185
sensitive test for maldistribution) is normal at rests and on exercise.6 We therefore do not accept criticism of the technique on the grounds of maldistribution. We agree that exercise stages of two minutes duration will not aclueve a steady state. That is why we chose three minute periods of exercise for steady-state evaluation. The main reason for doing a progressive exercise test is not to achieve steady state but to stress the subject maximally; hence exercise stages less than three minutes are not only valid but desirable. Clark and Coats suggest that increasing the inspired concentration lowers ventilation by mechanisms other than by reducing the carbon dioxide drive. We know that measurement of carbon dioxide production during the progressive exercise test is not ideal ; however, measurements were continuous and identical for every oxygen concentration, and any cyclical variations in carbon dioxide excretion would not have affected the overall result. We clearly state that the reduction in ventilation may have been attributable to correction of the increased physiological dead space m patients with heart failure. We did not rule out an inhibitory effect on arterial chemoreceptors produced by a rise in arterial oxygen tension on 50% inspired oxygen. Indeed, exercise heart rate also fell at higher oxygen concentrations, suggesting that relief of hypoxaemia may have reduced sympathetic drive.7 Nor did we conclude that ventilation is reduced at these submaximum workloads via some change in oxygen delivery; in fact, total delivery was unchanged comparing air with 50% oxygen.
Royal Postgraduate Medical School, Hammersmith Hospital, London W12 0NN, UK
D. P. MOORE A. R. WESTON J. M. B. HUGHES C. M. OAKLEY J. C. F. CLELAND
1 Sullivan MJ, Higginbotham MB, Cobb FR. Increased exercise ventilation in patients with chronic heart failure: intact ventilatory control despite haemodynamic and pulmonary abnormalities. Circulation 1988; 77: 552-59. 2 Franciosa JA, Ziesche RN, Wilen M. Functional capacity of patients with chronic left ventricular failure: relationship of bicycle exercise performance to clinical and hemodynamic characterisation. Ann JMed 1979; 67: 460-66. 3 Jones HA, Lakshminarayan S, Becket JM, Hughes JMB. Companson of estimates of cardiac output by indicator dilution and freon 22 uptake during gas mixing in dogs. Cardiovasc Res 1991; 25: 523-28. 4 Moore DP, Weston AR, Jones HA, Cleland JCF, Hughes JMB, Oakley CM. Non-invasive determination of exercise cardiac output: a rebreathing method developed for use in heart failure. Eur Heart J 1991; 12: S102. 5 Frank NR, Cugell DW, Gaensler EA, Ellis LB. Ventilation studies m mitral stenosis.
Am J Med 1953; 15: 60-76. 6 Jebavy P, Widimsky J, Hurych J, Stanek
V. Relationships between orthostatic changes pulmonary diffusing capacity and haemodynamics of lesser circulation Respiration 1971; 28: 101-13. Escourrou P, Johnson DG, Rowell LB. Hypoxaemia increases plasma catecholamine concentrations m exercising humans. J Appl Physiol 1984; 57: 1507-11. of
SIR,- There is no recognised therapy for vincristine overdose apart from symptomatic treatment possibly combined with folinic acid.’ Kosmidis et aP reported three cases treated by a
JEAN-YVES PIERGA PHILIPPE BEUZEBOC THIERRY DORVAL THAO PALANGIE PIERRE POUILLART
Medical Oncology Department, Institut Curie, 75 231 Paris Cedex 05, France 1. Grush OC, Morgan SK. Folinic add 14: 71-78.
rescue
for vincristine toxicity. Clin Toxicol 1979;
2. Kosmidis HV, Bouhoutsou DO, Varvoutsi MC, et al. Vincristine overdose: experience with 3 patients. Pediatr Hematol Oncol 1991; 8: 171-78. 3. Neslon RL, Dyke RW, Root MA. Comparative pharmacokinetics of vindesine, vincristine and vinblastine in patients with cancer. Cancer Treat Rev 1980; 7: 17-24.
