- Email: [email protected]
FLUCONAZOLE IN RENAL CANDIDOSIS
163 2. Jeannee E. Soins gratuits, maladie pour tous. Dév Santé 1 986; 62: 23-25. 3 Jancloes M, Seck B, van de Velden L, Ndiaye B Participation des habitants d’une ville du Sénégal aux soins de santé primaires. Forum Mondial Santé 1982; 3: 425-29. 4 Reveillon M. Aspects économiques et financiers de la participation des populations au développement des services de santé de base à Pikine (Senégal). Brussels: Medicus
Mundi, 1987. 5. Fassin D, Jeannee E, Cebe D, Reveillon M. Who consults and where? Sociocultural J 1988; 17: 4. differentiation in access to health care in urban Africa. Int Epidemiol 6. Fassin D, Jeannee E. Immunization coverage and social differentiation in urban Senegal. Am J Pub Health (in press). 7 Ministry of Public Health. Participation des population à l’effort de santé. Principes et directives méthodologiques. Dakar, 1980
A PATIENT VOICE AT THE GENERAL MEDICAL COUNCIL
SIR,-Sir John Walton, president of the General Medical Council (GMC), in his response (Dec 3, p 1312) to your Nov 12 account of Jean Robinson’s report’ implies that her report has many "significant" errors, outlined in a six-page letter to us. This is untrue. A full reply has been sent to the GMC. What the GMC has done is a "nit-picking" exercise in an attempt to distract attention from serious criticisms by an experienced lay member, who is known to care for the interests of doctors as well as patients. The instructions under which GMC staff deal with complaints are clearly explained by Robinson. Walton sidesteps her account of how GMC standing instructions to staff to direct complainants to the National Health Service complaints procedure result in: (1) Failure of the GMC to carry out primary investigation of clear allegations of serious professional misconduct. (2) Breach of rules approved by Parliament, saying that such allegations shall be submitted to the president. (3) Telling complainants that the GMC will be informed if NHS authorities find complaints to be established and serious, when in many cases this is untrue, especially for hospital complaints. (4) A gross discrepancy in the number of general practitioner and hospital complaints reaching the Preliminary Proceedings Committee and Professional Conduct Committee, simply because the GMC in effect uses the NHS complaints system as a sifting mechanism, and general practitioners are subject to a tribunal system whereas hospital doctors are not. Robinson reports seeing only one complaint from a member of the public about clinical care bya hospital doctor during six years on the Preliminary Proceedings Committee. (5) Dangerous doctors being able to continue in practice for a long period before the GMC investigation even begins, since NHS procedures may take up to two years. Meanwhile the complainant or key witnesses may die or become unavailable-or, as often happens, the complainant gives up in despair. (6) Discrepancy in treatment of complaints about private and public care since private patients cannot be told to first take their complaints to the NHS. Walton says that complainants are told that they "may" take their complaints to the NHS. We can only say, from GMC letters complainants have sent to us, that the response from the Council gives them an invitation they cannot refuse; no alternative is offered. He mentions that complainants are told they can come back to the Council at the completion of NHS investigations: he does not mention that this change was made only after pressure from
comparison with the Swedish Medical Responsibility Board,2 a federal government agency which consists of lay members, advised by doctors. Robinson asks "how effectively does a body which consists largely of doctors, the majority of whom are now elected by doctors, carry out the duty entrusted to it by Parliament to protect the public?" The evidence she gives is far from reassuring. If the Council-and the profession-are to retain public confidence, we hope they will give more serious consideration to her report than the retiring President’s inadequate response. Health Rights, 344 South Lambeth London SW8 IUQ
Road,
BELINDA PRATTEN, Hon chair
1 Robinson J A patient voice at the GMC. London: Health Rights, 1988. 2. Rosenthal M. Dealing with medical malpractice The British and Swedish experience. London Tavistock, 1987.
