Ethics roundtable debate: Child with severe brain damage and an underlying brain tumour

A young person presents with a highly malignant brain tumour with hemiparesis and limited prognosis after resection. She then suffers an iatrogenic cardiac and respiratory arrest that results in profound anoxic encephalopathy. A difference in opinion between the treatment team and the parent is based on a question of futile therapy. Opinions from five intensivists from around the world explore the differences in ethical and legal issues. A Physician-ethicist comments on the various approaches.     

Expression of phosphorylation of N-methyl-D-aspartate receptor subunits during graded hypoxia in the cerebral cortex of newborn piglets

The present study tests the hypothesis that during graded hypoxia, N-methyl-D-aspartate (NMDA) receptor expression and phosphorylation are altered in the cerebral cortex of newborn piglets. Studies were performed in anesthetized, ventilated piglets, 6 normoxic and 9 exposed to different lengths of decreased fractions of inspired oxygen to achieve varying biochemical levels of phosphocreatine (PCr). P(2) membrane proteins were immunoprecipitated with antiphosphoserine, antiphosphotyrosine, or antiphosphothreonine antibodies and separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Proteins were transblotted and probed with NMDA receptor subunit 1 (NR1), NR2A or NR2B antibodies. As tissue PCr levels decreased from 3.5 to 0.5 micromol/g brain during hypoxia, NR1, NR2A and NR2B protein increased by 84, 56 and 38%, respectively. Phosphorylated serine, tyrosine and threonine residues also increased during hypoxia on the three subunits. However, the increase in subunit protein exceeded the increase in phosphorylated residues for all three subunits. Therefore, the ratio of phosphorylated/dephosphorylated serine, tyrosine and threonine residues decreased with worsening hypoxia. We speculate that an alteration in the ratio of phosphorylated/dephosphorylated residues of the NMDA receptor may regulate receptor activation during hypoxia.     

NMDA receptor modification during graded hypoxia in the cerebral cortex of newborn piglets

Previous studies have shown that the cerebral N-methyl-D-aspartate (NMDA) receptor is altered during hypoxia in newborn piglets. The present study tests whether modification of the glutamate and ion channel sites of the NMDA receptor correlates with the progressive decrease in cerebral energy metabolism induced by hypoxia. Degrees of cerebral hypoxia were attained by exposure of ventilated piglets to decreased oxygen at different concentrations and confirmed by tissue phosphocreatine levels. During graded hypoxia, the number of glutamate sites decreased, the affinity of the ion channel site increased, the inhibition by Zn(2+) increased, the activation by glutamate increased, and the activation by glycine decreased. Therefore, modification of the NMDA receptor correlates with the energy state of the tissue. Alterations in receptor phosphorylation may gradually modify the NMDA receptor and may be initiated by subtle decreases in tissue oxygenation in the newborn brain.     

Structural studies on the impurities of troglitazone

The impurity profile study of troglitazone has been carried out primarily by (liquid chromatography-mass spectrometry) LC-MS. Four process-related impurities have been detected by LC-MS and were confirmed by co-injection with authentic samples. Apart from the process-related impurities, two polar by-products were characterized by mass spectral data and comparison with reference samples, while one non-polar by-product and one degradation product have been isolated by means of preparative HPLC and characterized by 2D NMR and mass spectral study. Single-crystal X-ray diffraction studies have been carried out on the degradation product. The formation and characterization of these by-products and degradation product are discussed.     