Ondansetron in carcinoid syndrome SIR,-Dr Platt and colleagues (June 6, p 1416) report a beneficial effect of ondansetron in a patient with carcinoid syndrome. This finding accords with previous reports of symptomatic effect of serotonin antagonists in this disease.’ We have treated several patients with symptoms of carcinoid disease with ondansetronpreferably as an antiemetic in combination with a somatostatinanalogue after embolisation of liver metastases. 5-HT3-specific receptors are thought to be unable to induce extrapyramidal side-effects,2and as far as we are aware no stimulatory effect of ondansetron on this receptor has been reported. We have, however, seen severe dystonia, tremor, mouth dryness, gait disturbances, and impaired vision in a 73-year-old man with multiple liver metastases from a carcinoid pancreatic tumour. These symptoms developed one week after the initiation of 8 mg ondansetron orally per day, as sole therapy for nausea. Discontinuation of the therapy two months ago improved, but has not completely resolved, the symptoms. The possible induction of true extrapyramidal symptoms may indicate modulation by ondansetron of a receptor different from the 5-HT3 receptor. Previous experience with other serotonin antagonists (ketanserin, methysergide) in carcinoid disease has warned us about the possible enhancement of side-effects seen in these patients. A randomised, controlled trial of long-term treatment of carcinoid patients with ondansetron is therefore called for. Medical
Department A, Rikshospitalet,
MORTEN BJ.
JACOBSEN
1. Hodgson HJF. Controlling the carcinoid syndrome. BMJ 1988; 297: 1213-14. 2. Priestman TJ. Clinical studies with ondansetron in the control of radiation-induced emesis. Eur J Cancer Clin Oncol 1989; 25 (suppl 1): 29-33.
Idarubicin
cardiotoxicity in acute myeloid leukaemia
a
second phase of 1-2 h, and a third phase of about 85 h. Vincristine is predominantly excreted in the bile and is highly bound to plasma proteins (50-80%). The volume of distribution in the third phase is large, reflecting intense tissue uptake with a high tissue/blood ratio. In vincristine poisoning, plasmapheresis may be justified because of the mtense protein binding, especially since vincristine cannot be
dialysed. An 18-year-old patient treated for osteosarcoma received in error times the intended dose of vincristine by two 8 mg injections 12 h apart. Plasmapheresis of 1 ’5 times the plasma volume was done 6 h after the second injection. Vincristine sulphate was assayed by ELISA’LiUy) immediately before and after plasmapheresis, with concentrations of 7-1 and 5-5 ng/ml, respectively. Assay of pldsma-exchange fluid showed 11-6 ng/ml. The plasma concentrations were 2-3 and 2.11 ng/ml 24 and 48 h later. The clinical course was favourable with grade IV neutropenia for 4 days. Central nuerotoxicity was confined to drowsiness with a slowed ten
but without vinca alkaloids.
