- Email: [email protected]
Megadose methylprednisolone pulse therapy in adult idiopathic thrombocytopenic purpura
56
suggests that whatever mechanism is at work in this disorder it is probably not the same as those underlying AD and dementia pugilistica. The observation reported here is important since PDG/ALS now appears to be the only disease characterised by pure neurofibrillary tangle formation without &bgr;(A4).
PDG/ALS
Supported by the Medical Research Council and Mental Health Foundation. Department of Anatomy and Cell Biology, Mary’s Hospital Medical School
St
S. M. GENTLEMAN
Neuropathology Division, Mount Sinai Medical Center, New York, NY, USA
D. PERL
Division of Biochemistry, Queen’s University, Belfast, N Ireland, UK
D. ALLSOP
Department of Anatomy and Cell Biology, St Mary’s Hospital Medical School
J. CLINTON
Department of Physiological Sciences, Medical School,
M. C. ROYSTON
University of Manchester Department of Anatomy and
Cell
substantially.
Biology,
St Mary’s Hospital Medical School, London W2 1PG, UK
the platelet count dropped slightly to pretreatment values. A second course of MDMP was begun to increase the platelet count, followed by splenectomy at the end of the second week of this treatment, before the platelet count was critical. Two patients, however, (including one of those who had been splenectomised), showed long-term remission after the first MDMP treatment. These two patients still have normal platelet counts 1 year after MDMP. These results indicate that, as seen in Ozsoylu’s paediatric patients,1,2 MDMP therapy is effective in adults within the first week of treatment and causes a rapid increase in platelets. However, in most patients, a reduction of the corticosteroid dose leads to a fall in the platelet count, and these patients need further treatment with MDMP. Therefore the effect of MDMP seems to be temporary in adults, in contrast to the effect seen in children. We believe that MDMP should be tried in all adults who are refractory to other treatment. This treatment can be life saving in those with severe bleeding episodes since it corrects thrombocytopenia very rapidly. However, it should be borne in mind that in most adults this will be temporary and patients should be followed up and have surgery before the platelet count drops TEVF&Ibreve;K AKOGLU
G. W. ROBERTS
1. Roberts GW. Immunocytochemistry of neurofibrillary tangles in dementia pugilistica and Alzheimer’s disease: evidence of a common pathogenesis. Lancet 1988; ii: 1456-58. 2. Shankar SK, Yanagihara R, Garruto RM, et al. Immunocytochemistry characterisation of neurofibrillary tangles in amyotrophic lateral sclerosis and parkinsonian-dementia of Guam Ann Neurol 1989; 25: 146-51. 3. Ikeda S, Allsop D, Glenner GG. Morphology and distnbution of plaque and related deposits in the brain of Alzheimer’s disease and control cases: an immunohistochemical study using amyloid antibody. Lab Invest 1988; 60: 113-22. 4. Ikeda S, Yanagisawa N, Allsop D, et al. Evidence of amyloid B-protein immunoreactive plaque lesions in Down’s syndrome brains. Lab Invest 1989; 61: 133-37. 5. Roberts GW, Allsop D, Bruton C. The occult aftermath of boxing. J Neurol Neurosurg Psychiatry 1990; 53: 373-78. 6. St George-Hyslop PH, Haines JL, Farrer LA, et al. Genetic linkage studies suggest that Alzheimer’s disease is not a single homogeneous disorder. Nature 1990; 437: 194-97. 7. Perl DP, Steele JC. Amyotrophic lateral sclerosis parkinsoman dementia complex (ALS-PDC) of Guam as a model of Alzheimer’s disease: an overview. Second International Conference on Alzheimer’s Disease: Environmental Factors: 1990. abstr 54. 8. Kurland LT. Amyotrophic lateral sclerosis and Parkinson’s disease complex on Guam linked to an environmental neurotoxin. TINS 1988; 51-54. 9. Garruto RM, Fukatsu R, Yanagihara R, et al. Imaging of calcium and aluminium in neurofibrillary tangle-bearing neurones in parkinsonian-dementia of Guam. Proc Natl Acad Sci (USA) 1984; 81: 1875-79.
