462 research outputs found
Predicting neuropathy and reactions in leprosy at diagnosis and before incident events. Results from the INFIR cohort study
No full textBackgroundLeprosy is a disease of skin and peripheral nerves. The process of nerve injury occurs gradually through the course of the disease as well as acutely in association with reactions. The INFIR (ILEP Nerve Function Impairment and Reactions) Cohort was established to identify clinically relevant neurological and immunological predictors for nerve injury and reactions.Methodology/Principal FindingsThe study, in two centres in India, recruited 188 new, previously untreated patients with multi-bacillary leprosy who had no recent nerve damage. These patients underwent a series of novel blood tests and nerve function testing including motor and sensory nerve conduction, warm and cold detection thresholds, vibrometry, dynamometry, monofilament sensory testing and voluntary muscle testing at diagnosis and at monthly follow up for the first year and every second month for the second year. During the 2 year follow up a total of 74 incident events were detected. Sub-clinical changes to nerve function at diagnosis and during follow-up predicted these new nerve events. Serological assays at baseline and immediately before an event were not predictive; however, change in TNF alpha before an event was a statistically significant predictor of that event.Conclusions/SignificanceThese findings increase our understanding of the processes of nerve damage in leprosy showing that nerve function impairment is more widespread than previously appreciated. Any nerve involvement, including sub-clinical changes, is predictive of further nerve function impairment. These new factors could be used to identify patients at high risk of developing impairment and disability
UvA-DARE (Digital Academic Repository) Predicting Neuropathy and Reactions in Leprosy at Diagnosis and Before Incident Events-Results from the INFIR Cohort Study
No full textPredicting neuropathy and reactions in leprosy at diagnosis and before incident eventsResults from the INFIR Cohort Study Smith, W.C.S.; Nicholls, P.G.; Das, L.; Barkataki, P.; Suneetha, S.; Suneetha, L.; Jadhav, R.; Rao, P.S.S.S.; Wilder-Smith, E.P.; Lockwood, D.N.J.; van Brakel, W.H. General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulations If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: https://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible
Effects of chemical reaction on combined heat and mass transfer by laminar mixed convection flow from vertical surface with induced magnetic field and radiation
No full textThe elevated temperature electromagnetic materials production system in chemical engineering requires increasingly more refined theoretical and computational models for describing multiple, simultaneous thermophysical effects. Motivated by this application, the present paper addresses heat and mass transfer in a chemically reacting laminar mixed convection flow from a vertical sheet with inducedmagnetic field. The governing equations of the flow are solved analytically using a perturbation technique. The influences of various established parameters on the flow, induced magnetic field, and heat and mass transfer are studied graphically in the present analysis. Finally, we also obtained expressions for shear stress, current density and Nusselt number, and discussed the results through tables
Standardizing endpoints in perioperative research
No full textMeasuring patient-relevant, clinically important, and valid outcomes is fundamental to the delivery of high-quality clinical care and to the innovation and development of such care through research. As surgical innovations become more complex and the burden of age and comorbidities in the surgical patient population continues to increase, understanding the benefits and harms of surgical interventions becomes ever more important. Nevertheless, we can understand only what we can adequately describe. Truly collaborative decision-making, delivery of safe effective care, and on-going quality improvement are also critically dependent on reliable valid measurement of patient-relevant and clinically important data. Attempts to describe the full spectrum of outcomes following surgery necessarily entail moving beyond the traditional endpoints of mortality and resource use towards more complex measures of morbidity, patient-reported outcomes, and functional status. Without standardization and consensus to guide the use of increasingly complex and nuanced endpoints, there is a real risk that perioperative research will become embroiled in a mire of inconsistent heterogeneous outcome measures that cannot be meaningfully compared and contrasted between trials or combined within meta-analyses. This would result in limiting the value of the research effort and depriving patients and clinicians of definitive answers. Collaboration in perioperative medicine-whether between institutions or across continents-has enormous potential to improve the value of research output. Standardizing endpoints for outcome measurement is fundamental to maximizing the quality of such collaboration and ensuring the impact of future perioperative research
The histological diagnosis of leprosy type 1 reactions: identification of key variables and an analysis of the process of histological diagnosis
No full textBackground: Type 1 leprosy reactions (T1R) are a major inflammatory complication of leprosy affecting 30% of patients with borderline leprosy, but there has been no diagnostic evaluation of the histological diagnosis of this entity. Methods: In a prospective study based in India, skin biopsies were taken from 99 patients with clinically diagnosed T1R and 52 non-reactional controls. These were assessed histologically by four histopathologists whose assessments were then compared. Results: Reactions were under-diagnosed, with 32–62% of clinically diagnosed reactions being given a histological diagnosis. The pathologists showed good specificities (range 72% to 93%) but much poorer sensitivities (range 42% to 78%). The most commonly reported histological features of TIR were cell maturity, oedema and giant cells. Five key variables were identified that the pathologists used in diagnosing a reaction: intra-granuloma oedema, giant cell size, giant cell numbers, dermal oedema and HLA-DR expression. A predictive model for the diagnosis of T1R was developed using stepwise logistic regression analysis, with clinical diagnosis of reaction as an outcome, and then identification of the key variables that each pathologist used in making the diagnosis of T1R. 34–53% of the variation between pathologists could be accounted for. The four pathologists used a similar diagnostic model and for all of them their estimations of epithelioid cell granuloma oedema, dermal oedema, plasma cells and granuloma fraction were significant variables in the diagnosis of T1R. Each pathologist then added in variables that were specific to themselves. Conclusions: This study has identified T1R as being under-diagnosed in comparison with clinical assessments. Key variables for diagnosing T1R were established. This comparative masked study highlights the need for such studies in other inflammatory conditions. <br/
The INFIR Cohort Study: investigating prediction, detection and pathogenesis of neuropathy and reactions in leprosy. Methods and baseline results of a cohort of multibacillary leprosy patients in North India
No full textThe aim of this study was to find predictors of neuropathy and reactions, determine the most sensitive methods for detecting peripheral neuropathy, study the pathogenesis of neuropathy and reactions and create a bank of specimen, backed up by detailed clinical documentation. A multi-centre cohort study of 303 multibacillary leprosy patients in Northern India was followed for 2 years. All newly registered MB patients requiring a full course of MDT, who were smear positive and/or had six or more skin lesions and/or had two or more nerve trunks involved, were eligible. A detailed history was taken and physical and neurological examinations were performed. Nerve function was assessed at each visit with nerve conduction testing, warm and cold detection thresholds, vibrometry, dynamometry, monofilaments and voluntary muscle testing. Because the latter two are widely used in leprosy clinics, they were used as ‘gold standard’ for sensory and motor impairment. Other outcome events were type 1 and 2 reactions and neuritis. All subjects had a skin biopsy at registration, repeated at the time of an outcome event, along with a skin biopsy at registration, repeated at the time of an outcome event, along with a nerve biopsy. These were examined using a variety immunohistological techniques. Blood sampling for serological testing was done at every 4-weekly clinic visit. At diagnosis, 115 patients had an outcome event of recent onset. Many people had skin lesions overlying a major nerve trunk, which were shown to be significantly associated with an increased of sensory or motor impairment. The most important adjusted odds ratios for motor impairment were, facial 4.5 (1.3-16) and ulnar 3.5 (1.0-8.5); for sensory impairment they were, ulnar 2.9 (1.3-6.5), median 3.6 (1.1-12) and posterior tibial 4.0 (1.8-8.7). