- Email: [email protected]
GREY MOOD: GREY COLOURS
573 antibodies adversely affected the outcome of IFN -ClN 1 treatment in both these patients, although the second seems to have been interferon resistant from the outset (baseline sera not available).
(ISCTR), held in Lagos, in 1971, continued to respond well to ATM, P & T, and melarsen sodium, even in a focus where tryparsamide had been in continuous use for 30 years.
of neutralising activity in these sera was low and the 2 positive sera had titres that were either (1-6%), unrecordable or low (t 80). A reference serum provided by Dr P. von Wussows had a t value of 8300 in our assay. Retrospective comparisons of the immunogenicity of different interferons are unsatisfactory because of differences in treatment regimens and assay methods. Nevertheless, loss of therapeutic response due to neutralising antibodies seems to be less frequent with IFN-fxNlI than has been reported for recombinant interferons.
It was a disaster that manufacture of tryparsamide had ceased by 1973. Change there has been over the past 40 years, not all of it beneficial. Although this Nigerian experience has been persistently ignored in francophone and some international publications (eg, tryparsamide was roundly condemned in the 1968 report from the ISCTR), this should not happen in The Lancet.
The
frequency
=
10 Chittick Place, Wanganui, New Zealand
K. D. B. THOMSON
1.
We thank Dr N. C. Allan (MRC CML trial coordinator), Dr H. Schmidt (Tubingen), Dr F. Lauria (Bologna), Dr J. Leslie (Norwich), Dr D. R. Edwards, Bodelwyddan, and all other physicians participating in the CML and HCL studies.
JANE E. GALTON Department of Clinical Investigation, Wellcome Research Laboratories, Beckenham, Kent BR3 3BS 1. von Wussow
PHILIP BEDFORD JEAN E. SCOTT COLIN M. BRAND ANTHONY B. W. NETHERSELL
P, Frund M, Black B, Deidrich H, Poliwoda H, Deicher H. Clinical
van Hoof L. Observations on trypanosomiasis in the Belgian Congo. Trans R Soc Trop Med Hyg 1947; 40: 728-54. 2. Debeir O. Troubles oculaires et amblyopie toxique au cours du traitement de la trypanosomiase humaine africaine. Ann Soc Belg Méd Trop 1954; 34: 841-74. 3. Neujean G, Evens F. Diagnostic et traitement de la maladie du sommeil a T gambiense Mem Acad R Sci Coloniales 1958 (nouv sér); 7 (2): 174. 4. Richer P, Lotte M, Foucher G. Resultats des traitements de la trypanosomiase humaine à T gambiense par le Mel B ou l’arsobal, dans le secteur special no 43 a Natitingou (Nord Dahomey). Méd Trop 1959; 19: 253-65. 5. Duggan AJ. A survey of sleeping sickness in Northern Nigeria from the earliest times to the present day. Trans R Soc Trop Med Hyg 1962; 56: 439-86. 6. Butler GC, Duggan AJ, Hutchinson MP. Melarsen in the treatment of Trypanosoma gambiense infection in man. Trans R Soc Trop Med Hyg 1957; 51: 69-74.
significance of anti-IFN-&agr; antibody titres during interferon therapy. Lancet 1987; ii: 635.
Steis RG, Smith JW, Urba WJ, et al Resistance to recombinant interferon alpha-2a in hairy cell leukemia associated with neutralising anti-interferon antibodies. N Engl J Med 1988; 318: 1409-13 3. Week PK, Leventhal BG, Brand C, Finter N. Detection and incidence of neutralising antibodies in interferon alpha-N1. J Interferon Res (in press). 4. Kawade Y. Quantitation of neutralisation of interferon by antibody. Methods Enzymol 1986; 119: 558-73.
2.
5. Anon. Human antibodies to interferons: report of a National Institutes of Health Workshop, Bethesda, MD. J Interferon Res 1988: v-vii.
