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that of levodopa. It might, therefore, help patients with advanced disease when loss of striatal dopaminergic neurons is massive. Since the drug seems to act directly on post-synaptic dopamine receptors the therapeutic effect is independent of the activity of presynaptic

dopamine neurons. INSERM U 289, Hôital de la Salpêtrière, 75013 Paris, France, and Clinical Investigation Unit, Smith Kline & French Research Ltd, Paris la Défense

M. J. VIDAILHET A. M. BONNET

S. BELAL B. DUBOIS

C. MARLE Y. AGID

Early combination of bromocriptine and levodopa in the treatment of Parkinson’s disease: a 5-year follow-up. Neurology 1987; 37: 826-28. 2. Lees AJ, Stem GM. Sustained bromocriptine therapy in previously untreated patients with Parkinson’s disease. J Neurol Neurosurg Psychiatry 1981; 44: 1020-23. 3. Rascol A, Guiraud B, Montastruc JL, David J, Clanet M. Long term treatment of Parkinson’s diease with bromocriptine. J Neurol Neurosurg Psychiatry 1979; 42: 143-50. 4. Gallagher G, Lavancher PG, Wilson JW, Hieble JP, Demarinis RM. 4-(2-(di-npropylamino)ethyl)-2(3H)-indolone: a prejunctional dopamine receptor agonist. J Med Chem 1985; 28: 1533-36. 5. Kapoor R, Pirtosek Z, Frankek JP, et al. Treatment of Parkinson’s disease with novel dopamine D2 agonist SKF 101468. Lancet 1989; ii: 1445-46. 6. Hoehn MM, Yahr MD. Parkinsonism: onset, progression and mortality. Neurology 1. Rinne UK.

1967; 17: 427-42. Esteguy M, Bonnet AM, Lhermitte F, Agid Y. "Le test à la L-dopa" dans la maladie de Parkinson. Rev Neurol (Paris) 1985; 141: 413-15. 8. Agid Y, Pollak P, Bonnet AM, Signoret JL, Lhermitte F. Bromocriptine associated with a peripheral blocking agent in treatment of Parkinson’s disease. Lancet 1979; i 7.

570-72. 9. Fahn S, Elton RL. UPDRS Development Committee. Unified Parkinson’s disease rating scale. In: Fahn S, Marsden CD, Calne DB, Goldstein M, eds. Recent developments in Parkinson’s disease: vol II. Florham Park, New Jersey: Macmillan Healthcare Information, 1987: 153-63, 293-304.

HTLV-I/II antibodies in UK blood donors SIR,-Dr Coste and colleagues (May 12, p 1167) report antibody to HTLV-I/II in 0-011% of French blood donors. We tentatively estimate the prevalence in North London blood donors to be much lower. Serum from 4134 consecutive routine donors and from 2376 donors selected, on the basis of their ethnic origin, for sickle cell trait screening were tested for anti HTLV-1/11 by gelatin particle agglutination (Fujirebio). Repeatedly reactive samples were tested by ELISA (Abbott, DuPont) and by "in-house" competitive ELISA, and competitive and IgG antibody capture radioimmunoassays, and samples found reactive by Abbott or DuPont ELISA were further tested by radioimmunoprecipitation assay. These samples and the 45 ELISA negative samples with the highest titres in the Fujirebio test were also tested by western blot (DuPont). Lymphocytes were obtained from one serologically reactive donor for HTLV-1 DNA amplification by the polymerase chain reaction. Of 6510 samples tested, 379 (5-8%) were initially and 87 (1-34%) repeatedly reactive by gelatin particle agglutination: 4 of the 87 had a titre in excess of 1000, 27 a titre of between 128 and 512, and the other 55 a titre of less than 128. 4 of these 87 samples were also reactive by ELISA (table), but only 2 were confirmed as antiHTLV-1/11 positive on the criterion of reactivity to both gag and env

