Cross-cultural adaption,reliability and validity of an Indian (Tamil) version for the Shoulder Pain and Disability Index

The objective of the study was to cross-culturally adapt the Shoulder Pain and Disability Index (SPADI) into a regional Indian language (Tamil) and to test the reliability and linguistic validity of the index in Tamil-speaking Indian participants. Cross-cultural adaptation and psychometric testing of SPADI was undertaken at the Outpatient Physiotherapy Department of the Sri Ramachandra University Hospital in Chennai, India. The Test-retest reliability was quantified using the interclass correlation coefficient (ICC) and Cronbach alpha was calculated to assess internal consistency of the Tamil questionnaire. The construct validity was assessed using Spearman rank correlation coefficients. The reliability of the total Tamil SPADI and its subsets (Intraclass correlation coefficient >0.90) were found to be higher than that of the English SPADI and the German SPADI in this population. The internal consistency of the Tamil SPADI (Cronbach's alpha >0.95) was slightly higher than the English and the German versions. Thus, the cross-culturally adapted version of the English SPADI into a regional Indian language (Tamil) is easy to use and is a reliable and valid measure of shoulder pain and disability in the Tamil speaking population.     

Hexokinase Domain Containing 1 (HKDC1) Gene Variants and their Association with Gestational Diabetes Mellitus in a South Indian Population

Hexokinase domain containing 1 (HKDC1), a novel human hexokinase gene, is known to affect glucose metabolism and was shown to have a strong association with 2‐h plasma glucose in pregnant women in a recent genome wide association study. This study aimed to evaluate the association of these regulatory variants of HKDC1 (rs1076224, rs4746822, rs2394529 and rs9645501) with gestational diabetes mellitus (GDM) in a South Indian population. The regulatory variants of HKDC1 were genotyped in unrelated 500 women with GDM and 510 non‐GDM individuals by using the MassARRAY system and by direct DNA sequencing. The minor alleles of the HKDC1 gene regulatory variants, namely rs10762264 and rs4746822, showed a significant association with GDM and these alleles conferred as much as 1.24 and 1.34 times higher risk for GDM, respectively. This is the first study to demonstrate the association of HKDC1 genetic variants with susceptibility to GDM.     

Dietary phytochemicals induce p53- and caspase-independent cell death in human neuroblastoma cells

Neuroblastoma (NB) is the most prevalent pediatric solid tumor and a leading cause of cancer-related death in children. In the present study, a novel cytotoxic role for the dietary compounds, curcumin, andrographolide, wedelolactone, dibenzoylmethane, and tanshinone IIA was identified in human S-type NB cells, SK-N-AS and SK-N-BE(2). Mechanistically, cell death appeared apoptotic by flow cytometry; however, these effects proceeded independently from both caspase-3 and p53 activation, as assessed by both genetic (shRNA) and pharmacological approaches. Notably, cell death induced by both curcumin and andrographolide was associated with decreased NFκB activity and a reduction in Bcl-2 and Bcl-xL expression. Finally, curcumin and andrographolide increased cytotoxicity following co-treatment with either cisplatin or doxorubicin, two chemotherapeutic agents widely used in the clinical management of NB. Coupled with the documented safety in humans, dietary compounds may represent a potential adjunct therapy for NB.     

Astrocyte‐derived glutathione attenuates hemin‐induced apoptosis in cerebral microvascular cells

Intracerebral hemorrhage (ICH) induces neurovascular injury via poorly defined mechanisms. The aim of this study was to determine whether gliovascular communication may restrict hemorrhagic vascular injury. Hemin, a hemoglobin by‐product, concentration‐ and time‐dependently increased apoptotic cell death in mouse bEnd.3 cells and in primary human brain microvascular endothelial cells, at least in part, via a caspase‐3 dependent pathway. Cell death was preceded by a NFκB‐mediated increase in inflammatory gene expression, including upregulation of inducible nitric oxide synthase (iNOS) expression and activity. Functionally, inhibition of iNOS or the addition of a peroxynitrite decomposition catalyst reduced cell death. Interestingly, co‐treatment with astrocyte‐conditioned media (ACM) reversed hemin‐induced NFκB activation, nitrotyrosine formation, and apoptotic cell death, at least in part, via the release of the endogenous antioxidant, reduced glutathione (GSH). Prior treatment of astrocytes with the GSH‐depleting agent, DL‐buthionine (S,R)‐sulfoximine or direct addition of diethyl maleate, a thiol‐depleting agent, to ACM reversed the observed protection. In contrast, neither exogenous GSH nor the GSH precursor, N‐acetylcysteine, was protective in bEnd.3 cells. Together, these data support an important role for astrocyte‐derived GSH in the maintenance of oxidative balance in the vasculature and suggest therapeutic targeting of the GSH system may reduce neurological injury following ICH. © 2010 Wiley‐Liss, Inc.     

