Quantitative thermal sensory testing in patients with amyotrophic lateral sclerosis using reaction time exclusive method of levels (MLE)

OBJECTIVES: Quantitative thermal sensory testing (QST) systems are used for the noninvasive quantification of sensory nerve function including the small myelinated and unmyelinated fibres which is not provided by classical sensory nerve conduction studies. Although Amyotrophic Lateral Sclerosis (ALS) is a pure motor disorder, nevetheless involvement of the sensory fires has been reported occasionally by various techniques. In the present study Reaction Time Exclusive Method of Levels (MLE) was used to detect somatic small fibre involvement in ALS patients with no sensory abnomalities on routine NCS. MATERIAL & METHOD: Twenty patients of clinically definite ALS, were evaluated with QST using the reaction time exclusive method of Levels (MLE) for detecting the thresholds of cold sensation (CS) and warm sensation (WS). They were compared with 20 age matched controls. RESULTS: No abnormalities were detected in the thresholds for CS and WS in patients with ALS as compared to the controls. CONCLUSION: Thus ALS is essentially a pure motor disorder with normal thermal thresholds as revealed by QST.     

Cyclooxygenase inhibitors in urinary bladder cancer: in vitro and in vivo effects

More than 14,000 people die from invasive transitional cell carcinoma (TCC) of the urinary bladder yearly in the United States. Cyclooxygenase (COX)-inhibiting drugs are emerging as potential antitumor agents in TCC. The optimal in vitro or in vivo systems to investigate COX inhibitor antitumor effects have not been defined. The purpose of this study was to determine COX-1 and COX-2 expression and antitumor effects of COX inhibitors in human TCC cell lines (HT1376, RT4, and UMUC3 cells) and xenografts derived from those cell lines. COX-2 expression (Western blot, immunocytochemistry) was high in HT1376, modest in RT4, and absent in UMUC3 cells in vitro. Similarly, COX-2 expression was noted in RT4 but not UMUC3 xenografts. COX-2 expression in HT1376 xenografts was slightly lower than that observed in vitro. None of four COX inhibitors evaluated (celecoxib, piroxicam, valeryl salicylate, and NS398) reduced TCC growth in standard in vitro proliferation assays at concentrations that could be safely achieved in vivo (< or =5 micromol/L). Higher celecoxib concentrations (> or =50 micromol/L) inhibited proliferation and induced apoptosis in all three cell lines. Celecoxib or piroxicam treatment in athymic mice significantly delayed progression of HT1376 xenografts, which express COX-2, but not UMUC3 xenografts that lack COX-2 expression. In conclusion, standard in vitro assays were not useful in predicting COX inhibitor antitumor effects observed in vivo. Athymic mice bearing TCC xenografts provide a useful in vivo system for COX inhibitor studies. Results of this study provide justification for further evaluation of COX inhibitors as antitumor agents against TCC.     

Synthetic Toll-like receptor agonists for the development of powerful malaria vaccines: a patent review

ABSTRACT

Introduction: Currently, there is no efficient vaccine available against clinical malaria. However, continuous efforts have been committed to develop powerful antimalarial vaccine by discovery of novel antigens with in-depth understanding of its nature, immunogenicity, and presentation (delivery adjuvants). Moreover, another important part of vaccine development includes discovery of better immunostimulatory formulation components (immunostimulants). A protective vaccine against malaria requires antigen-specific B and T helper cell responses as well as cytotoxic T lymphocyte (CTL) responses. A long-lasting B and T memory cell production is also required for effective malaria vaccine. Since activation of Toll-like receptors (TLRs) promotes both innate inflammatory responses as well as the induction of adaptive immunity, several initiatives have been mounted during the last few years for the use of TLR agonists as malaria vaccine adjuvants.

Areas covered: The review summarizes reports related to the use and development of TLR agonists as malaria vaccine adjuvants and describes various strategies involved for the selection of specific antigens and TLR agonists.

Expert opinion: TLR agonists are promising adjuvants for the development of effective malaria vaccine, allowing for both innate inflammatory responses as well as the induction of adaptive immunity.     

First detection of measles genotype D7 from India

National Institute of Virology, India has instituted molecular surveillance of measles strains in the country. In phased manner, three major cities Pune, Chennai and Bangalore were covered. Throat swab and urine from suspected measles cases from Chennai and Pune and freshly frozen brain tissues, CSF from suspected SSPE case from Bangalore were subjected to RNA extraction and Measles N&H gene RT-PCR as per WHO standard protocols. PCR positive products were sequenced. Sequence alignment and phylogenetic analysis was carried out using WHO standard reference sequences. Virus isolation was attempted using B95a cell line. Measles genotype D7 was detected from two classical measles cases (Chennai and Pune) and in a fulminant SSPE case (Bangalore). This is the first detection of measles genotype D7 from India.     

Desmoplastic trichoepithelioma with pseudocarcinomatous hyperplasia: a report of three cases

We report three cases of desmoplastic trichoepithelioma (DTE) with overlying pseudocarcinomatous hyperplasia. All three cases developed on the face of patients in their second decade. In spite of their young age, a diagnosis of squamous cell carcinoma was considered for each case, given the unusual juxtaposition of these two well‐known simulators of malignancy. Awareness of this potential association may avert a misdiagnosis of malignancy.     

Ostium primum atrial septal defect with persistent left superior vena cava opening into unroofed coronary sinus—A rare entity

Raghib syndrome is a rare developmental complex consisting of termination of the left superior vena cava in the left atrium, absence of the coronary sinus, and an atrial septal defect commonly located at the posterior‐inferior angle of the atrial septum. This complex was considered unique to Raghib syndrome; however, cases with a normal atrial septum have been reported where the orifice of the unroofed coronary sinus functions as the inter‐atrial communication. Our patient demonstrated an isolated persistent left superior vena cava draining into the left atrium through unroofed coronary sinus and presence of ostium primum atrial septal defect.