0027 Oslo, Norway
Favourable outcome after plasmapheresis for vincristine overdose
plasmapheresis. The pharmacokinetics of vincristineobey three-companment model with an exponential phase of 5 min,
electroencephalogram, and peripheral neurological involvement consisted of accentuation of the abolition of deep tendon reflexes without any occlusive syndrome or any motor or sensory deficits on clinical examination or electromyogram. However, antidiuretic hormone secretion was inappropriate with serum sodium of 119 mmol/1 on day 12, which was corrected by fluid restriction. The scheduled chemotherapy could be given 5 weeks after this episode,
SIR,-Your June 6 editorial on anthracycline-related cardiotoxicity suggests that the newer anthracycline analogues idarubicin and epirubicin retain their antitumour activity without cardiotoxicity. In the south-west England trial of cytotoxic chemotherapy of de novo AML, patients were given idarubicin 12 mg/m2 intravenously for 2 days and cytarabine 400 mg/m2 by continuous intravenous infusion for 5 daYS.1 Patients not achieving marrow clearance of leukaemic blasts by day 21 received a second identical course. Patients achieving complete remission of AML were given a further identical course as consolidation therapy, followed by a final course of cytarabine 1 g/m2 daily by continuous infusion for 5 daYS.1 All other recently reported trials of idarubicin in AML used at least 50% more drug in remission induction therapy but similar doses in consolidation therapy.2-s In twenty-four patients (mean age 62 years, range 27-75) receiving 1-2 courses, left ventricular ejection fractions (LVEF) were measured pre and post treatment by echocardiography or
186
isotope cardiac multiple-gated acquisition scan. The mean LVEF fell from 56-7% before to 50-8% after treatment (mean fall 5-9%, 95 % confidence interval 2 4-9 4). This modest but significant fall in LVEF indicates that idarubicin is cardiotoxic and that cardiac function should be monitored. All anthracyclines should be regarded as potentially cardiotoxic. There are no prospective comparative studies that analyse rigorously and objectively the cardiotoxicity of different anthracyclines given in doses of equivalent tumoricidal activity. The maximum cumulative dose of idarubicin has not yet been defined in terms of cardiotoxicity. Department of Haematology, Derriford Hospital, Plymouth PL6 8DH. UK
D. CHAN-LAM J. A. COPPLESTONE A. PRENTICE
Department of Haematology, Musgrove Park Hospital, Taunton
R. PRICE S. JOHNSON M. PHILLIPS
SA, Prentice AG, Pearce R. Open study of idarubicin/ara-C for induction myeloid leukaemia analysed by comparison with mathematical models of prior studies with daunorubicin/ara-C and mitozantrone/ara-C. (Presented at the 5th international symposium on therapy of acute leukaemias, Rome, 1991: abstr 354.) 2. Reiffers J, Rigal-Huguet F, Stoppa AM, et al. Idarubicin versus daunorubicin as treatment of acute myeloid leukaemia in elderly patients. (Presented at the 5th international symposium on therapy of acute leukaemias, Rome, 1991: abstr 24.) 1. Johnson
treatment of acute
3. Rotoli B. Idarubicin as first line treatment for adult acute myeloid leukaemia. (Presented at the 5th international symposium on therapy of acute leukaemias, Rome, 1991: abstr 25.) 4. Vogler WR, Velez-Garcia E, Weiner RS, et al. A phase III trial comparing idarubicin and daunorubicin in combination with cytosine arabioside in acute myeloid leukaemia. (Presented at the 5th international symposium on therapy of acute leukaemias, Rome, 1991: abstr 26.) 5. Wiemik PH, Banks PLC, Case DC, Arlin ZA. Cytarabine plus idarubicin or daunorubicin for adults with previously untreated acute myeloid leukaemia. (Presented at the 5th international symposium on therapy of acute leukaemias,
Rome, 1991: abstr 27.)
Preliminary diagnosis of Parkinson’s disease by olfactory bulb pathology SIR,--80-90% of patients with Parkinson’s disease have profound disturbances of smell.1,2 Thus, we decided to investigate the pathology of the olfactory bulb and tract in Parkinson’s disease. Olfactory bulbs and tracts were removed from formalin-fixed half-brains of 9 patients with a clinical diagnosis of Parkinson’s disease and from 9 age-matched controls. Tissue was processed in paraffin wax and 7um serial horizontal sections of the entire nerve The first and every tenth sections were stained with and the immediately adjacent sections with antisera for ubiquitin (Dako, polyclonal 1/150) and modified Bielschowsky silver impregnation. Sections were examined "blind" to clinical status. On the basis of whether Lewy bodies were observed, cases were classified as either probable Parkinson’s disease or not, and results were compared with the findings of full neuropathological examination. 8 cases were diagnosed probable Parkinson’s disease with Lewy bodies involving various different neuronal types throughout the olfactory bulb and tract. Lewy bodies were best identified by ubiquitin staining and were most common in the anterior olfactory nucleus (figure). Lewy bodies at this site resembled their cortical counterparts and inclusions with a classic trilaminar structure were rare. 2 cases had many Lewy bodies associated with distended ubiquitin immunoreactive neurites. In 1 case there were many neurofibrillary tangles and several senile plaques in the anterior olfactory nucleus. In the olfactory bulb and tract of the ninth patient, there were occasional glial cytoplasmic inclusions. Full histological examination of the brains confirmed the diagnosis of Parkinson’s disease in 8 cases; in the 2 cases with numerous olfactory Lewy bodies, cortical Lewy bodies were also abundant. 1 patient also had Alzheimer’s disease, which was suspected by the finding of dual pathology in the anterior olfactory nucleus. The case with olfactory glial cytoplasmic inclusions showed striatonigral and olivopontocerebellar degeneration, characteristic of multiple system atrophy. Age-related degenerative changes with numerous corpora amylacea were identified in all were cut.
