seen on further ultrasonography and in biopsy speci-mens. Several treatments were required for eachtumour, and injecting alcohol was often associatedwith considerable pain, whereas our patients did notreport pain. These reports did not mention changesseen on ultrasound scans during or immediately afterinjection, which we found useful in laser treatment.The most important advantage of the laser is its

precision. It is unlikely that it will ever be possible topredict the extent of necrosis around a site at whichabsolute alcohol has been injected with an accuracycomparable to that already possible with the lasertechnique.

In conclusion, interstitial laser hyperthermia isfeasible and seems to be safe. A multiple fibresystem makes it feasible to treat tumours of clinicallyrelevant size in the centre of solid organs. The realchallenge for the future will be to develop diagnostictechniques that disclose exactly how far individualtumours extend in a wider range of organs (unlike thewell defined tumours treated in this pilot study) and toestablish the conditions of laser treatment that givecomplete tumour ablation with safe healing. Thiscombination of technologies may be valuable fortreating otherwise untreatable tumours in a range ofsolid organs and for the primary treatment of smallneoplasms such as tumours of the prostate and adrenalglands.

We thank Mr R C G Russell, Mr P Hawley, Mr W Slack,and the late Professor C G Clark for referring these patients

and for permission to report these results. We also thank Dr TN Mills, Mr P Hill, and Miss L A Potter of the department ofmedical physics for their help. Mr Steger was supported byLiving Technology Ltd, Glasgow, and Dr Bown by thespecial medical development on lasers from the Departmentof Health and by the Imperial Cancer Research Fund.

1 Storm KF, Kaiser L-R, Goodnight JE, ei al. *Fhermotherapy for melanomametastascs in liser. Cancer 1982;49: 1243-s.

2 Lindholm C-E, K'ellan E, Nilson P, Hertzman S. Microwave indtuccdhy-perthermia and radiotherapy in human superficial tumotirs clinicalresults with a comparative study of combined treatment versus radiothcrapyalone. lnr,7 s'p1erpthermia 1987;3:393-41 1.

3 Milligan AJ. Whole body hypcrthertmia iinductioni tcchniqtucs. Cancer Res1984;44 (10 Suppl):4869-72.

4 Shiplc WU, Nardi GL, Cohen AM, Cliftoin Ling C. Iodine-'"' implant andcxtcrnal bceam irradiation in patienits with localized pancreatic carciinoma.Cancer 19X0;45:709-14.

5 Dritclilo A, (irant EG, Harter KW;, Holt RWY, Rustigi SN, Rodgers JE.Intcrstitial radiation therapy for hcpatic metastases: sonographic guidancefor applicator placement. Am,7 Radtol 1986;164:275-8.

6 Bown SG. Phototherapy of tumors World.7 Surg 1983;7:700-9.7 Matthewson K, Coleridge-Smith 1, O'Sullisan JP, Northfield PIC, Bown SG.

Biological effects of intrahepatic Nd-YAG lascr photocoagulation in rats.Gastrosnicrologv 987;93:550-7

8 Stcger AC, Bown SG, Clarke C(G Intcrstitial lascr hypcrthermia-stttdics in thenortmal liver. fBrj Surg 1988;75:59X

9 Mlatthewson K, Coleridge-Smith 1P, Northlfield I,, Bowil SG. Cotoparisonl ofcontintUoUs uave attd puIlsed excitationi for interstitial Nd-YA( iidttdccdhvprthermia. lasers inn Medical Sciunce 1986;1 197-201.

10 Hashimoto 1). Ultrasonography guidcd lasers and sphcric lasers. In: RicmannJF, Ell C, cds. Lasers in gastrocnicrologs' Gec)rg Thiemc V'crlag Inc,Stuittgart: Thicmc P'uLblishicrs, 1989:134-8.

11 Godlewski (i, Sambtc P, Eledjam JJ, Pignodel C, Ould-Said A, Bourgeois JM.A new device ftr inducing deep localised vaptrisation in liver with the Nd-YAG laser. lasers inMedical Science 19XX;3: 111-7.

12 Shiina S, Yasuda H, Aluto H, et al. P'ercutaneous ethanol iijectioin in thetreatment of liser neoplasms. Amj7 Radiol 1987;149:949-52.

13 Livraghi T, Fcsti Ml, Monti F, Salmi A, Vcttori C. US-guidcd pcrCutatlcousalcohol iIjectioIn of small hepatic aind abdomiial tuimiors. Radiology1986;161 :3(9-12.

(A.4septsd31 .IlaY 1919

Departments ofRheumatology and ClinicalPharmacology, StBartholomew's Hospital,London ECIA 7BEPeter Fisher, FFHOM, visitintgrheumatologistAlison Greenwood, SRN,clinical metrologistE C Huskisson, FRCP, head ofrheumatolopv departmentPaul Turner, FRCIP, projfessorof clinical pharmtacology

Laboratoires Boiron, 69110Ste Foy les Lyon, FrancePhilippe Belon, MD, researchdirector

Correspondence to: DrFisher.