Pulmonary function tests in children with adenotonsillar hypertrophy

OBJECTIVE: Adenotonsillar hypertrophy, a common malady in children may lead on to cardiopulmonary dysfunction in untreated cases. The present study was designed to see alteration in pulmonary function tests i.e. spirometric parameters and blood oxygen saturation consequent to adenotonsillar hypertrophy and subsequent changes after adenotonsillectomy. METHODS: Spirometry and pulse oximetry were carried out in 40 children with adenotonsillar hypertrophy of both sexes between the age of 7 and 14 years and 40 age and sex matched healthy children. The test was repeated one and half months after surgery in study group and data was statistically analyzed using students' t-test. RESULTS: The flow volume plot was abnormal in all the patients along with hypoxia, reduced FIF50% and, increased FEF50%/FIF50%, FEV1/PEFR, FEV1/FEV0.5 ratios. There was statistically significant improvement in above parameters following surgery. CONCLUSIONS: Spirometry can prove an useful diagnostic tool in adenotonsillar hypertrophy for deciding early intervention to prevent cardio pulmonary complications.     

LC determination and purity evaluation of nefazodone HCl in bulk drug and pharmaceutical formulations

A thin layer chromatographic-densitometric method for identification and quantitation of neomycin sulfate, polymixin B sulfate, zinc bacytracin and auxiliary substances (methyl and propyl hydroxybenzoates) in ophthalmic ointment was developed. To separate these constituents the silica gel coated TLC plates and two mobile phases were used. The suitable mobile phases were: methanol-n-butanol-ammonia 25%-chloroform (14:4:9:12, v/v/v/v) for determination of antibiotics and n-pentane-glacial acetic acid (66:9, v/v) for methyl and propyl hydroxybenzoates. The antibiotic chromatograms were detected by using ninhydrin ethanol solution, while densitometric measurements were made at lambda = 550 nm. Hydroxybenzoates were identified by UV measurements at lambda = 260 nm. The constituents under consideration were well separated at sufficient detection level. The recovery for all constituents ranged from 98.08% to 104.95%.     

An epidemiological study of smoking in urban school boys of Ajmer

In a survey of 1000 school boys aged 8–16 years, 52 (5.2%) were smokers Thirty of them were regular smokers, of whom 27 took to smoking between 10–14 years of age. Only six children thought that they smoked for pleasure. None of the children, whose mothers had university or higher vocational education smoked, (P<0.01) Parental smoking also seemed to influence smoking behaviour of their children. Type of the family-nuclear or joint-did dot affect the smoking prevalence, but children occupying special position in the family smoked more frequently, (P<0.001). Most of the smokers belonged to middle or poor socio-economic group and none to upper socioeconomic group (P<0.001).     

Poly (ethylene)-glycol conjugated solid lipid nanoparticles of noscapine improve biological half-life,brain delivery and efficacy in glioblastoma cells

Noscapine crosses blood–brain-barrier and inhibits proliferation of glioblastoma cells. However, short plasma half-life and rapid elimination necessitate the administration of multiple injections for successive chemotherapy. Noscapine bearing solid lipid nanoparticles, Nos-SLN and poly (ethylene)-glycol conjugated solid lipid nanoparticles of noscapine, Nos-PEG-SLN of 61.3 ± 9.3-nm and 80.5 ± 8.9-nm containing 80.4 ± 3.2% and 83.6 ± 1.2% of Nos, were constructed. First order kinetic and Higuchi equation were followed to release the Nos at intracellular pH ~ 4.5. Further, a decrease in IC₅₀ (Nos; 40.5 μM > Nos-SLN; 27.2 μM > 20.8 μM) and enhanced subG1 population were observed in U87cells. Plasma half-life was enhanced up to ~ 11-fold and ~ 5-fold by Nos-PEG-SLN and Nos-SLN which significantly (P < 0.05) deposits 400.7 μg/g and 313.1 μg/g of Nos in comparison to 233.2 μg/g by drug solution. This is first report demonstrating a workable approach to regulate the administration of multiple injections of Nos, warranting further in vivo tumor regression study for superior management of brain cancer.From the Clinical EditorThis report describes a possible approach to regulate the administration of multiple injections of Noscapine using solid lipid nanoparticles. The data warrant further in vivo tumor regression studies for optimal management of glioblastoma, a generally very poorly treatable brain cancer.