Substantial archaeocortical atrophy and neuronal loss in multiple sclerosis

Recent studies have revealed extensive neocortical pathology in multiple sclerosis (MS). The hippocampus is a unique archaeocortical structure understudied in MS. It plays a central role in episodic and anterograde memory—the most frequently impaired cognitive modalities in MS. This histopathological study aimed to investigate inflammatory demyelination and neurodegenerative changes in the MS archaeocortex. A detailed quantitative analysis was performed on hippocampal autopsy tissue from 45 progressive MS cases and seven controls. Forty-one lesions were identified in 28 of the 45 hippocampal MS-blocks examined, with percentage area of demyelination averaging 30.4%. The majority of lesions were chronic and subpially or subependymally located. Compared to controls, neuronal numbers were decreased by 27% in CA1 and 29.7% in CA3-2. Furthermore, the size of neurones was decreased by 17.4% in CA1. There was evidence of gross hippocampal atrophy with a 22.3% reduction in the average cross-sectional area, which correlated with neuronal loss. Our study provides evidence of substantial archaeocortical pathology largely resembling patterns seen in the neocortex and suggests that hippocampal involvement could contribute to memory impairments often seen in MS.     

Chronic pain following a Lichtenstein inguinal hernia repair: a clinical and legal dilemma

Background: Chronic pain following a Lichtenstein inguinal hernia is frequent and raises major concerns regarding informed consent recall Objective: To assess the frequency of chronic pain and associated factors following inguinal hernia repair in a district general hospital. To assess patient recall of the consent process as it pertains to chronic pain. Methods: A random sample (170/293 patients) of those who underwent a Lichtenstein inguinal hernia repair between 2002 and 2004 were retrospectively assessed for the frequency, intensity and other co‐factors of chronic pain. They were also questioned about their recollection of the consent process and information given regarding chronic pain. Results: 50 percent of patients reported chronic pain at a median follow‐up of 62 months with 30% reporting a significant impact on daily activities. Younger age, the absence of a lump at presentation, pre‐operative pain and elective repair were the only factors significantly shown to increase the likelihood of post‐operative pain. Patients with post‐operative pain were significantly more likely to report that they had not been informed of the possibility of chronic pain pre‐operatively or at the time of consent. Twenty percent of these patients stated that they would not have undergone the operation if they had been informed of the possibility of chronic pain. Conclusion: Chronic pain is frequent and debilitating. Documentation of chronic pain as a possible outcome at the time of consent should be mandatory as patient recall is poor.     

18α-glycyrrhetinic acid targets prostate cancer cells by down-regulating inflammation-related genes

Glycyrrhetinic acid is an active triterpenoid metabolite of glycyrrhizin abundantly present in licorice roots. Glycyrrhetinic acid exists as α and β stereo-isomeric forms. Both stereo-isomeric forms are known to have anti-inflammatory and anticancer activity. However, the effects and anticancer mechanism of α glycyrrhetinic acid in prostate cancer cells has not yet been evaluated. Therefore, we investigated the growth inhibition, induction of apoptosis and the anticancer mechanisms of 18α-glycyrrhetinic acid (AGA), on the androgen-independent metastatic prostate cancer cell line DU-145. Our results showed that AGA inhibited proliferation and growth of these cells by inducing apoptosis as determined by Annexin V and flow cytometry analyses. Our studies also showed that HUVEC tube formation was drastically reduced when cultured in conditioned medium of AGA-treated DU-145 cells. In addition, AGA treatment prevented the invasion of DU-145 prostate cancer cells on matrigel coated transwells via down-regulation of NF-κB (p65), VEGF and MMP-9 expression. Furthermore, AGA treatment also down-regulated the expression of pro-inflammatory cytokine/growth factor genes HMGB1, IL-6 and IL-8 in DU-145 cells. Interestingly, AGA simultaneously upregulated the expression of non-steroidal anti-inflammatory gene-1 (NAG-1) in DU-145 cells suggesting its anti-inflammatory activity on prostate cancer cells. Taken together, the results of this study suggest that AGA may be a promising anticancer agent that merits further investigation for the chemoprevention and treatment of prostate cancer.     

Requirement of MyD88 for macrophage-mediated islet xenograft rejection after adoptive transfer