BEZAFIBRATE-INDUCED HEADACHE
S!R,—Two cases of gemfibrozil-induced headache have been reported. 12 Bezafibrate is also a lipid-lowering agent and we report a case of headache induced by this compound. A 36-year-old woman with hyperlipidaemia (type IIa; familial essential hypercholesterolaemia) for several years presented with seronegative polyarthritis. Sustained-release diclofenac, 100 mg at night and 50 mg in the morning, produced symptomatic improvement without side-effects. Repeated measurements of fasting serum lipids demonstrated that diet was not adequately controlling her hyperlipidaemia and 1 month after presentation bezafibrate 200 mg thrice daily was started. After the fourth dose she had
severe recurrent
headaches about 1 h after the dose of
bezafibrate; these headaches were pulsatile and holocephalic, but predominantly occipital. The headaches were relieved within 3-4 h by ’Migraleve’. She had a 10-year history of migraine, but these headaches were usually unilateral and preceded by teichopsiae. She discontinued bezafibrate after three severe headaches and did not incur any further pains. 4 weeks later bezafibrate was restarted and again produced the same headaches after four or five doses. She continued to take bezafibrate for a week with three headaches a day (including being woken at night after the nocturnal dose) before being recommended to stop the lipid-lowering agent. Diclofenac was taken continuously throughout with no change in dosage. There have been five notifications to the Committee on Safety of Medicines between 1981 and 1988 of bezafibrate-induced headache (information from the manufacturers). Headache is listed as a side-effect of gemfibrozil but not of bezafibrate in all current prescribing texts (British National Fornmlary 1988: no 16; ABPI Data Sheet Compendium 1988-89; and Monthly Index of Medical Specialities 1989: January). The headache induced by bezafibrate is similar to that of gemfibrozil in nature and in time of onset after dose, but in our case it occurred after only 24 h of therapy with bezafibrate compared with the week reported for gemfibrozil. British Military Hospital, BFPO 33, Hannover, West Germany
T. J. HODGETTS C. TUNNICLIFFE
Robinson. Whether or not long-overdue improvements are made in NHS complaints procedures, the GMC has a duty to investigate primary allegations of serious professional misconduct. The Nursing Council does not require complainants to embark on the NHS complaints marathon before investigating an allegation that a nurse may be unfit to remain on the register. Doubtless there were several reasons why the GMC set up its current working party on disciplinary procedures, including a desire for improvement among staff and members, both medical and lay. Our view that concern expressed by the Department of Health and Members of Parliament was an important influence in the decision remains unchanged. What led to the decision is a minor pomt. What matters is that the working party and the Council should be aware that there is great public unease-which existed long before our report was published-about the role of the Council. The GMC does not emerge well in Rosenthal’s
1. Arellano F, Dé Cos M, Valiente R, Quirós C. Gemfibrozil-induced headache. Lancet 1988,i: 705. 2. Alvarez-Sabin J, Codina A, Rodriguez C, Laporte J-R. Gemfibrozil-induced headache. Lancet 1988; ii: 1246.
FLUCONAZOLE IN RENAL CANDIDOSIS 29 editorial on urinary tract candidosis the problems associated with treating deep-seated renal infection and noted that fluconazole might prove useful. This antifungal agent is well absorbed after an oral dose, is predominantly excreted in the urine, is effective against a wide range of yeasts, is relatively non-toxic, and is, therefore, of potential benefit in this condition.1,2 A 59-year-old diabetic man with idiopathic renal papillary necrosis had high fever, loin pain, hypotension, and deteriorating renal function 2 weeks after nephrostomy for ureteric obstruction.
SIR,-Your Oct
highlights
164 His glomerular filtration rate was 16 ml/min. Significant numbers of Candida albicans (more than 108 organisms/1) were recovered from several midstream urine specimens and from a renal papilla passed per urethrum; blood cultures were sterile. No other organisms were isolated. The candida was fully sensitive to antifungal agents and the patient was given a single dose of fluconazole 3 mg/kg. 24 h and 96 h serum trough levels were 3-8 mg/1 and 2.0 mg/1, respectively (the minimum inhibitory concentration for the strain was 0-8 mg/1). This dose of fluconazole was, therefore, continued every 96 h with regular monitoring. Rapid clinical and microbiological response ensued, urine cultures becoming negative at 4 days and remaining so while the patient was on treatment. 4 weeks later fluconazole was discontinued. This was followed by relapse, requiring further therapy, which produced an equally rapid response. The patient is now being maintained on oral fluconazole and is symptom-free. The ideal duration of therapy with fluconazole has not been established and probably has to be tailored to each patient’s particular type of renal candidosis. In this case of renal papillary candidosis complicating idiopathic papillary necrosis, it is unlikely that any chemotherapeutic agent would eradicate the deepseated candidal infection. Fluconazole, however, does appear to be a promising new antifungal agent and is probably the best available for this condition. We thank Dr R. Watts for allowing us
Departments of Medical Microbiology and Infectious Diseases, Northwick Park Hospital, Harrow, Middlesex HA1 3UJ
to
report on his
patient.
