knee-131227101050-phpapp01

8/10/2019 knee-131227101050-phpapp01

1/96

Vinod Naneria

Osteoarthritis of Knee

8/10/2019 knee-131227101050-phpapp01

2/96

Definition

The name osteoarthritis comes from three

Greek words meaning bone, joint, and

inflammation.

It is a progressive disorder of the joints

caused by gradual loss of articular cartilage

with secondary changes in the bone and

synovium.

8/10/2019 knee-131227101050-phpapp01

3/96

Osteoarthritisoldest

Remains of the

dinosaur Diplodocus

show evidence of

osteoarthritis 150

million years ago.

Earliest evidence of

human osteoarthritishas been found in the

remains of Neanderthal

man. ( 0.60.03 M)

New man from a valley

8/10/2019 knee-131227101050-phpapp01

4/96

Knee joint of an Elephant

8/10/2019 knee-131227101050-phpapp01

5/96

Knee joint of a bird

8/10/2019 knee-131227101050-phpapp01

6/96

Osteoarthritis

10% adult populationacross the world

About a quarter of all

consultations in generalpractice.

Symptoms of the disease

manifest much late. There is no known cure of

the disease.

Progress can be controlled or delayed

8/10/2019 knee-131227101050-phpapp01

7/96

Articular cartilage - unique

No blood supply,

No lymphatic drainage,

No neural elements, Chondrocytes are shielded from

immunological recognition.

6080% of human cartilage is water.

8/10/2019 knee-131227101050-phpapp01

8/96

Chondrocytes

Chondrocytes are the

cellular manufacturing

sites of cartilage and

are responsible for theproduction and

maintenance of the

surrounding matrix .

Chondrocyte

8/10/2019 knee-131227101050-phpapp01

9/96

Collagens:

Protein macromoleculesthat contain characteristichelical amino acid chains.

Provide the tensile strengthand form of cartilage

Proteoglycans are attached

to the collagen framework.

8/10/2019 knee-131227101050-phpapp01

10/96

Proteoglycan

It consist of a core protein, Aggrecan, to whichare covalently bound glycosaminoglycan sidechains of chondroitin and keratan sulfate.

These charged side chains account for the

hydration and resistance to compression ofthe cartilage matrix.

8/10/2019 knee-131227101050-phpapp01

11/96

Cartilage Matrix Organization Zones

Superficial (gliding)cells are horizontal,

Middle (transitional)cells are crisscross,

Deep (radial)cells are perpendicular,

Calcified cartilage.

Subchondral bone.

8/10/2019 knee-131227101050-phpapp01

12/96

Articular Cartilage Matrix Organization

Zones

Morphologic,

biochemical &

functional differences

between zones basedon depth from articular

surface.

Superficialshearing

Deep - compression

8/10/2019 knee-131227101050-phpapp01

13/96

8/10/2019 knee-131227101050-phpapp01

14/96

Normal Articular Cartilage

8/10/2019 knee-131227101050-phpapp01

15/96

Articular cartilage in Osteoarthritis

8/10/2019 knee-131227101050-phpapp01

16/96

Pathogenesis of osteoarthritis of the knee

Chronological age is the single most importantrisk factor.

In younger patients unfavourable

biomechanical environment at the joint is themain cause.

This results in mechanical demand that

exceeds the ability of a joint to repair andmaintain itself, predisposing the articularcartilage to premature degeneration.

Chondrocyte apoptosis - telomere or mechanical overloading

8/10/2019 knee-131227101050-phpapp01

17/96

OA is characterized by two phases

A biosynthetic phase, during which theChondrocytes, attempt to repair the damagedextracellular matrix.

A degradative phase, in which the activity ofenzymes produced by the chondrocytesdigests the matrix, matrix synthesis isinhibited, and the consequent erosion of thecartilage is accelerated.

8/10/2019 knee-131227101050-phpapp01

18/96

8/10/2019 knee-131227101050-phpapp01

19/96

8/10/2019 knee-131227101050-phpapp01

20/96

Sequence of events

Superficial layer abrasion,

Superficial layer fissuring,

Attempt at repair by chondrocytes, Excess production of new cells and matrixes,

Deep layer cleavage.

8/10/2019 knee-131227101050-phpapp01

21/96

Sequence of events

Chondrocytes start secreting lysosomal

enzymes which start dissolving matrixes.