haematoxylin/eosin,
Neurons containing Lewy bodies in anterior olfactory nucleus in Parkinson’s disease.
Ubiquitin x175. Insert= ubiquitin-immunoreactive Lewy body, x875
elderly control had occasional neurofibrillary tangles in anterior olfactory neurons. Our observations suggest that Parkinson’s disease can be diagnosed by finding Lewy bodies in the olfactory bulb and tract. The occurrence in these areas of the glial cytoplasmic inclusions found in multiple system atrophy3 enabled us to make a correct diagnosis, although this condition was unsuspected clinically. The presence of disease-specific inclusions in the olfactory bulb and tract in Parkinson’s disease and multiple system atrophy provides a quick and easy means of preliminary diagnosis before brain cutting. Whether this involvement is an initial site of damage requires further investigation and may provide some clues about aetiology. cases; 1
Parkinson’s Disease Society Brain Bank Institute of Neurology, London WC1 N 1PJ, UK
SUSAN E. DANIEL CHRISTOPHER H. HAWKES
Doty RD, Deems DA, Stellar S. Olfactory dysfunction in parkinsonism: a general defect unrelated to neurological signs, disease stage or disease duration. Neurology 1988; 38: 1237-44. 2. Hawkes CH, Shephard BC. Disordered olfactory evoked potentials and smell identification in Parkinson’s disease. J Neurol (in press). 3. Papp MI, Kahn JE, Lantos PL. Glial cytoplasmic inclusions in the CNS of patients with multiple system atrophy (striatonigral degeneration, olivopontocerebellar atrophy and Shy-Drager syndrome).J Neurol Sci 1989; 94: 79-100. 1.
Primary gastric lymphoma and occupational exposures
SIR,-Dr Doglioni and colleagues (April 4, p 834) report a high incidence of primary gastric lymphoma in northeastern Italy. To find an explanation for an increasing incidence of malignant lymphoma with that anatomical site occupational exposures should be assessed. We have reported an association between malignant lymphoma-both Hodgkin’s disease and non-Hodgkin lymphoma exposure to organic solvents, chlorophenols, or phenoxyacetic acids.1 Of the 60 patients with Hodgkin’s disease, 8 (13%) lymphomas were mainly located in the gastrointestinal tract. 2 had been exposed to organic solvents,1 to chlorophenols, and 4 to phenoxyacetic acids.2 All 5 patients with gastric lymphoma had been exposed to these substances. Primary gastrointestinal NHL was found in 14 (13%) of the 109 patients.1 Of the 10 cases with gastric NHL, all but 2 had been exposed to these chemicals, and of the 4 with intestinal lymphoma, 3 had been exposed.