Megadose methylprednisolone pulse therapy in adult idiopathic thrombocytopenic purpura SIR,-Dr Ozsoylu and colleagues (Oct 27, p 1078) describe megadose methylprednisolone therapy (MDMP) in immune thrombocytopenic purpura (ITP). Since Ozsoylul first introduced MDMP for childhood ITP we have used similar treatment in adults as a second or third line treatment. Although we had no control group we have noted a rapid increase of platelet count in all ITP patients after MDMP. Nine patients (aged between 24 and 56 years, mean 39-7) with ITP (platelet count below 50 000/µl with increased or normal number of megakaryocytes in bone marrow) were given MDMP. Any possible underlying cause such as systemic lupus erythematosus was excluded by laboratory investigations. All patients were first treated with conventional corticosteroid therapy (I mg/kg daily). Vincristine (1 mg per week; five patients) and antilymphocyte-globulin (one) were also tried without success, before MDMP was begun. Two patients had a history of splenectomy, one for ITP 5 years earlier, and the other for accidental splenic rupture 24 years previously. In all patients treated with MDMP (30 mg/kg daily for three days, 20 mg/kg daily for four days, and then 10, 5, 2, and 1 mg/kg daily, each administered weekly) platelet count became normal in about three to five days and the peak rise was seen during the second week. In seven of the nine patients this lasted only for a few weeks (mean three weeks) and then
SEMRA PAYDAŞ Marmara University Hospital, Altunizade, Istanbul, Turkey
MAHMUT BAYIK ROGER LAWRENCE TULIN FIRATLI
1. Özsoylu Ş. High dose intravenous methylprednisolone for the treatment of childhood
chronic idiopathic thrombocytopenic purpura. Pediatr Rev Commun 1987; 2: 29 2. Ozsoylu Ş. High-dose intravenous methylprednisolone for immune thrombocytopenic purpura. Blood 1989, 73: 354
Tuberculosis
or persistent generalised lymphadenopathy in HIV disease?
where both HIV infection and tuberculosis are endemic the clinical diagnosis of sputum-negative epidemic tuberculosis is becoming increasingly difficult. Decisions about treatment of suspected tuberculosis depend mainly on the diagnostic facilities available and on whether or not the clinician is willing to start anti-tuberculosis treatment without proper diagnostic evidence. To investigate possible alternatives in the diagnosis of tuberculosis lymphadenitis at district level in African countries 40 consecutive patients (aged 15-55 years) presenting with extra-lingual lymphadenopathy unresponsive to first-line antibiotic treatment were investigated. The patients were from Kaoma district in Zambia, where tuberculosis and HIV infection are common. All patients underwent aspiration before biopsy. The gland specimens were divided and smears were made from the cut surfaces. All lymph glands were macroscopically examined by the surgeon and visible caseation, if any, was recorded. Specimens were fixed in formalin and examined histopathologically. Aspiration material and smears were stained (Ziehl-Neelsen) and examined at the district hospital laboratory. No mycobacterial culture facilities were available. Serum samples from 39 patients were tested for HIV by ’HIV-Check’ (DuPont) and/or ’Wellcozyme’ ELISA. HIV infection was diagnosed when both tests were positive or when the clinical criteria for AIDS were met together with one positive test. From the 40 specimens obtained, one showed only connective tissue on histological examination. In 1 patient, Kaposi’s sarcoma was diagnosed histologically. 34 (85 %) of the remaining 38 patients had tuberculosis of typical granulomatous or of non-reactive patterns.’ Hyperplastic changes consistent with HIV infection were seen in the specimens from the other 4 patients (table). Of the 39 patients tested, 30 were positive for HIV and 74% (25 of 34) of the patients with tuberculous lymphadenitis were HIV positive. The 5 positive smears were all from histologically confirmed tuberculosis patients, all of whom were HIV positive; in 1 of these 5 lymph nodes macroscopic caseation was reported. Aspiration specimens gave the same result in the same patients apart from 1 in whom only the smear was positive for acid-fast bacilli. Macroscopic examination of the lymph nodes as the sole diagnostic tool for tuberculosis gave a sensitivity of 67.6% with a specificity of
SIR,—In
areas
or
suggests that whatever mechanism is at work in this disorder it is probably not the same as those underlying AD and dementia pugilistica. The observation reported here is important since PDG/ALS now appears to be the only disease characterised by pure neurofibrillary tangle formation without &bgr;(A4).