Release of degradation products in the joint

leading to synovitis

Loss of shock absorption property

Subchondral bone fractures

Healing of subchondral fractures by sclerosis,

and osteophyte formation.

8/10/2019 knee-131227101050-phpapp01

22/96

Treatment chart

Medical

Surgical

Regenerative

8/10/2019 knee-131227101050-phpapp01

23/96

Treatment Option - Medical

Life stylemodifications

Physiotherapy

Nsaids

Braces

Supports

8/10/2019 knee-131227101050-phpapp01

24/96

Treatment Option - invasive

Injections (HydrocortisoneHyaluronic acid)

Arthroscopy(debridement)

Alignment corrective surgery (HTO)

Total / partial joint replacement

Regenerative medicine ( cartilage transplantation)

8/10/2019 knee-131227101050-phpapp01

25/96

Life style modification:

Sitting on ground

Squatting

Sit-ups

Climbing Commode

High heels

Shoe modification (lateral

wedges) Cane/walker

Braces

8/10/2019 knee-131227101050-phpapp01

26/96

Life style

Walking instead of running, Use alternative exercise program

Walking within the limit of pain.

Walk on soft earth. Limp if required.

Overweight Patients, should lose a minimum

of five percent (5%) of body weight. low-impact aerobic fitness exercises.

Dont scratch your wounds

8/10/2019 knee-131227101050-phpapp01

27/96

Life style

Range of motion/flexibility exercises.

Swimming is good exercise.

Quadriceps strengthening (static)

Delay quadriceps against resistance or avoid it.

Use of high heel increases anterior knee pain.

Correct your shoe frequently if the heel is

getting wear from one side.

8/10/2019 knee-131227101050-phpapp01

28/96

Role of Physiotherapist

Specific instruction should be given for bettercooperation from physio in the interest ofpatient.

Pain: Heat therapy, SWD, US ROM: bicycle, CPM, free swing, Stretching

Correction of deformity,

Strengthening of Quad + Hamstrings

Static Quadriceps, Improvement in gait & Balance,

Resistive exerciseswith weights?

Choice of modalities should be left to physiotherapist

8/10/2019 knee-131227101050-phpapp01

29/96

Exercises4 Ds Golden rules:

Do it

Do it regularly

Do it correctly Do not over do it

Exercises for prevention of OA

knee is like brushing teeth.

It should be gentle &continuous for rest of the life.

Free cycling for 510 minutes at

zero resistance. Can be repeated

twice a day

overdoing can

damage the knee

further.

Free cycling for 510 minutes / 5 km are very good form of

exercise. Static cycle is better. It help in cartilage nutrition by

CPM type action. Can be repeated twice a day.

Bicycling for knee arthritis is not a weight reduction tool,

overdoing can damage the knee further.

Skipping: Soft surfacein garden or wooden

platform. Avoid high impact.

8/10/2019 knee-131227101050-phpapp01

30/96

Free cycling

Free cycling for 510 minutes / 5 km are verygood form of exercise.

Static cycle is better.

It help in cartilage nutrition by CPM typeaction.

Can be repeated twice a day.

Bicycling for knee arthritis is not a weightreduction tool, overdoing can damage theknee further.

ZERO - RESISTANCE

8/10/2019 knee-131227101050-phpapp01

31/96

overdoing can damage

the knee further.

Free cycling for 510

minutes at zero resistance.

Can be repeated twice a day.

8/10/2019 knee-131227101050-phpapp01

32/96

Skipping

Skipping

Soft surfacein garden or wooden platform

Avoid high impact.

8/10/2019 knee-131227101050-phpapp01

33/96

Treadmill

Climbing uphillincreases loading on thedamaged cartilage andat times precipitate

acute pain and effusionin knee.

It is a high impactexercise.

Specially precipitate PFpain.

8/10/2019 knee-131227101050-phpapp01

34/96

8/10/2019 knee-131227101050-phpapp01

35/96

Braces

Instability / lack of

confidence,

Insecurity /

apprehension Meniscus tear

Ligamentous laxity

Unicompartmentaldisease

8/10/2019 knee-131227101050-phpapp01

36/96

Life style modification

Unilateral joint unloading

braces are not

recommended for general

use. They are commonlyprescribed for uni-

compartmental disease of

the knee.

