- Email: [email protected]
Pulmonary tuberculosis in HIV-infected patients in Zaire
41
Notes chemotherapy via the portal vein for patients with operable colorectal carcinoma might be due to the systemic effects of the portal chemotherapy. Rcglonalspilal
I! Laffer (3) Biel CH - 2502 Biel, SwitLcrland
Fluid membranes in NIDDM Impaired insulin mediated glucose metabolism in insulin sensitive tissues is a characteristic feature of noninsulin-dependent diabetes mellitus (NIDDM). The cell membrane, being the barrier between the metabolic unit of the cell and its immediate environment, occupies a strategically important site and may modulate insulin actions. To test the hypothesis that insulin resistance in NIDDM could be related to changes in cell membrane properties, we measured membrane lipid fluidity of mononuclear leukocytes in 21 normal subjects and I5 NIDDM patients using steady state fluorescence polarisation. Fluidity in the hydrophobic core of the lipid bilayer was significantly higher in leukocytes from diabetic patients. Whole body insulin sensitivity w’as positively correlated with the core-region fluidity. Both the core region membrane fluidity and insulin sensitivity were significantly related to plasma triglycerides. These findings suggest that cell membrane dynamics are related to insulin sensitivity. The underlying mechanism for the relation is not clear, though it could be secondary to abnormal organisation of membrane lipids and proteins. In addition. it may be a consequence of the metabolic derangement or merely an cpiphenomenon. Further work is required to understand the relationship between cell membrane properties and insulin action. especially in insulin target tissues such as skeletal muscle. If cell membrane dynamics prove to be a significant modulating factor on insulin action, then it would provide a therapeutic target in NIDDM. P Tong (1) Unlvrr\ity of Newcastle, Newcastle upon Tync NE2 4HH. UK
Control of EBV-associated lymphoproliferation with gene-marked cytotoxic T cells Epstein-Barr virus-associated lymphoproliferative ease is a common and usually fatal complication transplantation of T cell-depleted bone marrow
disafter from
HLA-mismatched or unrelated donors. Donor-derived EBV-specific cytotoxic T cells (CTLs) efficiently kill virus-infected tumor cells in vitro, therefore we surmised that CTLs should be able to protect recipients against lymphoproliferative disease in viva. We have treated thirteen bone marrow recipients prophylactically with donor derived EBV-specific CTLs that had been genetically marked with a retrovirus vector. We then determined their safety, persistence and biological efficacy. No patient who received CTLs developed any toxicity that could be attributed to the CTLs. Marked CTLs could be detected in recipient peripheral blood for up to I6 weeks post infusion and in EBV-specific CTLs amplified from recipient blood in vitro, for up to eleven months. Infused CTLs demonstrated both anti-viral and anti-lymphoproliferative effects in viva. In five patients whose blood EBV DNA levels were elevated to a level that we had previously shown to correlate with the development of lymphoproliferative disease, levels were reduced dramatically after treatment, Most striking, was rapid resolution of tumor nodules and associated symptoms in a patient who had developed frank lymphoprotiferative disease. The patient remains well more than one year after the development of his tumor. The low toxicity. long term persistence and biological efficacy of this treatment suggest that cellular immunotherapy may be effective for other malignancies where tumor-specific antigens have been identified. One candidate for early exploration is Hodgkin’s disease. a lymphoid malignancy in which EBV is implicated. CM Rooney (5) St Jude Children’s Research Hospital, Memphis, TN 38101-0318, USA
Pulmonary tuberculosis tients in Zaire
in HIV-infected
pa-
The key message of this paper is that pulmonary tuberculosis (TB) can be successfully treated on an outpatient basis with a 6-month short course anti-TB regimen. administered only twice a week in the last four months of treatment. regardless of whether the patient has HIV infection or not. even under the extreme conditions of a developing country TB control programme. It is the first study to document that intermittent TB therapy is acceptable for HIV-infected patients with a cure rate of 96.2% at the end of treatment. However, after completion of a 6-month course of treatment, their I-elapse rate was higher (9%) than that of non HIV-infected patients (5.3%). The incidence of relapse among