TRYPARSAMIDE
:)!R,—1was delighted to learn (June 3, p 1246) that the efficacy of
prednisolone in preventing encephalopathy associated with melarsoprol treatment of gambiense sleeping sickness seems now to have been put beyond reasonable doubt. However, the opening sentence of Dr Pepin and colleagues’ paper ("The treatment of human African sleeping sickness has not changed for forty years") is untrue of the most populous country in Africa, Nigeria. In 1963-73 I was in charge of the sleeping sickness service at Kaduna, northern Nigeria. In francophone Africa melarsoprol long ago replaced tryparsamide as a mainstay of treatment. In the former Belgian Congo, over 50% of cases were resistant to tryparsamide by 1947.1 16 of one group of 127 patients had serious ocular complications;2 9 of 20 patients died after treatment with pentamidine and tryparsamide.3 In some countries tryparsamide was phased out partly due to limitations attached to its use; treatment of patients with central nervous system involvement required admission to a hypnoserie, from which patients could be discharged most quickly after melarsoprol therapy-often, but not always, with better prospects of cure than with suramin/tryparsamide.4 In Nigeria, however, tryparsamide held an important place as an effective and safe agent right up to 1973. Duggan commented in 1962: "It is remarkable that the toxicity of these drugs in Nigerian hands has been so low ... blindness is nearly always traceable to a serious mistake in case-management".5 From 1934, tryparsamide was never used alone; and during the 1940s the mainstay of treatment became weekly outpatient intravenous injections of suramin and tryparsamide mixed in the same syringe (ATM) or pentamidine isethionate daily by intramuscular injection followed by weekly tryparsamide (P&T).6 After field trials6melarsen sodium became the standard outpatient treatment for advanced cases and relapses during the late 1950s; nothing was observed that would permit agreement with van Hoofl that melarsen was "too toxic for man and should defmitely be abandoned". The change to melarsoprol for the above two categories of patient was made around 1970 when inpatient treatment became feasible. However, this hazardous therapy remained unnecessary for most epidemic and for early cases, which, as I reported to the 13th meeting of the International Scientific Committee for Trypanosomiasis Research
GREY MOOD: GREY COLOURS
SiR,—The relation between memory impairment and mood disorders is well established. Major depression is associated with the slowing down of cognitive functions, whereas depression generally is related to learning difficulties.l3 Cognitive impairment seems to depend on the severity of the depression but, as suggested by Beck,’ it should be remembered that the exaggeration of symptoms, complaints, or negative perceptions may reflect an underlying personality structure.4,5 In depressed subjects memory impairment seems to be linked to the complexity of the association processes in the tests used. This impairment seems to be less if the information is presented in a simpler form.6,7 In addition, the affective content of the items of a given test plays an important part; depressive subjects tend to remember more items with an unpleasant content than those having a neutral or pleasant content.8 During a study on the relation between the type and the severity of depression and cognitive performances we added a further battery of tests to the protocol to improve the measurement of memory function. We used three tests: the learning of 15 commonly used words (eg, home, Sunday, husband); the learning of photographs of the faces of 15 unknown people of different ages; and the learning of 15 colours, including the 8 "fundamental" colours of Luscher and 7 other easily distinguished colours. The method of administration was identical in all tests: ten items (five basic and five "distractors") were observed and learnt for 60 s. Following this, five new distractors were added to the basic items, and subjects were asked to recall the first ten items. Our sample consisted of 13 men and 18 women subjects, mean age 67-9 (SD 7-6) years, diagnosed as depressed by three psychiatrists. 24 were dysthymic, 2 had major depression (recurrent), and 5 had adjustment disorder with depressed mood according to DSM-III-R criteria.9 The controls consisted of 11 men and 20 women, mean age 66-8 (SD 7-7) years. The level of education in the two groups was similar. No signs of mental deterioration were detected by the mini mental status examination in any subject. In the patient group, besides the clinical diagnosis, the depressive scores were higher than 18 on the 21-item Hamilton scale and 45 (row-score) on the Zung scale for depression. Patient and control test scores differed significantly (t test p<0001) with respect to recall of colours, with a greater number of errors in the depressive group. The two groups did not differ with respect to memory for words and faces. Colour-test scores in the patients were significantly lower than those for other tests (which did not differ). In the controls there were no differences between the test scores. In the depressed subjects colour-text responses did not correlate with age or sex, and no particular colour was selectively forgotten. The evidence of an overall difference between depressives and controls, and between colour-test scores and those of the other two