(NHL)-and
During the past year we have treated 6 patients with gastric NHL and 1 with intestinal NHL, representing 17% of all NHL cases. Of these 7 patients, 2 reported occupational exposure to organic solvents and 2 to phenoxyacetic acids. Additionally, 1 woman was
sensitive test for maldistribution) is normal at rests and on exercise.6 We therefore do not accept criticism of the technique on the grounds of maldistribution. We agree that exercise stages of two minutes duration will not aclueve a steady state. That is why we chose three minute periods of exercise for steady-state evaluation. The main reason for doing a progressive exercise test is not to achieve steady state but to stress the subject maximally; hence exercise stages less than three minutes are not only valid but desirable. Clark and Coats suggest that increasing the inspired concentration lowers ventilation by mechanisms other than by reducing the carbon dioxide drive. We know that measurement of carbon dioxide production during the progressive exercise test is not ideal ; however, measurements were continuous and identical for every oxygen concentration, and any cyclical variations in carbon dioxide excretion would not have affected the overall result. We clearly state that the reduction in ventilation may have been attributable to correction of the increased physiological dead space m patients with heart failure. We did not rule out an inhibitory effect on arterial chemoreceptors produced by a rise in arterial oxygen tension on 50% inspired oxygen. Indeed, exercise heart rate also fell at higher oxygen concentrations, suggesting that relief of hypoxaemia may have reduced sympathetic drive.7 Nor did we conclude that ventilation is reduced at these submaximum workloads via some change in oxygen delivery; in fact, total delivery was unchanged comparing air with 50% oxygen.
Royal Postgraduate Medical School, Hammersmith Hospital, London W12 0NN, UK
D. P. MOORE A. R. WESTON J. M. B. HUGHES C. M. OAKLEY J. C. F. CLELAND
1 Sullivan MJ, Higginbotham MB, Cobb FR. Increased exercise ventilation in patients with chronic heart failure: intact ventilatory control despite haemodynamic and pulmonary abnormalities. Circulation 1988; 77: 552-59. 2 Franciosa JA, Ziesche RN, Wilen M. Functional capacity of patients with chronic left ventricular failure: relationship of bicycle exercise performance to clinical and hemodynamic characterisation. Ann JMed 1979; 67: 460-66. 3 Jones HA, Lakshminarayan S, Becket JM, Hughes JMB. Companson of estimates of cardiac output by indicator dilution and freon 22 uptake during gas mixing in dogs. Cardiovasc Res 1991; 25: 523-28. 4 Moore DP, Weston AR, Jones HA, Cleland JCF, Hughes JMB, Oakley CM. Non-invasive determination of exercise cardiac output: a rebreathing method developed for use in heart failure. Eur Heart J 1991; 12: S102. 5 Frank NR, Cugell DW, Gaensler EA, Ellis LB. Ventilation studies m mitral stenosis.
Am J Med 1953; 15: 60-76. 6 Jebavy P, Widimsky J, Hurych J, Stanek
V. Relationships between orthostatic changes pulmonary diffusing capacity and haemodynamics of lesser circulation Respiration 1971; 28: 101-13. Escourrou P, Johnson DG, Rowell LB. Hypoxaemia increases plasma catecholamine concentrations m exercising humans. J Appl Physiol 1984; 57: 1507-11. of
SIR,- There is no recognised therapy for vincristine overdose apart from symptomatic treatment possibly combined with folinic acid.’ Kosmidis et aP reported three cases treated by a
JEAN-YVES PIERGA PHILIPPE BEUZEBOC THIERRY DORVAL THAO PALANGIE PIERRE POUILLART
Medical Oncology Department, Institut Curie, 75 231 Paris Cedex 05, France 1. Grush OC, Morgan SK. Folinic add 14: 71-78.
rescue
for vincristine toxicity. Clin Toxicol 1979;
2. Kosmidis HV, Bouhoutsou DO, Varvoutsi MC, et al. Vincristine overdose: experience with 3 patients. Pediatr Hematol Oncol 1991; 8: 171-78. 3. Neslon RL, Dyke RW, Root MA. Comparative pharmacokinetics of vindesine, vincristine and vinblastine in patients with cancer. Cancer Treat Rev 1980; 7: 17-24.
