Transforming growth factor-beta and tumor necrosis factor-alpha cooperate to induce apoptosis in the oligodendroglial cell line OLI-neu

As shown previously, transforming growth factor-beta (TGF-beta) plays an important role during the period of developmental cell death in the nervous system. As with neurons, oligodendrocytes are generated in excess and eliminated by apoptosis. The present study was aimed at investigating the possible interaction of TGF-beta with tumor necrosis factor-alpha (TNF-alpha) in the regulation of cell death in oligodendroglial precursor cells and analyzing the underlying signaling mechanisms. We show that both factors induce apoptosis independently, but cooperate when applied together. The investigation of the signaling events revealed an important role of the JNK pathway during induction of apoptosis. TGF-beta seemed to be more efficient at inducing a release in cytochrome c from mitochondria than TNF-alpha. This might be the consequence of decreased Bcl-xL levels observed in cells treated with TGF-beta but not with TNF-alpha. Both factors stimulated caspase-3 activity, which could be inhibited by caspase-8 or caspase-9 inhibitors. Therefore, we conclude that TNF-alpha and TGF-beta affect partially common pathways but also regulate different steps in the apoptotic cascade.     

Acetazolamide treatment for infantile central sleep apnea

Central sleep apnea is a common respiratory pattern in healthy neonates. Nevertheless, frequent central sleep apnea associated with drops in oxygen saturation may contribute to infantile morbidity. Recently, low-dose acetazolamide was shown to reduce symptomatic central sleep apnea in adults. We treated 12 infants, median conceptional age 42 weeks (range, 40-44 weeks), with central sleep apnea. In all cases, the central apnea index was >40/h total sleeping time (apnea > or = 3 sec). The cumulative duration of drops in oxygen saturation below 90% was more than 3 min/h total sleeping time. All individuals received acetazolamide 7 mg/kg/day (orally, divided in three doses) for 11 weeks. Polysomnography was begun 10 hours before the first dose and continued for 10 hours after the third dose. Polysomnography was repeated after 6 weeks of treatment and 1 week after acetazolamide therapy was discontinued. Comparison of the respiratory patterns before and after treatment (10-hour recording after the third dose) showed a decrease in the median central apnea index from 74/h (range, 42-152/h) to 13/h (range, 6-49/h). The median of the cumulative duration of drops in oxygen saturation below 90% decreased from 3.6 min/h (range, 3.1-9.2 min/h) to 0.07 min/h (range, 0-0.5 min/h). Basal oxygen saturation increased from 95 (92-97%) to 98% (96-99%). This improvement was maintained in the final polysomnography (12 weeks after therapy was begun and 1 week after completion of the 11-week course). No adverse effects were noted. We conclude that low-dose acetazolamide treatment may be useful for the treatment of central infantile sleep apnea associated with hypoxemia.     

Informed Consent

There have been significant changes in the doctor patient relationship with the impact of technology in day-to-day practice. More and more patients are aware of their rights and are keen to make free choice and decision on their treatment. This helps them to choose the treatment of their choice from the options available and to select a physician of their choice. Doctor's decisions are being questioned regarding their correctness and there is a need to educate the patient, on what one offers by way of treatment. In some procedures and types of treatment, patient needs to be educated and informed of the merits and demerits of the treatment available. This will help the patient to make appropriate choice and also to accept some adverse outcome of treatment. Towards this end, all countries are looking afresh at the necessity of Informed Consent. Methods adopted by some countries are highlighted to help our physicians practice them in an appropriate way. A lot of remedial work needs to be done to minimize future litigation, as many doctors misunderstand their legal obligations and haven't caught up with the change in judge's thinking.     

Chloride losing diarrhoea and metabolic alkalosis in an infant with cystic fibrosis

A case of hypochloraemic metabolic alkalosis in an infant with chloride losing ileostomy drainage and cystic fibrosis is described. It is speculated that intestinal loss of chloride played a major role in the development of metabolic alkalosis.     