574 tests in the depressives, is noteworthy. Nevertheless, an explanation for these findings is difficult, since the neurophysiology of affective disorders is not yet completely understood. Obviously the feelings of a depressed person contribute to rendering his world
Obituary
"monochromatic", thereby transferring his emotional blunting to
NEIL STAMFORD PAINTER MB, MS Lond, FRCS, FACS
realitv. Psychogeriatric Unit, Department of Clinical Psychiatry, University of Padua, 35128 Padua, Italy
D. DE LEO P. L. ROCCO M. R. DELLO BUONO G. F. DALLA BARBA
JO. Memory functions in endogenous depressions. Arch Gen Psychiatry 1961; 5: 193-99. 2. Lewinsohn PM, Steinez JL, Larson DW, et al. Depression-related cognition: antecedence or consequence? J Abnorm Psychology 1981; 90: 213-19. 3. Dent J, Teasdale JD. Negative cognition and the persistence of depression. J Abnorm Psychology 1988; 97: 29-34. 4. Beck AT. Depression: clinical experimentatal and theoretical aspects. New York: Paul B. Hoeber, 1971. 5. Kahn RL, Zarit SH, Hilbert NM, et al. Memory complaint and impairment in aged. Arch Gen Psychiatry 1975; 32: 1569-73. 6. Reus VI, Silberman E, Post RM, et al. D-amphetamine: effects on memory in a depressed population. Biol Psychiatry 1979; 14: 345-56. 7. Cohen RM, Weingartner H, Smallberg S, et al. Effort and cognition in depression. Arch Gen Psychiatry 1982; 39: 593-97. 8. Dunbar GC, Lishman WA. Depression, recognition memory and hedonic tone; a signal detection analysis. Br J Psychiatry 1984; 144: 376-82. 9. Diagnostic and Statistical Manual of Mental Disorder (DSM-III). 3rd ed Washington DC: American Psychiatric Association, 1987. 1. Cronholm B, Ottosson
TOXIC EPIDERMAL NECROLYSIS AND CO-TRIMOXAZOLE
SiR,—Ireport two deaths of elderly people following toxic epidermal necrolysis (TEN) after brief co-trimoxazole therapy (sulphamethoxazole 400 mg and trimethoprim 80 mg). A 79-year-old man had postoperative urinary tract infection in hospital and was treated with co-trimoxazole. After two doses (four tablets), fever and a widespread erythematous rash developed, followed by severe blistering (TEN), affecting 50% of the body surface. He died 10 days after starting therapy. 18 years previously his general practitioner had treated a persistent prostatitis with co-trimoxazole without ill effect. An 86-year-old man was admitted with an exacerbation of his chronic bronchitis. He was thought to be allergic to penicillin and was treated with erythromycin but, because of only partial improvement, co-trimoxazole was substituted. After three doses (six tablets) an extensive peeling exudative reaction developed affecting between 40% and 50% of the skin (TEN). He died 7 days after taking the first tablets. About 2 years earlier, in another hospital, he had been given co-trimoxazole, which was stopped after three doses (six tablets) because of a blistering rash believed to be a Stevens-Johnson reaction. He recovered fully. His general practitioner also recorded a rash after co-trimoxazole. The second hospital was unware of this history of co-trimoxazole sensitivity. Sulphonamides are the commonest drugs that cause TEN, especially the combination of sulphamethoxazole with trimethoprim,l although trimethoprim alone has been blamed.2 Data sheets refer to the possibility of TEN after co-trimoxazole treatment but state that it is rarely fatal. The Committee on Safety of Medicines (CSM) seemed unaware of the danger though they listed 25 reports of TEN after co-trimoxazole, including 12 deaths (CSM, personal communication, 1989).3 The reports included 11people over age 60 years and 9 over 65. Future information will be amended by pointing out the high mortality of TEN, especially in the elderly
(CSM, personal communication). Co-trimoxazole is frequently prescribed for common recurring infections. The possibility of TEN associated with repeated co-trimoxazole therapy should be borne in mind when treating elderly patients, especially if there is a history of skin reaction. Coroner’s Court,
Birmingham B4 6NE
RICHARD M. WHITTINGTON
Neil Painter, who was well known for his work diverticular disease, died on Aug 7, aged 66.