gene products.1

The specificity of anti-HTLV-I/II screening assays remains in doubt. The gelatin particle agglutination method-though simple, economical, and highly sensitive--gave an unacceptable number of false-positive reactions. Reagents with better specificity are now

available in the UK, but these await full evaluation. The Abbott and DuPont ELI SAs, though apparently more specific, gave 2 reactions not confirmed as anti HTLV-1/11 positive. It has been estimated that the positive predictive value of the DuPont ELISA, for screening populations with low seroprevalence rates, is less than 10%.2 The in-house assays identified the 2 seropositive donors, but it was necessary to use radioimmunoprecipitation in conjunction with western blot to demonstrate reactivity to both gag and env gene products. These are complex and labour intensive confirmatory assays that can only be done in specialised laboratories, which underlines the need for screening tests that will generate fewer false-positive reactions. The 2 anti-HTLV-I/II positive donors identified in this investigation were from the sickle trait screening panel; none of the routine blood donors was positive. Since an estimated 0-43% of our donor panel are "sickle-screened" donors, this implies an overall seropositivity rate of 1 in 276 000 (0-00036%) in our donor population. Larger surveys are essential to validate this figure, and we plan to do this using a more specific screening assay. The outcome of these studies may show whether unselective or selective screening of UK blood donors for anti-HTLV-I/II is feasible or even worthwhile. North London Blood Transfusion Centre, London NW9 5BG, UK; Virus Reference Laboratory, Central Public Health Laboratory, London NW9, and Department of Medical Microbiology,

University College and Middlesex School of Medicine, London WC1

R. SALKER J. H. C. TOSSWILL J. A. J. BARBARA J. RUNGANGA M. CONTRERAS R. S. TEDDER N. PARRA-MEJIA P. P. MORTIMER

1. US Public Health Service Working Group. Licensure of screening tests for antibody to human T-lympotropic virus type I. MMWR 1988; 37: 736-17. 2. Khabbaz RF, Hartley TM, Lairmore MD, Kaplan JE. Epidemiologic assessment of screening tests for antibody to human T lymphotropic virus type I (HTLV-I). Am J Publ Health 1990; 80: 190-92

False-positive autoantibodies in infection

SIR,-Dr Koderisch and colleagues (May 19, p 1227) report that patients infected with HIV may have detectable anti-neutrophil cytoplasmic antibodies (ANCA). Previous studies from the same workers had suggested that ANCA were restricted to patients with Wegener’s granulomatosis and/or microscopic polyarteritis.l We too have seen a case of HIV infection associated with a false-positive ANCA test. A 31-year-old heterosexual male, who was not a drug abuser, was admitted with a history of an influenza-like illness followed some 6 weeks later by a painful neuropathy progressing from legs to hands. He noticed difficulty in starting micturition and in swallowing fluids. Nerve conduction studies confirmed the peripheral neuropathy; CSF examination revealed increased protein (1 g/dl) and IgG (80 g/1, normal < 40), but there were no oligoclonal bands on electrophoresis. On admission he had a normal white blood cell count and differential; a blood film revealed the occasional atypical lymphocyte; serum globulin was normal; liver-function tests (alkaline phosphatase and aspartate transaminase) were abnormal; serum IgG at 17-9 g/1 and IgM at 2-28 g/1 were slightly increased; and complement values and C-reactive protein were normal on repeated testing. During his time in hospital tests for several

ANTI-HTLV-1/11 RESULTS ON 4 DONORS REACTIVE BY BOTH GELATIN PARTICLE AGGLUTINATION AND ELISA

*HTLV-I DNA detected

by PCR.

