograms/ml. The interpretation of this MIC depends on the organism/antibiotic pair being tested, and is made following standard NCCLS guidelines.

Minimum inhibitory concentration

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(MIC), in microbiology, is the lowest concentration of an antimicrobial that will inhibit the visible growth of a microorganism after overnight incubation. Minimum inhibitory concentrations are important in diagnostic laboratories to confirm resistance of microorganisms to an antimicrobial agent and also to monitor the activity of new antimicrobial agents.[1] An MIC is generally regarded as the most basic laboratory measurement of the activity of an antimicrobial agent against an organism.[2]

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[edit] Determination

MICs can be determined by agar or broth dilution methods usually following the guidelines of a reference body such as the CLSI, BSAC or EUCAST. There are several commercial methods available, including the well established Etest strips and the recently launched Oxoid MICEvaluator method.

The Etest system comprises a predefined and continuous concentration gradient of different antimicrobial agents, which when applied to inoculated agar plates and incubated, create ellipses of microbial inhibition.[1] The MIC is determined where the ellipse of inhibition intersects the strip, and is easily read off the MIC reading scale on the strip.[2]

[edit] Clinical significance

Clinically, the minimum inhibitory concentrations are used not only to determine the amount of antibiotic that the patient will receive but also the type of antibiotic used, which in turn lowers the opportunity for microbial resistance to specific antimicrobial agents.

Intrauterine contraceptive device.

Nosocomial infections (pronounced, nos-uh-KOH-mee-uhl), are infections that are a result of treatment in a hospital or a healthcare service unit. Infections are considered nosocomial if they first appear 48 hours or more after hospital admission or within 30 days after discharge.[citation

needed] Nosocomial comes from the Greek word nosokomeion (νοσοκομείον) meaning hospital (nosos = disease, komeo = to take care of). This type of infection is also known as a hospital-acquired infection (or, in generic terms, healthcare-associated infection).

In the United States, the Centers for Disease Control and Prevention estimates that roughly 1.7 million hospital-associated infections, from all types of bacteria combined, cause or contribute to 99,000 deaths each year.[1] In Europe, where hospital surveys have been conducted, the category of Gram-negative infections are estimated to account for two-thirds of the 25,000 deaths each year. Nosocomial infections can cause severe pneumonia and infections of the urinary tract, bloodstream and other parts of the body. Many types are difficult to attack with antibiotics, and antibiotic resistance is spreading to Gram-negative bacteria that can infect people outside the hospital.[1]

Nosocomial infections are commonly transmitted when hospital officials become complacent and personnel do not practice correct hygiene regularly. Also, increased use of outpatient treatment means that people who are hospitalized are more ill and have more weakened immune systems than may have been true in the past. Moreover, some medical procedures bypass the body's natural protective barriers. Since medical staff move from patient to patient, the staff themselves serve as a means for spreading pathogens.

Hospitals have sanitation protocols regarding uniforms, equipment sterilization, washing, and other preventative measures. Thorough hand washing and/or use of alcohol rubs by all medical personnel before and after each patient contact is one of the most effective ways to combat nosocomial infections.[2] More careful use of antimicrobial agents, such as antibiotics, is also considered vital.[3]

Despite sanitation protocol, patients cannot be entirely isolated from infectious agents. Furthermore, patients are often prescribed antibiotics and other antimicrobial drugs to help treat illness; this may increase the selection pressure for the emergence of resistant strains.

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[edit] Epidemiology

[edit] Categories and treatment

Among the categories of bacteria most known to infect patients are the category MRSA, Gram-positive bacteria and Acinetobacter, which is Gram-negative. While there are antibiotic drugs that can treat diseases caused by Gram-positive MRSA, there are currently few effective drugs for Acinetobacter. However, Acinetobacter germs are evolving and becoming immune to existing antibiotics. "In many respects it’s far worse than MRSA," said a specialist at Case Western Reserve University.[1]

Another growing disease, especially prevalent in New York City hospitals, is the drug-resistant Gram-negative germ, Klebsiella pneumoniae. It is estimated that more than 20 percent of the Klebsiella infections in Brooklyn hospitals "are now resistant to virtually all modern antibiotics. And those supergerms are now spreading worldwide."[1]

The bacteria, classified as Gram-negative because of their reaction to the Gram stain test, can cause severe pneumonia and infections of the urinary tract, bloodstream, and other parts of the body. Their cell structure makes them more difficult to attack with antibiotics than Gram-positive organisms like MRSA. In some cases, antibiotic resistance is spreading to Gram-negative bacteria that can infect people outside the hospital. "For Gram-positives we need better drugs; for Gram-negatives we need any drugs," said Dr. Brad Spellberg, an infectious-disease specialist at Harbor-UCLA Medical Center, and the author of Rising Plague, a book about drug-resistant pathogens.[1]

One-third of nosocomial infections are considered preventable. Ms. magazine reports that as many as 92 percent of deaths from hospital infections could be prevented.[4] The most common nosocomial infections are of the urinary tract, surgical site and various pneumonias.[5]

[edit] Country estimates

The methods used differ from country to country (definitions used, type of nosocomial infections covered, health units surveyed, inclusion or exclusion of imported infections, etc.), so that international comparisons of nosocomial infection rates should be made with the utmost care.

United States: The Centers for Disease Control and Prevention (CDC) estimates that roughly 1.7 million hospital-associated infections, from all types of bacteria combined, cause or contribute to

99,000 deaths each year.[1] Other estimates indicate that 10%, or 2 million, patients a year become infected, with the annual cost ranging from $4.5 billion to $11 billion.

France: estimates ranged from 6.7% in 1990 to 7.4% (patients may have several infections).[6] At national level, prevalence among patients in health care facilities was 6.7% in 1996,[7] 5.9% in 2001[8] and 5.0% in 2006.[9] The rates for nosocomial infections were 7.6% in 1996, 6.4% in 2001 and 5.4% in 2006.

In 2006, the most common infection sites were urinary tract infections (30,3 %), pneumopathy (14,7 %), infections of surgery site (14,2 %). infections of the skin and mucous membrane (10,2 %), other respiratory infections (6,8%) and bacterial infections / blood poisoning (6,4 %).[10] The rates among adult patients in intensive care were 13,5% in 2004, 14,6% in 2005, 14,1% in 2006 and 14.4% in 2007.[11]

It has also been estimated that nosocomial infections make patients stay in the hospital 4-5 additional days. Around 2004-2005, about 9,000 people died each year with a nosocomial infection, of which about 4,200 would have survived without this infection.[12]

Italy: since 2000, estimates show that about 6.7 % infection rate, i.e. between 450,000 and 700,000 patients, which caused between 4,500 and 7,000 deaths.[13] A survey in Lombardy gave a rate of 4.9% of patients in 2000.[14]

United Kingdom: estimates of 10% infection rate,[15] with 8.2% estimated in 2006.[16]

Switzerland: estimates range between 2 and 14%.[17] A national survey gave a rate of 7.2% in 2004.[18]

Finland: estimated at 8.5% of patients in 2005[19]

[edit] Transmission

The drug-resistant Gram-negative germs for the most part threaten only hospitalized patients whose immune systems are weak. The germs can survive for a long time on surfaces in the hospital and enter the body through wounds, catheters, and ventilators.[1]

Main routes of transmission

Route Description

Contact transmission

the most important and frequent mode of transmission of nosocomial infections.

Droplet transmission

occurs when droplets are generated from the source person mainly during coughing, sneezing, and talking, and during the performance of certain procedures such as bronchoscopy. Transmission occurs when droplets containing germs from the infected

person are propelled a short distance through the air and deposited on the host's body.