on
He served as a fighter pilot in the Fleet Air Arm in the Atlantic, Mediterranean, and Far Eastern zones, during the 1939-45 war before starting his medical training at St Bartholomew’s Hospital Medical School in 1946. He remained in the Reserve throughout his days as a medical student and continued flying until 1957. In 1965 he was appointed senior surgeon to the Manor House Hospital, London. His reputation stems from the studies he carried out under the supervision of Dr Sidney Truelove at the Radcliffe Infirmary on pressures in the colon in health and diverticulosis. He demonstrated the effects of drugs on colonic pressures and elucidated the mechanism responsible for the pathogenesis of diverticula. Aspects of this work were reported in Gut, in his MS thesis, in his Hunterian Lecture at the Royal College of Surgeons in 1963, and at the American Proctological Society in Philadelphia in 1964. In 1966 he collaborated with Surgeon Captain T. L. Cleave and Dr G. D. Campbell in a book deprecating the high content of refined carbohydrates in modern diet. In this book, a second edition of which was published in 1969, he advocated the addition of unprocessed bran as treatment of constipation and diverticular disease. The elucidation of colonic pressure effects and the demonstration that high-fibre diets had a beneficial effect both in prevention and in treatment of diverticular disease completely overturned the management of this disorder. Low-residue diets, the creation of permanent or semipermanent colostomy, and colonic resection were gradually abandoned. In almost no other condition has scientific investigation so totally reversed the treatment. Others have carried on the work that Neil initiated and he was hurt that some later writers did not acknowledge his contributions. He was a quiet "clubbable" man, keen to chat over a "noggin" of ale. He identified those whom he found to be sincere and even-handed, marking them out as friends and thereafter remaining loyal to them. He is survived by his wife Joy and his two sons. R. M. K.
International
Diary
1989
International symposium on Achieving Health For All-Economic and Social Policy: Washington, USA, Sept 10-13 (Symposium Secretariat, University of Washington, GH-22, Seattle, Washington 98195).
Meeting
on
the ]International Association of Cancer
Registries:
Maastricht, Netherlands, Sept 17-20 (Dr Leo Schouten, Secretary, Programme Committee, Comprehensive Cancer Centre Limburg (IKL), Parallelweg 45 c, NL 6221 BD Maastricht). Annual meeting of the European Society for Pediatric Research: Vienna, Austria, Sept 23-27 (Scientific Secretariat, Prof K. Widhalm, Department of Pediatrics, University of Vienna, Waehringer Guertell8-20, 1090 Vienna). 1990
3rd international congress of the World Apheresis Association: Amsterdam, the Netherlands, April 9-12 (Congress Secretariat, c/o RAI Organisatie Bureau Amsterdam, Europaplein 12, 1078 GZ Amsterdam). 1st European Stroke conference: Dusseldorf, Germany, May 10-12 (Dr M. Hennerici, Neurologische Klinik, Universitat Dusseldorf, Moorenstrasse
5,4000 Dusseldorf 1). J-C, Roujeau J-C, Revuz J, et al. The culprit drugs in 87 cases of toxic epidermal necrolysis (Lyall’s syndrome). Arch Dermatol 1987; 123: 1166-70. 2. Nwokolo C, Byrne L, Misch KJ. Toxic epidermal necrolysis occurring during treatment with terimethoprim alone. Br Med J 1988; 296: 970. 1. Guillaume
2nd international conference on Small Cell Lung Cancer: Ravenna, Italy, May 11-12 (Organising Secretariat, Augustea S.r.l., Via di Roma 86, 48100 Ravenna).