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were noted to be positive on one or more occasions (double-stranded DNA, smooth muscle, and ANCA). ANCA was detected by routine immunofluorescence2 with alcohol-fixed neutrophils; staining was perinuclear with some focal intracytoplasmic positivity. Subsequently HIV antibody was detected in three sera, confirming the diagnosis of HIV-induced neuropathy. The history and clinical findings followed the pattern

autoantibodies

described with HIV seroconversion.3 Patients infected with HIV may have circulating immune complexes, usually composed of IgG or IgM.4 Others have noted antinuclear antibodies in up to 12% of patients;5 double-stranded DNA antibodies have rarely been reported, and usually in association with severe systemic infection.5 Although doublestranded DNA antibodies were detected at times during this man’s illness, the cytoplasmic staining obtained during the ANCA test differed from that reported with systemic lupus erythematosus.6 As suggested by Koderisch and co-workers false-positive testing for ANCA (and other autoantibodies) by indirect immunofluorescence techniques probably reflects non-specific IgG binding to Fc receptors. HIV infection should be considered in cases where autoantibodies are weakly positive or where atypical immunofluorescence patterns are obtained. Department of Medicine, University of Leeds, Leeds LS1 3EX, UK

A. DAVENPORT P. J. GRANT

the same physicians over a short period of time that the possibility of disease dawned. The necessary existence of a small cluster before novel associations are detected by clinicians is an epidemiological truism.5 Because of the loss of scientific status of the case-report over the past two decades, it is very possible that early reports on P carinii pneumonia in previously well adults are hidden in medical journals in a variety of languages--or were presented orally at clinicopathological conferences (CPC) or local medical meetings. Pathology reports, hospital information systems, and records of CPCs could be perused for the major HIV-associated diagnoses such as P carinii pneumonia, cytomegalovirus infection, and Kaposi sarcoma. Specific searches might be made for the early epidemiology of Kaposi sarcoma or directed at countries where the likelihood of early isolated cases is high, such as Belgium with its historical links with central Africa. Case-reports would have to be reviewed by a physician experienced in infectious diseases, preferably with access to the original patient file. The potential of retrospective diagnosis by polymerase chain reaction and HIVspecific probes makes these searches worthwhile, since they might allow to map the early spread of the AIDS epidemic.

a new

Department of Clinical Epidemiology, Leiden University Hospital, 2300RC Leiden, Netherlands

1.

1. Andrassy K, Koderisch J, Rufer M, Erb A, Waldherr R, Ritz E. Detection and clinical implication of anti-neutrophil cytoplasm antibodies in Wegener’s granulomatosis and rapidly progressive glomerulonephritis Clin Nephrol 1989; 32: 159-67. 2. Wiik A. Delineation of a standard procedure for indirect immunofluorescence detection of ANCA. APMIS 1989, 97 (suppl 6). 12-14 3. Piette AM, Tusseau F, Vignon D, et al. Acute neuropathy coincident with seroconversion for anti LAV/HTLV 111. Lancet 1986, i:852. 4. Euler HH, Kern P, Loffler H, Dietrich M. Precipitable immune complexes in healthy homosexual men, acquired immunodeficiency syndrome and the related lymphadenopathy syndrome. Clin Exp Immunol 1985; 59: 267-75. 5. Kopelman RG, Zolla-Pazner S. Association of human immunodeficiency virus infection and autoimmune phenomena. Am J Med 1988; 84: 82-88. 6. Wiik A. Granulocyte specific antinuclear antibodies. Allergy 1980; 35: 263-65.