Airborne transmission

occurs by dissemination of either airborne droplet nuclei (small-particle residue {5 µm or smaller in size} of evaporated droplets containing microorganisms that remain suspended in the air for long periods of time) or dust particles containing the infectious agent. Microorganisms carried in this manner can be dispersed widely by air currents and may become inhaled by a susceptible host within the same room or over a longer distance from the source patient, depending on environmental factors; therefore, special air handling and ventilation are required to prevent airborne transmission. Microorganisms transmitted by airborne transmission include Legionella, Mycobacterium tuberculosis and the rubeola and varicella viruses.

Common vehicle transmission

applies to microorganisms transmitted to the host by contaminated items such as food, water, medications, devices, and equipment.

Vector borne transmission

occurs when vectors such as mosquitoes, flies, rats, and other vermin transmit microorganisms.

Contact transmission is divided into two subgroups: direct-contact transmission and indirect-contact transmission.

Routes of contact transmission

Route Description

Direct-contact transmission

involves a direct body surface-to-body surface contact and physical transfer of microorganisms between a susceptible host and an infected or colonized person, such as occurs when a person turns a patient, gives a patient a bath, or performs other patient-care activities that require direct personal contact. Direct-contact transmission also can occur between two patients, with one serving as the source of the infectious microorganisms and the other as a susceptible host.

Indirect-contact transmission

involves contact of a susceptible host with a contaminated intermediate object, usually inanimate, such as contaminated instruments, needles, or dressings, or contaminated gloves that are not changed between patients. In addition, the improper use of saline flush syringes, vials, and bags has been implicated in disease transmission in the US, even when healthcare workers had access to gloves, disposable needles, intravenous devices, and flushes.[20]

[edit] Risk factors

Factors predisposing a patient to infection can broadly be divided into three areas:

People in hospitals are usually already in a poor state of health, impairing their defense against bacteria – advanced age or premature birth along with immunodeficiency (due to drugs, illness, or irradiation) present a general risk, while other diseases can present specific risks - for instance, chronic obstructive pulmonary disease can increase chances of respiratory tract infection.

Invasive devices, for instance intubation tubes, catheters, surgical drains, and tracheostomy tubes all bypass the body’s natural lines of defence against pathogens and provide an easy route for infection. Patients already colonised on admission are instantly put at greater risk when they undergo an invasive procedure.

A patient’s treatment itself can leave them vulnerable to infection – immunosuppression and antacid treatment undermine the body’s defences, while antimicrobial therapy (removing competitive flora and only leaving resistant organisms) and recurrent blood transfusions have also been identified as risk factors.

[edit] Prevention

[edit] Isolation

Isolation precautions are designed to prevent transmission of microorganisms by common routes in hospitals. Because agent and host factors are more difficult to control, interruption of transfer of microorganisms is directed primarily at transmission.

[edit] Handwashing and gloving

Handwashing frequently is called the single most important measure to reduce the risks of transmitting skin microorganisms from one person to another or from one site to another on the same patient. Washing hands as promptly and thoroughly as possible between patient contacts and after contact with blood, body fluids, secretions, excretions, and equipment or articles contaminated by them is an important component of infection control and isolation precautions.

Although handwashing may seem like a simple process, it is often performed incorrectly. Healthcare settings must continuously remind practitioners and visitors on the proper procedure in washing their hands to comply with responsible handwashing. Simple programs such as Henry the Hand, and the use of handwashing signals can assist healthcare facilities in the prevention of nosocomial infections.

All visitors must follow the same procedures as hospital staff to adequately control the spread of infections. Visitors and healthcare personnel are equally to blame in transmitting infections. Moreover, multidrug-resistant infections can leave the hospital and become part of the community flora if we do not take steps to stop this transmission.

In addition to handwashing, gloves play an important role in reducing the risks of transmission of microorganisms. Gloves are worn for three important reasons in hospitals. First, gloves are worn to provide a protective barrier and to prevent gross contamination of the hands when touching blood, body fluids, secretions, excretions, mucous membranes, and nonintact skin. In the USA, the Occupational Safety and Health Administration has mandated wearing gloves to reduce the risk of bloodborne pathogen infecition.[21] Second, gloves are worn to reduce the likelihood that

microorganisms present on the hands of personnel will be transmitted to patients during invasive or other patient-care procedures that involve touching a patient's mucous membranes and nonintact skin. Third, gloves are worn to reduce the likelihood that hands of personnel contaminated with microorganisms from a patient or a fomite can transmit these microorganisms to another patient. In this situation, gloves must be changed between patient contacts, and hands should be washed after gloves are removed.

Wearing gloves does not replace the need for handwashing, because gloves may have small, non-apparent defects or may be torn during use, and hands can become contaminated during removal of gloves. Failure to change gloves between patient contacts is an infection control hazard.

[edit] Surface sanitation

Sanitizing surfaces is an often overlooked, yet critical component of breaking the cycle of infection in health care environments. Modern sanitizing methods such as NAV-CO2 have been effective against gastroenteritis, MRSA, and influenza. Use of hydrogen peroxide vapor has been clinically proven to reduce infection rates and risk of acquisition. Hydrogen peroxide is effective against endospore-forming bacteria, such as Clostridium difficile, where alcohol has been shown to be ineffective.[22]

[edit] Aprons

Wearing an apron during patient care reduces the risk of infection.[citation needed] The apron should either be disposable or be used only when caring for a specific patient.

[edit] Mitigation

The most effective technique of controlling nosocomial infection is to strategically implement QA/QC measures to the health care sectors and evidence-based management can be a feasible approach. For those VAP/HAP diseases (ventilator-associated pneumonia, hospital-acquired pneumonia), controlling and monitoring hospital indoor air quality needs to be on agenda in management [23] whereas for nosocomial rotavirus infection, a hand hygiene protocol has to be enforced.[24][25][26] Other areas that the management needs to be covered include

Tonsillectomy

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Typical appearance of the back of the throat three days post tonsillectomy.

A tonsillectomy is a 2,000 year-old [1] surgical procedure in which the tonsils are removed from either side of the throat. The procedure is performed in response to cases of repeated occurrence of acute tonsillitis or adenoiditis, obstructive sleep apnea, nasal airway obstruction, snoring, or peritonsillar abscess. Sometimes the adenoids are removed at the same time, a procedure called adenoidectomy. Although tonsillectomy is being performed less frequently than in the 1950s, it remains one of the most common surgical procedures in children in the United States.

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[edit] Indications

Tonsillectomy may be indicated when the patient:

Experiences recurrent infections of acute tonsillitis. The number requiring tonsillectomy varies with the severity of the episodes. One case, even severe, is generally not enough for most surgeons to decide tonsillectomy is necessary. Paradise in 1983 defined recurrent tonsillitis warranting surgery by the attack frequency standard as "Seven or more in a year, five or more per year for two years, or three or more per year for three years."[2] However according to the current guidelines (2000) of the American Academy of Otolaryngology & Head and Neck Surgery (AAO-HNS), tonsillectomy is indicated if a patient contracts "Three or more attacks of sore throat per year despite adequate medical therapy."[3]

Has chronic tonsillitis, consisting of persistent, moderate-to-severe throat pain. Has multiple bouts of peritonsillar abscess. Has sleep apnea (stopping or obstructing breathing at night due to enlarged tonsils or adenoids) Has difficulty eating or swallowing due to enlarged tonsils (very unusual reason for

tonsillectomy) Produces tonsilloliths (tonsil stones) in the back of their mouth.

Has abnormally large tonsils with crypts (Craters or impacts in the tonsils)

[edit] Controversy over indications

The American Academy of Otolaryngology & Head and Neck Surgery (AAO-HNS) stated that "In many cases, tonsillectomy may be a more effective treatment, and less costly, than prolonged or repeated treatments for an infected throat...For the past several years, the Academy has been developing clinical guidelines based on evidence and outcomes research, including ‘Quality of Life after Tonsillectomy,’ a January 2008 supplement to the journal Otolaryngology—Head and Neck Surgery."