8/10/2019 knee-131227101050-phpapp01

37/96

Acupuncture

There is no recommendations for or against

the use of acupuncture as an adjunctive

therapy for pain relief in patients with

symptomatic OA of the knee.

8/10/2019 knee-131227101050-phpapp01

38/96

Prolotherapy or proliferation therapy

It involves injecting an non-pharmacological and non-activeirritant solution into the region oftendons or ligaments.

It re-initiate the inflammatoryprocess that deposits new additionalfibres to repair a perceived injury.

dextrose, lidocaine, phenol,

glycerine, or cod liver oil extract. Theinjection is given into joints ortendons where they connect to bone

Not covered by Medicare in USA

8/10/2019 knee-131227101050-phpapp01

39/96

Pain Relievers

Patients with symptomatic OA of the knee can

receive one of the following analgesics forpain unless there are contraindications to thistreatment:

Acetaminophen NSAIDs only in acute flare for short term.

Avoid them in cases of hypertension, CRF andCAD.

Oral cortisone have no role.

Tx - Malaria by Crocin

Prolonged use can cause neuropathic joint

8/10/2019 knee-131227101050-phpapp01

40/96

Glucosamine & Chondroitin

Chondroitin is the most abundantglycosaminoglycan in cartilage and isresponsible for the resiliency of cartilage.

Oral consumption of the substances mayincrease the rate of formation of new cartilageby providing more of the necessary buildingblocks.

Approved by FDA as food supplements

Not recommended by AAOS for OA

8/10/2019 knee-131227101050-phpapp01

41/96

Chondroprotactive drugs

Recommendations for or against Glucosamine

and/or Chondroitin sulfate or hydrochloride

are inconclusive for symptomatic OA of the

knee.

There are proteoglycons synthesised by

chondrocytes in normal cartilage, there

supplementation logically have no effect indisease progression.

FDAfood supplements

8/10/2019 knee-131227101050-phpapp01

42/96

Diacerein (interleukin alpha 1 blocker)

The IL-1 mediated enhancement of collagenase

production in chondrocytes is actively inhibited by

Diacerein.

Diacerein has a different spectrum of anti-inflammatory activity to that of the classical NSAIDs

naproxen and ibuprofen. While NSAID drugs inhibit

cyclooxygenase, diacerein does not inhibit

prostaglandin synthesis.

Inflammation is a response to disease and not the cause of disease

8/10/2019 knee-131227101050-phpapp01

43/96

Diacerein

Inhibition of IL-1, which distinguishes it from

other drugs indicated for the treatment of

osteoarthritis

Stimulate anabolic processes.

Diacerein and rhein inhibit the production of

IL-1b by chondrocytes in the superficial and

deep zones of human osteoarthritic cartilage

Anti-inflammatory reduce pain in brain not at knee

8/10/2019 knee-131227101050-phpapp01

44/96

Role of Vitamin D and calcium

A weak quadriceps due to Vitamin D

deficiency can be a precipitating factor for

early OA.

A weak muscle increases mechanical

overloading on the knee articular surface.

There can be disuse quadriceps weakness due

to pain.

Vitamin D and calcium can be supplemented.

8/10/2019 knee-131227101050-phpapp01

45/96

Osteoporosis & Osteoarthritis

Do not coexist together.

BMI 22 & >OA

BMI below 22 (< 19) OS

Both can have a presenting symptom of

difficulty in getting up from sitting position(typical of OA). This is due to Vitamin D

deficiency.

8/10/2019 knee-131227101050-phpapp01

46/96

Injections

Visco supplementations.

Hydrocortisone.

Benefit of viscosupplementation in patients

with symptomatic osteoarthritis is minimal or

nonexistent.

Increased risks for serious adverse events and

local adverse events, the administration of

these preparations should be discouraged.

8/10/2019 knee-131227101050-phpapp01

47/96

Intra-Articular Injections

Intra-articular corticosteroids for short-term pain

relief for patients with symptomatic OA of the

knee.

AAOS does not recommend the routine use ofintra-articular corticosteroids, for patients with

mild to moderate symptomatic OA of the knee.

It may give symptomatic relief for few months. It can precipitate early damage in young patients

due to over activity on a damaged cartilage.

Rest for 2 -3 weeks after a shot

8/10/2019 knee-131227101050-phpapp01

48/96

Corticosteroids

Known anti-inflammatory, but their

mechanism of action is not completely known.