Ondansetron in carcinoid syndrome SIR,-Dr Platt and colleagues (June 6, p 1416) report a beneficial effect of ondansetron in a patient with carcinoid syndrome. This finding accords with previous reports of symptomatic effect of serotonin antagonists in this disease.’ We have treated several patients with symptoms of carcinoid disease with ondansetronpreferably as an antiemetic in combination with a somatostatinanalogue after embolisation of liver metastases. 5-HT3-specific receptors are thought to be unable to induce extrapyramidal side-effects,2and as far as we are aware no stimulatory effect of ondansetron on this receptor has been reported. We have, however, seen severe dystonia, tremor, mouth dryness, gait disturbances, and impaired vision in a 73-year-old man with multiple liver metastases from a carcinoid pancreatic tumour. These symptoms developed one week after the initiation of 8 mg ondansetron orally per day, as sole therapy for nausea. Discontinuation of the therapy two months ago improved, but has not completely resolved, the symptoms. The possible induction of true extrapyramidal symptoms may indicate modulation by ondansetron of a receptor different from the 5-HT3 receptor. Previous experience with other serotonin antagonists (ketanserin, methysergide) in carcinoid disease has warned us about the possible enhancement of side-effects seen in these patients. A randomised, controlled trial of long-term treatment of carcinoid patients with ondansetron is therefore called for. Medical
Department A, Rikshospitalet,
MORTEN BJ.
JACOBSEN
1. Hodgson HJF. Controlling the carcinoid syndrome. BMJ 1988; 297: 1213-14. 2. Priestman TJ. Clinical studies with ondansetron in the control of radiation-induced emesis. Eur J Cancer Clin Oncol 1989; 25 (suppl 1): 29-33.
Idarubicin
cardiotoxicity in acute myeloid leukaemia
a
second phase of 1-2 h, and a third phase of about 85 h. Vincristine is predominantly excreted in the bile and is highly bound to plasma proteins (50-80%). The volume of distribution in the third phase is large, reflecting intense tissue uptake with a high tissue/blood ratio. In vincristine poisoning, plasmapheresis may be justified because of the mtense protein binding, especially since vincristine cannot be
dialysed. An 18-year-old patient treated for osteosarcoma received in error times the intended dose of vincristine by two 8 mg injections 12 h apart. Plasmapheresis of 1 ’5 times the plasma volume was done 6 h after the second injection. Vincristine sulphate was assayed by ELISA’LiUy) immediately before and after plasmapheresis, with concentrations of 7-1 and 5-5 ng/ml, respectively. Assay of pldsma-exchange fluid showed 11-6 ng/ml. The plasma concentrations were 2-3 and 2.11 ng/ml 24 and 48 h later. The clinical course was favourable with grade IV neutropenia for 4 days. Central nuerotoxicity was confined to drowsiness with a slowed ten
but without vinca alkaloids.