(ISCTR), held in Lagos, in 1971, continued to respond well to ATM, P & T, and melarsen sodium, even in a focus where tryparsamide had been in continuous use for 30 years.
of neutralising activity in these sera was low and the 2 positive sera had titres that were either (1-6%), unrecordable or low (t 80). A reference serum provided by Dr P. von Wussows had a t value of 8300 in our assay. Retrospective comparisons of the immunogenicity of different interferons are unsatisfactory because of differences in treatment regimens and assay methods. Nevertheless, loss of therapeutic response due to neutralising antibodies seems to be less frequent with IFN-fxNlI than has been reported for recombinant interferons.
It was a disaster that manufacture of tryparsamide had ceased by 1973. Change there has been over the past 40 years, not all of it beneficial. Although this Nigerian experience has been persistently ignored in francophone and some international publications (eg, tryparsamide was roundly condemned in the 1968 report from the ISCTR), this should not happen in The Lancet.
The
frequency
=
10 Chittick Place, Wanganui, New Zealand
K. D. B. THOMSON
1.
We thank Dr N. C. Allan (MRC CML trial coordinator), Dr H. Schmidt (Tubingen), Dr F. Lauria (Bologna), Dr J. Leslie (Norwich), Dr D. R. Edwards, Bodelwyddan, and all other physicians participating in the CML and HCL studies.
JANE E. GALTON Department of Clinical Investigation, Wellcome Research Laboratories, Beckenham, Kent BR3 3BS 1. von Wussow
PHILIP BEDFORD JEAN E. SCOTT COLIN M. BRAND ANTHONY B. W. NETHERSELL
P, Frund M, Black B, Deidrich H, Poliwoda H, Deicher H. Clinical
van Hoof L. Observations on trypanosomiasis in the Belgian Congo. Trans R Soc Trop Med Hyg 1947; 40: 728-54. 2. Debeir O. Troubles oculaires et amblyopie toxique au cours du traitement de la trypanosomiase humaine africaine. Ann Soc Belg Méd Trop 1954; 34: 841-74. 3. Neujean G, Evens F. Diagnostic et traitement de la maladie du sommeil a T gambiense Mem Acad R Sci Coloniales 1958 (nouv sér); 7 (2): 174. 4. Richer P, Lotte M, Foucher G. Resultats des traitements de la trypanosomiase humaine à T gambiense par le Mel B ou l’arsobal, dans le secteur special no 43 a Natitingou (Nord Dahomey). Méd Trop 1959; 19: 253-65. 5. Duggan AJ. A survey of sleeping sickness in Northern Nigeria from the earliest times to the present day. Trans R Soc Trop Med Hyg 1962; 56: 439-86. 6. Butler GC, Duggan AJ, Hutchinson MP. Melarsen in the treatment of Trypanosoma gambiense infection in man. Trans R Soc Trop Med Hyg 1957; 51: 69-74.
significance of anti-IFN-&agr; antibody titres during interferon therapy. Lancet 1987; ii: 635.
Steis RG, Smith JW, Urba WJ, et al Resistance to recombinant interferon alpha-2a in hairy cell leukemia associated with neutralising anti-interferon antibodies. N Engl J Med 1988; 318: 1409-13 3. Week PK, Leventhal BG, Brand C, Finter N. Detection and incidence of neutralising antibodies in interferon alpha-N1. J Interferon Res (in press). 4. Kawade Y. Quantitation of neutralisation of interferon by antibody. Methods Enzymol 1986; 119: 558-73.
2.
5. Anon. Human antibodies to interferons: report of a National Institutes of Health Workshop, Bethesda, MD. J Interferon Res 1988: v-vii.
