Ketoconazole was given at a dose of 200 mg twice daily for 15 days, and in the absence of any response the dose was increased to 400 mg twice daily for another 15 days. Patients were evaluated daily and spleen punctures and haematological tests were done weekly. No patient showed any clinical or haematological improvement. The parasite load did not decrease, and in one patient the load increased from 3 + to 5 + during therapy. This discouraging experience led us to cut short this study of
ketoconazole. Department of Medicine,
SHYAM SUNDAR KAILASH KUMAR V. P. SINGH
Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India 1.
Urcuyo FG, Zaias M. Oral ketoconazole in the Dermatol 1982; 21: 414-16.
Joliffe DS. Cutaneous leishmaniasis from Belize—treatment with ketoconazole. Clin Exp Dermatol 1986; 11: 62-66. 3. Dedet JP, Jamet P, Esterre P, Ghippori PM, Genn C, Laland G. Failure to cure 2.
Leishmania braziliensis guyanensis cutaneous leishmaniasis with oral ketoconazole (letter). Trans R Soc Trop Med Hyg 1986; 80: 176. 4. Chulay JD, Brycesen ADM. Quantification of amastigotes of Leishmania donovani in smears of splenic aspirates from patients with visceral leishmaniasis. Am J Trop Med Hyg 1983; 32: 475-79.
Is renal vasculitis
increasing in incidence?
SIR,-Renal disease due to microscopic polyarteritis and Wegener’s granulomatosis is being diagnosed more frequently’2 but there is doubt about whether this reflects a true increase or more precise diagnosis by a specific serological test for antineutrophil cytoplasmic antibodies (ANCA). We have evidence of a real increase in renal disease due to arteritis since the mid-1980s. 1505 patients with severe acute renal failure (ARF) have been treated at Leeds General Infirmary since 1956, and in 189 the acute uraemic emergency was due to histologically proven renal parenchymal disease. Although the incidence of intrinsic renal disease as a cause of ARF has remained constant throughout the study periodthe proportion of acute glomerulonephritis due to vasculitis has risen from 144% in 1956-79 to 36.6% in 1980-90 (figure). Arteritis is now the commonest cause of rapidly progressive glomerulonephritis (RPGN) in our unit. The agedistribution of the arteritides and of other RPGN differs, with a unimodal rather than bimodal distribution and with median age of 56and 47-1years, respectively. Despite the fact that microscopic polyarteritis and Wegener’s granulomatosis are both multisystem disorders of predominantly older patients requiring aggressive immunosuppressive therapy, the prognosis is good. One-year patient survival since 1980 has been 72% for all arteritides, 54% for those presenting as ARF, and 83% in the 12 patients who required
long-term renal replacement therapy by dialysis. (Before the introduction of immunosuppressive therapy 1-year survival of patients with renal arteritis in our unit was less than 20%.) Thus we have seen an increase in renal arteritis presenting since 1980, both in absolute numbers and proportion of acute glomerulonephritis. Unlike the report from Leicester,’ the rise in Leeds started in 1985 and the incidence has remained constant since then. This increase began 2-3 years before serological assays for ANCA were available to us. We conclude that the incidence of renal arteritis has increased, that this increase predates the availability of tests for ANCA, and that the commonest mode of presentation is RPGN due to microscopic polyarteritis in older patients. From discussion with colleagues, it would appear that this increased incidence since the mid 1980s has occurred throughout the UK. Our impression is that certain other causes of RPGN, such as Goodpasture’s syndrome, have become more rare. G. WOODROW Regional Renal Unit, General Infirmary at Leeds, Leeds LS1 3EX, UK
presenting with ARF due to acute glomerulonephritis or to arteritis (Wegener’s granulomatosis or microscopic polyarteritis), 1956-90.
A. M. BROWNJOHN J. H. TURNEY
M, Edmunds M, Campbell A, Walls J, Feehally J. Systemic vasculitis in the 1980s: is there an increasing incidence of Wegener’s granulomatosis and microscopic polyarteritis? J R Coll Physicians (Lond) 1990; 24: 284-88.
Rodgers H, Guthrie JA, Brownjohn AM, Turney JH. Microscopic polyarteritis: clinical features and treatment. Postgrad Med J 1989; 65: 515-18. 3. Turney JH, Marshall DH, Brownjohn AM, Ellis CM, Parsons FM. The evolution of acute renal failure, 1956-1988. QJ Med 1990; 74: 83-104. 2.