42
Notes
HIV-infected patients could be reduced to 1.97r by extending treatment to 12 months, but this did not improve survival. The regimen used in the study is similar to that used in the industrialized countries for directly observed treatment of TB. and selection of multi-resistant TB was very rare. When short course chemotherapy with rifampicin and isoniazid throughout treatment is used and when TB relapses can be readily detected. it appeared from a TB control perspective unnecessary to document whether patients are HIV-infected. Indeed. the societal benefits of extending treatment for HIV-infected patients were limited to preventing TB relapses that remained treatable. Documenting HIV infection is still useful for individual HIV-infected patients because they might benefit from prophylaxis of opportunistic infections and antiretroviral therapy, and be able to protect their loved ones against HIV infection. However, when relapses are not readily detectable, such as in impoverished inner cities or developing countries, the decision to extend treatment for known HIV-infected patients should. in the absence of increased survival, balance increased programme costs and inconvenience against the potential societal impact of a relapse of TB through increased TB transmission. WHO,
(6)
N Engl
J Med
CH-1211
Geneva
JH Perriens (6) 27, Switzerland
1995;332:779-84
Brain abnormalities dystrophy
in Duchenne muscular
Duchenne muscular dystrophy (DMD) is a genetic disorder primarily affecting young boys. It forms part of the spectrum of muscular dystrophies caused by abnormalities of the short arm of the X chromosome (Xp21) often causing intellectual impairment in addition to progressive muscular weakness. Normal dystrophin expression is lacking both in skeletal muscle and brains of affected subjects. “P magnetic resonance spectroscopy c3’P MRS) is a non-invasive technique which, when applied in vivo, yields information concerning ratios of metabolites important in adenosine triphosphate (ATP) synthesis. “P MRS has shown abnormal high energy phosphate metabolism within skeletal muscle in DMD. Nineteen boys, diagnosed as having DMD, and 19 similarly-aged controls underwent non-localised brain
“‘P MRS. IQ was assessed with the Wechsler Intelligence Scale for children. Significantly increased ratios of inorganic phosphate (Pi) to ATP, phosphomonoesters and phosphocreatine were found in the patients’ brains compared to controls. Changes in these ratios suggest both an increase in [Pi] and a decrease in [ATP] occur in the brain in DMD. Full scale IQ (FIQ), performance IQ and verbal IQ were significantly different between controls and patients with DMD. but there was no clear relationship between brain bioenergetics and neuropsychological dysfunction. These altered high energy phosphate ratios parallel the findings in dystrophic muscle and suggest bioenergetic similarities in tissues which lack dystrophin. MRC
(7)
Lnncet
1995;345:
C Thompson (7) Magnetic Resonance Spectroscopy, Oxford OX3 9DU, UK
1260-64
Vitamin C is linked to death from stroke in the elderly Vitamin C is an important naturally occurring antioxidant. It protects against the damaging effect of free radicals that are produced by cell metabolism. It may be particularly important in reducing the tendency of cholesterol and other fats to cause atherosclerosis. Researchers followed up 730 elderly men and women over the age of 65 who had taken part in a nutritional survey in the 1970s and analysed their subsequent mortality from cardiovascular disease. People whose vitamin C intake had been over 45 mg per day had less than half the risk of dying from stroke of those whose intake had been below 28 mg. Vitamin C intake was as strong a risk factor for stroke as raised diastolic blood pressure, though it was not related to death from coronary heart disease. In England and Wales, 25,000 people die of stroke every year and many more are disabled. The findings of this study point to a safe and straightforward way in which it might be possible to prevent some of these strokes. C Gale (8) Soulhampton General Hospital, Southampton SO16 6YD, UK