J. DAVE M. M. HICKEY E. G. L. WILKINS
MJ, Jevons S, Tarbit MH. Pharmacokinetic evaluation of UK-49,858, a metabolically stable triazole antifungal drug, in animals and humans. Antimicrob Agents Chemother 1985; 28: 648-53 Van’t Wout JW, Mattie H, van Furth R. A prospective study of the efficacy of fluconazole (UK-49,858) against deep-seated fungal infections. J Antimicrob Chemother 1988; 21: 665-72.
1. Humphrey
2
TREATMENT OF ULCERATIVE COLITIS BY IMPLANTATION OF NORMAL COLONIC FLORA
SIR,--One of us (J. D. B.) has proposed that bacterial metabolites of bile acids or cholesterol are involved in the aetiology of ulcerative colitis.’ Using himself as a subject he found that alphatocopherylquinone (ot-TQ) suppressed disease activity in ulcerative colitis, possibly due to its ability to interfere with bacterial oxidation of bile acids by an anti-vitamin K activity.2 He report a further experiment implicating colonic flora in the pathogenesis of ulcerative colitis. J. D. B. had continuously active, severe ulcerative colitis for 7 years, confirmed endoscopically and histologically. The condition was refractory to standard management including steroids and sulphasalazine and every time daily prednisone dosage was reduced below 30 mg severe symptoms (bloody diarrhoea, cramping, tenesmus, skin lesions, and arthritis) recurred. For the past 4 years disease activity has been well controlled with ot-TQ (42 g per day) and a very low fat diet. Although this regimen was effective at reducing the severity of symptoms the underlying disease process remained active-when a-TQ was discontinued or reduced in dosage severe symptoms recurred in 1-2 days. 6 months ago we undertook an experiment designed to replace his colonic flora with that of a disease-free donor. With a protocol developed to "sterilise" the bowel before surgery his flora was greatly reduced.3 The donor flora was introduced by large-volume retention enemas. 1 week later Ci.- TQ was discontinued without any recurrence of symptoms. It has now been six months since this implantation of "normal" flora, and J. D. B. has been symptom-free for the first time in 11years without any medication. Biopsy specimens of the colonic mucosa taken at flexible sigmoidoscopy 3 months after implantation of the donor flora revealed long-standing chronic inflammation (branching of the colonic glands) but no active inflammation. Before implantation, when symptoms were well controlled by oc-TQ, biopsy revealed prominent mononuclear cell infiltration in the lamina propria. Studies in man and animals have demonstrated that the
composition of the colonic flora in an individual is stable and is difficult to alter permanently, even with the use of antibiotics. However, if the natural flora is reduced by pretreatment with antibiotics, new strains of bacteria can be introduced.4 In this case an entire flora was transferred with the idea that the complex inter-relations between the many organisms present might be maintained to increase the chances of long-term survival in the new host. Although the composition of the transferred flora in its new environment has not been determined, and it is too early to tell how permanent the benefit of transfer might be, the presumptive replacement of the flora of a patient with ulcerative colitis with that from a disease-free donor has produced remarkable results, in one case at
least.
4213 Adams B, Kansas City, Kansas 66103, USA
JUSTIN D. BENNET MARK BRINKMAN
1. Bennet JD. Ulcerative colitis: the results of an altered bacterial metabolism of bile acids or cholesterol. Med Hypotheses 1986; 20: 125. 2. Bennet JD. Use of alpha-tocopherylquinone in the treatment of ulcerative colitis Gut
1986; 27: 695. RL, Condon RE, Gorbach SL, et al. Efficacy of preoperative antimicrobial preparation of the bowel. Ann Surg 1972; 176: 227. Gorbach SL. Intestinal microflora. Gastroenterology 1971; 60: 1110
