Intranasal versus intravenous lorazepam for control of acute seizures in children: a randomized open-label study

Purpose: Intravenous lorazepam is considered the drug of first choice for control of acute convulsive seizures. However, resource or personnel constraints necessitate the study of alternative routes and medications. This study compared the efficacy and adverse effects of intranasal versus intravenous lorazepam in children aged 6–14 years who presented with acute seizures. Methods: This was a randomized open‐label study conducted at an Indian hospital from August 2008 to April 2009. One hundred forty‐one consecutive children aged 6–14 years who presented convulsing to the emergency room were included. After stabilization, the children were randomized to receive either intravenous or intranasal lorazepam (0.1 mg/kg, maximum 4 mg). The primary outcome measure was clinical seizure remission within 10 min of drug administration. The study was registered with clinicaltrials.gov (NCT00735527). Key Findings: Seventy patients were randomized to receive intravenous and 71 to receive intranasal lorazepam. The patients in the two groups were comparable at baseline. Clinical seizure remission within 10 min of drug administration was found in 80% of the intravenous group as compared to 83.1% of intranasal group. The lower limit of 95% confidence interval for effect size was approximately −9.7%, with an a priori cutoff for noninferiority of −10%. Significance: Intranasal administration of lorazepam is not found to be inferior to intravenous administration for termination of acute convulsive seizures in children.     

Disseminated cysticercosis in a child: whole-body MR diagnosis with the use of parallel imaging

Cysticercosis is a parasitic disease caused by infestation with the encysted larval stage of the pork tapeworm, Taenia solium. Disseminated cysticercosis is an exceptional expression of this disease characterized by high morbidity due to massive symptomatic parasite burden in the central nervous system, striated muscles, subcutaneous tissues and other organs. Less than 50 such cases have been reported worldwide, and fewer than 10 children. We report on the whole-body MR diagnosis of extensively disseminated cysticercosis in a child. The critical role of whole-body MR as a stand-alone modality in the diagnosis and management of this pleomorphic disease is highlighted. Whole-body MR diagnosis of an infectious disease is unique.     

Molecular cloning and characterization of Plasmodium falciparum transketolase

The pentose phosphate pathway (PPP) is an important metabolic pathway for yielding reducing power in the form of NADPH and production of pentose sugar needed for nucleic acid synthesis. Transketolase, the key enzyme of non-oxidative arm of PPP, plays a vital role in the survival/replication of the malarial parasite. This enzyme in Plasmodium falciparum is a novel drug target as it has least homology with the human host. In the present study, the P. falciparum transketolase (PfTk) was expressed, localized and biochemically characterized. The recombinant PfTk harboring transketolase activity catalyzed the oxidation of donor substrates, fructose-6-phosphate (F6P) and hydroxypyruvate (HP), with K(m)(app) values of 2.25 and 4.78 mM, respectively. p-Hydroxyphenylpyruvate (HPP) was a potent inhibitor of PfTk, when hydroxypyruvate was used as a substrate, exhibiting a K(i) value of 305 microM. At the same time, noncompetitive inhibition was observed with F6P. The native PfTk is a hexamer with subunit molecular weight of 70kDa, which on treatment with low concentrations of guanidine hydrochloride (GdmCl) dissociated into functionally active dimers. This protein was localized in the cytosol and nucleus of the parasite as studied by confocal microscopy. A model structure of PfTk was constructed based on the crystal structure of the transketolases of Saccharomyces cerevisae, Leishmania mexicana and Escherichia coli to assess the structural homology. Consistent with the homology modeling predictions, CD analysis indicated that PfTk is composed of 39% alpha-helices and 26% beta-sheets. The availability of a structural model of PfTk and the observed differences in its kinetic properties compared to the host enzyme may facilitate designing of novel inhibitors of PfTk with potential anti-malarial activity.     

Cerebrospinal fluid lactate: Is it a reliable and valid marker to distinguish between acute bacterial meningitis and aseptic meningitis?

Cerebrospinal fluid (CSF) lactate assay has been a subject of research since 1925. A systematic review by Huy and colleagues in the previous issue of Critical Care summarizes data from 25 studies evaluating the role of CSF lactate in the differential diagnosis between acute bacterial and aseptic meningitis. The authors concluded that CSF lactate is a good single indicator and a better marker compared with conventional markers. But concerns remain because of poor quality of included studies, lack of proper 'gold standard', and limited applicability. More studies with a rigorous design are needed to determine definitively whether CSF lactate assay is a reliable and valid marker to distinguish between acute bacterial meningitis and aseptic meningitis.     

Water Quality Interaction with Alkaline Phosphatase in the Ganga River: Implications for River Health

Carbon, nitrogen and phosphorus inputs through atmospheric deposition, surface runoff and point sources were measured in the Ganga River along a gradient of increasing human pressure. Productivity variables (chlorophyll a, gross primary productivity, biogenic silica and autotrophic index) and heterotrophy (respiration, substrate induced respiration, biological oxygen demand and fluorescein diacetate hydrolysis) showed positive relationships with these inputs. Alkaline phosphatase (AP), however, showed an opposite trend. Because AP is negatively influenced by available P, and eutrophy generates a feedback on P fertilization, the study implies that the alkaline phosphatase can be used as a high quality criterion for assessing river health.     

Hydrotalcite catalyzed N-alkylation: A practical greener approach towards Carbon-Nitrogen bond formation

Main driving force of this research work is to focus 9th principle (Catalysis) out of 12 principles of green chemistry so as to protect environment concerned with the reduction in generation of carbon dioxide, one of the green house gas. An innovative development of chemical pathway regarding N-alkylation reaction carried out by adding and recycling only catalytic amount of Hydrotalcite as solid base instead of stoichiometric amount, as per prior art techniques, has attempted. Synthesis of 3° amines, important Active Pharmaceutical Ingredients (APIs) and their intermediates, maintaining the same quality attributes resulting in to minimum generation of carbon dioxide are described. These concept is designed, synthesized, characterized, quantified and compared using “Carbon Efficiency”, a Green Chemistry Metrics, with already reported work to prove its sustainability. It is industrially advantageous by getting improvement in carbon efficiency and yield as outcome. Here we show a practical greener approach towards Carbon – Nitrogen bond formation with the help of calculation of Carbon efficiency and rate of reaction for first time.