Dogma, denial, and drinking problems SIR,-We read, with equal measures of interest and dismay, Mr Woodley’s comments (Dec 1, p 1384) on our study of specialist versus general practitioner (GP) treatment of problem drinkers (Oct 13, p 915). In his experience "the average GP is often ill-prepared to deal with the [severely alcohol dependent] patient" and is variously naive, and lacking in knowledge, interest, and skill. "... the most effective thing for the GP to do is to refer the patient to a specialist", he concludes. Several official reports and research studies (including ours) are in broad agreement with the assertion that GPs are often less than eager to treat patients with drinking problems.1-5 Where we differ with Woodley is on what should be done about this situation. comments highlight the gulf between the views of institutional and treatment personnel and the increasing body of data from epidemiological and controlled research on addictions. Ideological differences sustain this division. There is the type of problem drinker who is deemed worthy of treatment intervention. The exclusiveness of alcoholism treatment
facilities (exemplified by Woodley’s letter) continues to deny help to people in need, but who do not meet the criterion of a "severely dependent drinker". For how long will specialist treatment personnel continue to deny the overwhelming epidemiological evidence that serious alcohol problems are not confined to the narrow alcoholic stereotype? The number of people with serious drinking problems in need of help greatly exceeds the availability of specialist treatment places.6 One population-based study, for example, found that only between a quarter and a ninth of needful (severe) cases were known to apposite treatment agencies.7 A recent US survey8 found that, on a broad definition of "treatment", there were 1 ’7 treatment places per 1000 population. This represents about a tenth of the number of people with severe drinking problems in the population.9 With such a shortfall in specialist treatment the support of as many professional and voluntary agencies as possible needs to be enlisted urgently. Clinical decisions should be based on controlled studies rather than anecdote, dogma, and received wisdom. Your correspondent urges readers to accept that GPs are unsuccessful in treating problem drinkers whereas with his treatment "the success rate... is high". Where is the evidence for this claim? Why do professional treatment personnel, especially some of those in the private sector, continue to deny the overwhelming evidence from research studies? The answer is that alcohol problems support a large "industry", 10 the survival of which many
Numbers of patients
J. A. COOK
depends on the continued recognition of an alcoholic stereotype and the promulgation of the message that intensive, specialist treatment is not only effective but also better than other approaches. How else could its considerable cost be justified? Rather than drawing an arbitrary line between primary care and specialist services, across which patients and professionals must not venture, we would like to see a new spirit of detente and collaboration-a policy of shared care. Instead of berating the generalist for his lack of skill and motivation we should be engaging in dialogue and training. In doing so, treatment personnel must learn to take account of hard evidence instead of being guided by dogma. Addiction Research Unit, National Addiction Centre, Institute of Psychiatry, London SE5 8AF, UK
D. COLIN DRUMMOND GRIFFITH EDWARDS
Advisory Committee on Alcoholism. The pattern and range of services for problem drinkers. London: Department of Health and Social Security, 1978. 2. Alcohol: a balanced view. London: Royal College of General Practitioners, 1986. 3. Shaw W, Cartwright A, Spratley T, Harwin J. Responding to drinking problems. 1.
London: Croom Helm, 1978. 4. Clement S. The identification of alcohol-related problems by general practitioners. Br J Addict 1986; 81: 257-64. 5. Thorn B, Telez C. A difficult business. detecting and managing alcohol problems in general practice. Br J Addict 1986; 81: 405-18. 6. Caviston P. Alcohol services: exhortations rather than commitment. Br Med J 1988; 297: 241-42. 7. Edwards G, Hawker A, Hensman C, Peto J, Williamson V. Alcoholics known or unknown to agencies: epidemiological studies in a London suburb. Br J Psychiatry 1973; 123: 169-83. 8. Highlights from the 1987 National Drug and Alcoholism Treatment Unit Survey (NDATUS). Rockville: National Institute on Drug Abuse/National Institute on Alcohol Abuse and Alcoholism, 1989. 9. Drummond DC. Comprehensive strategies for the therapy of alcoholism; where have we gone wrong? In: Kalant H, ed. Proceedings of the 5th Congress of the International Society for Biomedical Research on Alcoholism. Alcohol Alcoholism
(in press). 10. Miller WR, Hester RK.
who benefits? Am
1986; 41: 794-805.