3. Nichols 4.
ANTIMYCOBACTERIAL THERAPY INEFFECTIVE IN CROHN’S DISEASE AFTER A YEAR
SIR,-In some patients with Crohn’s disease a slow-growing mycobacterium has been isolated. This has been identified as Mycobacterium paratuberculosis.2 In 1986 Warren et aP reported on a patient with Crohn’s disease who responded to a combination of pyrazinamide, rifampicin, isoniazid, and ethambutol. Later, similar reports appeared.4-ó We know of reports on nineteen such cases and the response has been good or even dramatic in fourteen. However, follow-up was usually short. We report five additional patients treated for up to a year with this quadruple regimen. Case 1 (24, F; colonic Crohn’s disease since 1980).-Several severe relapses managed with corticosteroids. Sulphasalazine and metronidazole ineffective. She refused azathioprine and proctocolectomy. October, 1987, she had at least ten daily bowel movements and two to four at night, and she a rectovaginal fistula. On antimycobacterial therapy she slowly improved. By July, 1988, she had gained weight and had only one or two bowel movements per day. The fistula healed. Laboratory tests were normal. Colonoscopy revealed mucosal healing except for a few minor ulcerations in the rectosigmoid area. In November, when she was still on the antimycobacterial therapy, she had a severe flare-up with bloody diarrhoea, hypoalbuminaemia, and a raised erythrocyte sedimentation rate (ESR). Sigmoidoscopy revealed severe Crohn’s disease. Case 2
(21, M; Crohn’s disease affecting whole of small bowel diagnosed 7 years earlier).-Colonoscopy normal. Corticosteroids and metronidazole only moderately effective. Azathioprine was beneficial at first but in October, 1987, he had a flare-up, which responded to corticosteroids. Quadruple antimycobacterial therapy started in March, 1988. The disease was stable until October, 1988, when he lost 4 kg in weight and felt generally ill. The
was
quadruple therapy was withdrawn after 72 months. Case 3 (22, F; pancolonic Crohn’s disease also affecting ileum since 1984).-Sulphasalazine, corticosteroids, and azathioprine not effective. In September, 1987, she was severely ill with abdominal pain, vomiting, diarrhoea, fever, and weight loss. Early on during antimycobacterial therapy tachycardia developed, requiring betablocker treatment. After 2 months she had gained 6 kg and had normal bowel movements. The abdominal pain had disappeared. In February, 1988, the ESR had dropped from 65 to 22 mm/h and the haemoglobin (Hb) level had increased from 9-0 to 12.3 g/dl. She was still 10 kg below her normal weight but was back to work after a long sick leave. Colonoscopy in September, 1988, revealed inactive colitis in the right and transverse colon but minor ulcerations in the left
colon.
In
October,
1988, when she had been
on
antimycobacterial therapy for a year, she had a severe relapse with acute dilatation. After a split ileostomy she is doing well.
Mundi, 1987. 5. Fassin D, Jeannee E, Cebe D, Reveillon M. Who consults and where? Sociocultural J 1988; 17: 4. differentiation in access to health care in urban Africa. Int Epidemiol 6. Fassin D, Jeannee E. Immunization coverage and social differentiation in urban Senegal. Am J Pub Health (in press). 7 Ministry of Public Health. Participation des population à l’effort de santé. Principes et directives méthodologiques. Dakar, 1980
A PATIENT VOICE AT THE GENERAL MEDICAL COUNCIL
SIR,-Sir John Walton, president of the General Medical Council (GMC), in his response (Dec 3, p 1312) to your Nov 12 account of Jean Robinson’s report’ implies that her report has many "significant" errors, outlined in a six-page letter to us. This is untrue. A full reply has been sent to the GMC. What the GMC has done is a "nit-picking" exercise in an attempt to distract attention from serious criticisms by an experienced lay member, who is known to care for the interests of doctors as well as patients. The instructions under which GMC staff deal with complaints are clearly explained by Robinson. Walton sidesteps her account of how GMC standing instructions to staff to direct complainants to the National Health Service complaints procedure result in: (1) Failure of the GMC to carry out primary investigation of clear allegations of serious professional misconduct. (2) Breach of rules approved by Parliament, saying that such allegations shall be submitted to the president. (3) Telling complainants that the GMC will be informed if NHS authorities find complaints to be established and serious, when in many cases this is untrue, especially for hospital complaints. (4) A gross discrepancy in the number of general practitioner and hospital complaints reaching the Preliminary Proceedings Committee and Professional Conduct Committee, simply because the GMC in effect uses the NHS complaints system as a sifting mechanism, and general practitioners are subject to a tribunal system whereas hospital doctors are not. Robinson reports seeing only one complaint from a member of the public about clinical care bya hospital doctor during six years on the Preliminary Proceedings