BACKGROUND: Porcine antigen primed and CD4+ T-cell activated macrophages are able to migrate to and destroy porcine xenografts. However, the specific signaling mechanisms involved remain to be identified. METHODS: In this study macrophages which lack the universal toll-like receptor (TLR) adaptor MyD88 were used to investigate the role of TLR in the recognition and activation of macrophages in islet xenograft rejection. Macrophages were isolated from rejecting MyD88(-/-) and wild-type C57BL/6 mice that were recipients of neonatal porcine pancreatic cell cluster (NPCC) xenografts, and were transferred to NPCC recipient NOD-SCID mice. RESULTS: Both wild-type C57BL/6 and MyD88(-/-) mice rejected NPCC xenografts 8 and 10 days, respectively after transplantation, and the grafts were heavily infiltrated with CD4+ T cells and macrophages. However, graft infiltrating macrophages from rejecting MyD88(-/-) recipients demonstrated impaired up-regulation of TLR expression and impaired activation phenotype, when compared to those from rejecting C57BL/6 recipients. Transfer of NOD-SCID recipients with macrophages from rejecting C57BL/6 mice resulted in NPCC xenograft rejection along with massively infiltrated macrophages 8 days after transfer, whereas NPCC xenografts in NOD-SCID mice transferred with macrophages from rejecting MyD88(-/-) mice remained intact until the end of this study, 90 days after transfer, with insulin-positive islets and no infiltration by macrophages. CONCLUSION: This study demonstrates that deletion of MyD88 causes impaired macrophage activation after pig islet xenotransplantation. However, graft survival is not prolonged and xenografts are rejected rapidly by alternate mechanisms.     

Scoring satisfaction among patients,attending ART Centre of a medical college in north-west India

Patient satisfaction is a measurable concept comprising multidimensional elements such as access to care, quality of the provider patient interpersonal relationship and affordability of care. This further influences the decisions to seek care and outcomes of diseases. Although stigma and discrimination are potential barriers to effective implementation of the antiretroviral therapy (ART) programme, higher satisfaction levels of patients are also crucial for treatment adherence. A hospital-based cross-sectional study was conducted at the ART centre of IG Medical College, Shimla from November 2008 through May 2009. Three hundred and eighty four consecutive adult (≥18 years) patients attending the ART centre and on ART who consented to participate in the study were enrolled. Of the 384 patients, 209 (54.4%) were males. Majority were in the age bracket of 25–44 years. About 61.6% of the patients were satisfied to the services being provided. Mean Patient Satisfaction Questionnaire (PSQ) scores were the highest for technical quality of care and lowest for financial aspects. About 69.4% of the patients were satisfied towards their care provider. Although a majority of the patients were satisfied, several areas of patient care need improvement.     

Actinomycosis of the parotid gland

Abstract - Actinomycosis is a slowly progressive infection caused by anaerobic bacteria with relatively decreasing incidence now-a-days. The Parotid gland is a quite rere site to be involved in cervico-facial actinomycosis as compared to the other sites in the face & neck region. We report a successfully managed case of Actinomycosis involving the parotid gland.     

Effect of Body Mass Index on Outcomes of Peritoneal Dialysis Patients in India

♦ Objectives: We studied the effect of body mass index (BMI) at peritoneal dialysis (PD) initiation on patient and technique survival and on peritonitis during follow-up.♦ Methods: We followed 328 incident patients on PD (176 with diabetes; 242 men; mean age: 52.6 ± 12.6 years; mean BMI: 21.9 ± 3.8 kg/m²) for 20.0 ± 14.3 months. Patients were categorized into four BMI groups: obese, ≥25 kg/m²; overweight, 23 - 24.9 kg/m²; normal, 18.5 - 22.9 kg/m² (reference category); and underweight, <18.5 kg/m². The outcomes of interest were compared between the groups.♦ Results: Of the 328 patients, 47 (14.3%) were underweight, 171 (52.1%) were normal weight, 53 (16.2%) were overweight, and 57 (17.4%) were obese at commencement of PD therapy. The crude hazard ratio (HR) for mortality (p = 0.004) and the HR adjusted for age, subjective global assessment, comorbidities, albumin, diabetes, and residual glomerular filtration rate (p = 0.02) were both significantly greater in the underweight group than in the normal-weight group. In comparison with the reference category, the HR for mortality was significantly greater for underweight PD patients with diabetes [2.7; 95% confidence interval (CI): 1.5 to 5.0; p = 0.002], but similar for all BMI categories of nondiabetic PD patients.Median patient survival was statistically inferior in underweight patients than in patients having a normal BMI. Median patient survival in underweight, normal, overweight, and obese patients was, respectively, 26 patient-months (95% CI: 20.9 to 31.0 patient-months), 50 patient-months (95% CI: 33.6 to 66.4 patient-months), 57.7 patient-months (95% CI: 33.2 to 82.2 patient-months), and 49 patient-months (95% CI: 18.4 to 79.6 patient-months; p = 0.015). Death-censored technique survival was statistically similar in all BMI categories. In comparison with the reference category, the odds ratio for peritonitis occurrence was 1.8 (95% CI: 0.9 to 3.4; p = 0.086) for underweight patients; 1.7 (95% CI: 0.9 to 3.2; p = 0.091) for overweight patients; and 3.4 (95% CI: 1.8 to 6.4; p < 0.001) for obese patients.♦ Conclusions: In our PD patients, mean BMI was within the normal range. The HR for mortality was significantly greater for underweight diabetic PD patients than for patients in the reference category. Death-censored technique survival was similar in all BMI categories. Obese patients had a greater risk of peritonitis.