BrAfedj 1989;299:365-6

Effect of homoeopathictreatment on fibrositis (primaryfibromyalgia)

Peter Fisher, Alison Greenwood, E C Huskisson,Paul Turner, Philippe Belon

In scientific research negative results are often moredifficult to interpret than positive ones, as was shownby a clinical trial in which the homoeopathic medicineRhus toxicodendron 6x was compared with a placeboand fenoprofen in the treatment of osteoarthritis. Thehomoeopathic medicine was found to be ineffectivewhereas fenoprofen gave an improvement.' Therewere two interpretations: either the effects of homoeo-pathy are only a placebo effect-that is, a true negative-or the result was a false negative one because offlaws in the design. Another trial had previouslysuggested that homoeopathy was effective in rheuma-toid arthritis.We designed a trial to clarify these results by

overcoming the methodological criticisms while retain-ing a rigorous design. The main problem in designingclinical trials of homoeopathy is that prescriptions arebased on criteria such as the pattern of symptoms aswell as the diagnosis. A clinical trial based solely ondiagnosis is therefore inappropriate. In a pilot studywe had shown that R toxicodenidron 6c was the mostcommonly indicated homoeopathic medicine forfibrositis in our patients, being indicated in 42%.

Patients, methods, and resultsWe used the diagnostic criteria of Yunus et al for

fibrositis.' Only patients with this syndrome, in whomthe homoeopathic medicine R toxicodendron 6c waspositively indicated were entered into the study.Thirty patients meeting the admission criteria were

recruited in the rheumatology clinic of this hospital.The clinical characteristics of the patients were similarto those of other reported series regarding age, sexdistribution, duration of symptoms, modalities, andnumber of tender points. The trial was doubleblind, placebo controlled, and of crossover design.After entry there was no further contact between thehomoeopathic doctor and the patient until the treat-ment was finished. The clinical metrologist dispensedthe treatment and performed the assessments andanalyses blind. Patients received active treatment andan identical placebo for one month each in randomsequence. The dose was two tablets sucked three timesdaily.The active preparation was R toxicodendron 6c

(Boiron) prepared from a tincture of the leaves ofpoison oak diluted 1:99 in ethanol and then vigorouslyshaken. This process was repeated six times to give the6c potency-a dilution of 102 of the tincture. This wasthen put up on 125 mg lactose tablets (2% volume perweight). Preparation was as specified in the Frenchnational pharmacopoeia. The placebo was identicallactose tablets to which only pharmaceutical ethanolhad been added (2% volume per weight). Blind testingof the active and placebo preparations for a battery ofdrugs yielded negative results. Assessment comprisedthe number of tender spots, 10 cm visual analoguescales of pain and sleep, and overall assessment.Comparison was made between values at the end ofactive and placebo treatment periods.The patients did better in all variables when they

took active treatment rather than placebo. The numberof tender spots was reduced by about a quarter(p<0005). We reduced subjective data to nominalmeasurements (worse or better). If the null hypothesiswere correct the direction of change after placeboand active treatment would be randomly distributed.Analysis showed a significant difference in favour ofthe homoeopathic medicine (table). Overall assess-ment also showed a preference for the active treatment,which was not significant.

BMJ VOLUME 299 5 AUGUST 1989 365

Assessment of patients with fibrositis after treatment with Rhustoxicodendron (ac-tive) and placebo

Placebo Active p Value

Mean No of tender points 14-1 10-6 <0.005*No of patients with improved pain

or sleep (visual analogue scores) 27 53 0-0052t

*Wilcoxon rank sum test. tPaircd t test.

CommentFibrositis (primary fibromyalgia) is a controversial

condition but is becoming increasingly accepted.4 It isdifficult to treat. We showed that the homoeopathicmedicine R toxicodendron 6c was effective for a selectedsubgroup of patients with fibrositis. The improvementin tenderness, which is the best discriminator of

fibrositis,5 was particularly distinct. The improvementexperienced by our patients while receiving activetreatment was at least as great as that reported for anyother treatment that has been assessed double blind.

We thank Jean Boiron for his advice and encouragement.

I Shipley M, Berry H, Brostcr G, Jeilkinis M, Closer A, Williams 1. Conitrolledtrial ott homoeopathic treatment of osteoarthritis. Lancet 1983;i:97-8.

2 Gibsott RU, Gibson SLMNI, MacNeill DA, Watson-Buchanan W. Homoeopathictherapy in rhettmatoid arthritis: evalitation by double-blind clinical trial.Br] Clin Phtarmacol 1980;9:453-9.

3 Yttnus M, Alasi AT, Calabro JJ, et al. IPrimary fibromyalgia (fibrositis): clinicalstudy of 50 paticnts with matched normal controls. Semin Arthritis Rthe2m1981;11:151-71.

4 Yunus MB. Fibromyalgia syndrome: new research on an old condition.Br Medj 1989;289:474-5.

S Wolfe F, Hawley DJ, Cathey MA, et a/. Fibrositis: symptom frequency andcriteria for diagnosis.]7 Rheumatol 1985;12:1159-68.