Committee. (5) Dangerous doctors being able to continue in practice for a long period before the GMC investigation even begins, since NHS procedures may take up to two years. Meanwhile the complainant or key witnesses may die or become unavailable-or, as often happens, the complainant gives up in despair. (6) Discrepancy in treatment of complaints about private and public care since private patients cannot be told to first take their complaints to the NHS. Walton says that complainants are told that they "may" take their complaints to the NHS. We can only say, from GMC letters complainants have sent to us, that the response from the Council gives them an invitation they cannot refuse; no alternative is offered. He mentions that complainants are told they can come back to the Council at the completion of NHS investigations: he does not mention that this change was made only after pressure from
comparison with the Swedish Medical Responsibility Board,2 a federal government agency which consists of lay members, advised by doctors. Robinson asks "how effectively does a body which consists largely of doctors, the majority of whom are now elected by doctors, carry out the duty entrusted to it by Parliament to protect the public?" The evidence she gives is far from reassuring. If the Council-and the profession-are to retain public confidence, we hope they will give more serious consideration to her report than the retiring President’s inadequate response. Health Rights, 344 South Lambeth London SW8 IUQ
Road,
BELINDA PRATTEN, Hon chair
1 Robinson J A patient voice at the GMC. London: Health Rights, 1988. 2. Rosenthal M. Dealing with medical malpractice The British and Swedish experience. London Tavistock, 1987.
BEZAFIBRATE-INDUCED HEADACHE
S!R,—Two cases of gemfibrozil-induced headache have been reported. 12 Bezafibrate is also a lipid-lowering agent and we report a case of headache induced by this compound. A 36-year-old woman with hyperlipidaemia (type IIa; familial essential hypercholesterolaemia) for several years presented with seronegative polyarthritis. Sustained-release diclofenac, 100 mg at night and 50 mg in the morning, produced symptomatic improvement without side-effects. Repeated measurements of fasting serum lipids demonstrated that diet was not adequately controlling her hyperlipidaemia and 1 month after presentation bezafibrate 200 mg thrice daily was started. After the fourth dose she had
severe recurrent
headaches about 1 h after the dose of
bezafibrate; these headaches were pulsatile and holocephalic, but predominantly occipital. The headaches were relieved within 3-4 h by ’Migraleve’. She had a 10-year history of migraine, but these headaches were usually unilateral and preceded by teichopsiae. She discontinued bezafibrate after three severe headaches and did not incur any further pains. 4 weeks later bezafibrate was restarted and again produced the same headaches after four or five doses. She continued to take bezafibrate for a week with three headaches a day (including being woken at night after the nocturnal dose) before being recommended to stop the lipid-lowering agent. Diclofenac was taken continuously throughout with no change in dosage. There have been five notifications to the Committee on Safety of Medicines between 1981 and 1988 of bezafibrate-induced headache (information from the manufacturers). Headache is listed as a side-effect of gemfibrozil but not of bezafibrate in all current prescribing texts (British National Fornmlary 1988: no 16; ABPI Data Sheet Compendium 1988-89; and Monthly Index of Medical Specialities 1989: January). The headache induced by bezafibrate is similar to that of gemfibrozil in nature and in time of onset after dose, but in our case it occurred after only 24 h of therapy with bezafibrate compared with the week reported for gemfibrozil. British Military Hospital, BFPO 33, Hannover, West Germany
T. J. HODGETTS C. TUNNICLIFFE
Robinson. Whether or not long-overdue improvements are made in NHS complaints procedures, the GMC has a duty to investigate primary allegations of serious professional misconduct. The Nursing Council does not require complainants to embark on the NHS complaints marathon before investigating an allegation that a nurse may be unfit to remain on the register. Doubtless there were several reasons why the GMC set up its current working party on disciplinary procedures, including a desire for improvement among staff and members, both medical and lay. Our view that concern expressed by the Department of Health and Members of Parliament was an important influence in the decision remains unchanged. What led to the decision is a minor pomt. What matters is that the working party and the Council should be aware that there is great public unease-which existed long before our report was published-about the role of the Council. The GMC does not emerge well in Rosenthal’s
1. Arellano F, Dé Cos M, Valiente R, Quirós C. Gemfibrozil-induced headache. Lancet 1988,i: 705. 2. Alvarez-Sabin J, Codina A, Rodriguez C, Laporte J-R. Gemfibrozil-induced headache. Lancet 1988; ii: 1246.