[edit] Morbidity and mortality

The morbidity rate associated with tonsillectomy is 2% to 4% due to post-operative bleeding; the mortality rate is 1 in 25,000, due to bleeding, airway obstruction, or anesthesia.[4]

[edit] Effectiveness

The effectiveness of the tonsillectomy has been questioned in a 2009 systematic review of 7765 papers, published in the journal Otolaryngology—Head and Neck Surgery. The review found that it was most likely not effective all the time, but rather was modestly effective, and that "not a single paper reported that tonsillectomy is invariably effective in eliminating sore throats"[5]. Another systematic review of cases involving children found that there was only a short-term benefit - "A child who meets these strict criteria will probably suffer from 6 throat infections in the next two years. A child who has surgery now will probably suffer from 3 throat infections. In two years there will probably be no difference."[6]

[edit] Post-operative care

A sore throat will persist for around two weeks. Most patients do not feel like swallowing anything during the first few days after surgery. Patients should try to get as much fluid down as possible, as it will help speed recovery. Very cold drinks will help bring down swelling. Ice cream, frozen yogurt and other dairy products are not recommended because they leave a film in the mouth that is difficult to swallow. Sherbet and popsicles, on the other hand, are recommended. Additionally, Slushies are particularly helpful for sore throats, especially when sugar-free.

Pain following the procedure is significant and may include a hospital stay.[7] Recovery can take from 10 up to 20 days, during which narcotic analgesics are typically prescribed. Patients are encouraged to maintain diet of liquid and very soft foods for several days following surgery. Rough textured, acidic or spicy foods may be irritating and should be avoided. Proper hydration is very important during this time, since dehydration can increase throat pain, leading to a vicious cycle of poor fluid intake.[8][9]

At some point, most commonly 7–11 days after the surgery (but occasionally as long as two weeks (14 days) after), bleeding can occur when scabs begin sloughing off from the surgical sites. The overall risk of bleeding is approximately 1%–2% higher in adults.[10] Approximately 3% of adult patients develop significant bleeding at this time. The bleeding might naturally stop quickly or else mild intervention (e.g., gargling cold water) could be needed (but ask the doctor before gargling because it might bruise the area of the skin that has been cauterized). Otherwise, a surgeon must repair the bleeding immediately by cauterization, which presents all the risks associated with emergency surgery (primarily the administration of anesthesia particularly on a patient whose stomach may not be empty).

Generally speaking, tonsils will be removed if a patient needs antibiotics to be prescribed 6 times a year for tonsilitis, and the General Practitioner's recommendation is based on how the quality of life will be improved after the operation. Tonsillectomies can be performed while the patient is actually suffering from tonsillitis, however this increases the risk of bleeding.

[edit] Common causes, demographics

Infections requiring tonsillectomy are often a result of Streptococcus ("strep throat"), particularly Streptococcus pyogenes; some may be due to other bacteria, such as Streptococcus viridans, Staphylococcus aureus, and Haemophilus influenzae. However, the etiology of the condition is largely irrelevant in determining whether tonsillectomy is required.[11]

Most tonsillectomies are performed on children, although many are also performed on teenagers and adults; in the United States, it is the most common major surgical procedure performed on children.[12] The number of tonsillectomies in the United States has dropped significantly from over a million cases per year in the 1950s[12] to approximately 600,000 in the late 1990s.[citation

needed] This has been due in part to more stringent guidelines for tonsillectomy and adenoidectomy (see tonsillitis and adenoid). Still, debate about the usefulness of tonsillectomies continues. Enlarged tonsils are removed more often among adults and children for sleep apnea (airway obstruction while sleeping), snoring, and upper airway obstruction. Children who have sleep apnea can do poorly in school, are tired during the day, may be bedwetters beyond what is normal, and have some links to ADHD.[13][14]

Tonsillectomy in adults is more painful[citation needed] than in children, although each patient will have a different experience. Various procedures are available to remove tonsils, each with different advantages and disadvantages. Children and teenagers sometimes exhibit a noticeable change in voice[15] after the operation.[16]

[edit] Surgical procedure

The generally accepted procedure for tonsillectomy involves separating and removing the tonsils from the subcapsular plane – a fascia of tissue that surrounds the tonsils.[17] Removal is typically achieved using a scalpel and blunt dissection or with electrocautery, although harmonic scalpels or lasers have also been used. Bleeding is stopped with electrocautery, ligation of sutures, and the topical use of thrombin, a protein that induces blood clotting.

The procedure is carried out with the patient lying flat on their backs, with the shoulders elevated on a small pillow so that the neck is hyperextended – the so-called 'Rose' position. A mouth gag is used to prop the mouth open; if an adenoidectomy is also being performed, the adenoids are first removed with a curette; the nasopharynx is then packed with sterile gauze. A tonsil is removed by holding it by the upper part, pulling it slightly medially, and making a cut over the anterior faucial pillar. After the tonsil is removed from its position, a snare can be used to make a small cut on the lower portion prior to removal of the tonsil. The use of electrocautery minimizes the blood loss.[18]

[edit] Other methods

The scalpel is the preferred surgical instrument of many ear, nose, and throat specialists. However, there are other procedures available – the choice may be dictated by the extent of the procedure (complete tonsil removal versus partial tonsillectomy) and other considerations such as pain and post-operative bleeding. A quick review of each procedure follows:

Dissection and snare method: Removal of the tonsils by use of a forceps and scissors with a wire loop called a 'snare' is the most common method practiced by otolaryngologists today. The procedure requires the patient to undergo general anesthesia; the tonsils are completely removed and the skin is cauterized. The patient will leave with minimal post-operative bleeding.

Electrocautery : Electrocautery burns the tonsillar tissue and assists in reducing blood loss through cauterization. Research has shown that the heat of electrocautery (400°C) results in thermal injury to surrounding tissue. This may result in more discomfort during the postoperative period.

Harmonic scalpel: This medical device uses ultrasonic energy to vibrate its blade at 55kHz. Invisible to the naked eye, the vibration transfers energy to the tissue, providing simultaneous cutting and coagulation. The temperature of the surrounding tissue reaches 80°C. Proponents of this procedure assert that the end result is precise cutting with minimal thermal damage.

Radiofrequency ablation: Monopolar radiofrequency thermal ablation transfers radiofrequency energy to the tonsil tissue through probes inserted in the tonsil. The procedure can be performed in an office (outpatient) setting under light sedation or local anesthesia. After the treatment is performed, scarring occurs within the tonsil causing it to decrease in size over a period of several weeks. The treatment can be performed several times. The advantages of this technique are minimal discomfort, ease of operations, and immediate return to work or school. Tonsillar tissue remains after the procedure but is less prominent. This procedure is recommended for treating enlarged tonsils and not chronic or recurrent tonsillitis.

Thermal Welding: A new technology which uses pure thermal energy to seal and divide the tissue. The absence of thermal spread means that the temperature of surrounding tissue is only 2-3 °C higher than normal body temperature. Clinical papers show patients with minimal post-operative pain (no requirement for narcotic pain-killers), zero edema (swelling) plus almost no incidence of bleeding. Hospitals in the US are advertising this procedure as "Painless Tonsillectomy". Also known as Tissue Welding.

Carbon dioxide laser: Laser tonsil ablation (LTA) finds the otolaryngologist employing a hand-held CO2 or KTP laser to vaporize and remove tonsil tissue. This technique reduces tonsil volume and eliminates recesses in the tonsils that collect chronic and recurrent infections. This procedure is recommended for chronic recurrent tonsillitis, chronic sore throats, severe halitosis, or airway obstruction caused by enlarged tonsils. The LTA is performed in 15 to 20

minutes in an office setting under local anesthesia.[19] The patient leaves the office with minimal discomfort and returns to school or work the next day. Post-tonsillectomy bleeding may occur in 2-5% of patients. Previous research studies state that laser technology provides significantly less pain during the post-operative recovery of children, resulting in less sleep disturbance, decreased morbidity, and less need for medications. On the other hand, some believe that children are adverse to outpatient procedures without sedation.