0027 Oslo, Norway
Favourable outcome after plasmapheresis for vincristine overdose
plasmapheresis. The pharmacokinetics of vincristineobey three-companment model with an exponential phase of 5 min,
electroencephalogram, and peripheral neurological involvement consisted of accentuation of the abolition of deep tendon reflexes without any occlusive syndrome or any motor or sensory deficits on clinical examination or electromyogram. However, antidiuretic hormone secretion was inappropriate with serum sodium of 119 mmol/1 on day 12, which was corrected by fluid restriction. The scheduled chemotherapy could be given 5 weeks after this episode,
SIR,-Your June 6 editorial on anthracycline-related cardiotoxicity suggests that the newer anthracycline analogues idarubicin and epirubicin retain their antitumour activity without cardiotoxicity. In the south-west England trial of cytotoxic chemotherapy of de novo AML, patients were given idarubicin 12 mg/m2 intravenously for 2 days and cytarabine 400 mg/m2 by continuous intravenous infusion for 5 daYS.1 Patients not achieving marrow clearance of leukaemic blasts by day 21 received a second identical course. Patients achieving complete remission of AML were given a further identical course as consolidation therapy, followed by a final course of cytarabine 1 g/m2 daily by continuous infusion for 5 daYS.1 All other recently reported trials of idarubicin in AML used at least 50% more drug in remission induction therapy but similar doses in consolidation therapy.2-s In twenty-four patients (mean age 62 years, range 27-75) receiving 1-2 courses, left ventricular ejection fractions (LVEF) were measured pre and post treatment by echocardiography or
186
isotope cardiac multiple-gated acquisition scan. The mean LVEF fell from 56-7% before to 50-8% after treatment (mean fall 5-9%, 95 % confidence interval 2 4-9 4). This modest but significant fall in LVEF indicates that idarubicin is cardiotoxic and that cardiac function should be monitored. All anthracyclines should be regarded as potentially cardiotoxic. There are no prospective comparative studies that analyse rigorously and objectively the cardiotoxicity of different anthracyclines given in doses of equivalent tumoricidal activity. The maximum cumulative dose of idarubicin has not yet been defined in terms of cardiotoxicity. Department of Haematology, Derriford Hospital, Plymouth PL6 8DH. UK
D. CHAN-LAM J. A. COPPLESTONE A. PRENTICE
Department of Haematology, Musgrove Park Hospital, Taunton
R. PRICE S. JOHNSON M. PHILLIPS
SA, Prentice AG, Pearce R. Open study of idarubicin/ara-C for induction myeloid leukaemia analysed by comparison with mathematical models of prior studies with daunorubicin/ara-C and mitozantrone/ara-C. (Presented at the 5th international symposium on therapy of acute leukaemias, Rome, 1991: abstr 354.) 2. Reiffers J, Rigal-Huguet F, Stoppa AM, et al. Idarubicin versus daunorubicin as treatment of acute myeloid leukaemia in elderly patients. (Presented at the 5th international symposium on therapy of acute leukaemias, Rome, 1991: abstr 24.) 1. Johnson
treatment of acute
3. Rotoli B. Idarubicin as first line treatment for adult acute myeloid leukaemia. (Presented at the 5th international symposium on therapy of acute leukaemias, Rome, 1991: abstr 25.) 4. Vogler WR, Velez-Garcia E, Weiner RS, et al. A phase III trial comparing idarubicin and daunorubicin in combination with cytosine arabioside in acute myeloid leukaemia. (Presented at the 5th international symposium on therapy of acute leukaemias, Rome, 1991: abstr 26.) 5. Wiemik PH, Banks PLC, Case DC, Arlin ZA. Cytarabine plus idarubicin or daunorubicin for adults with previously untreated acute myeloid leukaemia. (Presented at the 5th international symposium on therapy of acute leukaemias,
Rome, 1991: abstr 27.)
Preliminary diagnosis of Parkinson’s disease by olfactory bulb pathology SIR,--80-90% of patients with Parkinson’s disease have profound disturbances of smell.1,2 Thus, we decided to investigate the pathology of the olfactory bulb and tract in Parkinson’s disease. Olfactory bulbs and tracts were removed from formalin-fixed half-brains of 9 patients with a clinical diagnosis of Parkinson’s disease and from 9 age-matched controls. Tissue was processed in paraffin wax and 7um serial horizontal sections of the entire nerve The first and every tenth sections were stained with and the immediately adjacent sections with antisera for ubiquitin (Dako, polyclonal 1/150) and modified Bielschowsky silver impregnation. Sections were examined "blind" to clinical status. On the basis of whether Lewy bodies were observed, cases were classified as either probable Parkinson’s disease or not, and results were compared with the findings of full neuropathological examination. 8 cases were diagnosed probable Parkinson’s disease with Lewy bodies involving various different neuronal types throughout the olfactory bulb and tract. Lewy bodies were best identified by ubiquitin staining and were most common in the anterior olfactory nucleus (figure). Lewy bodies at this site resembled their cortical counterparts and inclusions with a classic trilaminar structure were rare. 2 cases had many Lewy bodies associated with distended ubiquitin immunoreactive neurites. In 1 case there were many neurofibrillary tangles and several senile plaques in the anterior olfactory nucleus. In the olfactory bulb and tract of the ninth patient, there were occasional glial cytoplasmic inclusions. Full histological examination of the brains confirmed the diagnosis of Parkinson’s disease in 8 cases; in the 2 cases with numerous olfactory Lewy bodies, cortical Lewy bodies were also abundant. 1 patient also had Alzheimer’s disease, which was suspected by the finding of dual pathology in the anterior olfactory nucleus. The case with olfactory glial cytoplasmic inclusions showed striatonigral and olivopontocerebellar degeneration, characteristic of multiple system atrophy. Age-related degenerative changes with numerous corpora amylacea were identified in all were cut.