Fungal Mycotic Aneurysm in a Case of Acute Lymphoblastic Leukemia

Chronic graft versus host disease (cGVHD) is a common late complication of allogenic hematopoietic stem cell transplant (HSCT). We analyzed risk factors, pattern and long term transplant outcomes of cGVHD at a tertiary cancer centre. Seventy-seven consecutive patients who underwent HSCT for acute leukemia were included. Forty (52 %) patients developed cGVHD; 24 (60 %) extensive stage while 16 (40 %) limited stage. Oral cavity was the commonest site of involvement (25 patients) followed by liver, skin and lung. We found that female donor to male recipient transplant and diagnosis of acute lymphoblastic leukemia (ALL) were the only factors associated with increased risk of cGVHD. The incidence of leukemia relapse was 18 % in patients who developed cGVHD compared to 51 % in those who did not (P = 0.002). Four year overall survival and relapse free survival (RFS) were 62 and 46 % in patients who developed cGVHD compared to 29 % (P < 0.001) and 29 % (P < 0.001) in patients who did not develop cGVHD, respectively. We conclude that cGVHD is more common in male patients with female donors and in patients transplanted for ALL. Oral cavity is the commonest site of cGVHD in our patients and transplant related survival outcomes are superior in patients who develop cGVHD.     

A comparison of five immunohistochemical biomarkers and HER-2/neu gene amplification by fluorescence in situ hybridization in white and Korean patients with early-onset breast carcinoma

BACKGROUND: The objective of this article was to compare five tumor markers between white women in the U.S. and native Korean women with early-onset breast carcinoma. METHODS: Sixty Korean women who were diagnosed with breast carcinoma at age 45 years or younger and 60 white women with breast carcinoma who were matched by age were selected for this study. The median age of both groups was 37 years. Paraffin embedded blocks of the primary tumor were processed for immunohistochemical staining of estrogen receptor (ER), progesterone receptor (PR), p53, cyclin D1, and HER-2/neu. RESULTS: The proportion of tumors that stained positive for ER, PR, p53, and cyclin D1 in the Korean women were 47.5%, 42.4%, 28.8%, and 40.9%, respectively; in the white women, the proportions were 43.9%, 52.6%, 21.1%, and 59.1%, respectively. The differences between the white patients and the Korean patients were not statistically significant with respect to any of those variables. A significant difference was found in the expression of HER-2/neu. Specifically, positive HER-2/neu status was observed in 47.5% of Korean women, compared with overexpression in only 15.8% of white women (P < 0.001). Fluorescence in situ hybridization analysis for HER-2/neu gene amplification on all HER-2/neu positive samples that scored 2 + and 3 + demonstrated a significant difference (P = 0.007) in gene amplification between the two populations. Differences in HER-2/neu positivity were observed for the entire cohort as well as among the subsets of patients with negative and positive lymph node status. No association was found between immunoreactivity for the five markers and axillary lymph node metastasis. CONCLUSIONS: The findings of high positivity of HER-2/neu expression and gene amplification in Korean women with early-onset breast carcinoma may have potential implications for local and systemic management of breast carcinoma, especially anti-HER-2/neu therapy for patients with hormone receptor negativity. Further research will be needed to identify biologic and genetic factors and their effects on the survival between different racial groups.     

ACTH increment post total bilateral adrenalectomy for Cushing’s disease: a consistent biosignature for predicting Nelson’s syndrome

Purpose

Nelson’s syndrome (NS) is regarded as an aggressive complication of total bilateral adrenalectomy (TBA) for Cushing’s disease (CD). This challenge may be addressed by using clinical criteria to guide frequency of neuroimaging to enable timely management of NS and also avoid unnecessary frequent imaging.

Methods

All patients (n?=?43) with CD subjected to TBA over 35 years at a tertiary care centre were included. NS was defined as a newly appearing or expanding (>?2 mm) pituitary adenoma with or without ACTH levels exceeding 500 pg/ml. Pre-and post-TBA parameters like clinical symptomatology, cortisol, ACTH and radiology were analysed for the prediction of NS.

Results

NS developed in 39.5% (n?=?17) patients with a median follow-up of 7 years. Half of them had new appearance, while rest had an expansion of pre-existing pituitary tumour. Majority (90%) had ACTH above 500 pg/ml. On Cox proportional hazards analysis, frequent discriminatory features of protein catabolism (≥?4) (HR 1.15, CI 0.18, 7.06), proximal myopathy (HR 8.82, CI 1.12, 69.58) and annual ACTH increment of 113 pg/ml (HR 12.56, CI 1.88, 88.76) predicted NS. First post-operative year ACTH indices predicting NS included ACTH rise of 116 pg/ml and absolute ACTH of 142 pg/ml (sensitivity, specificity exceeding 90%). Annual ACTH increment exceeding 113 pg/ml, ≥?4 discriminatory features and uncontrolled hypertension had the best overall prediction.

Conclusion

Patients who developed NS had higher rebound rise of ACTH following TBA and a more severe disease phenotype at baseline. Consistent ACTH increment can be used as a marker for predicting the development of NS.