Microdebrider: The microdebrider is a powered rotary shaving device with continuous suction often used during sinus surgery. It is made up of a cannula or tube, connected to a hand piece, which in turn is connected to a motor with foot control and a suction device. The endoscopic microdebrider is used in performing a partial tonsillectomy, by partially shaving the tonsils. This procedure entails eliminating the obstructive portion of the tonsil while preserving the tonsillar capsule. A natural biologic dressing is left in place over the pharyngeal muscles, preventing injury, inflammation, and infection. The procedure results in less post-operative pain, a more rapid recovery, and perhaps fewer delayed complications. However, the partial tonsillectomy is suggested for enlarged tonsils – not those that incur repeated infections.

Bipolar Radiofrequency Ablation (see Coblation tonsillectomy): This procedure produces an ionized saline layer that disrupts molecular bonds without using heat. As the energy is transferred to the tissue, ionic dissociation occurs. This mechanism can be used to remove all or only part of the tonsil. It is done under general anesthesia in the operating room and can be used for enlarged tonsils and chronic or recurrent infections. This causes removal of tissue with a thermal effect of 45-85 °C. It has been claimed that this technique results in less pain, faster healing, and less post operative care [20]. However, review of 21 studies gives conflicting results about levels of pain, and its comparative safety has yet to be confirmed [21]. This technique has been criticized for a higher than expected rate of bleeding presumably due to the low temperature which may be insufficient to seal the divided blood vessels.

Bacteremia (also Bacteraemia or Bacteræmia) is the presence of bacteria in the blood. The blood is normally a sterile environment, so the detection of bacteria in the blood (most commonly with blood cultures) is always abnormal.

Bacteria can enter the bloodstream as a severe complication of infections (like pneumonia or meningitis), during surgery (especially when involving mucous membranes such as the gastrointestinal tract), or due to catheters and other foreign bodies entering the arteries or veins (including intravenous drug abuse).

Bacteremia can have several consequences. The immune response to the bacteria can cause sepsis and septic shock, which has a relatively high mortality rate. Bacteria can also use the blood to spread to other parts of the body (which is called hematogenous spread), causing infections away from the original site of infection. Examples include endocarditis or osteomyelitis. Treatment is with antibiotics, and prevention with antibiotic prophylaxis can be given in situations where problems are to be expected.

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[edit] Definition

Bacteremia is the presence of viable bacteria in the blood stream. Bacteremia is different from sepsis (so-called blood poisoning or toxemia), which is a condition where bacteremia is associated with an inflammatory response from the body (causing systemic inflammatory response syndrome, characterised by rapid breathing, low blood pressure, fever, etc.). Common dental procedures, such as brushing teeth, are the most common cause of bacteremia, introducing a detectable amount of bacteria into the bloodstream, even if these rarely cause any clinical condition. Some patients with prosthetic heart valves however need antibiotic prophylaxis for dental surgery because bacteremia might lead to endocarditis (infection of the interior lining of the heart). Salmonella - which is assumed to only cause gastroenteritis in much of the middle-class or developed world - can cause a specific and virulent form of bacteremia in the developing world, especially in Africa. This form of bacteremia is particularly deadly to infants and people whose immune systems have been damaged by HIV, according to studies done by the Universities of Malawi and Liverpool at the Wellcome Trust Clinical Research Programme in Blantyre. Researchers announced in March 2008 in the Journal of Clinical Investigation that a study of 352 Malawian children had revealed antibodies against salmonella when the bacteria leaves the safety of the cells and moves into the bloodstream, and these antibodies may form the basis of an eventual vaccine.

Septicemia is an ill-defined non-scientific term introducing more confusion between sepsis and bacteremia: it suggests there is something in the bloodstream causing sepsis.

[edit] Causes

In the hospital, indwelling catheters are a frequent cause of bacteremia and subsequent nosocomial infections, because they provide a means by which bacteria normally found on the skin can enter the bloodstream. Other causes of bacteremia include dental procedures (occasionally including simple tooth brushing), herpes (including herpetic whitlow), urinary tract infections, intravenous drug use, and colorectal cancer. Bacteremia may also be seen in oropharyngeal, gastrointestinal or genitourinary surgery or exploration.

[edit] Consequences

Bacteremia, as noted above, frequently elicits a vigorous immune system response. The constellation of findings related to this response (such as fever, chills, or hypotension) is referred to as sepsis. In the setting of more severe disturbances of temperature, respiration, heart rate or white blood cell count, the response is characterized as septic shock, and may result in multiple organ dysfunction syndrome.

Bacteremia is the principal means by which local infections are spread to distant organs (referred to as hematogenous spread). Bacteremia is typically transient rather than continuous, due to a

vigorous immune system response when bacteria are detected in the blood. Hematogenous dissemination of bacteria is part of the pathophysiology of meningitis and endocarditis, and of Pott's disease and many other forms of osteomyelitis.

[edit] Diagnosis

Bacteremia is most commonly diagnosed by blood culture, in which a sample of blood is allowed to incubate with a medium that promotes bacterial growth. Since blood is normally sterile, this process does not normally lead to the isolation of bacteria. If, however, bacteria are present in the bloodstream at the time the sample is obtained, the bacteria will multiply and can thereby be detected. Any bacteria that incidentally find their way to the culture medium will also multiply. For this reason, blood cultures must be drawn with great attention to sterile process. Occasionally, blood cultures will reveal the presence of bacteria that represent contamination from the skin through which the culture was obtained. Blood cultures must be repeated at intervals to determine if persistent — rather than transient — bacteremia is present.

Septicemia: Systemic (bodywide) illness with toxicity due to invasion of the bloodstream by virulent bacteria coming from a local seat of infection. The symptoms of chills, fever and

exhaustion are caused by the bacteria and substances they produce. The disorder is treated with massive doses of antibiotics. Also known as blood poisoning.

Intrauterine growth restriction: The growth of the fetus is abnormally slow. When born, the baby appears too small, considering its' dates. Intrauterine growth restriction is associated with

increased risk of medical illness and death in the newborn.

Intrauterine growth restriction is also referred to as intrauterine growth retardation.

PIH (or more specifically, pregnancy-induced hypertension) is a type of high blood pressure that an expectant mother can experience during pregnancy. Hypertension means that there is an increase in resistance in the patients blood vessels, which could potentially interfere with blood flow to vital organs, including the uterus and placenta. Though this only occurs in 5 to 8 percent of pregnancies, it is can be more common if the mother has preexisting hypertension, kidney disease, diabetes, or multiple fetuses.

Once an obstetrician, nurse, or any other medical staff member discovers this condition, they are responsible for treating you with an optimal level of care and minimizing complications. If this is not done in the proper manner (or at all), medical malpractice may have occurred. If you believe you have been mistreated by a medical professional, contact an attorney right away.

Certain complications that can be related to PIH include the following:

Restricted blood flow to liver, kidneys, brain, uterus and placenta Placental abruption Intrauterine growth restriction Stillbirth Seizures

Death

Once you notice the symptoms of PIH (increased blood pressure, sudden weight gain, blurred vision, nausea, etc.), you should immediately contact your obstetrician. Once he or she knows of the problem, he or she should be able to treat you in the proper manner and take special consideration to your condition. If you feel that you have been neglected or mistreated and complications arose from it, you may have a right to bring that individual to court.

The best way to bring justice to a careless or negligent medical professional is by bringing them to court and letting the court system determine who is at-fault. If malpractice did indeed occur, you may be entitled to financial compensation to help you pay for any damages that resulted.