haematoxylin/eosin,
Neurons containing Lewy bodies in anterior olfactory nucleus in Parkinson’s disease.
Ubiquitin x175. Insert= ubiquitin-immunoreactive Lewy body, x875
elderly control had occasional neurofibrillary tangles in anterior olfactory neurons. Our observations suggest that Parkinson’s disease can be diagnosed by finding Lewy bodies in the olfactory bulb and tract. The occurrence in these areas of the glial cytoplasmic inclusions found in multiple system atrophy3 enabled us to make a correct diagnosis, although this condition was unsuspected clinically. The presence of disease-specific inclusions in the olfactory bulb and tract in Parkinson’s disease and multiple system atrophy provides a quick and easy means of preliminary diagnosis before brain cutting. Whether this involvement is an initial site of damage requires further investigation and may provide some clues about aetiology. cases; 1
Parkinson’s Disease Society Brain Bank Institute of Neurology, London WC1 N 1PJ, UK
SUSAN E. DANIEL CHRISTOPHER H. HAWKES
Doty RD, Deems DA, Stellar S. Olfactory dysfunction in parkinsonism: a general defect unrelated to neurological signs, disease stage or disease duration. Neurology 1988; 38: 1237-44. 2. Hawkes CH, Shephard BC. Disordered olfactory evoked potentials and smell identification in Parkinson’s disease. J Neurol (in press). 3. Papp MI, Kahn JE, Lantos PL. Glial cytoplasmic inclusions in the CNS of patients with multiple system atrophy (striatonigral degeneration, olivopontocerebellar atrophy and Shy-Drager syndrome).J Neurol Sci 1989; 94: 79-100. 1.
Primary gastric lymphoma and occupational exposures
SIR,-Dr Doglioni and colleagues (April 4, p 834) report a high incidence of primary gastric lymphoma in northeastern Italy. To find an explanation for an increasing incidence of malignant lymphoma with that anatomical site occupational exposures should be assessed. We have reported an association between malignant lymphoma-both Hodgkin’s disease and non-Hodgkin lymphoma exposure to organic solvents, chlorophenols, or phenoxyacetic acids.1 Of the 60 patients with Hodgkin’s disease, 8 (13%) lymphomas were mainly located in the gastrointestinal tract. 2 had been exposed to organic solvents,1 to chlorophenols, and 4 to phenoxyacetic acids.2 All 5 patients with gastric lymphoma had been exposed to these substances. Primary gastrointestinal NHL was found in 14 (13%) of the 109 patients.1 Of the 10 cases with gastric NHL, all but 2 had been exposed to these chemicals, and of the 4 with intestinal lymphoma, 3 had been exposed.
(NHL)-and
During the past year we have treated 6 patients with gastric NHL and 1 with intestinal NHL, representing 17% of all NHL cases. Of these 7 patients, 2 reported occupational exposure to organic solvents and 2 to phenoxyacetic acids. Additionally, 1 woman was
