380
of 21 studied by kidney biopsy) had histological findings characteristic of HUS/TTP. Plasmapheresis was done in 14 patients 8 times on average (range 4-14), 13 units of fresh-frozen plasma being replaced each time. 1 patient died after the second session, 3 had end-stage renal failure (1 after frequent relapses,1 with pre-existing renal failure), and 10 had a good renal function at discharge (serum creatinine 1 36 [SD 0 19] mg/dl). The outcome in the 14 patients not given plasmapheresis was 2 deaths, 9 cases of end-stage renal failure, and 3 cases of impaired renal function (creatinine 2-80 [1.78] mgjdl) at discharge. Our findings accord with the experience of others who have found benefit from infusions of fresh-frozen plasma or plasmapheresis.3 Plasmapheresis enables huge amounts of freshfrozen plasma to be given in a short time, and the treatment may be removing an unknown pathogenetic factor. In our patients plasmapheresis greatly improved the prognosis in respect of kidney function but survival was not affected. We support early and frequent plasmapheresis with fresh-frozen plasma in adults with HUS/TTP, irrespective of the underlying disease. We cannot yet say decisively whether non-invasive therapy is justified m subgroups of patients with HUS/TTP. In some cases of HUS/ TTP, related to gastrointestinal disease and with short-term onset of symptoms, the prognosis was good even without invasive therapy, as reported in children.’ To clarify this issue a prospective controlled trial would be necessary.
Detection of lI.Fso8 mutation in CF
MARKUS HOLLENBECK ULRIKE ZAWISCHA
family.
Amplification of 50/47 base pairfragmentsof CF gene as described by Mathew et al.1 Haplotypes of lmked markers to CF locus are shown for comparison: 1 = absence and 2 = presence of polymorphic site
Department of Nephrology, Heinrich Heine University, D-4000 Dusseldorf, West Germany
JUTTA PASSLICK-DEETJEN FRIEDRICH KEMMER BERND GRABENSEE
*CF chromosomes
of CF must still rely on RFLP analysis. Until the second major mutation of the CF gene, predicted by linkage disequilibrium analysis in southern European populations, has been identified, direct analysis will be limited to a few families.
F. ANGLANI C. CAMPORESE L. PICCI N. A. GREGGIO A. BARBATO F. ZACCHELLO
Department of Paediatrics, University of Padua, 35128 Padua, Italy
BS, Rommens JM, Buchanan JA, et al Identification of the cystic fibrosis gene genetic analysis. Science 1989, 245: 1073-80. 2. Estivill X, Gasparini P, Novelli G, et al &Dgr;F508 gene deletion in cystic fibrosis in southern Europe Lancet 1989; ii: 1404. 3. Anglani F, Camporese C, Greggio NA, Murgia A, Zacchello F The use of biotinylated probes in the DNA analysis for diagnostic purposes Chimiaoggi (Int J Chem Biotech) (in press) 4. Mathew CG, Roberts RG, Harris A, Bentley DR, Bobrow M Rapid screening for 1 Kerem
&Dgr;F508 deletion in cystic fibrosis
Lancet 1989;
ii:
1346
Gasparini P, Nov elh G, et al Linkage disequilibrium for DNA haplotypes near the cystic fibrosis locus in two south European populations Hum Genet 1989,
5 Estivill X,
83: 175-78.