Pre-eclampsia is a medical condition in which hypertension arises in pregnancy (pregnancy-induced hypertension) in association with significant amounts of protein in the urine. Pre-eclampsia refers to a set of symptoms rather than any causative factor, and there are many different causes for the condition. It appears likely that there are substances from the placenta that can cause endothelial dysfunction in the maternal blood vessels of susceptible women.[1] While blood pressure elevation is the most visible sign of the disease, it involves generalized damage to the maternal endothelium, kidneys, and liver, with the release of vasoconstrictive factors being secondary to the original damage.

Pre-eclampsia may develop from 20 weeks gestation (it is considered early onset before 32 weeks, which is associated with increased morbidity). Its progress differs among patients; most cases are diagnosed pre-term. Pre-eclampsia may also occur up to six weeks post-partum. Apart from Caesarean section or induction of labor (and therefore delivery of the placenta), there is no known cure. It is the most common of the dangerous pregnancy complications; it may affect both the mother and the unborn child.[1]

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[edit] Diagnosis

Pre-eclampsia is diagnosed when a pregnant woman develops high blood pressure (two separate readings taken at least 6 hours apart of 140/90 or more) and 300 mg of protein in a 24-hour urine sample (proteinuria). A rise in baseline BP of 30mmHg systolic or 15mmHg diastolic while not meeting the absolute criteria of 140/90 is still considered important to note but is not considered diagnostic. Swelling or edema (especially in the hands and face) was originally considered an important sign for a diagnosis of pre-eclampsia, but in current medical practice only hypertension and proteinuria are necessary for a diagnosis. Pitting edema (unusual swelling, particularly of the hands, feet, or face, notable by leaving an indentation when pressed on) can be significant, and should be reported to a health care provider.

"Severe preeclampsia" involves a BP over 160/110,[2][3] and additional symptoms.

Pre-eclampsia may progress to eclampsia, characterized by the appearance of tonic-clonic seizures. This happens only very rarely with proper treatment.

Although eclampsia is potentially fatal, pre-eclampsia is often asymptomatic, and so its detection depends on signs or investigations. Nonetheless, one symptom is crucially important because it is often misinterpreted. The epigastric pain, which reflects hepatic involvement and is typical of the HELLP syndrome, may easily be confused with heartburn, a very common problem of pregnancy. It can be distinguished from heartburn when it is not burning in quality, does not spread upwards towards the throat, is associated with hepatic tenderness, may radiate through to the back, and is not relieved by giving antacids. It is often very severe, described by sufferers as the worst pain that they have ever experienced. Affected women are not uncommonly referred to general surgeons as suffering from an acute abdomen (for example, acute cholecystitis).

In general, none of the signs of pre-eclampsia are specific, and even convulsions in pregnancy are more likely to have causes other than eclampsia in modern practice. Diagnosis, therefore, depends on finding a coincidence of several pre-eclamptic features, the final proof being their regression after delivery.

Some women develop high blood pressure without proteinuria (protein in urine), which is called Pregnancy-induced hypertension (PIH) or gestational hypertension. Both pre-eclampsia and PIH are regarded as very serious conditions and require careful monitoring of mother and fetus.

[edit] Epidemiology

Pre-eclampsia occurs in as many as 10% of pregnancies, usually in the second or third trimester and after the 32nd week. Some women will experience pre-eclampsia as early as 20 weeks, though this is rare. It is much more common in women who are pregnant for the first time,[4] and its frequency drops significantly in second pregnancies. While change of paternity in a subsequent pregnancy is now thought to lower risk except in those with a family history of hypertensive pregnancy,[5] since increasing maternal age raises risk[6], it has been difficult to evaluate how significant paternity change actually is and studies are providing conflicting data on this point.

Pre-eclampsia is also more common in women who have preexisting hypertension, diabetes, autoimmune diseases such as lupus, various inherited thrombophilias such as Factor V Leiden, renal disease, women with a family history of pre-eclampsia, obese women, and women with a multiple gestation (twins or multiple birth). The single most significant risk for developing pre-eclampsia is having had pre-eclampsia in a previous pregnancy.

Pre-eclampsia may also occur in the immediate post-partum period. This is referred to as "postpartum pre-eclampsia." The most dangerous time for the mother is the 24–48 hours postpartum and careful attention should be paid to pre-eclampsia signs and symptoms.[7]

[edit] Causes

The pre-eclampsia syndrome is thought in many cases to be caused by a shallowly implanted placenta which becomes hypoxic, leading to an immune reaction characterized by secretion of upregulated inflammatory mediators from the placenta, and acting on the vascular endothelium. The shallow implantation is thought to stem from the maternal immune system's response to the placenta. This theory emphasizes the role of the maternal immune system, and refers to evidence suggesting a lack of established immunological tolerance in pregnancy, resulting in an immune response against paternal antigens from the fetus and its placenta.[8] In some cases of pre-eclampsia it is thought that the mother lacks the receptors for the proteins the placenta is using to downregulate the maternal immune system's response to it.[9] This view is also consistent with evidence showing many miscarriages to be an immunological disorder where the mother's immune system "unleashes a destructive attack on the tissues of the developing fetus."[10]

In many cases of the pre-eclampsia syndrome, however, the maternal response to the placenta appears to have allowed for normal implantation. It is possible that women with higher baseline levels of inflammation stemming from underlying conditions such as chronic hypertension or autoimmune disease may have less tolerance for the inflammatory burden of pregnancy.

If severe, preeclampsia progresses to fulminant pre-eclampsia, with headaches, visual disturbances, and epigastric pain, and further to HELLP syndrome and eclampsia. Placental abruption is associated with hypertensive pregnancies. These are life-threatening conditions for both the developing baby and the mother.

Many theories have attempted to explain why preeclampsia arises, and have linked the syndrome to the presence of the following:

endothelial cell injury immune rejection of the placenta compromised placental perfusion altered vascular reactivity imbalance between prostacyclin and thromboxane decreased glomerular filtration rate with retention of salt and water decreased intravascular volume increased central nervous system irritability disseminated intravascular coagulation uterine muscle stretch (ischemia) dietary factors, including vitamin deficiency genetic factors[11]

air pollution[12]

obesity [13]

The current understanding of the syndrome is as a two-stage process, with a highly variable first stage which predisposes the placenta to hypoxia, followed by the release of soluble factors which result in many of the other observed phenomena. Many of the older theories can be subsumed under this umbrella, as the soluble factors have been shown to cause, for example, endothelial

cell injury, altered vascular reactivity, the classic lesion of glomerular endotheliosis, decreased intravascular volume, inflammation, etc. Underlying maternal susceptibility to the damage is likely implicated as well.

[edit] Pathogenesis

Although much research into the etiology and mechanism of pre-eclampsia has taken place, its exact pathogenesis remains uncertain. Some studies support notions of inadequate blood supply to the placenta making it release particular hormones or chemical agents that, in mothers predisposed to the condition, leads to damage of the endothelium (lining of blood vessels), alterations in metabolism, inflammation, and other possible reactions.[1]

Some studies suggest that hypoxia resulting from inadequate perfusion upregulates sFlt-1, a VEGF and PlGF antagonist, leading to a damaged maternal endothelium and restriction of placental growth.[14] In addition, endoglin, a TGF-beta antagonist, is elevated in pregnant women who develop preeclampsia.[15] Soluble endoglin is likely upregulated by the placenta in response to an upregulation of cell-surface endoglin produced by the maternal immune system, although there is also the potential that sEng is produced by the maternal endothelium. Levels of both sFlt-1 and sEng increase as severity of disease increases, with levels of sEng surpassing levels of sFlt-1 in HELLP syndrome cases. Recent data indicate that Gadd45a stress signaling regulates elevated sFlt-1 expression in preeclampsia.[16]

Both sFlt-1 and sEng are upregulated in all pregnant women to some extent, supporting the idea that hypertensive disease in pregnancy is a normal pregnancy adaptation gone awry. As natural killer cells are intimately involved in placentation and as placentation involves a degree of maternal tolerance for a foreign placenta which requires maternal resources for its support, it is not surprising that the maternal immune system might respond more negatively to the arrival of some placentae under certain circumstances, such as a placenta which is more invasive than normal. Initial maternal rejection of the placental cytotrophoblasts may be the cause of the inadequately remodeled spiral arteries in those cases of preeclampsia associated with shallow implantation, leading to downstream hypoxia and the appearance of maternal symptoms in response to upregulated sFlt-1 and sEng. (See parent-offspring conflict.)