TRYPARSAMIDE
:)!R,—1was delighted to learn (June 3, p 1246) that the efficacy of
prednisolone in preventing encephalopathy associated with melarsoprol treatment of gambiense sleeping sickness seems now to have been put beyond reasonable doubt. However, the opening sentence of Dr Pepin and colleagues’ paper ("The treatment of human African sleeping sickness has not changed for forty years") is untrue of the most populous country in Africa, Nigeria. In 1963-73 I was in charge of the sleeping sickness service at Kaduna, northern Nigeria. In francophone Africa melarsoprol long ago replaced tryparsamide as a mainstay of treatment. In the former Belgian Congo, over 50% of cases were resistant to tryparsamide by 1947.1 16 of one group of 127 patients had serious ocular complications;2 9 of 20 patients died after treatment with pentamidine and tryparsamide.3 In some countries tryparsamide was phased out partly due to limitations attached to its use; treatment of patients with central nervous system involvement required admission to a hypnoserie, from which patients could be discharged most quickly after melarsoprol therapy-often, but not always, with better prospects of cure than with suramin/tryparsamide.4 In Nigeria, however, tryparsamide held an important place as an effective and safe agent right up to 1973. Duggan commented in 1962: "It is remarkable that the toxicity of these drugs in Nigerian hands has been so low ... blindness is nearly always traceable to a serious mistake in case-management".5 From 1934, tryparsamide was never used alone; and during the 1940s the mainstay of treatment became weekly outpatient intravenous injections of suramin and tryparsamide mixed in the same syringe (ATM) or pentamidine isethionate daily by intramuscular injection followed by weekly tryparsamide (P&T).6 After field trials6melarsen sodium became the standard outpatient treatment for advanced cases and relapses during the late 1950s; nothing was observed that would permit agreement with van Hoofl that melarsen was "too toxic for man and should defmitely be abandoned". The change to melarsoprol for the above two categories of patient was made around 1970 when inpatient treatment became feasible. However, this hazardous therapy remained unnecessary for most epidemic and for early cases, which, as I reported to the 13th meeting of the International Scientific Committee for Trypanosomiasis Research
GREY MOOD: GREY COLOURS
SiR,—The relation between memory impairment and mood disorders is well established. Major depression is associated with the slowing down of cognitive functions, whereas depression generally is related to learning difficulties.l3 Cognitive impairment seems to depend on the severity of the depression but, as suggested by Beck,’ it should be remembered that the exaggeration of symptoms, complaints, or negative perceptions may reflect an underlying personality structure.4,5 In depressed subjects memory impairment seems to be linked to the complexity of the association processes in the tests used. This impairment seems to be less if the information is presented in a simpler form.6,7 In addition, the affective content of the items of a given test plays an important part; depressive subjects tend to remember more items with an unpleasant content than those having a neutral or pleasant content.8 During a study on the relation between the type and the severity of depression and cognitive performances we added a further battery of tests to the protocol to improve the measurement of memory function. We used three tests: the learning of 15 commonly used words (eg, home, Sunday, husband); the learning of photographs of the faces of 15 unknown people of different ages; and the learning of 15 colours, including the 8 "fundamental" colours of Luscher and 7 other easily distinguished colours. The method of administration was identical in all tests: ten items (five basic and five "distractors") were observed and learnt for 60 s. Following this, five new distractors were added to the basic items, and subjects were asked to recall the first ten items. Our sample consisted of 13 men and 18 women subjects, mean age 67-9 (SD 7-6) years, diagnosed as depressed by three psychiatrists. 24 were dysthymic, 2 had major depression (recurrent), and 5 had adjustment disorder with depressed mood according to DSM-III-R criteria.9 The controls consisted of 11 men and 20 women, mean age 66-8 (SD 7-7) years. The level of education in the two groups was similar. No signs of mental deterioration were detected by the mini mental status examination in any subject. In the patient group, besides the clinical diagnosis, the depressive scores were higher than 18 on the 21-item Hamilton scale and 45 (row-score) on the Zung scale for depression. Patient and control test scores differed significantly (t test p<0001) with respect to recall of colours, with a greater number of errors in the depressive group. The two groups did not differ with respect to memory for words and faces. Colour-test scores in the patients were significantly lower than those for other tests (which did not differ). In the controls there were no differences between the test scores. In the depressed subjects colour-text responses did not correlate with age or sex, and no particular colour was selectively forgotten. The evidence of an overall difference between depressives and controls, and between colour-test scores and those of the other two