FLUCONAZOLE IN RENAL CANDIDOSIS 29 editorial on urinary tract candidosis the problems associated with treating deep-seated renal infection and noted that fluconazole might prove useful. This antifungal agent is well absorbed after an oral dose, is predominantly excreted in the urine, is effective against a wide range of yeasts, is relatively non-toxic, and is, therefore, of potential benefit in this condition.1,2 A 59-year-old diabetic man with idiopathic renal papillary necrosis had high fever, loin pain, hypotension, and deteriorating renal function 2 weeks after nephrostomy for ureteric obstruction.
SIR,-Your Oct
highlights
164 His glomerular filtration rate was 16 ml/min. Significant numbers of Candida albicans (more than 108 organisms/1) were recovered from several midstream urine specimens and from a renal papilla passed per urethrum; blood cultures were sterile. No other organisms were isolated. The candida was fully sensitive to antifungal agents and the patient was given a single dose of fluconazole 3 mg/kg. 24 h and 96 h serum trough levels were 3-8 mg/1 and 2.0 mg/1, respectively (the minimum inhibitory concentration for the strain was 0-8 mg/1). This dose of fluconazole was, therefore, continued every 96 h with regular monitoring. Rapid clinical and microbiological response ensued, urine cultures becoming negative at 4 days and remaining so while the patient was on treatment. 4 weeks later fluconazole was discontinued. This was followed by relapse, requiring further therapy, which produced an equally rapid response. The patient is now being maintained on oral fluconazole and is symptom-free. The ideal duration of therapy with fluconazole has not been established and probably has to be tailored to each patient’s particular type of renal candidosis. In this case of renal papillary candidosis complicating idiopathic papillary necrosis, it is unlikely that any chemotherapeutic agent would eradicate the deepseated candidal infection. Fluconazole, however, does appear to be a promising new antifungal agent and is probably the best available for this condition. We thank Dr R. Watts for allowing us
Departments of Medical Microbiology and Infectious Diseases, Northwick Park Hospital, Harrow, Middlesex HA1 3UJ
to
report on his
patient.
J. DAVE M. M. HICKEY E. G. L. WILKINS
MJ, Jevons S, Tarbit MH. Pharmacokinetic evaluation of UK-49,858, a metabolically stable triazole antifungal drug, in animals and humans. Antimicrob Agents Chemother 1985; 28: 648-53 Van’t Wout JW, Mattie H, van Furth R. A prospective study of the efficacy of fluconazole (UK-49,858) against deep-seated fungal infections. J Antimicrob Chemother 1988; 21: 665-72.
1. Humphrey
2
TREATMENT OF ULCERATIVE COLITIS BY IMPLANTATION OF NORMAL COLONIC FLORA
SIR,--One of us (J. D. B.) has proposed that bacterial metabolites of bile acids or cholesterol are involved in the aetiology of ulcerative colitis.’ Using himself as a subject he found that alphatocopherylquinone (ot-TQ) suppressed disease activity in ulcerative colitis, possibly due to its ability to interfere with bacterial oxidation of bile acids by an anti-vitamin K activity.2 He report a further experiment implicating colonic flora in the pathogenesis of ulcerative colitis. J. D. B. had continuously active, severe ulcerative colitis for 7 years, confirmed endoscopically and histologically. The condition was refractory to standard management including steroids and sulphasalazine and every time daily prednisone dosage was reduced below 30 mg severe symptoms (bloody diarrhoea, cramping, tenesmus, skin lesions, and arthritis) recurred. For the past 4 years disease activity has been well controlled with ot-TQ (42 g per day) and a very low fat diet. Although this regimen was effective at reducing the severity of symptoms the underlying disease process remained active-when a-TQ was discontinued or reduced in dosage severe symptoms recurred in 1-2 days. 6 months ago we undertook an experiment designed to replace his colonic flora with that of a disease-free donor. With a protocol developed to "sterilise" the bowel before surgery his flora was greatly reduced.3 The donor flora was introduced by large-volume retention enemas. 1 week later Ci.- TQ was discontinued without any recurrence of symptoms. It has now been six months since this implantation of "normal" flora, and J. D. B. has been symptom-free for the first time in 11years without any medication. Biopsy specimens of the colonic mucosa taken at flexible sigmoidoscopy 3 months after implantation of the donor flora revealed long-standing chronic inflammation (branching of the colonic glands) but no active inflammation. Before implantation, when symptoms were well controlled by oc-TQ, biopsy revealed prominent mononuclear cell infiltration in the lamina propria. Studies in man and animals have demonstrated that the
composition of the colonic flora in an individual is stable and is difficult to alter permanently, even with the use of antibiotics. However, if the natural flora is reduced by pretreatment with antibiotics, new strains of bacteria can be introduced.4 In this case an entire flora was transferred with the idea that the complex inter-relations between the many organisms present might be maintained to increase the chances of long-term survival in the new host. Although the composition of the transferred flora in its new environment has not been determined, and it is too early to tell how permanent the benefit of transfer might be, the presumptive replacement of the flora of a patient with ulcerative colitis with that from a disease-free donor has produced remarkable results, in one case at
least.