It has been documented that fetal cells such as fetal erythroblasts as well as cell-free fetal DNA are increased in the maternal circulation in women who develop preeclampsia. These findings have given rise to the hypothesis that preeclampsia is a disease process by which a placental lesion such as hypoxia allows increased fetal material into maternal circulation that leads to an immune response and endothelial damage ultimately resulting in preeclampsia and eclampsia.

[edit] Differential diagnosis

Preeclampsia-eclampsia can mimic and be confused with many other diseases, including chronic hypertension, chronic renal disease, primary seizure disorders, gallbladder and pancreatic disease, immune or thrombotic thrombocytopenic purpura, antiphospholipid syndrome and hemolytic-uremic syndrome. It must always be considered a possibility in any pregnant woman

beyond 20 weeks of gestation. It is particularly difficult to diagnose when preexisting disease such as hypertension is present.[17]

[edit] Complications

Eclampsia can occur after the onset of pre-eclampsia. Eclampsia, which is a more serious condition, complicates 1 in 2000 maternities in the United Kingdom and carries a maternal mortality of 1.8 percent.[18] The HELLP syndrome is more common, probably about 1 in 500 maternities, but may be as dangerous as eclampsia itself. These two major maternal crises can present unheralded by prodromal signs of pre-eclampsia.

Cerebral hemorrhage is a lesion that can kill women with pre-eclampsia or eclampsia. In that cerebral hemorrhage is a known complication of severe hypertension in other contexts, it must be assumed that this is a major predisposing factor in this situation, although this has not been proven. Adult respiratory distress syndrome appears to have become more common, it is not known whether this is a consequence of modern methods of respiratory support rather than of the disease itself.

Uric acid levels may help to predict maternal complications among patients with preeclampsia according to a systematic review and decision analysis. [19] In this study, the sensitivity was 68% and specificity was 68%. In this study which assumed a prevalence of maternal complications was 5%, the positive predictive value of 6.2% and negative predictive value of 98.6% ( click here to adjust these results for patients at higher or lower risk of maternal complications). In their clinical decision analysis, they presumed initially a distress ratio of 10 (defined as being the expected distress of severe complications valued as 10 times worse the the expected distress of a caesarean section), and under these assumptions, they concluded that there would be the least expected distress from using serum uric acid for clinical decision making. The writers of this study acknowledged that there were significant limitations to their review due to heterogeneity of the individual studies they examined with regards to several variables.

[edit] Treatment and prevention

The only known treatments for eclampsia or advancing pre-eclampsia are abortion or delivery, either by labor induction or Caesarean section. However, post-partum pre-eclampsia may occur up to 6 weeks following delivery even if symptoms were not present during the pregnancy. Post-partum pre-eclampsia is dangerous to the health of the mother since she may ignore or dismiss symptoms as simple post-delivery headaches and edema. Hypertension can sometimes be controlled with anti-hypertensive medication, but any effect this might have on the progress of the underlying disease is unknown.

Women with underlying inflammatory disorders such as chronic hypertension or autoimmune diseases would likely benefit from aggressive treatment of those conditions prior to conception, tamping down the overactive immune system.[citation needed]

Thrombophilias may be weakly linked to pre-eclampsia. There are no high quality studies to suggest that blood thinners will prevent pre-eclampsia in thrombophilic women.[20]

Smoking reduces risk of preeclampsia[21][22] (though smoking is discouraged in pregnancy in general.)

[edit] Anti-Hypertensive Therapy

Antihypertensives may reduce maternal and fetal mortality among pregnancy patients with hypertension as compared to placebo according to a randomized controlled trial . [23] Overall, after 3 weeks of treatment, MAP was lower in the isradipine group, but when compared with the placebo group, the difference in MAP did not have statistical significance. After treatment with isradipine, those patients with no proteinuria experienced a decrease of between 8.5 and 11.3 mmHg whereas those with proteinuria experienced about only 1 mmHg difference in systolic blood pressure. Those treated with placebo in both groups did not experience much change in systolic blood pressure, regardless of proteinuria being present or not. Therefore, the authors concluded that proteinuric patients may respond differently than non-proteinuric patients to this treatment, where the nonproteinuric patients responded the most to treatment with isradipine.

[edit] Magnesium sulphate

In some cases, women with preeclampsia or eclampsia can be stabilized temporarily with magnesium sulfate intravenously to forestall seizures while steroid injections are administered to promote fetal lung maturation. Magnesium sulfate as a possible treatment was considered at least as far back as 1955,[24] but only in recent years did its use in the UK replace the use of diazepam or phenytoin.[25] Evidence for the use of magnesium sulfate came from the international MAGPIE study.[26] When induced delivery needs to take place before 37 weeks gestation, it is accepted that there are additional risks to the baby from premature birth that will require additional monitoring and care.

[edit] Dietary and nutritional factors

Studies of protein/calorie supplementation have found no effect on preeclampsia rates, and dietary protein restriction does not appear to increase preeclampsia rates.[27] No mechanism by which protein or calorie intake would affect either placentation or inflammation has been proposed.

Studies conducted on the effect of supplementation with antioxidants such as vitamin C and E found no change in pre-eclampsia rates.[28] However, Drs. Padayatty and Levine with the NIH criticized the studies for overlooking several key factors that would have been important to the success of the supplementation.[29]

Low levels of vitamin D may be a risk factor for preeclampsia,[30] and calcium supplementation in women with low-calcium diets found no change in preeclampsia rates but did find a decrease in the rate of severe preeclamptic complications.[31] Low selenium status is associated with higher incidence of pre-eclampsia.[32][33] Some other vitamin may also play a role.[34]

The late Dr. Thomas Brewer, OBGYN, believed in the role that diet can play in contributing to pre-eclampsia, especially HELLP syndrome. Although Dr. Brewer's approach has been seen as

unconventional by western medicine because there is no evidence for it,[original research?] some pregnancy practitioners adhere religiously to his recommendations.[citation needed] Women who previously had pre-eclampsia or HELLP present anecdotes claiming that following Dr. Brewer's guidelines has allowed them to go on to have healthy pregnancies, even in cases where their physicians believed their pre-eclampsia could reoccur.[citation needed] Subsequent pregnancies are known to be at lower risk of pre-eclampsia.[citation needed] The Brewer dietary theory is over 40 years old but lacks peer-reviewed support; modern research provides no role for diet in placentation or in tolerance induction.[citation needed]

[edit] Aspirin supplementation

Aspirin supplementation is still being evaluated as to dosage, timing, and population and may provide a slight preventative benefit in some women; however, significant research has been done on aspirin and the results thus far are unimpressive.[35]

[edit] Exercise

There is insufficient evidence to recommend either exercise[36] or bedrest[37] as preventative measures.

[edit] Induction of paternal tolerance

Many studies have also suggested the importance of a woman's immunological tolerance to her baby's father, whose genes are present in the young fetus and its placenta and which may pose a challenge to her immune system.[8][38] As the theory is further investigated,[39] researchers are increasingly studying the importance of a woman's continued exposure to her partner's semen as early as several years before conception. One study published in the American Journal of Obstetrics and Gynecology involved several hundreds of women and found that "women with a short period of cohabitation (less than 4 months) who used barrier methods for contraception had a substantially elevated risk for the development of pre-eclampsia compared with women with more than 12 months of cohabitation before conception."[40] However, the results from a study conducted in 2004 show that the theory is still not conclusive. In that study, the researchers found that after adjustment and stratification, the effect of barrier contraceptive use on the development of pre-eclampsia had disappeared, with both arms having identical rates of pre-eclampsia.[41] Although the study has since then been criticized for its subjective adjustment of data, it remains important because it demonstrates that there is still some contention over the degree to which failure of tolerance induction can be attributed to prior exposure to the partner's sperm.

