A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial of Retinol Palmitate (Vitamin A) for Symptomatic Chronic Radiation Proctopathy

PURPOSE This study was designed to determine whether oral retinol palmitate (vitamin A) can reduce the symptoms of radiation proctopathy.METHODS A randomized, double-blind trial comparing retinol palmitate (10,000 IU by mouth for 90 days) to placebo was conducted. Eligible patients were more than six months postpelvic radiotherapy and had significant symptoms as measured with the Radiation Proctopathy System Assessments Scale. Nineteen patients were randomized in total: ten to retinol palmitate and nine to placebo. The Radiation Proctopathy System Assessments Scale scores before and every 30 days for 90 days were measured. Five placebo nonresponders were crossed over to the retinol palmitate for another 90 days. Response was defined as a reduction in two or more symptoms by at least two Radiation Proctopathy System Assessments Scale points.RESULTS Seven of ten retinol palmitate patients responded, whereas two of nine responded to placebo (P = 0.057). Mean pre-post-treatment change in Radiation Proctopathy System Assessments Scale ( Radiation Proctopathy System Assessments Scale) in the retinol palmitate group was 11 ± 5, whereas Radiation Proctopathy System Assessments Scale in the placebo group was 2.5 ± 3.6 (P = 0.013, Mann-Whitney U test). Additionally, all five placebo nonresponders who were crossed over to treatment with retinal palmitate responded to treatment.CONCLUSIONS In our trial, retinol palmitate significantly reduced rectal symptoms of radiation proctopathy, perhaps because of wound-healing effects. The current results can serve as the foundation for future trials examining retinol palmitate in the multi-institutional setting.Supported in part by a private grant from Arthur C. Nielsen, Jr.     

A small molecule accelerates neuronal differentiation in the adult rat

Adult neurogenesis occurs in mammals and provides a mechanism for continuous neural plasticity in the brain. However, little is known about the molecular mechanisms regulating hippocampal neural progenitor cells (NPCs) and whether their fate can be pharmacologically modulated to improve neural plasticity and regeneration. Here, we report the characterization of a small molecule (KHS101) that selectively induces a neuronal differentiation phenotype. Mechanism of action studies revealed a link of KHS101 to cell cycle exit and specific binding to the TACC3 protein, whose knockdown in NPCs recapitulates the KHS101-induced phenotype. Upon systemic administration, KHS101 distributed to the brain and resulted in a significant increase in neuronal differentiation in vivo. Our findings indicate that KHS101 accelerates neuronal differentiation by interaction with TACC3 and may provide a basis for pharmacological intervention directed at endogenous NPCs.     

Oligoclonality and innate-like features in the TCR repertoire of type II NKT cells reactive to a β-linked self-glycolipid

TCR-mediated recognition of β-linked self-glycolipids bound to CD1d is poorly understood. Here, we have characterized the TCR repertoire of a CD1d-restricted type II NKT cell subset reactive to sulfatide involved in the regulation of autoimmunity and antitumor immunity. The sulfatide/CD1d-tetramer⁺ cells isolated from naïve mice show an oligoclonal TCR repertoire with predominant usage of the Vα3/Vα1-Jα7/Jα9 and Vβ8.1/Vβ3.1-Jβ2.7 gene segments. The CDR3 regions of both the α- and β-chains are encoded by either germline or nongermline gene segments of limited lengths containing several conserved residues. Presence of dominant clonotypes with limited TCR gene usage for both TCR α- and β-chains in type II NKT cells reflects specific antigen recognition not found in the type I NKT cells but similar to the MHC-restricted T cells. Although potential CD1d-binding tyrosine residues in the CDR2β region are conserved between most type I and type II NKT TCRs, CDR 1α and 3α regions differ significantly between the two subsets. Collectively, the TCR repertoire of sulfatide-reactive type II NKT cells exhibits features of both antigen-specific conventional T cells and innate-like cells, and these findings provide important clues to the recognition of β-linked glycolipids by CD1d-restricted T cells in general.     

Diversification of complex butterfly wing patterns by repeated regulatory evolution of a Wnt ligand

Although animals display a rich variety of shapes and patterns, the genetic changes that explain how complex forms arise are still unclear. Here we take advantage of the extensive diversity of Heliconius butterflies to identify a gene that causes adaptive variation of black wing patterns within and between species. Linkage mapping in two species groups, gene-expression analysis in seven species, and pharmacological treatments all indicate that cis-regulatory evolution of the WntA ligand underpins discrete changes in color pattern features across the Heliconius genus. These results illustrate how the direct modulation of morphogen sources can generate a wide array of unique morphologies, thus providing a link between natural genetic variation, pattern formation, and adaptation.     

Cardiac catheterization through ipsilateral radial and ulnar artery access during the same procedure

We evaluated the safety and feasibility of ipsilateral radial and ulnar artery cannulation during the same catheterization procedure. Crossover from radial to femoral was done in 122 patients. Both ipsilateral radial and ulnar catheterization were performed in 16 patients without any complications, which was further supported by Doppler ultrasonography.     

Circulating T-Cell Subsets,Monocytes, and Natural Killer Cells in Peripartum Cardiomyopathy: Results From the Multicenter IPAC Study

Objective

The aim of this work was to evaluate the hypothesis that the distribution of circulating immune cell subsets, or their activation state, is significantly different between peripartum cardiomyopathy (PPCM) and healthy postpartum (HP) women.

A study of prophylactic use of 15-methyl prostalglandin F2alpha in the active management of third stage of labour

To compare active management of third stage of labour with 15-methyl prostaglandin F2alpha (PGF2alpha) and conventional management with methylergometrine as prophylaxis for postpartum hemorrhage, a randomised comparative study was carried out at Calcutta National Medical College and Hospital, Kolkata on 100 women. They were randomly allotted to one of the two groups. Group A included 50 women who received 15-methyl PGF2alpha (125 microg) intramusculary at the time of delivery of the anterior shoulder and group B included 50 women who underwent conventional management of the third stage of labour where methylergometrine 0.2 mg was given after delivery of placenta. Main outcome measured were duration of third stage, amount of bleeding and side-effects. The present study showed that there were significent reduction of the duration of third stage as well as reduction of amount of bleeding particularly when 125 microg of 15-methyl PGF2alpha was given intramuscularly at the time of delivery of the anterior shoulder in comparison to coventional method of management of third stage of labour with methylergometrine. Placental expulsion occurred within 4 minutes in group A and 16.5 minutes in group B. The amount of bleeding following delivery was 95.6 ml in average in group A and 249.6 ml in average in group B. 15-methyl PGF2alpha (125 microg) is certainly effective in prevention of postpartum haemorrhage particularly in developing country like India where this complication contributes a major factor for maternal mortality.     

Analysis of 88 nephrectomies in a rural tertiary care center of India

Nephrectomy is not an uncommon surgery in day-to-day practice of urology. Trauma is the most common cause of emergency nephrectomy. On the other hand, elective nephrectomy is done for both benign and malignant diseases of the kidney. This study has been performed to know the different causes of nephrectomy in a rural, tertiary care center of India. In our series, we have studied all the elective nephrectomies done in our hospital during a period of eight years. We have analyzed 88 cases of nephrectomies regarding their age, sex, laterality of disease, and histopathologic report of the nephrectomy specimens. Out of 88 cases, 61 were males and 27 were females. In our series, 62.5% cases of nephrectomies were done for benign causes and 37.5% cases for malignant causes. Among the benign causes, neglected pelviureteric junction obstruction was the leading cause, followed by calculus disease resulting in obstruction. On the other hand, renal cell carcinoma was the most common malignant pathology requiring nephrectomy.