Tracking AIDS epidemic in libraries SiR,—The confirmation (July 7, p 51) that a 1960 case-report on Pneumocystis carinii penumonia and cytomegalovirus infection in a previously healthy young man was indeed the description of an early victim of HIV infection prompted me to wonder whether similar isolated case-reports could be traced in the medical literature. As a preliminary test of the idea, I looked for major reviews on pneumocystis pneumonia published in the pre-AIDS era and identified two comprehensive reviews in standard textbooks.l.2 Both books stressed that the ubiquitous pneumocystis gives rise to pneumonia in the severely immunocompromised host only, with very rare exceptions. One thorough review, published in 1973, mentioned six documented cases of P carinii pneumonia in previously healthy people.3 The Manchester patient whose HIV status has now been confirmed (July 7 issue) was in this review albeit under the heading "Diseases treated with corticosteroids, Lymphoreticular malignancies". A 1974 review from the Centers for Disease Control (CDC), and covering a three-year period during which the CDC was the sole US supplier of pentamidine isethionate, revealed that in one patient the only underlying predisposing condition was cryptococcus infection (see table 2, ref 4). Presumably, more cases of isolated pneumonia might be found if the lists of references in reviews were to be read afresh. The idea that an underlying predisposing condition was necessary might have influenced the judgment of authors and reviewers in the past. For as long as there have been written records in medicine, case-reports and case series have been published, serving a variety of purposes: the description of novel disease, the study of pathogenesis, first therapeutic claims, side-effects reporting, teaching, and warning colleagues of pitfalls in diagnosis and therapy. Astute clinicians have always felt the urge to write down and publish the unusual. My preliminary hunt makes it likely that early reports of isolated AIDS patients are hidden in medical journals. It is only when a handful of cases came to the attention of

JAN P. VANDENBROUCKE

Hughes WT. Pneumocystis carinii. In: Weatherall DJ, Ledingham JGG, Warrell DA, eds. Oxford textbook of medicine. Oxford: Oxford University Press, 1983: 399-400.

Ray CG. Pneumocystis carinii pneumonia. In: Isselbacher KJ, Adams RA, Braunwald E, et al. Harrison’s principles of internal medicine, 9th ed. New York: McGraw-Hill, 1980: 885-87. 3. Burke BA, Good RA. Pneumocystis carinii infection. Medicine 1973; 52: 23-51. 4. Walzer PD, Perl DP, Krogstad DJ, et al. Pneumocystis carinii pneumonia in the United 2.

States. Ann Intern Med 1974; 80: 83-93. JAH, Vaughan TL, Diehr PH, Haertle RA. The recognition of new kinds of occupational toxicity. In: Castellani A. Epidemiology and quantitation of environmental risks in humans from radiation and other agents. New York. Plenum Press, 1985: 307-37.

5. Lee

Death from diabetic ketoacidosis after cessation of octreotide in acromegaly SIR,- The somatostatin analogue octreotide (’Sandostatin’) reduces circulating growth hormone (GH) concentration by more than half in 86% of patients with acromegaly and returns somatomedin C concentrations to normal in 36%.’ We report a patient with acromegaly and insulin-resistant diabetes mellitus who was treated with octreotide. A man underwent trans-sphenoidal 30-year-old hypophysectomy in April, 1987, for a large GH secreting pituitary tumour with suprasellar and parasellar extension, causing blindness in the left eye and a right temporal visual field defect (preoperative GH concentration greater than 100 ng/ml). He had insulin-resistant diabetes and needed 170 units insulin daily (2-1 U/kg), despite which glucose control remained poor (HbA1c 20%; normal 6-9%). Urine was negative for ketones, and blood pressure was 120/80 mm Hg. Despite postoperative pituitary irradiation the acromegaly remained active (mean basal GH 22 ng/ml) and diabetes mellitus was difficult to control. In February, 1988, treatment with octreotide (kindly provided by Sandoz Products) was begun after failure to respond to dopamine agonist therapy. The patient was eventually maintained on octreotide 400 ng daily, with a 37% reduction in the mean basal GH concentration (to 13-7 ng/ml), improved glucose control (mean daily insulin requirements 2-75 U/kg, HbA1c reduced to 11 -9%), relief of headache due to tumour, improvement in acral features, and reduced soft tissue swelling. In October, 1988, he had about a 15% reduction in tumour size on computed tomographic scan, but substantial suprasellar extension of tumour persisted and visual symptoms had not improved. On Oct 18 the patient had transfrontat hypophysectomy. Octreotide was stopped at that time. The visual defect remained unchanged postoperatively and circulating GH concentrations were raised. Octreotide was recommenced. The metabolic responses were maintained for the next 12 months. In November, 1989, octreotide