Continued exposure to a partner's semen has a strong protective effect against pre-eclampsia, largely due to the absorption of several immune modulating factors present in seminal fluid.[42][43]

Long periods of sexual cohabitation with the same partner fathering a woman's child significantly decreased her chances of suffering pre-eclampsia.[40][43] As one early study described, "although preeclampsia is a disease of first pregnancies, the protective effect of multiparity is lost with change of partner."[44] The study also concluded that although women

with changing partners are strongly advised to use condoms to prevent sexually transmitted diseases, "a certain period of sperm exposure within a stable relation, when pregnancy is aimed for, is associated with protection against preeclampsia."[44]

Several other studies have since investigated the strongly decreased incidence of pre-eclampsia in women who had received blood transfusions from their partner, those with long, preceding histories of sex without barrier contraceptives, and in women who had been regularly performing oral sex,[45][46] with one study concluding that "induction of allogeneic tolerance to the paternal HLA molecules of the fetus may be crucial. Data collected strongly suggests that exposure, and especially oral exposure to soluble HLA from semen can lead to transplantation tolerance."[46]

Other studies have investigated the roles of semen in the female reproductive tracts of mice, showing that "insemination elicits inflammatory changes in female reproductive tissues,"[47] concluding that the changes "likely lead to immunological priming to paternal antigens or influence pregnancy outcomes." A similar series of studies confirmed the importance of immune modulation in female mice through the absorption of specific immune factors in semen, including TGF-Beta, lack of which is also being investigated as a cause of miscarriage in women and infertility in men.

According to the theory, the fetus both contain "foreign" proteins from paternal genes, but regular, preceding and coincident exposure to the father's semen may promote immune acceptance and subsequent implantation, a process which is significantly supported by as many as 93 currently identified immune regulating factors in seminal fluid.[8][38]

Having already noted the importance of a woman's immunological tolerance to her baby's paternal genes, several Dutch reproductive biologists decided to take their research a step further. Consistent with the fact that human immune systems tolerate things better when they enter the body via the mouth, the Dutch researchers conducted a series of studies that confirmed a surprisingly strong correlation between a diminished incidence of pre-eclampsia and a woman's practice of oral sex, and noted that the protective effects were strongest if she swallowed her partner's semen.[45][46][48][49][50][51] The researchers concluded that while any exposure to a partner's semen during sexual activity appears to decrease a woman's chances for the various immunological disorders that can occur during pregnancy, immunological tolerance could be most quickly established through oral introduction and gastrointestinal absorption of semen.[46][48]

Recognizing that some of the studies potentially included the presence of confounding factors, such as the possibility that women who regularly perform oral sex and swallow semen also engage in more frequent intercourse, the researchers also noted that, either way, "the data still overwhelmingly supports the main theory" behind all their studies—that repeated exposure to semen establishes the maternal immunological tolerance necessary for a safe and successful pregnancy.[43][48]

A team from the University of Adelaide has also investigated to see if men who have fathered pregnancies which have ended in miscarriage or pre-eclampsia had low seminal levels of critical immune modulating factors such as TGF-Beta. The team has found that certain men, dubbed "dangerous males," are several times more likely to father pregnancies that would end in either preeclampsia or miscarriage.[43] Among other things, most of the "dangerous males" seemed to

lack sufficient levels of the seminal immune factors necessary to induce immunological tolerance in their partners.[52]

[edit] Administration of immune factors

As the theory of immune intolerance as a cause of pre-eclampsia has become accepted, women who suffer repeated pre-eclampsia, miscarriages, or In Vitro Fertilization failures could potentially be administered key immune factors such as TGF-beta along with the father's foreign proteins, possibly either orally, as a sublingual spray, or as a vaginal gel to be applied onto the vaginal wall before intercourse.[43]

In 2006, researchers at the University of Adelaide developed a gel containing TGF-Beta for use in human populations.[53] Later, GroPep, the company which was awarded the patent on a TGF-Beta3 variant, conducted trials where the miscarriage rate was halved in the mice studied. According to a GroPep news release later published, "a faulty immune response is implicated in the etiology of as many as 50% of all miscarriages."[54] Their drug, PV903, was "targeted to treat recurrent miscarriages caused by an abnormal immune response to the foetus, a condition for which there is no current [drug] treatment." [54] Stage I clinical trials of their vaginal gel were partly successful, succeeding in establishing the safety of the drug, but failing in their aim of increasing the number of specific immune cells measured in circulation, the necessary condition for affecting a desired immunological desensitization.[54][55] The trials were later criticized for failing to recognize the synergistic effects of a large variety of immune factors naturally present in seminal fluid, which, acting together and with the localized presence of the foreign paternal proteins, modulate the female immune response so as to allow for implantation, and then the subsequent immune acceptance of the (foreign) fetus throughout a successful pregnancy. GroPep was later acquired by the biotechnology giant, Novozymes. The development of the PV903 drug has since then been placed on hold.

Postpartum hemorrhage

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Postpartum hemorrhage

Classification and external resources

ICD-10 O 72.

ICD-9 666

Hemorrhage after delivery, or postpartum hemorrhage, is the loss of greater than 500 ml of blood following vaginal delivery, or 1000 ml of blood following cesarean section. It is the most common cause of perinatal maternal death in the developed world and is a major cause of maternal morbidity worldwide.[1]

Contents[show]

[edit] Causes

Causes of postpartum hemorrhage and their incidence[1]

Cause Incidence

Uterine atony 70%

Trauma 20%

Retained tissue 10%

Coagulopathy 1%

Causes of postpartum hemorrhage are uterine atony, trauma, retained placenta, and coagulopathy, commonly referred to as the "four Ts":[1]

Tone : uterine atony is the inability of the uterus to contract and may lead to continuous bleeding. Retained placental tissue and infection may contribute to uterine atony.

Trauma : trauma from the delivery may tear tissue and vessels leading to significant postpartum bleeding.

Tissue : retention of tissue from the placenta or fetus may lead to bleeding. Thrombin : a bleeding disorder occurs when there a failure of clotting, such as with diseases

known as coagulopathies.

[edit] Management

[edit] Medication

Intravenous oxytocin is the drug of choice for postpartum hemorrhage. Misoprostol may also be effective if oxytocin is not available.[2]

[edit] Protocol

A detailed stepwise management protocol has been introduced by the California Maternity Quality Care Collaborative.[3] It describes 4 stages of obstetrical hemorrhage after a delivery and its application reduces maternal mortality.[4]

Stage 0: normal - treated with fundal massage and oxytocin. Stage 1: more than normal bleeding - establish large-bore intravenous access, assemble

personnel, increase oxytocin, consider use of methergine, perform fundal massage, prepare 2 units of packed red cells.

Stage 2: bleeding continues - check coagulation status, assemble response team, move to operating room, place intrauterine balloon, administer additional uterotonics (misoprostol, carboprost tromethamine), consider: uterine artery embolization, dilatation and curettage, and laparotomy with uterine compression stitches or hysterectomy.

Stage 3: bleeding continues - activate massive transfusion protocol, mobilize additional personnel, recheck laboratory tests, perform laparotomy, consider hysterectomy.

A Cochrane database study[5] suggests that blood loss and the risk of postpartum bleeding will be reduced in women offered active management of the third stage of labour, rather than expectant management. However, that review was withdrawn in 2009 pending an update after the validity of its findings was questioned. The use of ergometrine for active management was associated with nausea or vomiting and hypertension, and controlled cord traction requires the immediate clamping of the umbilical cord.