Haemolytic-uraemic syndrome
in adults
SiR,—Dr Crosse and Dr Naylor (June 23, p 1528) report five cases haemolytic-uraemic syndrome (HUS) in adults after haemorrhagic colitis. One patient died; the outcome in the other four was not noted. Their letter does not mention the large variety of causes of HUS or the use of plasmapheresis for treatment. The aetiology of HUS and thrombotic-thrombocytopenic purpura (HUS/TTP), which is probably an entity with different clinical expressions of one disease, is unknown. Gastrointestinal infections apart, HUS;TTP can be associated with systemic vasculitis, cyclosporin, oral contraceptives, and pregnancy, for example. We describe in detail elsewhere 28 adults with HUS/TTPAll had thrombocytopenia (mean platelet count 37 3001 [SD 32 000]), Coombs-negative haemolytic anaemia, and severely fragmented red blood cells in the peripheral blood smear. 20 (out of
1. Remuzzi G, Garella S. HUS and TTP: variable expression of a single entity Kidney Int 1987; 32: 292-308. 2 Hollenbeck M, Zawischa U, Passlick-Deetjen J, Grabensee B. Hamolytisch Uramisches Syndrom Thrombotisch Thrombopenische Purpura (HUS/TTP) im Erwachsenenalter. Nieren-Hochdruckkrankh (in press). 3. Misiani R, Appiani AC, Edefonti A, et al. Haemolytic uraemic syndrome therapeutic effect of plasma infusion. Br Med J 1982, 285: 1304-06 4. Trompeter RS, Schwartz R, Chantler C, Dillon MJ, Haycock GB. Haemolytic uraemic syndrome an analysis of prognostic features Arch Dis Child 1983, 58: 101-05
Relapse in chronic depressives on withdrawal of L-tryptophan SIR,-L-tryptophan was withdrawn (in mid-April in the UK) because of its association with eosinophilia-myalgia syndrome (EMS). In the USA there have been numerous cases of EMS (often associated with over-the-counter dietary supplements containing L-tryptophan), some of which have developed permanent sequelae, and 19 fatalities. 1In the UK one confirmed and one possible case of EMS following the prescription of L-tryptophan for depression led to withdrawal of ’Pacitron’ and ’Optimax’.3 We have used L-tryptophan in the treatment of severe chronic depression (defined as a symptomatic non-recovery despite adequate treatment over a period of 2 years or more)’ in combination with the monoamine oxidase inhibitor (MAOI) phenelzine and lithium. 11 patients treated this way (4 men, 7 women, mean [SD] age 46 [13] years) had a good response with striking reduction in morbidity and hospital admissions, and, in most cases, a return to pre-morbid levels of
functioning. Within a week of stopping L-tryptophan relapse was noticed by relatives and health professionals. 2 of the relapses were severe, necessitating hospital admission (1in a patient with severe bipolar disorder who had been maintained out of hospital for many years). We have been able to reinstate Ltryptophan therapy on a named-patient basis (through an arrangement with Merck UK Ltd, makers of optimax), and have seen rapid and complete recovery in 4 patients, partial recovery in 2, and no recovery in 3 others. 2 patients have only just restarted L-tryptophan. It is possible that relapses were unrelated to the stopping of L-tryptophan, but only in 2 patients was there evidence of independent life events. The relapses may have had a
of 21 studied by kidney biopsy) had histological findings characteristic of HUS/TTP. Plasmapheresis was done in 14 patients 8 times on average (range 4-14), 13 units of fresh-frozen plasma being replaced each time. 1 patient died after the second session, 3 had end-stage renal failure (1 after frequent relapses,1 with pre-existing renal failure), and 10 had a good renal function at discharge (serum creatinine 1 36 [SD 0 19] mg/dl). The outcome in the 14 patients not given plasmapheresis was 2 deaths, 9 cases of end-stage renal failure, and 3 cases of impaired renal function (creatinine 2-80 [1.78] mgjdl) at discharge. Our findings accord with the experience of others who have found benefit from infusions of fresh-frozen plasma or plasmapheresis.3 Plasmapheresis enables huge amounts of freshfrozen plasma to be given in a short time, and the treatment may be removing an unknown pathogenetic factor. In our patients plasmapheresis greatly improved the prognosis in respect of kidney function but survival was not affected. We support early and frequent plasmapheresis with fresh-frozen plasma in adults with HUS/TTP, irrespective of the underlying disease. We cannot yet say decisively whether non-invasive therapy is justified m subgroups of patients with HUS/TTP. In some cases of HUS/ TTP, related to gastrointestinal disease and with short-term onset of symptoms, the prognosis was good even without invasive therapy, as reported in children.’ To clarify this issue a prospective controlled trial would be necessary.
Detection of lI.Fso8 mutation in CF
MARKUS HOLLENBECK ULRIKE ZAWISCHA
family.
Amplification of 50/47 base pairfragmentsof CF gene as described by Mathew et al.1 Haplotypes of lmked markers to CF locus are shown for comparison: 1 = absence and 2 = presence of polymorphic site
Department of Nephrology, Heinrich Heine University, D-4000 Dusseldorf, West Germany
JUTTA PASSLICK-DEETJEN FRIEDRICH KEMMER BERND GRABENSEE
*CF chromosomes
of CF must still rely on RFLP analysis. Until the second major mutation of the CF gene, predicted by linkage disequilibrium analysis in southern European populations, has been identified, direct analysis will be limited to a few families.
