124
290 mg/dl by diet or drugs in men and women above 60 years of age. These values should not be classified as "hypercholesterolaemia", and we should not forget that for many elderly people dieting has a negative impact on quality of life. Centre for Internal Medicine, Medizinishe Hochschule Hannover, D 3000 Hannover 61,
CHRISTOPH
Germany
J. OLBRICHT
Steinberg D Chairman Consensus Conference. Lowering blood cholesterol to prevent heart disease JAMA 1985; 253: 2080-86. 2. Assmann G, Lewis B, Mancini M, European Atherosclerosis Society. The recognition and management of hyperlipidaemia in adults: a policy statement of the European Atherosclerosis Society. Eur Heart J 1988; 9: 571-600. 3. Kannel WB, Neaton JD, Wentworth D, et al. Overall and coronary heart disease mortality rates in relation to major risk factors in 325 348 men screened for the MRFIT. Am Heart J 1986; 112: 825-36. 4. Agner E, Hansen PF. Fasting serum cholesterol and triglycerides in a ten-year prospective study in old age. Acta Med Scand 1983; 214: 33-41. 5. Aronow WS, Starling L, Etienne F, et al. Risk factors for coronary artery disease in persons older than 62 years in a long-term health care facility. Am J Cardiol 1986; 1.
57: 518-20. 6. Anderson KM, Castelli WP,
Levy D. Cholesterol and mortality: 30 years of follow-up from the Framingham study. JAMA 1987; 257: 2176-80. 7. Siegel D, Kuller L, Lazarus NB, et al. Predictors of cardiovascular events and mortality in the systolic hypertension in the elderly program pilot project. Am J
Epidemiol 1987; 126: 385-99. 8. Dayton S, Pearce ML, Hashimoto S, Dixon WJ, Tomiyasu U. A controlled trial of a diet high in unsaturated fat m preventing complications of atherosclerosis. Circulation 1969; 39/49 (suppl II): II-1-63. 9. Buchwald H, Varco RL, Marts JP, et al. Effect of partial ileal bypass surgery on mortality and morbidity from coronary heart disease in patients with hypercholesterolemia: report of the program on the surgical control of the hyperlipidemias. N Engl J Med 1990; 323: 946-55
be readily available in the tropics. Unsystematic application of heat (eg, from an electric light cradle) is less effective. Case-to-case transmission 3,1 is unusual, and a remarkable feature of this disease is the way that relatives sharing the same environment with patients who shed vast numbers of M ulcerans remain uninfected. not
Department of Pathology, University of Melbourne, Repatriation General Hospital, Heidelberg West,
JOHN HAYMAN
Victoria 3081, Australia
P, Tolhurst JC, Buckle G, Sissons HA. A new mycobacterial infection m J Pathol Bacteriol 1948; 60: 93-122. 2. Abrahams EW, Tonge JI. Mycobacrerium ulcerans infection in Queensland. Med J Aust 1964; i: 334. 3. Hayman J. Mycobacterium ulcerans infection in Victoria: celebration of a golden jubilee? Australas J Dermatol 1987; 28: 99-105. 4. Hayman J, McQueen A. The pathology of Mycobaterium ulcerans infection. Pathology 1985; 17: 594-600. 5. Uganda Buruli Group. Clinical features and treatment of preulcerative Buruli lesions (Mycobacterium ulcerans infection): report II. Br Med J 1970; ii: 390-93. 6. Forbes BRV, Wannan JS, Kirkland WB. Indolent cutaneous ulceration due to infection with Mycobacterium ulcerans. Med J Aust 1954; i: 475-79. 7. Lindo SD, Daniels F. Buruli ulcer in New York city. JAMA 1974; 228: 1138-39. 8. Glynn PJ. The use of surgery and local temperature elevation in Mycobacterium ulcerans infection. Aust NZ J Surg 1972; 41: 312-17. 9. Reid IS. Mycobacterium ulcerans infection; a report of 13 cases at the Port Moresby General Hospital, Papua. Med J Aust 1967; i: 427-31. 10. Meyers WM, Shelly WM, Connor DH. Heat treatment of Mycobacterium ulcerans infections without surgical excision. Am JTrop Med Hyg 1974; 23: 924-29 1 MacCallum man.