574 tests in the depressives, is noteworthy. Nevertheless, an explanation for these findings is difficult, since the neurophysiology of affective disorders is not yet completely understood. Obviously the feelings of a depressed person contribute to rendering his world
Obituary
"monochromatic", thereby transferring his emotional blunting to
NEIL STAMFORD PAINTER MB, MS Lond, FRCS, FACS
realitv. Psychogeriatric Unit, Department of Clinical Psychiatry, University of Padua, 35128 Padua, Italy
D. DE LEO P. L. ROCCO M. R. DELLO BUONO G. F. DALLA BARBA
JO. Memory functions in endogenous depressions. Arch Gen Psychiatry 1961; 5: 193-99. 2. Lewinsohn PM, Steinez JL, Larson DW, et al. Depression-related cognition: antecedence or consequence? J Abnorm Psychology 1981; 90: 213-19. 3. Dent J, Teasdale JD. Negative cognition and the persistence of depression. J Abnorm Psychology 1988; 97: 29-34. 4. Beck AT. Depression: clinical experimentatal and theoretical aspects. New York: Paul B. Hoeber, 1971. 5. Kahn RL, Zarit SH, Hilbert NM, et al. Memory complaint and impairment in aged. Arch Gen Psychiatry 1975; 32: 1569-73. 6. Reus VI, Silberman E, Post RM, et al. D-amphetamine: effects on memory in a depressed population. Biol Psychiatry 1979; 14: 345-56. 7. Cohen RM, Weingartner H, Smallberg S, et al. Effort and cognition in depression. Arch Gen Psychiatry 1982; 39: 593-97. 8. Dunbar GC, Lishman WA. Depression, recognition memory and hedonic tone; a signal detection analysis. Br J Psychiatry 1984; 144: 376-82. 9. Diagnostic and Statistical Manual of Mental Disorder (DSM-III). 3rd ed Washington DC: American Psychiatric Association, 1987. 1. Cronholm B, Ottosson
TOXIC EPIDERMAL NECROLYSIS AND CO-TRIMOXAZOLE
SiR,—Ireport two deaths of elderly people following toxic epidermal necrolysis (TEN) after brief co-trimoxazole therapy (sulphamethoxazole 400 mg and trimethoprim 80 mg). A 79-year-old man had postoperative urinary tract infection in hospital and was treated with co-trimoxazole. After two doses (four tablets), fever and a widespread erythematous rash developed, followed by severe blistering (TEN), affecting 50% of the body surface. He died 10 days after starting therapy. 18 years previously his general practitioner had treated a persistent prostatitis with co-trimoxazole without ill effect. An 86-year-old man was admitted with an exacerbation of his chronic bronchitis. He was thought to be allergic to penicillin and was treated with erythromycin but, because of only partial improvement, co-trimoxazole was substituted. After three doses (six tablets) an extensive peeling exudative reaction developed affecting between 40% and 50% of the skin (TEN). He died 7 days after taking the first tablets. About 2 years earlier, in another hospital, he had been given co-trimoxazole, which was stopped after three doses (six tablets) because of a blistering rash believed to be a Stevens-Johnson reaction. He recovered fully. His general practitioner also recorded a rash after co-trimoxazole. The second hospital was unware of this history of co-trimoxazole sensitivity. Sulphonamides are the commonest drugs that cause TEN, especially the combination of sulphamethoxazole with trimethoprim,l although trimethoprim alone has been blamed.2 Data sheets refer to the possibility of TEN after co-trimoxazole treatment but state that it is rarely fatal. The Committee on Safety of Medicines (CSM) seemed unaware of the danger though they listed 25 reports of TEN after co-trimoxazole, including 12 deaths (CSM, personal communication, 1989).3 The reports included 11people over age 60 years and 9 over 65. Future information will be amended by pointing out the high mortality of TEN, especially in the elderly
(CSM, personal communication). Co-trimoxazole is frequently prescribed for common recurring infections. The possibility of TEN associated with repeated co-trimoxazole therapy should be borne in mind when treating elderly patients, especially if there is a history of skin reaction. Coroner’s Court,
Birmingham B4 6NE
RICHARD M. WHITTINGTON
Neil Painter, who was well known for his work diverticular disease, died on Aug 7, aged 66.