(8) Br Med
.I 1995;310:1563-6
Notes chemotherapy via the portal vein for patients with operable colorectal carcinoma might be due to the systemic effects of the portal chemotherapy. Rcglonalspilal
I! Laffer (3) Biel CH - 2502 Biel, SwitLcrland
Fluid membranes in NIDDM Impaired insulin mediated glucose metabolism in insulin sensitive tissues is a characteristic feature of noninsulin-dependent diabetes mellitus (NIDDM). The cell membrane, being the barrier between the metabolic unit of the cell and its immediate environment, occupies a strategically important site and may modulate insulin actions. To test the hypothesis that insulin resistance in NIDDM could be related to changes in cell membrane properties, we measured membrane lipid fluidity of mononuclear leukocytes in 21 normal subjects and I5 NIDDM patients using steady state fluorescence polarisation. Fluidity in the hydrophobic core of the lipid bilayer was significantly higher in leukocytes from diabetic patients. Whole body insulin sensitivity w’as positively correlated with the core-region fluidity. Both the core region membrane fluidity and insulin sensitivity were significantly related to plasma triglycerides. These findings suggest that cell membrane dynamics are related to insulin sensitivity. The underlying mechanism for the relation is not clear, though it could be secondary to abnormal organisation of membrane lipids and proteins. In addition. it may be a consequence of the metabolic derangement or merely an cpiphenomenon. Further work is required to understand the relationship between cell membrane properties and insulin action. especially in insulin target tissues such as skeletal muscle. If cell membrane dynamics prove to be a significant modulating factor on insulin action, then it would provide a therapeutic target in NIDDM. P Tong (1) Unlvrr\ity of Newcastle, Newcastle upon Tync NE2 4HH. UK
Control of EBV-associated lymphoproliferation with gene-marked cytotoxic T cells Epstein-Barr virus-associated lymphoproliferative ease is a common and usually fatal complication transplantation of T cell-depleted bone marrow
disafter from
HLA-mismatched or unrelated donors. Donor-derived EBV-specific cytotoxic T cells (CTLs) efficiently kill virus-infected tumor cells in vitro, therefore we surmised that CTLs should be able to protect recipients against lymphoproliferative disease in viva. We have treated thirteen bone marrow recipients prophylactically with donor derived EBV-specific CTLs that had been genetically marked with a retrovirus vector. We then determined their safety, persistence and biological efficacy. No patient who received CTLs developed any toxicity that could be attributed to the CTLs. Marked CTLs could be detected in recipient peripheral blood for up to I6 weeks post infusion and in EBV-specific CTLs amplified from recipient blood in vitro, for up to eleven months. Infused CTLs demonstrated both anti-viral and anti-lymphoproliferative effects in viva. In five patients whose blood EBV DNA levels were elevated to a level that we had previously shown to correlate with the development of lymphoproliferative disease, levels were reduced dramatically after treatment, Most striking, was rapid resolution of tumor nodules and associated symptoms in a patient who had developed frank lymphoprotiferative disease. The patient remains well more than one year after the development of his tumor. The low toxicity. long term persistence and biological efficacy of this treatment suggest that cellular immunotherapy may be effective for other malignancies where tumor-specific antigens have been identified. One candidate for early exploration is Hodgkin’s disease. a lymphoid malignancy in which EBV is implicated. CM Rooney (5) St Jude Children’s Research Hospital, Memphis, TN 38101-0318, USA
Pulmonary tuberculosis tients in Zaire
in HIV-infected
pa-
The key message of this paper is that pulmonary tuberculosis (TB) can be successfully treated on an outpatient basis with a 6-month short course anti-TB regimen. administered only twice a week in the last four months of treatment. regardless of whether the patient has HIV infection or not. even under the extreme conditions of a developing country TB control programme. It is the first study to document that intermittent TB therapy is acceptable for HIV-infected patients with a cure rate of 96.2% at the end of treatment. However, after completion of a 6-month course of treatment, their I-elapse rate was higher (9%) than that of non HIV-infected patients (5.3%). The incidence of relapse among