Capacitation

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This article is about a biological process related to reproduction; for the other use, see Capacitation (NGO).

Capacitation is the penultimate[1] step in the maturation of mammalian spermatozoa and is required to render them competent to fertilize an oocyte. This step is a biochemical event; the sperm move normally and look mature prior to capacitation. In vivo this step typically occurs after ejaculation, in the female reproductive tract. In vitro, capacitation can occur in sperm that have either undergone ejaculation or have been extracted from the epididymis.

By secreting sterol binding albumin, lipoproteins, proteolytic and glycosidasic enzymes such as heparin, the uterus aids in the steps of capacitation.

Non-mammalian spermatozoa do not require this capacitation step and are ready to fertilize an oocyte immediately after release from the male. After this capacitation the sperm must undergo activation involving the acrosome reaction.

Contents[show]

[edit] Result of capacitation

Capacitation involves the destabilisation of the acrosomal sperm head membrane rendering it more fusigenic. This change is facilitated by the removal of steroids (e.g. cholesterol) and non-covalently bound epididymal/seminal glycoproteins. The result is a more fluid membrane with an increased permeability to Ca2+.

An influx of Ca2+ produces increased intracellular cAMP levels and thus, an increase in motility. Hyperactivation is also part of capacitation and is the result of the increased Ca2+ levels. The tripeptide FPP (fertilization promoting factor) produced by the male is essential for capacitation. It has a synergistic stimulatory effect with adenosine that increases adenyl cyclase activity in the sperm. FPP is found in the seminal fluid, and comes into contact with the spermatozoa upon ejaculation.

[edit] Discovery

The discovery of this process was independently reported in 1951 by both Min Chueh Chang [2] and Colin Russell Austin [3] [4].

Historically, the term "capacitation" has evolved in meaning and this should be taken into account when consulting sources.

Medical Termination of Pregnancy [MTP]

What is a MTP?

MTP stands for Medical Termination of Pregnancy

Arthritis literally means joint inflammation. Arthritis is not a single disease. Arthritis refers to a group of more than 100 rheumatic diseases and other conditions that can cause pain, stiffness and swelling in the joints.

Any part of your body can become inflamed or painful from arthritis. Some rheumatic conditions can result in debilitating, even life-threatening complications or may affect other parts of the body including the muscles, bones, and internal organs.

Arthritis Screening Quiz Early Arthritis Symptoms Do I Have Arthritis? Fast Facts About Arthritis

10 Things You Should Know About Arthritis How to Recognize the Signs and Symptoms of Arthritis

The two most common types of arthritis are osteoarthritis and rheumatoid arthritis. Arthritis can affect anyone at any age, including children. The incidence of arthritis increases with age, but nearly three out of every five sufferers are under age 65.

If left undiagnosed and untreated, many types of arthritis can cause irreversible damage to the joints, bones, organs, and skin.

Osteoarthritis

Osteoarthritis, also known as degenerative joint disease, results from wear and tear. The pressure of gravity causes physical damage to the joints and surrounding tissues, leading to:

pain tenderness swelling decreased function

Initially, osteoarthritis is non-inflammatory and its onset is subtle and gradual, usually involving one or only a few joints. The joints most often affected are the:

knees hips hands spine

Risks of osteoarthritis increase with age. Other risk factors include joint trauma, obesity, and repetitive joint use.

Guide to Osteoarthritis Osteoarthritis Screening Quiz Fast Facts About Osteoarthritis Test Your Knowledge: Osteoarthritis 10 Things You Should Know About Osteoarthritis How to Recognize the Signs and Symptoms of Osteoarthritis

Rheumatoid Arthritis

Rheumatoid arthritis is an autoimmune disease that occurs when the body's own immune system mistakenly attacks the synovium (cell lining inside the joint). Rheumatoid arthritis is a chronic, potentially disabling disease which causes:

joint pain stiffness swelling

loss of joint function

While the cause remains elusive, doctors suspect that genetic factors are important. Rheumatoid arthritis can be difficult to diagnose early because it can begin gradually with subtle symptoms.

Guide to Rheumatoid Arthritis Rheumatoid Arthritis Screening Quiz Fast Facts About Rheumatoid Arthritis Test Your Knowledge: Rheumatoid Arthritis Rheumatoid Arthritis: Explained With Pictures 10 Things You Should Know About Rheumatoid Arthritis How to Recognize the Signs and Symptoms of Rheumatoid Arthritis

Juvenile Arthritis

Juvenile arthritis is a general term for all types of arthritis that occur in children. Juvenile rheumatoid arthritis is the most prevalent type of arthritis in children. There are three major types:

polyarticular (affecting many joints) pauciarticular (pertaining to only a few joints) systemic (affecting the entire body)

Signs and symptoms of juvenile rheumatoid arthritis vary from child to child. No single test can conclusively establish a diagnosis. Juvenile arthritis must be present consistently for six or more consecutive weeks before a correct diagnosis can be made.

Guide to Juvenile Arthritis Does My Child Have Arthritis? Arthritis Affects Children Too

Psoriatic Arthritis

Psoriatic arthritis is similar to rheumatoid arthritis. About 5 percent of people with psoriasis, a chronic skin disease, also develop psoriatic arthritis. In psoriatic arthritis, there is inflammation of the joints and sometimes the spine.

What is Psoriatic Arthritis? Psoriatic Arthritis Screening Quiz Fast Facts About Psoriatic Arthritis Test Your Knowledge: Psoriatic Arthritis 10 Things You Should Know About Psoriatic Arthritis How to Recognize the Signs and Symptoms of Psoriatic Arthritis

Fibromyalgia

Fibromyalgia syndrome is a painful condition characterized by:

muscle pain chronic fatigue poor sleep

The name fibromyalgia means pain in the muscles, ligaments and tendons. Fibromyalgia is a type of soft tissue or muscular rheumatism and does not cause joint deformities.

Fibromyalgia Screening Quiz Fast Facts About Fibromyalgia Test Your Knowledge: Fibromyalgia 10 Things You Should Know About Fibromyalgia How to Recognize the Signs and Symptoms of Fibromyalgia

Gout

Gout is a painful type of arthritis that causes sudden, severe attacks of pain, tenderness, redness, warmth, and swelling in the joints, especially the big toe. The pain and swelling associated with gout are caused by uric acid crystals that precipitate out of the blood and are deposited in the joint.

Guide to Gout Gout Screening Quiz Fast Facts About Gout Test Your Knowledge: Gout What Are Gout Risk Factors?

Pseudogout / CPPD

Pseudogout, which is also known as Calcium Pyrophosphate Dihydrate Deposition Disease (CPPD), is caused by deposits of calcium phosphate crystals (not uric acid) in the joints. CPPD is often mistaken as gouty arthritis. Since CPPD is a different disease than gout, treatment is not the same as gout.

What is CPPD? Is it Gout or Pseudogout? Guide to Pseudogout

Scleroderma

Scleroderma is a disease of the body's connective tissue that causes thickening and hardening of the skin. It can also affect the:

joints blood vessels internal organs

There are two types of scleroderma: localized and generalized.

Guide to Scleroderma Scleroderma Screening Quiz Fast Facts About Scleroderma Test Your Knowledge: Scleroderma Scleroderma: Not a Single Disease

Lupus / SLE

Systemic lupus erythematosus (SLE) is an autoimmune disease that can involve the:

skin kidneys blood vessels joints nervous system heart other internal organs

Symptoms vary, but may include a skin rash, arthritis, fever, anemia, fatigue, hair loss, mouth ulcers, and kidney problems. Symptoms usually first appear in women of childbearing age, but, can occur in children or older people. About 90 percent of those affected are women.