Corticosteroids inhibit the accumulation of

inflammatory cells, such as leukocytes and

neutrophils.

They prevent phagocytosis, lysosomal enzyme

release, and the synthesis of severalinflammatory mediators.

Ideal for elderly who are sedentary and not fit for surgery

8/10/2019 knee-131227101050-phpapp01

49/96

Hyaluronic acid

The name derived from the Greek word hyalosmeaning vitreous, and uronic acid.

Normally secreted in the synovium by Type Bsynoviocytes.

Act as a lubricant and shock absorber.

It is made of approximately 12,500 disaccharideunits and have molecular weight of 5 milliondaltons.

In pathological condition, the concentration andmolecular weight of indigenous hyaluronic acid isreduced.

8/10/2019 knee-131227101050-phpapp01

50/96

Hyaluronic acid

Hyaluronic acid has both viscous and elasticproperties.

At high shear forces, hyaluronic acid exhibits

increased elastic properties and reducedviscosity.

The opposite is true with low shear forces.

Therefore, hyaluronic acid acts as a shockabsorber during fast movements, and alubricant during slow movement.

8/10/2019 knee-131227101050-phpapp01

51/96

Hyaluronic acid

The use of HA as VS began in the late 1960s byBiotrics, Inc. The material was taken from humanumbilical cord.

The chondro-protective effects of HA has not

been clinically proven. The FDA classified VS as medical devices;

AAOS does not recommend it for patients withmild to moderate symptomatic OA of the knee.

Can be used for the patient who are on waitinglist for TKR.

8/10/2019 knee-131227101050-phpapp01

52/96

Arthroscopy Procedures

Joint debridement Removal of mechanical obstructions,

Joint lavage

Drilling of sclerotic lesions Abrasion chondroplasty

Autologous chondrocyte transplantation

Mosaicplasty

Cartilage transplantation Regenerative medicine

8/10/2019 knee-131227101050-phpapp01

53/96

Arthroscopy

Recommendations for performing arthroscopy

with debridement or lavage in patients with a

primary diagnosis of symptomatic OA of the

knee is not conclusive.

Arthroscopic partial meniscectomy or loose

body removal is advisable, in patients who

have primary signs and symptoms of a tornmeniscus and/or a loose body.

8/10/2019 knee-131227101050-phpapp01

54/96

Cartilage Replacement

Autologous transplantationfrom one placeto another in same knee. (Mosiacplasy)

Autologousgrow in labtransplantation

(two stageharvestinggrowth in labreimplantation with or without matrixes)

Stem cellcartilage grow in labtransplantation (iPP, induced mesenchymalpleuripotant stem cellsfrom bone marrow,skin, and other donar sites.

8/10/2019 knee-131227101050-phpapp01

55/96

Abrasion and Micro-fracture surgery

Abrasive procedures aimed at triggering

cartilage production.

Abrasion, drilling, and micro fractures rely on

the phenomenon of spontaneous repair of the

cartilage tissue following vascular injury to the

subchondral bone, which allow inflow of

naturally circulating stem cells (progenitors) inthe blood.

Proteoglycon are resistant to neovascularization

8/10/2019 knee-131227101050-phpapp01

56/96


Mosaicplasy - Technique

The patients chondrocytes are removed

arthroscopically from a non load-bearing area.

10,000 cells are harvested and grown in vitro

for approximately six weeks until the

population reaches 10-12 million cells.

Then these cells are injected into the cartilage

defect of the patient.

8/10/2019 knee-131227101050-phpapp01

57/96


Mosaicplasy - Technique

These cells are held in place by a periostealflap, which is sutured over the area to serve as

a watertight lid.

The implanted chondrocytes then divide andintegrate with surrounding tissue and

potentially generate hyaline-like cartilage.

8/10/2019 knee-131227101050-phpapp01

58/96

Technique cont

A second generation technique, called CarticelII uses a "fleece matrix" implanted with

chondrocyte cells that is arthroscopically

inserted into the joint. This procedure isknown as matrix autologous chondrocyte

implantation or (MACI) and is available in

Germany, UK, and Australia

8/10/2019 knee-131227101050-phpapp01

59/96

Mosaicplasy

8/10/2019 knee-131227101050-phpapp01

60/96

Chondroplasty

8/10/2019 knee-131227101050-phpapp01

61/96

Chondroplasty

8/10/2019 knee-131227101050-phpapp01

62/96

Corrective -Surgery

High Tibial Osteotomy

Realignment osteotomy is an option in active

patients with symptomatic unicompartmental

OA of the knee with mal-alignment.