Death knell for
guineapig test
SIR,-Let us hope that Dr Sheth’s observations (Dec 8, p 1440) last sound the death knell for the guineapig test for tuberculosis. His work confirms the observations of British microbiologists, demonstrating that this test can no longer be justified in modem laboratory practice. In 1972 Marksl showed that guineapig tests done in the Public Health Laboratory Service tuberculosis reference laboratory added very little to the results obtained through in-vitro culture. In a survey of 2000 specimens inoculated into guineapigs, he found that animal inoculations contributed only 1 additional positive to the 184 obtained by culture.’ In a retrospective survey of five years of guineapig inoculation at a London teaching hospital (1981-85), I found similar results.2 Of 677 animal tests, 34 were positive both on culture and in the guineapig, 22 were positive only on culture, and 5 were positive only in the guineapig. In only 3 of these 5 guineapig-positive/culturenegative cases was it possible to isolate tubercle bacilli from guineapig tissues. In all 3 such cases a firm diagnosis had already been made on clinical and histological grounds. Although, in one of these three cases, the guineapig isolate showed isoniazid resistance, this is of little significance when modem multidrug regimens are used.3 Guineapig testing carries little or no benefit, therefore, and any marginal utility is likely to disappear entirely once molecular techniques, such as the polymerase chain reaction,’ are adopted. Furthermore the guineapig test is costly (about c9000 was spent on the test during the five years of an earlier survey2); it is potentially hazardous, providing an opportunity for the accidental inoculation of tuberculous material into the handler’s skin;s it does not detect the increasingly important atypical mycobacteria; and it can be criticised on grounds of animal welfare. Given that, as Sheth points out, the test seems worthless in the very countries where tuberculosis is widespread, the time has come for it to be abandoned once and for all. at
Mycobacterium ulcerans infection SIR,-Dr Muelder and Dr Nourou (Nov 3, p 1109), in their paper on Mycobacterium ulcerans infection in Benin, report 28 patients followed up in difficult circumstances for as long as 4 years.
They refer
to the disease as "tropical" but the first cases of M ulcerans infection were reported from the Bairnsdale district of Victoria (38° S, 15° below the Tropic of Capricorn)l and cases have also been reported from Beerwah, near Brisbane (27° S).2 Infection in the Bairnsdale district occurs in relation to streams and lakes in the drainage areas of pockets of residual warm temperate rain forest3 in that part of Australia. In all other reported foci the disease occurs in association with warm temperate or tropical rain forest so the epithet "tropical disease" is appropriate even though M ulcerans infection may occur well south of the Tropic of Cancer. The infection in patients in Australia usually begins as an intradermal papule, and less frequently as a painful, swollen limb, which represents a necrotising panniculitis rather than cellulitis.4 The discrete subcutaneous nodule first described in Uganda’ has only rarely been identified in Queensland. These three are initial manifestations, and, if the disease is to be staged, they should all be considered as stage I (perhaps as la, Ib, and Ic, respectively). All three lesions may progress to ulceration (stage I I); ulceration may be very extensive in the oedematous form. Healing, with scar tissue, contractures, and sometimes subcutaneous calcification, could be considered stage III and deep or disseminated infection with bone involvement as stage IV. Patients with no clinical evidence of infection for months6-8 or even years after they have left an endemic zone, presumably harbour a localised collection of mycobacteria within a sebaceous gland or other skin appendage, and during this period could be considered as "stage zero". Antibiotics seem ineffective.3 Patients have had recurrent infection after surgical debridement and while on full doses of rifampicin and ethionamide, drugs to which the mycobacteria cultured from the ulcers were sensitive in vitro. Complete surgical excision of initial small lesions is usually curative whether antibiotics are given or not. Heat treatmenrB-l0 may be more effective after surgical curettage of necrotic material, and is clearly more suitable for the commoner peripheral lesions and not the disfiguring facial lesions (Dec 8, p 1440). To be effective heat must be constantly applied for days or weeks via an electric blanket or a heated water jacket with thermostat control. Such equipment may
Department of Medical Microbiology, St Bartholomew’s Hospital Medical College, London EC1A 7BE, UK 1. Marks J.
Ending the routine guinea-pig test.
M.
J. PALLEN
Tubercle 1972, 53: 31-34.