PDG/ALS
Supported by the Medical Research Council and Mental Health Foundation. Department of Anatomy and Cell Biology, Mary’s Hospital Medical School
St
S. M. GENTLEMAN
Neuropathology Division, Mount Sinai Medical Center, New York, NY, USA
D. PERL
Division of Biochemistry, Queen’s University, Belfast, N Ireland, UK
D. ALLSOP
Department of Anatomy and Cell Biology, St Mary’s Hospital Medical School
J. CLINTON
Department of Physiological Sciences, Medical School,
M. C. ROYSTON
University of Manchester Department of Anatomy and
Cell
substantially.
Biology,
St Mary’s Hospital Medical School, London W2 1PG, UK
the platelet count dropped slightly to pretreatment values. A second course of MDMP was begun to increase the platelet count, followed by splenectomy at the end of the second week of this treatment, before the platelet count was critical. Two patients, however, (including one of those who had been splenectomised), showed long-term remission after the first MDMP treatment. These two patients still have normal platelet counts 1 year after MDMP. These results indicate that, as seen in Ozsoylu’s paediatric patients,1,2 MDMP therapy is effective in adults within the first week of treatment and causes a rapid increase in platelets. However, in most patients, a reduction of the corticosteroid dose leads to a fall in the platelet count, and these patients need further treatment with MDMP. Therefore the effect of MDMP seems to be temporary in adults, in contrast to the effect seen in children. We believe that MDMP should be tried in all adults who are refractory to other treatment. This treatment can be life saving in those with severe bleeding episodes since it corrects thrombocytopenia very rapidly. However, it should be borne in mind that in most adults this will be temporary and patients should be followed up and have surgery before the platelet count drops TEVF&Ibreve;K AKOGLU
G. W. ROBERTS
1. Roberts GW. Immunocytochemistry of neurofibrillary tangles in dementia pugilistica and Alzheimer’s disease: evidence of a common pathogenesis. Lancet 1988; ii: 1456-58. 2. Shankar SK, Yanagihara R, Garruto RM, et al. Immunocytochemistry characterisation of neurofibrillary tangles in amyotrophic lateral sclerosis and parkinsonian-dementia of Guam Ann Neurol 1989; 25: 146-51. 3. Ikeda S, Allsop D, Glenner GG. Morphology and distnbution of plaque and related deposits in the brain of Alzheimer’s disease and control cases: an immunohistochemical study using amyloid antibody. Lab Invest 1988; 60: 113-22. 4. Ikeda S, Yanagisawa N, Allsop D, et al. Evidence of amyloid B-protein immunoreactive plaque lesions in Down’s syndrome brains. Lab Invest 1989; 61: 133-37. 5. Roberts GW, Allsop D, Bruton C. The occult aftermath of boxing. J Neurol Neurosurg Psychiatry 1990; 53: 373-78. 6. St George-Hyslop PH, Haines JL, Farrer LA, et al. Genetic linkage studies suggest that Alzheimer’s disease is not a single homogeneous disorder. Nature 1990; 437: 194-97. 7. Perl DP, Steele JC. Amyotrophic lateral sclerosis parkinsoman dementia complex (ALS-PDC) of Guam as a model of Alzheimer’s disease: an overview. Second International Conference on Alzheimer’s Disease: Environmental Factors: 1990. abstr 54. 8. Kurland LT. Amyotrophic lateral sclerosis and Parkinson’s disease complex on Guam linked to an environmental neurotoxin. TINS 1988; 51-54. 9. Garruto RM, Fukatsu R, Yanagihara R, et al. Imaging of calcium and aluminium in neurofibrillary tangle-bearing neurones in parkinsonian-dementia of Guam. Proc Natl Acad Sci (USA) 1984; 81: 1875-79.