It can be done as an isolated procedure or

may be combined with chondroplasty or

menisectomy.

8/10/2019 knee-131227101050-phpapp01

63/96

High tibial osteotomy

The fundamental goals is to unload diseased

articular surfaces and to correct angular

deformity at the tibiofemoral articulation.

HTO is effective for managing OA with varus,osteochondritis dissecans, osteonecrosis,

posterolateral instability, and chondral

resurfacing.

8/10/2019 knee-131227101050-phpapp01

64/96


Improved instrumentation and fixation plates for

medial opening / lateral closing wedge

osteotomy,

Dynamic external fixation for medial openingwedge osteotomy,

Concomitantly correcting mal-alignment when

performing chondral resurfacing procedures (ie,autologous chondrocyte transplantation,

mosaicplasty, and microfracture).

8/10/2019 knee-131227101050-phpapp01

65/96

High tibial osteotomy

A valgus alignment of 6 and 10 of valgus,

regardless of condylar width, baseline

tibiofemoral alignment, body weight, or

chondral defect size, demonstrated completeunloading of the medial compartment, which

favors cartilage repair at these alignments.

8/10/2019 knee-131227101050-phpapp01

66/96


8/10/2019 knee-131227101050-phpapp01

67/96

High Tibial Oateotomy

8/10/2019 knee-131227101050-phpapp01

68/96

Spontaneous correction due to stress

fracture

8/10/2019 knee-131227101050-phpapp01

69/96

8/10/2019 knee-131227101050-phpapp01

70/96

Replacement Surgery

Total knee replacement

Patients specific knee replacement

Unicondylar replacement

Patello-femoral replacement

Meniscus replacement

Metallurgy - replacing biology

Metallurgy has a date of expiry

8/10/2019 knee-131227101050-phpapp01

71/96

Patellofemoral replacement

oxidised zirconium oxinium

Uni-condylar replacement

8/10/2019 knee-131227101050-phpapp01

72/96

Our experience

We did our first THR in 1985.

We were amongst the first to start TKR on a

routine basis way back 1993.

We conducted a national workshop on THR in

1987.

8/10/2019 knee-131227101050-phpapp01

73/96

8/10/2019 knee-131227101050-phpapp01

74/96

INOR TKR

8/10/2019 knee-131227101050-phpapp01

75/96

8/10/2019 knee-131227101050-phpapp01

76/96

Bilateral TKR

8/10/2019 knee-131227101050-phpapp01

77/96

An interesting case

8/10/2019 knee-131227101050-phpapp01

78/96

g

1995 - 2012

8/10/2019 knee-131227101050-phpapp01

79/96

Tissue engineering

Defined as the application of engineering

science and technology to the combined field

of cellular and molecular biology with the goal

of regulating the growth, differentiation, andmetabolic activity of cells that are either

transplanted or recruited to heal or

regenerate a joint surface

8/10/2019 knee-131227101050-phpapp01

80/96

Regeneration: Growth of New Cartilage

Because of the limited capacity of cartilage to heal, amore attractive approach is to transplant cells or atissue with chondrogenic potential into the joint (so-called biological resurfacing).

Bentley and Greer were apparently the first to showthat chondrocytes could be transplanted into articularcartilage defects and improve healing compared withthat in controls.

Chondrocytes, stem cells, an undifferentiated tissue

(such as periosteum or perichondrium) containing stemcells or chondrocyte precursors, or any combination ofthese can be used.

i l f

8/10/2019 knee-131227101050-phpapp01

81/96

Autogenous periosteal grafts

Osteochondral defects in the knees of rabbits

that were resurfaced with use of autogenous

periosteal grafts healed with predominantly

hyaline cartilage containing more than 90percent type-II collagen and normal water,

proteoglycan, chondroitin, and keratan sulfate

contents.