2. Pallen MJ. The inoculation of tissue specimens into guinea-pigs in suspected cases of
it aid diagnosis and treatment? Tubercle 1987; 68: 51-57. 3. Mitchison DA. Drug resistance in mycobacteria. Br Med Bull 1984, 40: 84-90 4. Pallen MJ, Butcher PD. New strategies in microbiological diagnosis. J Hosp Infect (in
mycobactenal infection does
press). SA, Pierson DJ. Primary cutaneous inoculation of drug resistant tuberculosis. AmJ Med 1974; 57: 676-78
5. Sahn
290 mg/dl by diet or drugs in men and women above 60 years of age. These values should not be classified as "hypercholesterolaemia", and we should not forget that for many elderly people dieting has a negative impact on quality of life. Centre for Internal Medicine, Medizinishe Hochschule Hannover, D 3000 Hannover 61,
CHRISTOPH
Germany
J. OLBRICHT
Steinberg D Chairman Consensus Conference. Lowering blood cholesterol to prevent heart disease JAMA 1985; 253: 2080-86. 2. Assmann G, Lewis B, Mancini M, European Atherosclerosis Society. The recognition and management of hyperlipidaemia in adults: a policy statement of the European Atherosclerosis Society. Eur Heart J 1988; 9: 571-600. 3. Kannel WB, Neaton JD, Wentworth D, et al. Overall and coronary heart disease mortality rates in relation to major risk factors in 325 348 men screened for the MRFIT. Am Heart J 1986; 112: 825-36. 4. Agner E, Hansen PF. Fasting serum cholesterol and triglycerides in a ten-year prospective study in old age. Acta Med Scand 1983; 214: 33-41. 5. Aronow WS, Starling L, Etienne F, et al. Risk factors for coronary artery disease in persons older than 62 years in a long-term health care facility. Am J Cardiol 1986; 1.
57: 518-20. 6. Anderson KM, Castelli WP,
Levy D. Cholesterol and mortality: 30 years of follow-up from the Framingham study. JAMA 1987; 257: 2176-80. 7. Siegel D, Kuller L, Lazarus NB, et al. Predictors of cardiovascular events and mortality in the systolic hypertension in the elderly program pilot project. Am J
Epidemiol 1987; 126: 385-99. 8. Dayton S, Pearce ML, Hashimoto S, Dixon WJ, Tomiyasu U. A controlled trial of a diet high in unsaturated fat m preventing complications of atherosclerosis. Circulation 1969; 39/49 (suppl II): II-1-63. 9. Buchwald H, Varco RL, Marts JP, et al. Effect of partial ileal bypass surgery on mortality and morbidity from coronary heart disease in patients with hypercholesterolemia: report of the program on the surgical control of the hyperlipidemias. N Engl J Med 1990; 323: 946-55
be readily available in the tropics. Unsystematic application of heat (eg, from an electric light cradle) is less effective. Case-to-case transmission 3,1 is unusual, and a remarkable feature of this disease is the way that relatives sharing the same environment with patients who shed vast numbers of M ulcerans remain uninfected. not
Department of Pathology, University of Melbourne, Repatriation General Hospital, Heidelberg West,
JOHN HAYMAN
Victoria 3081, Australia
P, Tolhurst JC, Buckle G, Sissons HA. A new mycobacterial infection m J Pathol Bacteriol 1948; 60: 93-122. 2. Abrahams EW, Tonge JI. Mycobacrerium ulcerans infection in Queensland. Med J Aust 1964; i: 334. 3. Hayman J. Mycobacterium ulcerans infection in Victoria: celebration of a golden jubilee? Australas J Dermatol 1987; 28: 99-105. 4. Hayman J, McQueen A. The pathology of Mycobaterium ulcerans infection. Pathology 1985; 17: 594-600. 5. Uganda Buruli Group. Clinical features and treatment of preulcerative Buruli lesions (Mycobacterium ulcerans infection): report II. Br Med J 1970; ii: 390-93. 6. Forbes BRV, Wannan JS, Kirkland WB. Indolent cutaneous ulceration due to infection with Mycobacterium ulcerans. Med J Aust 1954; i: 475-79. 7. Lindo SD, Daniels F. Buruli ulcer in New York city. JAMA 1974; 228: 1138-39. 8. Glynn PJ. The use of surgery and local temperature elevation in Mycobacterium ulcerans infection. Aust NZ J Surg 1972; 41: 312-17. 9. Reid IS. Mycobacterium ulcerans infection; a report of 13 cases at the Port Moresby General Hospital, Papua. Med J Aust 1967; i: 427-31. 10. Meyers WM, Shelly WM, Connor DH. Heat treatment of Mycobacterium ulcerans infections without surgical excision. Am JTrop Med Hyg 1974; 23: 924-29 1 MacCallum man.
