6-Hydroxylation of cortisol and urinary 6beta-hydroxycortisol.

The 6β-hydroxylation of steroids in vivo, and under in vitro conditions, is well documented. Incubation studies have demonstrated that the human adrenal contains a C-6β-hydroxylase system which, after further investigation, was reported to be present in several other normal and neoplastic tissues. 6β-Hydroxycortisol was first isolated and identified from guinea-pig urine and, subsequently, in humans, following oral administration of cortisol in both cases, and was found to be the largest fraction of unconjugated steroid excreted in urine. This steroid was also excreted in elevated concentrations in late human pregnancy urine, and in newborn infants, as well as in liquor amnii of normal and pathologic pregnancies. Abnormally high levels of 6β-hydroxycortisol were present in some disease states, and it was also found that the excretion of this steroid increased after the administration of ACTH, thus showing its adrenal origin. Treatment with estrogens, and with certain drugs, has a marked effect in stimulating the metabolism of cortisol to 6β-hydroxycortisol, causing severalfold increases in the urinary excretion of this steroid in man. Since 6β-hydroxylation plays a significant role in the metabolism of cortisol in man, and with a view to studying the importance of this metabolic pathway, the most reliable index would appear to be the measurement of 6β-hydroxycortisol in urine, for which sensitive methods such as fluorimetric and radioimmunoassay procedures have recently become available. A method for the determination of the production rate measurement of 6β-hydroxycortisol has also been developed. This review has shown that the estimation of 6β-hydroxycortisol could be applied for the study of 6β-hydroxylase activity under various conditions, and to assess adrenocortical function in health and disease.     

Acute renal failure due to intravascular hemolysis in the North Indian patients

Acute renal failure due to intravascular hemolysis is a common clinical problem in North Indian patients. It constituted 21.5 percent of 325 patients dialyzed for acute renal failure over an 11-year period at Chandigarh. Thirty patients had developed acute intravascular hemolysis in association with erythrocyte glucose-6 phosphate dehydrogenase (G-6PD) deficiency, 17 due to copper sulphate intoxication and 8 due to envenomation by snakes. Less frequent causes were insect stings, incompatible blood transfusion, intake of anti-leprosy drug--dapsone in non-G-6PD-deficient patients, and mercuric chloride toxicity in two patients each; naphthalene poisoning in one; and uncertain causes in six patients. Renal histology was available in 55 patients. Acute tubular necrosis was seen in 54 and bilateral diffuse cortical necrosis in one patient. Fifty patients (71.43 percent) survived and 20(28.6 percent) diet. G-6PD erythrocyte deficiency, which is present in 4.5 percent of the North Indian population, was the most frequent cause of acute renal failure in this group.     

Evaluation of oxygen saturation monitoring by pulse oximetry in neonates in the delivery system

The pulse oximeter was evaluated for use in neonates in the delivery room. One hundred neonates, delivered vaginally or by Caesarean section with general or epidural anaesthesia, were studied. After delivery, pulse oximetry probes were placed simultaneously on the ulnar side of the right hand and on the right Achilles tendon to determine whether there was a difference in arterial oxygenation (SpO2). Measurements of SpO2 were taken at 1, 5, 10 min, and 24 hr after delivery. At one and five minutes, SpO2 recorded from the right hand was higher than that recorded from the lower extremities (71.9% +/- 6.5% vs 63.4% +/- 4.3% and 83.3% +/- 4.2% vs 76% +/- 4.1%, mean +/- SD, respectively). At ten minutes these differences diminished, and had almost completely disappeared after 24 hr. These results can be explained by the presence of R-L shunting at the ductus arteriosus level, producing reduced SaO2 in the lower extremities. Oxygen saturation did not differ between neonates delivered vaginally or by Caesarean section, regardless of the presence or type of anaesthesia. We concluded that neonates remain relatively desaturated in the immediate postpartum period and that the SpO2 obtained from the right hand is a better index of neonatal oxygenation than that obtained from the heel.     

Predictors of Short Intensive Care Unit Stay for Patients with Diabetic Ketoacidosis Using a Novel Emergency Department–Based Resuscitation and Critical Care Unit

Background

The resuscitation and critical care unit is a novel emergency department–intensive care unit designed to provide early critical care to emergency department patients for ≤24 h.

Mutual concessions and compromises between stromal cells and cancer cells: driving tumor development and drug resistance

Background

Various cancers have been found to be associated with heterogeneous and adaptive tumor microenvironments (TMEs) and to be driven by the local TMEs in which they thrive. Cancer heterogeneity plays an important role in tumor cell survival, progression and drug resistance. The diverse cellular components of the TME may include cancer-associated fibroblasts, adipocytes, pericytes, mesenchymal stem cells, endothelial cells, lymphocytes and other immune cells. These components may support tumor development through the secretion of growth factors, evasion from immune checkpoints, metabolic adaptations, modulations of the extracellular matrix, activation of oncogenes and the acquisition of drug resistance. Here, we will address recent advances in our understanding of the molecular mechanisms underlying stromal-tumor cell interactions, with special emphasis on basic and pre-clinical information that may facilitate the design of novel personalized cancer therapies.

Conclusions

This review presents a holistic view on the translational potential of the interplay between stromal cells and cancer cells. This interplay is currently being employed for the development of promising preclinical and clinical biomarkers, and the design of small molecule inhibitors, antibodies and small RNAs for (combinatorial) cancer treatment options. In addition, nano-carriers, tissue scaffolds and 3-D based matrices are being developed to precisely and safely deliver these compounds.

     

New forensic challenges and detection of snake venom

Forensic Toxicology -     

A case of gastro-intestinal allergy

Indian Journal of Pediatrics -