Magnesium levels in serum and in C.S.F. in febrile convulsions in infants and children

Summary Magnesium levels in the serum and in the C.S.F. in 100 children presenting with febrile convulsions were determined. This was repeated in 36 children after 2 weeks, of which 23 could be re-examined after a further period of 2 weeks. Nearly one-half of the cases on admission had magnesium levels in the serum lower than the average observed in normal children in this region and in over two-thirds of the cases the levels in the C.S.F. were lower than the average in the same region. The C.S.F. magnesium levels rose after 2–4 weeks. This was not found in the case of serum levels. These findings bear out the suggestion made in a pervious communication that there is some aetiological relationship between the magnesium levels in these two body fluids on the one hand and febrile convulsions on the other. From the Department of Pediatrics, M.G.M. Medical College and M.Y. Hospital, Indore. (M.P.)     

Cross-linked polymeric nanogel formulations of 5'-triphosphates of nucleoside analogues: role of the cellular membrane in drug release

Activation of cytotoxic nucleoside analogues in vivo depends primarily on their cell-specific phosphorylation. Anticancer chemotherapy using nucleoside analogues may be significantly enhanced by intracellular administration of active phosphorylated drugs. However, the cellular transport of anionic compounds is very ineffective and restricted by many drug efflux transporters. Recently developed cationic nanogel carriers can encapsulate large amounts of nucleoside 5'-triphosphates that form polyionic complexes with protonated amino groups on the polyethylenimine backbone of the nanogels. In this paper, the 5'-triphosphate of an antiviral nucleoside analogue, 3'-azido-2',3'-dideoxythymidine (AZT), was efficiently synthesized and its complexes with nanogels were obtained and evaluated as potential cytotoxic drug formulations for treatment of human breast carcinoma cells. A selective phosphorylating reagent, tris-imidazolylphosphate, was used to convert AZT into the nucleoside analogue 5'-triphosphate using a one-pot procedure. The corresponding 3'-azido-2',3'-dideoxythymidine 5'-triphosphate (AZTTP) was isolated with high yield (75%). Nanogels encapsulated up to 30% of AZTTP by weight by mixing solutions of the carrier and the drug. The AZTTP/nanogel formulation showed enhanced cytotoxicity in two breast cancer cell lines, MCF-7 and MDA-MB-231, demonstrating IC50 values 130-200 times lower than those values for AZT alone. The exact mechanism of drug release from nanogels remains unclear. One mechanism could involve interaction with negatively charged counterions. A high affinity of nanogels to isolated cellular membranes has been observed, especially for nanogels made of amphiphilic block copolymer, Pluronic P85. Cellular trafficking of nanogel particles, contrasted by polyethylenimine-coordinated copper(II) ions, was studied by transmission electron microscopy (TEM), which revealed membranotropic properties of nanogels. A substantial release of encapsulated drug was observed following interactions of drug-loaded nanogels with cellular membranes. A drug release mechanism triggered by interaction of the drug-loaded nanogels with phospholipid bilayer is proposed. The results illustrate therapeutic potential of the phosphorylated nucleoside analogues formulated in nanosized cross-linked polymeric carriers for cancer chemotherapy.     

Retroperitoneal para-aortic paraganglioma

Paragangliomas or chemodectomas are neoplasms that arise from neural crest cells and histologically resemble their adrenal counterpart, the pheochromocytoma. Seventy-one percent of the extra-adrenal paragangliomas are located in the superior or inferior paraaortic area. This tumor usually presents as an abdominal mass producing back pain. Tumor localization has improved remarkably through the use of computed tomography and I131 metaiodobenzyl-guanidine scintigraphy, particularly when tumors are hormonally active. Surgical excision remains the mainstay of treatment, although vascularity can at times make excision difficult.     

Virological and pharmacological parameters predicting the response to lopinavir-ritonavir in heavily protease inhibitor-experienced patients

The genotypic inhibitory quotient (GIQ) has been proposed as a way to integrate drug exposure and genotypic resistance to protease inhibitors and can be useful to enhance the predictivity of virologic response for boosted protease inhibitors. The aim of this study was to evaluate the predictivity of the GIQ in 116 protease inhibitor-experienced patients treated with lopinavir-ritonavir. The overall decrease in human immunodeficiency virus type 1 (HIV-1) RNA from baseline to month 6 was a median of -1.50 log(10) copies/ml and 40% of patients had plasma HIV-1 RNA below 400 copies/ml at month 6. The overall median lopinavir study-state C(min) concentration was 5,856 ng/ml. Using univariate linear regression analyses, both lopinavir GIQ and the number of baseline lopinavir mutations were highly associated with virologic response through 6 months. In the multivariate analysis, only lopinavir GIQ, baseline HIV RNA, and the number of prior protease inhibitors were significantly associated with response. When the analysis was limited to patients with more highly mutant viruses (three or more lopinavir mutations), only lopinavir GIQ remained significantly associated with virologic response. This study suggests that GIQ could be a better predictor of the virologic response than virological (genotype) or pharmacological (minimal plasma concentration) approaches used separately, especially among patients with at least three protease inhibitor resistance mutations. Therapeutic drug monitoring for patients treated by lopinavir-ritonavir would likely be most useful in patients with substantially resistant viruses.     

Balloon dilatation of pulmonary valve in Tetralogy of Fallot's

In some children of Tetralogy of Fallot's (TOF) presenting with progressive cyanosis, are palliative Blalock-Taussing (BT) shunt may be required. There are no reports of this modality of management in India, though this has been practiced in the other countries. The author reports an infant with Tetralogy of Fallot's who successfully underwent ballon dilatation of the pulmonary valve. Review of literature shows 332 patients with TOF undergoing pulmonary valve balloon dilatation as an alternative to BT shunt in 12 studies with significant increase in pulmonary artery 'Z' score and low incidence of conversion to shunt. This modality of management should be considered in selected patients to change a palliative surgery to an intervention.