(Accepted 28 A-pril 1989)

Department of Medicine,General Hospital Linz,A 4020, AustriaG Biesenbach, MD, registrarin nephrologyJ Zazgornik, MD, professor ofmedicine

Correspondence to:Dr Biesenbach.

BrMedj 1989;299:366-7

Incidence of transient nephroticsyndrome during pregnancy indiabetic women with andwithout pre-existingmicroalbuminuria

G Biesenbach, J Zazgornik

Considerably different changes in renal protein excre-tion have been reported in diabetic women duringpregnancy.' 2 In pregnant diabetics with pre-existingmacroproteinuria (¢0 5 g protein in 24 hour urinesamples) there is often a clear increase in the protein-uria, often resulting in development of the transientnephrotic syndrome.34 In diabetic women with albu-min excretion <30 mg/day (normoalbuminuria) or30-250 mg/day (microalbuminuria) before pregnancy,however, the syndrome is rarely observed duringpregnancy. We determined to what extent micro-albuminuria (incipient diabetic nephropathy) affectsthe alterations of renal protein excretion and thevariables of kidney function during and after preg-nancy and the incidence of the syndrome duringpregnancy in these women.

Patients, methods, and resultsWe investigated seven pregnant women with type I

diabetes and pre-existing normoalbuminuria (mean(SD) age 22 (5) years, mean (SD) duration of diabetes10 (4) years) and seven pregnant type I diabetics withpre-existing microalbuminuria (mean (SD) age 23 (5)years, mean (SD) duration of diabetes 11 (3) years). Allwomen delivered between 36 and 40 weeks' gestation.Before one woman became pregnant, during weeks 12,24, 28, 32, and 36-40 of pregnancy, and in weeks 4, 12,and 24 after delivery we measured serum creatinineconcentration (autoanalyser), creatinine clearance,glycated haemoglobin concentration (Biorad), blood

pressure (Riva Rocci), albumin concentration(immunodiffusion), and total protein concentration(Biuret method) in 24 hour urine samples.

In the seven diabetic women with pre-existingnormoalbuminuria there was a 5 9-fold increase inalbumin and a 5-7-fold increase in total proteinexcretion in urine during pregnancy. In the sevendiabetic women with microalbuminuria we found a5 9-fold increase in albumin excretion and a 10 0-foldincrease in total protein excretion. After delivery theprotein excretion fell to the values before pregnancyin all patients. The difference between the absoluteincrease of proteinuria in the two groups was signifi-cant (p<0005, unpaired t test). Blood pressure andmetabolic control did not differ significantly duringpregnancy in both groups (table), and the variablesof renal function did not differ between normo-albuminuric and microalbuminuric women. Thetransient nephrotic syndrome with protein excretion>3 g in 24 hour samples of urine (3 178 g, 4 907 g, and4-761 g) occurred in three of the seven women withpre-existing microalbuminuria but in none of the sevenwith pre-existing normoalbuminuria.

CommentThe transient nephrotic syndrome is rare in preg-

nant diabetics without pre-existing heavy proteinuriaand decreased glomerular filtration rate as well asin healthy pregnant women.' The extent to whichalbumin excretion before pregnancy influences theincrease in proteinuria and the alterations of the kidneyfunction during pregnancy has not, to our knowledge,been previously investigated in diabetic women.

In our patients with normoalbuminuria the increasein proteinuria during pregnancy remained withinthe physiological range seen in healthy pregnantwomen.4' In the diabetic women with pre-existingmicroalbuminuria the increase in proteinuria duringpregnancy was significantly higher. Obviously theglomerular basement membrane develops a greaterpermeability for protein during pregnancy in diabeticwomen with pre-existing microalbuminuria in com-

Urtnary protein excretion and renalfunction before, during, and after pregnancy. Values are means (SD)

Diabetics with normoalbuminuria Diabetics with microalbuminuria

Before Third trimester 24 Weeks Before Third trimester 24 Weekspregnancy of pregnancy after deliverv pregnancy of pregnancy after deliverv

Albumin in urine (mg/day) 12 (3) 71('34) 13 (4) 80 (45) 478 (247) 114 (74)Total protein in urine (g/day) 0-073 (0-056) 0 417 (0 142) 0 096 (0-073) 0 233 (0-186) 2 353 (1 211) 0-239 (0-107)Serum creatinine (,tmol/l) 79(13) 68(10) 85 (7) 71(15) 63(9) 79(13)Creatinineclearance(mlUs) 1 72 (0 18) 2-07 (0-118) 1 72 (0 17) 1 83 (0-22) 2-12 (0 40) 1 80(0 28)Blood pressure (mm Hg) 120 (9)/79 (5) 121 (7)l77 (5) 118 (7)/79 (6) 118 (8)/80 (7) 118 (6)/79 (6) 117 (6)/78 (5)Glycatedhaemoglobin(%) 6-2(1-1) 4-7(0 8) 6-2(0 6) 6-8(0 6) 5-4(0 5) 6-8(0 5)

366 BMJ VOLUME 299 5 AUGUST 1989