8/10/2019 knee-131227101050-phpapp01

82/96

8/10/2019 knee-131227101050-phpapp01

83/96

8/10/2019 knee-131227101050-phpapp01

84/96

E i t l

8/10/2019 knee-131227101050-phpapp01

85/96

Experimental

intra-articular injection of growth factors, such astransforming growth factor-1, insulin-likegrowth factor-1, bone morphogenetic proteins,fibroblast growth factor, and epidermal growth

factor.

A single injection of transforming growth factor-1 stimulated a persistent increase in cartilage

proteoglycan synthesis and content, but multipleinjections induced substantial synovitis, synovialhyperplasia, and formation of osteophytes .

S ff ld

8/10/2019 knee-131227101050-phpapp01

86/96

Scaffolds

The many substances that have been testedinclude nonabsorbable materials, such as

carbon fiber, Dacron, and Teflon; porous metal

plugs; absorbable polymers or copolymers,such as polyglycolic acid and polylactic acid;

fibrin and collagen.

Future - Dolly

8/10/2019 knee-131227101050-phpapp01

87/96

Dolly(5 July 199614 February
http://localhost/var/www/apps/conversion/tmp/scratch_2//upload.wikimedia.org/wikipedia/commons/8/8c/Dolly_clone.svg

8/10/2019 knee-131227101050-phpapp01

88/96

2003) was a female domestic sheep,

and the first mammal to be cloned

from an adult somatic cell, using the

process of nuclear transfer.Dolly was born on 5 July 1996 to

three mothers (one provided the

egg, another the DNA and a third

carried the cloned embryo to term).

She was created using the

technique of somatic cell nucleartransfer, where the cell nucleus

from an adult cell is transferred into

an unfertilised oocyte (developing

egg cell) that has had its nucleus

removed. The hybrid cell is then

stimulated to divide by an electricshock, and when it develops into a

blastocyst it is implanted in a

surrogate mother.

D ll
http://localhost/var/www/apps/conversion/tmp/scratch_2//upload.wikimedia.org/wikipedia/commons/8/8c/Dolly_clone.svg

8/10/2019 knee-131227101050-phpapp01

89/96

Dolly

Normal age of sheep is around 11-12 years.

Dolly lived for six years.

It was speculated that Dolly's genetic age was

six years, the same age as the sheep from

which she was cloned. The basis for this idea

was the finding that Dolly's telomeres were

short, which is typically a result of the ageingprocess.

Nobel Prize in medicine 2012

8/10/2019 knee-131227101050-phpapp01

90/96

Shinya Yamanaka & Sir John B. Gurdon

Discovered that the developmental clock could beturned back in mature cells, transforming them into

immature cells with the ability to become any tissue

in the body pleuripotent stem cells. (iPS)

IlluminatingChondrogenesis: Pictured

are murine induced

8/10/2019 knee-131227101050-phpapp01

91/96

are murine induced

pluripotent stem cells

undergoing

chondrogenesis. In

addition to type II

collagen (red), F-actin

(magenta), and nucleus

(blue), upon

differentiation cells

express green fluorescentprotein under the control

of a chondrocyte-specific

promoter. Diekman et al.

employed cell sorting to

produce tissue-engineered

cartilage for potential use

in treating cartilage

defects or discovering new

drugs for osteoarthritis.

Future

8/10/2019 knee-131227101050-phpapp01

92/96

Future

Some day we will be able to replace a part orthe whole articular cartilage by new cartilages

cells developed in lab by induced

Mesenchymal Stem cells. It will be something like changing a punctured

tire as and when needed.

8/10/2019 knee-131227101050-phpapp01

93/96

Journey Continue.

8/10/2019 knee-131227101050-phpapp01

94/96

It is a crime to think small- A.P.J. Abdul Kalam

8/10/2019 knee-131227101050-phpapp01

95/96

DISCLAIMER

8/10/2019 knee-131227101050-phpapp01

96/96

Information contained and transmitted by this presentation isbased on personal experience and collection of cases atChoithram Hospital & Research centre, Indore, India, duringlast 34 years.

It is intended for use only by the students of orthopaedicsurgery.

Views and opinion expressed in this presentation are personal.

Depending upon the x-rays and clinical presentations, viewerscan make their own opinion.

For any confusion please contact the sole author forclarification.

Every body is allowed to copy or download and use the

material best suited to him. I am not responsible for anycontroversies arise out of this presentation.

For any correction or suggestion please [email protected]

knee-131227101050-phpapp01

Documents