42
Notes
HIV-infected patients could be reduced to 1.97r by extending treatment to 12 months, but this did not improve survival. The regimen used in the study is similar to that used in the industrialized countries for directly observed treatment of TB. and selection of multi-resistant TB was very rare. When short course chemotherapy with rifampicin and isoniazid throughout treatment is used and when TB relapses can be readily detected. it appeared from a TB control perspective unnecessary to document whether patients are HIV-infected. Indeed. the societal benefits of extending treatment for HIV-infected patients were limited to preventing TB relapses that remained treatable. Documenting HIV infection is still useful for individual HIV-infected patients because they might benefit from prophylaxis of opportunistic infections and antiretroviral therapy, and be able to protect their loved ones against HIV infection. However, when relapses are not readily detectable, such as in impoverished inner cities or developing countries, the decision to extend treatment for known HIV-infected patients should. in the absence of increased survival, balance increased programme costs and inconvenience against the potential societal impact of a relapse of TB through increased TB transmission. WHO,
(6)
N Engl
J Med
CH-1211
Geneva
JH Perriens (6) 27, Switzerland
1995;332:779-84
Brain abnormalities dystrophy
in Duchenne muscular
Duchenne muscular dystrophy (DMD) is a genetic disorder primarily affecting young boys. It forms part of the spectrum of muscular dystrophies caused by abnormalities of the short arm of the X chromosome (Xp21) often causing intellectual impairment in addition to progressive muscular weakness. Normal dystrophin expression is lacking both in skeletal muscle and brains of affected subjects. “P magnetic resonance spectroscopy c3’P MRS) is a non-invasive technique which, when applied in vivo, yields information concerning ratios of metabolites important in adenosine triphosphate (ATP) synthesis. “P MRS has shown abnormal high energy phosphate metabolism within skeletal muscle in DMD. Nineteen boys, diagnosed as having DMD, and 19 similarly-aged controls underwent non-localised brain
“‘P MRS. IQ was assessed with the Wechsler Intelligence Scale for children. Significantly increased ratios of inorganic phosphate (Pi) to ATP, phosphomonoesters and phosphocreatine were found in the patients’ brains compared to controls. Changes in these ratios suggest both an increase in [Pi] and a decrease in [ATP] occur in the brain in DMD. Full scale IQ (FIQ), performance IQ and verbal IQ were significantly different between controls and patients with DMD. but there was no clear relationship between brain bioenergetics and neuropsychological dysfunction. These altered high energy phosphate ratios parallel the findings in dystrophic muscle and suggest bioenergetic similarities in tissues which lack dystrophin. MRC
(7)
Lnncet
1995;345:
C Thompson (7) Magnetic Resonance Spectroscopy, Oxford OX3 9DU, UK
1260-64
Vitamin C is linked to death from stroke in the elderly Vitamin C is an important naturally occurring antioxidant. It protects against the damaging effect of free radicals that are produced by cell metabolism. It may be particularly important in reducing the tendency of cholesterol and other fats to cause atherosclerosis. Researchers followed up 730 elderly men and women over the age of 65 who had taken part in a nutritional survey in the 1970s and analysed their subsequent mortality from cardiovascular disease. People whose vitamin C intake had been over 45 mg per day had less than half the risk of dying from stroke of those whose intake had been below 28 mg. Vitamin C intake was as strong a risk factor for stroke as raised diastolic blood pressure, though it was not related to death from coronary heart disease. In England and Wales, 25,000 people die of stroke every year and many more are disabled. The findings of this study point to a safe and straightforward way in which it might be possible to prevent some of these strokes. C Gale (8) Soulhampton General Hospital, Southampton SO16 6YD, UK
(8) Br Med
.I 1995;310:1563-6