on
He served as a fighter pilot in the Fleet Air Arm in the Atlantic, Mediterranean, and Far Eastern zones, during the 1939-45 war before starting his medical training at St Bartholomew’s Hospital Medical School in 1946. He remained in the Reserve throughout his days as a medical student and continued flying until 1957. In 1965 he was appointed senior surgeon to the Manor House Hospital, London. His reputation stems from the studies he carried out under the supervision of Dr Sidney Truelove at the Radcliffe Infirmary on pressures in the colon in health and diverticulosis. He demonstrated the effects of drugs on colonic pressures and elucidated the mechanism responsible for the pathogenesis of diverticula. Aspects of this work were reported in Gut, in his MS thesis, in his Hunterian Lecture at the Royal College of Surgeons in 1963, and at the American Proctological Society in Philadelphia in 1964. In 1966 he collaborated with Surgeon Captain T. L. Cleave and Dr G. D. Campbell in a book deprecating the high content of refined carbohydrates in modern diet. In this book, a second edition of which was published in 1969, he advocated the addition of unprocessed bran as treatment of constipation and diverticular disease. The elucidation of colonic pressure effects and the demonstration that high-fibre diets had a beneficial effect both in prevention and in treatment of diverticular disease completely overturned the management of this disorder. Low-residue diets, the creation of permanent or semipermanent colostomy, and colonic resection were gradually abandoned. In almost no other condition has scientific investigation so totally reversed the treatment. Others have carried on the work that Neil initiated and he was hurt that some later writers did not acknowledge his contributions. He was a quiet "clubbable" man, keen to chat over a "noggin" of ale. He identified those whom he found to be sincere and even-handed, marking them out as friends and thereafter remaining loyal to them. He is survived by his wife Joy and his two sons. R. M. K.
International
Diary
1989
International symposium on Achieving Health For All-Economic and Social Policy: Washington, USA, Sept 10-13 (Symposium Secretariat, University of Washington, GH-22, Seattle, Washington 98195).
Meeting
on
the ]International Association of Cancer
Registries:
Maastricht, Netherlands, Sept 17-20 (Dr Leo Schouten, Secretary, Programme Committee, Comprehensive Cancer Centre Limburg (IKL), Parallelweg 45 c, NL 6221 BD Maastricht). Annual meeting of the European Society for Pediatric Research: Vienna, Austria, Sept 23-27 (Scientific Secretariat, Prof K. Widhalm, Department of Pediatrics, University of Vienna, Waehringer Guertell8-20, 1090 Vienna). 1990
3rd international congress of the World Apheresis Association: Amsterdam, the Netherlands, April 9-12 (Congress Secretariat, c/o RAI Organisatie Bureau Amsterdam, Europaplein 12, 1078 GZ Amsterdam). 1st European Stroke conference: Dusseldorf, Germany, May 10-12 (Dr M. Hennerici, Neurologische Klinik, Universitat Dusseldorf, Moorenstrasse
5,4000 Dusseldorf 1). J-C, Roujeau J-C, Revuz J, et al. The culprit drugs in 87 cases of toxic epidermal necrolysis (Lyall’s syndrome). Arch Dermatol 1987; 123: 1166-70. 2. Nwokolo C, Byrne L, Misch KJ. Toxic epidermal necrolysis occurring during treatment with terimethoprim alone. Br Med J 1988; 296: 970. 1. Guillaume
2nd international conference on Small Cell Lung Cancer: Ravenna, Italy, May 11-12 (Organising Secretariat, Augustea S.r.l., Via di Roma 86, 48100 Ravenna).