4213 Adams B, Kansas City, Kansas 66103, USA
JUSTIN D. BENNET MARK BRINKMAN
1. Bennet JD. Ulcerative colitis: the results of an altered bacterial metabolism of bile acids or cholesterol. Med Hypotheses 1986; 20: 125. 2. Bennet JD. Use of alpha-tocopherylquinone in the treatment of ulcerative colitis Gut
1986; 27: 695. RL, Condon RE, Gorbach SL, et al. Efficacy of preoperative antimicrobial preparation of the bowel. Ann Surg 1972; 176: 227. Gorbach SL. Intestinal microflora. Gastroenterology 1971; 60: 1110
3. Nichols 4.
ANTIMYCOBACTERIAL THERAPY INEFFECTIVE IN CROHN’S DISEASE AFTER A YEAR
SIR,-In some patients with Crohn’s disease a slow-growing mycobacterium has been isolated. This has been identified as Mycobacterium paratuberculosis.2 In 1986 Warren et aP reported on a patient with Crohn’s disease who responded to a combination of pyrazinamide, rifampicin, isoniazid, and ethambutol. Later, similar reports appeared.4-ó We know of reports on nineteen such cases and the response has been good or even dramatic in fourteen. However, follow-up was usually short. We report five additional patients treated for up to a year with this quadruple regimen. Case 1 (24, F; colonic Crohn’s disease since 1980).-Several severe relapses managed with corticosteroids. Sulphasalazine and metronidazole ineffective. She refused azathioprine and proctocolectomy. October, 1987, she had at least ten daily bowel movements and two to four at night, and she a rectovaginal fistula. On antimycobacterial therapy she slowly improved. By July, 1988, she had gained weight and had only one or two bowel movements per day. The fistula healed. Laboratory tests were normal. Colonoscopy revealed mucosal healing except for a few minor ulcerations in the rectosigmoid area. In November, when she was still on the antimycobacterial therapy, she had a severe flare-up with bloody diarrhoea, hypoalbuminaemia, and a raised erythrocyte sedimentation rate (ESR). Sigmoidoscopy revealed severe Crohn’s disease. Case 2
(21, M; Crohn’s disease affecting whole of small bowel diagnosed 7 years earlier).-Colonoscopy normal. Corticosteroids and metronidazole only moderately effective. Azathioprine was beneficial at first but in October, 1987, he had a flare-up, which responded to corticosteroids. Quadruple antimycobacterial therapy started in March, 1988. The disease was stable until October, 1988, when he lost 4 kg in weight and felt generally ill. The
was
quadruple therapy was withdrawn after 72 months. Case 3 (22, F; pancolonic Crohn’s disease also affecting ileum since 1984).-Sulphasalazine, corticosteroids, and azathioprine not effective. In September, 1987, she was severely ill with abdominal pain, vomiting, diarrhoea, fever, and weight loss. Early on during antimycobacterial therapy tachycardia developed, requiring betablocker treatment. After 2 months she had gained 6 kg and had normal bowel movements. The abdominal pain had disappeared. In February, 1988, the ESR had dropped from 65 to 22 mm/h and the haemoglobin (Hb) level had increased from 9-0 to 12.3 g/dl. She was still 10 kg below her normal weight but was back to work after a long sick leave. Colonoscopy in September, 1988, revealed inactive colitis in the right and transverse colon but minor ulcerations in the left
colon.
In
October,
1988, when she had been
on
antimycobacterial therapy for a year, she had a severe relapse with acute dilatation. After a split ileostomy she is doing well.