F. ANGLANI C. CAMPORESE L. PICCI N. A. GREGGIO A. BARBATO F. ZACCHELLO
Department of Paediatrics, University of Padua, 35128 Padua, Italy
BS, Rommens JM, Buchanan JA, et al Identification of the cystic fibrosis gene genetic analysis. Science 1989, 245: 1073-80. 2. Estivill X, Gasparini P, Novelli G, et al &Dgr;F508 gene deletion in cystic fibrosis in southern Europe Lancet 1989; ii: 1404. 3. Anglani F, Camporese C, Greggio NA, Murgia A, Zacchello F The use of biotinylated probes in the DNA analysis for diagnostic purposes Chimiaoggi (Int J Chem Biotech) (in press) 4. Mathew CG, Roberts RG, Harris A, Bentley DR, Bobrow M Rapid screening for 1 Kerem
&Dgr;F508 deletion in cystic fibrosis
Lancet 1989;
ii:
1346
Gasparini P, Nov elh G, et al Linkage disequilibrium for DNA haplotypes near the cystic fibrosis locus in two south European populations Hum Genet 1989,
5 Estivill X,
83: 175-78.
Haemolytic-uraemic syndrome
in adults
SiR,—Dr Crosse and Dr Naylor (June 23, p 1528) report five cases haemolytic-uraemic syndrome (HUS) in adults after haemorrhagic colitis. One patient died; the outcome in the other four was not noted. Their letter does not mention the large variety of causes of HUS or the use of plasmapheresis for treatment. The aetiology of HUS and thrombotic-thrombocytopenic purpura (HUS/TTP), which is probably an entity with different clinical expressions of one disease, is unknown. Gastrointestinal infections apart, HUS;TTP can be associated with systemic vasculitis, cyclosporin, oral contraceptives, and pregnancy, for example. We describe in detail elsewhere 28 adults with HUS/TTPAll had thrombocytopenia (mean platelet count 37 3001 [SD 32 000]), Coombs-negative haemolytic anaemia, and severely fragmented red blood cells in the peripheral blood smear. 20 (out of
1. Remuzzi G, Garella S. HUS and TTP: variable expression of a single entity Kidney Int 1987; 32: 292-308. 2 Hollenbeck M, Zawischa U, Passlick-Deetjen J, Grabensee B. Hamolytisch Uramisches Syndrom Thrombotisch Thrombopenische Purpura (HUS/TTP) im Erwachsenenalter. Nieren-Hochdruckkrankh (in press). 3. Misiani R, Appiani AC, Edefonti A, et al. Haemolytic uraemic syndrome therapeutic effect of plasma infusion. Br Med J 1982, 285: 1304-06 4. Trompeter RS, Schwartz R, Chantler C, Dillon MJ, Haycock GB. Haemolytic uraemic syndrome an analysis of prognostic features Arch Dis Child 1983, 58: 101-05
Relapse in chronic depressives on withdrawal of L-tryptophan SIR,-L-tryptophan was withdrawn (in mid-April in the UK) because of its association with eosinophilia-myalgia syndrome (EMS). In the USA there have been numerous cases of EMS (often associated with over-the-counter dietary supplements containing L-tryptophan), some of which have developed permanent sequelae, and 19 fatalities. 1In the UK one confirmed and one possible case of EMS following the prescription of L-tryptophan for depression led to withdrawal of ’Pacitron’ and ’Optimax’.3 We have used L-tryptophan in the treatment of severe chronic depression (defined as a symptomatic non-recovery despite adequate treatment over a period of 2 years or more)’ in combination with the monoamine oxidase inhibitor (MAOI) phenelzine and lithium. 11 patients treated this way (4 men, 7 women, mean [SD] age 46 [13] years) had a good response with striking reduction in morbidity and hospital admissions, and, in most cases, a return to pre-morbid levels of
functioning. Within a week of stopping L-tryptophan relapse was noticed by relatives and health professionals. 2 of the relapses were severe, necessitating hospital admission (1in a patient with severe bipolar disorder who had been maintained out of hospital for many years). We have been able to reinstate Ltryptophan therapy on a named-patient basis (through an arrangement with Merck UK Ltd, makers of optimax), and have seen rapid and complete recovery in 4 patients, partial recovery in 2, and no recovery in 3 others. 2 patients have only just restarted L-tryptophan. It is possible that relapses were unrelated to the stopping of L-tryptophan, but only in 2 patients was there evidence of independent life events. The relapses may have had a