Death knell for
guineapig test
SIR,-Let us hope that Dr Sheth’s observations (Dec 8, p 1440) last sound the death knell for the guineapig test for tuberculosis. His work confirms the observations of British microbiologists, demonstrating that this test can no longer be justified in modem laboratory practice. In 1972 Marksl showed that guineapig tests done in the Public Health Laboratory Service tuberculosis reference laboratory added very little to the results obtained through in-vitro culture. In a survey of 2000 specimens inoculated into guineapigs, he found that animal inoculations contributed only 1 additional positive to the 184 obtained by culture.’ In a retrospective survey of five years of guineapig inoculation at a London teaching hospital (1981-85), I found similar results.2 Of 677 animal tests, 34 were positive both on culture and in the guineapig, 22 were positive only on culture, and 5 were positive only in the guineapig. In only 3 of these 5 guineapig-positive/culturenegative cases was it possible to isolate tubercle bacilli from guineapig tissues. In all 3 such cases a firm diagnosis had already been made on clinical and histological grounds. Although, in one of these three cases, the guineapig isolate showed isoniazid resistance, this is of little significance when modem multidrug regimens are used.3 Guineapig testing carries little or no benefit, therefore, and any marginal utility is likely to disappear entirely once molecular techniques, such as the polymerase chain reaction,’ are adopted. Furthermore the guineapig test is costly (about c9000 was spent on the test during the five years of an earlier survey2); it is potentially hazardous, providing an opportunity for the accidental inoculation of tuberculous material into the handler’s skin;s it does not detect the increasingly important atypical mycobacteria; and it can be criticised on grounds of animal welfare. Given that, as Sheth points out, the test seems worthless in the very countries where tuberculosis is widespread, the time has come for it to be abandoned once and for all. at
Mycobacterium ulcerans infection SIR,-Dr Muelder and Dr Nourou (Nov 3, p 1109), in their paper on Mycobacterium ulcerans infection in Benin, report 28 patients followed up in difficult circumstances for as long as 4 years.
They refer
to the disease as "tropical" but the first cases of M ulcerans infection were reported from the Bairnsdale district of Victoria (38° S, 15° below the Tropic of Capricorn)l and cases have also been reported from Beerwah, near Brisbane (27° S).2 Infection in the Bairnsdale district occurs in relation to streams and lakes in the drainage areas of pockets of residual warm temperate rain forest3 in that part of Australia. In all other reported foci the disease occurs in association with warm temperate or tropical rain forest so the epithet "tropical disease" is appropriate even though M ulcerans infection may occur well south of the Tropic of Cancer. The infection in patients in Australia usually begins as an intradermal papule, and less frequently as a painful, swollen limb, which represents a necrotising panniculitis rather than cellulitis.4 The discrete subcutaneous nodule first described in Uganda’ has only rarely been identified in Queensland. These three are initial manifestations, and, if the disease is to be staged, they should all be considered as stage I (perhaps as la, Ib, and Ic, respectively). All three lesions may progress to ulceration (stage I I); ulceration may be very extensive in the oedematous form. Healing, with scar tissue, contractures, and sometimes subcutaneous calcification, could be considered stage III and deep or disseminated infection with bone involvement as stage IV. Patients with no clinical evidence of infection for months6-8 or even years after they have left an endemic zone, presumably harbour a localised collection of mycobacteria within a sebaceous gland or other skin appendage, and during this period could be considered as "stage zero". Antibiotics seem ineffective.3 Patients have had recurrent infection after surgical debridement and while on full doses of rifampicin and ethionamide, drugs to which the mycobacteria cultured from the ulcers were sensitive in vitro. Complete surgical excision of initial small lesions is usually curative whether antibiotics are given or not. Heat treatmenrB-l0 may be more effective after surgical curettage of necrotic material, and is clearly more suitable for the commoner peripheral lesions and not the disfiguring facial lesions (Dec 8, p 1440). To be effective heat must be constantly applied for days or weeks via an electric blanket or a heated water jacket with thermostat control. Such equipment may
Department of Medical Microbiology, St Bartholomew’s Hospital Medical College, London EC1A 7BE, UK 1. Marks J.
Ending the routine guinea-pig test.
M.
J. PALLEN
Tubercle 1972, 53: 31-34.
2. Pallen MJ. The inoculation of tissue specimens into guinea-pigs in suspected cases of
it aid diagnosis and treatment? Tubercle 1987; 68: 51-57. 3. Mitchison DA. Drug resistance in mycobacteria. Br Med Bull 1984, 40: 84-90 4. Pallen MJ, Butcher PD. New strategies in microbiological diagnosis. J Hosp Infect (in
mycobactenal infection does
press). SA, Pierson DJ. Primary cutaneous inoculation of drug resistant tuberculosis. AmJ Med 1974; 57: 676-78
5. Sahn