Megadose methylprednisolone pulse therapy in adult idiopathic thrombocytopenic purpura SIR,-Dr Ozsoylu and colleagues (Oct 27, p 1078) describe megadose methylprednisolone therapy (MDMP) in immune thrombocytopenic purpura (ITP). Since Ozsoylul first introduced MDMP for childhood ITP we have used similar treatment in adults as a second or third line treatment. Although we had no control group we have noted a rapid increase of platelet count in all ITP patients after MDMP. Nine patients (aged between 24 and 56 years, mean 39-7) with ITP (platelet count below 50 000/µl with increased or normal number of megakaryocytes in bone marrow) were given MDMP. Any possible underlying cause such as systemic lupus erythematosus was excluded by laboratory investigations. All patients were first treated with conventional corticosteroid therapy (I mg/kg daily). Vincristine (1 mg per week; five patients) and antilymphocyte-globulin (one) were also tried without success, before MDMP was begun. Two patients had a history of splenectomy, one for ITP 5 years earlier, and the other for accidental splenic rupture 24 years previously. In all patients treated with MDMP (30 mg/kg daily for three days, 20 mg/kg daily for four days, and then 10, 5, 2, and 1 mg/kg daily, each administered weekly) platelet count became normal in about three to five days and the peak rise was seen during the second week. In seven of the nine patients this lasted only for a few weeks (mean three weeks) and then
SEMRA PAYDAŞ Marmara University Hospital, Altunizade, Istanbul, Turkey
MAHMUT BAYIK ROGER LAWRENCE TULIN FIRATLI
1. Özsoylu Ş. High dose intravenous methylprednisolone for the treatment of childhood
chronic idiopathic thrombocytopenic purpura. Pediatr Rev Commun 1987; 2: 29 2. Ozsoylu Ş. High-dose intravenous methylprednisolone for immune thrombocytopenic purpura. Blood 1989, 73: 354
Tuberculosis
or persistent generalised lymphadenopathy in HIV disease?
where both HIV infection and tuberculosis are endemic the clinical diagnosis of sputum-negative epidemic tuberculosis is becoming increasingly difficult. Decisions about treatment of suspected tuberculosis depend mainly on the diagnostic facilities available and on whether or not the clinician is willing to start anti-tuberculosis treatment without proper diagnostic evidence. To investigate possible alternatives in the diagnosis of tuberculosis lymphadenitis at district level in African countries 40 consecutive patients (aged 15-55 years) presenting with extra-lingual lymphadenopathy unresponsive to first-line antibiotic treatment were investigated. The patients were from Kaoma district in Zambia, where tuberculosis and HIV infection are common. All patients underwent aspiration before biopsy. The gland specimens were divided and smears were made from the cut surfaces. All lymph glands were macroscopically examined by the surgeon and visible caseation, if any, was recorded. Specimens were fixed in formalin and examined histopathologically. Aspiration material and smears were stained (Ziehl-Neelsen) and examined at the district hospital laboratory. No mycobacterial culture facilities were available. Serum samples from 39 patients were tested for HIV by ’HIV-Check’ (DuPont) and/or ’Wellcozyme’ ELISA. HIV infection was diagnosed when both tests were positive or when the clinical criteria for AIDS were met together with one positive test. From the 40 specimens obtained, one showed only connective tissue on histological examination. In 1 patient, Kaposi’s sarcoma was diagnosed histologically. 34 (85 %) of the remaining 38 patients had tuberculosis of typical granulomatous or of non-reactive patterns.’ Hyperplastic changes consistent with HIV infection were seen in the specimens from the other 4 patients (table). Of the 39 patients tested, 30 were positive for HIV and 74% (25 of 34) of the patients with tuberculous lymphadenitis were HIV positive. The 5 positive smears were all from histologically confirmed tuberculosis patients, all of whom were HIV positive; in 1 of these 5 lymph nodes macroscopic caseation was reported. Aspiration specimens gave the same result in the same patients apart from 1 in whom only the smear was positive for acid-fast bacilli. Macroscopic examination of the lymph nodes as the sole diagnostic tool for tuberculosis gave a sensitivity of 67.6% with a specificity of
SIR,—In
areas
or