Castleman's disease-A case report

Castleman's disease is a rare clinicopathological entity characterized by non-neoplastic lymph node hypertrophy. Its incidence and etiology is unknown. It has been found in association with Kaposi's sarcoma thus necessitating investigations for HIV. Although its localized variety is benign other types can be multifocal with adverse systemic manifestations. A case report of a 42 yrs old female with a slowly enlarging highly vascular mass in the left iliac fossa is presented which lead to a histological diagnosis of this rare condition (see picture). Furthermore its clinical features, its types, relevant investigations and current treatment modalities are discussed.     

MIF intersubunit disulfide mutant antagonist supports activation of CD74 by endogenous MIF trimer at physiologic concentrations

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine. In addition to its known receptor-mediated biological activities, MIF possesses a catalytic site of unknown function between subunits of a homotrimer. Each subunit contributes three β-strands to adjacent subunits to form a core seven-stranded β-sheet for each monomer. MIF monomers, dimers, or trimers have been reported, but the active form that binds and activates the MIF receptor (CD74) is still a matter of debate. A cysteine mutant (N110C) that covalently locks MIF into a trimer by forming a disulfide with Cys-80 of an adjacent subunit is used to study this issue. Partial catalytic activity and receptor binding to CD74 are retained by N110C (locked trimer), but there is no cellular signaling. Wild-type MIF-induced cellular signaling, in vivo lung neutrophil accumulation, and alveolar permeability are inhibited with a fivefold excess of N110C. NMR and size-exclusion chromatography with light scattering reveal that N110C can form a higher-order oligomer in equilibrium with a single locked trimer. The X-ray structure confirms a local conformational change that disrupts the subunit interface and results in global changes responsible for the oligomeric form. The structure also confirms these changes are consistent for the partial catalytic and receptor binding activities. The absence of any potential monomer and the retention of partial catalytic and receptor binding activities despite changes in conformation (and dynamics) in the mutant support an endogenous MIF trimer that binds and activates CD74 at nanomolar concentrations. This conclusion has implications for therapeutic development.     

Anthropometric cut points for identification of cardiometabolic risk factors in an urban Asian Indian population

The aim of this study was to determine the anthropometric cut points for risk of cardiometabolic risk factors in an urban Asian Indian population. The Chennai Urban Rural Epidemiology Study representatively sampled 26001 individuals aged 20 years or older and detailed measures were obtained in every 10th subject: 90.4% (2350/2600). An oral glucose tolerance test was performed in all individuals except self-reported diabetic subjects. Anthropometric measurements such as body mass index (BMI) and waist circumference (WC) were obtained and serum lipid estimations were done in all subjects. Sensitivity, specificity, and distance on receiver operating characteristic curve were used to determine the optimal cut points for BMI and WC with cardiometabolic risk factors. Maximum sensitivity and specificity of BMI for all cardiometabolic risk factors such as diabetes mellitus, prediabetes, hypertension, hypertriglyceridemia, hypercholesterolemia, and low high-density lipoprotein cholesterol ranged from 22.7 to 23.2 kg/m(2) for men and 22.7 to 23.8 kg/m(2) for women, and that of WC ranged from 86 to 88.2 cm for men and 81 to 83.8 cm for women. The optimal BMI cut point for identifying any 2 cardiometabolic risk factors was 23 kg/m(2) in both sexes, whereas that of WC was 87 cm for men and 82 cm for women. The study validates the World Health Organization Asia Pacific guidelines of BMI of 23 kg/m(2) for the designation of overweight; WC of 87 cm for men and 82 cm for women appear to be appropriate cut points to identify cardiometabolic risk factors including prediabetes in urban Asian Indians.     

Spinal analgesia and auditory functions: a comparison of two sizes of Quincke needle

AIM: Spinal anaesthesia may produce complications ranging from minor problems such as pain on injection, backache and urinary retention to more serious consequences such as post-dural puncture headache (PDPH), neurological complications like meningitis, cranial and peripheral nerve palsies and even cardiac arrest. Impaired auditory function is a relatively lesser-recognized complication of spinal analgesia. The objective of this study was to investigate the effects of spinal analgesia on vestibular dysfunction, using different sizes of the same type of spinal needle. METHODS: The study included 30 ASA I patients who had received spinal analgesia for lower abdominal surgery. Pure tone audiometry was performed before surgery and on postoperative day 2. In addition, any patient with hearing impairment of >15 dB was scheduled to undergo electrocochleography. Hearing levels were measured from 250 Hz to 8 kHz. In group 1 (n=15), a 26gauge Quincke needle was used. In group 2 (n=15), a 23-gauge Quincke needle was used. RESULTS: Comparison of hearing thresholds showed a significant reduction in the hearing level (P<0.05) in 2 patients in group 2 but none in group 1. CONCLUSION: The use of a 23-gauge Quincke needle is associated with a greater reduction in the mean hearing level compared to a 26-gauge needle of the same type.     

Protective Effects of Pioglitazone Against Global Cerebral Ischemic-Reperfusion Injury in Gerbils

Despite of the huge socio-economic burden, stroke still represents an unmet therapeutic need. Researchers failed to reproduce preclinical efficacy in subsequent clinical development. To bridge this translation failure, the Stroke Therapy Academic Industry Round Table (STAIR) has suggested a rigorous, robust, and detailed preclinical evaluation in at least 2 species and multiple cerebral ischemia models to avoid the clinical failure. Considering these recommendations, in the present study, we have investigated the effects of pioglitazone in global model cerebral ischemic-reperfusion (IR) injury in gerbils. Global cerebral IR injury, produced by bilateral carotid artery occlusion for 5 min, was characterized by neurological deficits, hyperlocomotion, and neurodegeneration in the hippocampal CA1 region. Global ischemia was also associated with oxidative stress and DNA fragmentation as evident from increased malondialdehyde (MDA) levels and TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling)-positive cells. Global cerebral IR injury associated neurological damage was significantly attenuated by pioglitazone pretreatment as evident from reduction in neurological symptoms, hyperlocomotion, and CA1 hippocampal neuronal damage in IR-challenged gerbils. Pioglitazone pretreatment also attenuated the oxidative stress and DNA fragmentation after cerebral IR injury. Pioglitazone post-treatment has also significantly reduced the CA1 hippocampal neuronal damage and DNA fragmentation after cerebral IR injury in IR-challenged gerbils. This study demonstrates the neuroprotective activity of pioglitazone in global cerebral IR injury and its neuroprotective effects may be attributed to reduction in oxidative stress and DNA fragmentation.