The role of pancreatic venous sampling in the localization of occult insulinomas

The palpation and enucleation of occult insulinomas (less than 15 mm) can be a difficult surgical problem even with good arteriographic localization. In the authors' limited experience, confirmation of arteriographic findings by pancreatic venous sampling provided little additional localizing information. However, if arteriography is negative or equivocal, venous sampling can indicate the segment of pancreas to be "blindly" resected if the adenoma is not palpable. Venous sampling may be misleading in polyendocrine syndromes because of the frequency of multiple adenomas and variable hormone production.     

Intravenous digital subtraction renal angiography: use in screening for renovascular hypertension

Intravenous digital subtraction renal angiography (DSRA) has been compared with conventional angiography only in small, selected series of hypertensive patients. The authors prospectively examined with intravenous DSRA 94 patients at increased risk for renovascular hypertension and compared these studies with conventional angiography. A stenosis of at least one main renal artery was identified with intravenous DSRA in 22 patients and confirmed in 20 patients. No significant stenoses were seen with conventional angiography in any of the 64 patients in whom lesions were not seen with intravenous DSRA. Since inadequate DSRA studies were considered positive for renal artery stenosis, the sensitivity of intravenous DSRA was 100% (25 of 25); specificity, 93% (64 of 69); positive predictive value, 83% (25 of 30); and negative predictive value, 100% (64 of 64). The authors conclude that intravenous DSRA is a sensitive test for identifying stenosis of the main renal arteries and is appropriate to use as a screening test among patients at increased risk for renovascular hypertension.     

Cyclosporin nephrotoxicity in heart and lung transplant patients

Twenty-two patients with heart, lung or heart and lung transplants maintained on cyclosporin for periods ranging from 3 months to 10 years developed renal insufficiency which was investigated by renal biopsy. The histopathological changes were: (i) severe vascular and glomerular damage due to thrombotic microangiopathy (TM); (ii) a form of focal segmental glomerulosclerosis (FSGS); (iii) glomerular ischaemia. Rather than being separate entities, these changes appeared to represent a spectrum of pathology, some biopsies showing all three forms of glomerular injury. In all cases the glomerular changes were accompanied by arteriolar and arterial pathology, and we identified novel ultrastructural changes in the arteriolar endothelial basal lamina. Tubular atrophy was a consistent feature, the severity of which reflected the severity of the glomerular sclerosis, and which appeared to be a consequence of glomerular loss. Our findings are consistent with the nephrotoxic effects of cyclosporin being mediated chiefly via damage to preglomerular vessels and glomerular capillary endothelium. From an analysis of the clinical aspects of these cases, the effects of cyclosporin appear to be to some extent idiosyncratic, and therefore not entirely preventable, but strict monitoring of blood cyclosporin levels is essential to minimize the risk of permanent renal damage. Monitoring urinary protein in addition to plasma creatinine may detect the onset of FSGS, as proteinuria precedes creatinine elevation.      

Portuguese version of the Delirium Rating Scale-Revised-98: reliability and validity

OBJECTIVE: To assess the validity and the reliability of the Portuguese version of the Delirium Rating Scale-Revised-98 (DRS-R-98). METHODS: The scale was translated into Portuguese and back-translated into English. After assessing its face validity, five diagnostic groups (n=64; delirium, depression, dementia, schizophrenia and others) were evaluated by two independent researchers blinded to the diagnosis. Diagnosis and severity of delirium as measured by the DRS-R-98 were compared to clinical diagnosis, Mini-Mental State Exam, Confusion Assessment Method, and Clinical Global Impressions scale (CGI). RESULTS: Mean and median DRS-R-98 total scores significantly distinguished delirium from the other groups (p<0.001). Inter-rater reliability (ICC between 0.9 and 1) and internal consistency (alpha=0.91) were very high. DRS-R-98 severity scores correlated highly with the CGI. Mean DRS-R-98 severity scores during delirium differed significantly (p<0.01) from the post-treatment values. The area under the curve established by ROC analysis was 0.99 and using the cut-off value of 20 the scale showed sensitivity and specificity of 92.6% and 94.6%, respectively. CONCLUSION: The Portuguese version of the DRS-R-98 is a valid and reliable measure of delirium that distinguishes delirium from other disorders and is sensitive to change in delirium severity, which may be of great value for longitudinal studies.