kidney transplantation in Bombay
SiR,—Dr Al-Khader and colleagues (Oct 20,
improved graft survival in their patients who were recently transplanted in Bombay. Over the past 4 years, 42 of our end-stage renal patients (26 male, 16 female) have received living non-related kidneys, most from a single centre in Bombay, and returned to Doha where they continued under our care despite our opposition to such an unethical procedure. 5 patients died soon after transplant. A 65-year-old man, with poor cardiac function, had a fatal cardiac arrest 40 days after transplant. A 57-year-old man with diabetic nephropathy and peripheral vascular disease died from Fournier’s gangrene of the scrotum 3 months after transplant. A 55-year-old man had a severe acute rejection and was treated aggressively with steroids and anti-thymocyte globulin which predisposed him to fatal septicaemia. The fourth patient, a 17-year-old man, had previously had two failed renal allografts (in another country), and died with sepsis following an irreversible rejection episode. The final patient was a 12-year-old girl in a poor general condition who died the day she returned to Doha. 6 further patients lost their grafts: 3 were presensitised with very high cytotoxic antibody titres and had fulminant acute rejection, and in the other 3 chronic rejection developed. There was evidence of non-compliance with medication in 2 of the latter 3. All 6 were started on maintenance haemodialysis. The surviving 31 patients have a mean (SD) age of 31 (13) years (range 20-60), and transplant duration of 30 (16) months (3-56). They are doing quite well and their mean (SD) serum creatinine is 161 (63) tnol/1 (range 88-354). This group can be compared with 60 patients who received 62 grafts elsewhere: 4 of these died, and 13 more lost their grafts. The remaining 45 patients have a mean (SD) age of 39 (12) years (range 14-65), transplant duration of 65-8 (42-9) months (3-168), and serum creatinine of 140 (57) umol/1 (71-354). Recipients of living non-related renal allografts in India had increased early mortality, which seems to be related to accepting high-risk patients and lack of adequate postoperative care of these
patients, who, occasionally, want to go home prematurely. The other subset of patients that did badly were those presensitised with high cytotoxic antibodies; such patients require a special immunosuppressive protocol. However, most patients did reasonably well and have, so far, maintained serum creatinine levels comparable with those of patients transplanted elsewhere. Renal Unit, Hamad General Hospital, PO Box 3050, Doha, Qatar
SALEH H. ABU-ROMEH NADIA OSMAN AWAD RASHID
Inhibition of Helicobacter pylori by acetohydroxamic acid SiR,—Mooney et all have suggested inhibition of urease activity by acetohydroxamic acid (AHA) as a way to treat Helicobacter pylori infection. They found that in-vitro addition of AHA abolished the resistance of H pylori low acid levels of pH 1 and 2. We have shown that H pylori does not survive at low pj-1,2 but addition of urea is necessary for resistance to acid to occuras pointed out by Mooney et al.
However, Mooney et al are mistaken in thinking that AHA inhibits the in-vitro growth of this organism. We and others have shown that AHA inhibits the urease activity of H pylori but does not affect growth.45AHA alone does not have significant antimicrobial activity.6 Mooney’s reference to the work of McNulty et al (their ref 9) is therefore incorrect. Furthermore, the suggestion that the combination of AHA with other antimicrobials is likely to be more successful, since synergism has been observed when AHA was used in urinary-tract infections, needs further testing. Both synergy and antagonism have been found when AHA was combined with other antimicrobial agents to treat gram-negative urease-producing
organisms.6,7 Side-effects with AHA occur in up to 30% of patients, and these effects include bone-marrow depression, haemolytic anaemia, deep venous thrombosis, and thrombophlebitis.8 It remains to be seen whether orally ingested AHA results in urease inhibition and whether AHA can still exert its urease-inhibiting effect after it has been absorbed. Division of Gastroenterology, Dalhousie University, Halifax, Nova Scotia B3H 2Y9; and Division of Gastroenterology, Anatomic Pathology, and Laboratory Medicine, McMaster University Health Sciences Centre,
Hamilton, Ontario, Canada
S. J. O. VELDHUYZEN VAN ZANTEN J. GOLDIE RICHARD H. HUNT
Mooney C, Munster DJ, Bagshaw PF, Allardyce RA. Helicobacter pylori acid resistance. Lancet 1990; 335: 1232. 2. Goldie J, Hollingsworth J, Hunt RH. Campylobacter pylon does not grow m acid media. In: Campylobacter pylori: a multidisciplinary workshop (Keystone, Colorado, 1987). 3. Marshall BJ, Barrett LJ, Prakash C, McCallum RW, Guerrant RL. Urea protects Helicobacter pylon from the bactericidal effect of acid. Gastroenterology 1990; 99: 1.
697-702. 4. Goldie J, Jalali S, Veldhuyzen van Zanten SJO, Stowe C, Hunt RH. Acetohydroxamic add inhibits the urease of Campylobacter pylori. Am J Gastroenterol 1989; 84: 1160. 5. Mobley HLT, Cortesis MJ, Rosenthal LE, Jones BD. Characterization of urease from Campylobacter pylori. JClin Microbiol 1988; 26: 831-36. 6. Gale GR. Urease activity and antibiotic sensitivity of bacteria. J Bacteriol 1966; 91: 499-506. 7. Musher DM, Saenz C, Griffith Interaction between acetohydroxamic acid and 12 antibiotics against 14 gram-negative pathogenic bacteria. Antimicrob Agents Chemother 1974; 5: 106-10. 8. Williams JJ, Rodman JS, Petreson CM. A randomized double blind study of acetohydroxamic acid in struvite nephrolithiasis. N Engl J Med 1984; 311: 760-64.
*** This letter had been shown to Dr Munster and colleagues, whose reply follows.-ED. L. SiR,—Your correspondents cite two reports suggesting that acetohydroxamic acid (AHA) does not inhibit growth of Helicobacter pylori in vitro.1,2 Our letter referred to one report with a contrary finding.3 Unfortunately, the question was not adequately investigated (or documented), the reports consisting of two sentences in a full paper,’ an abstract,2 and a brief summary of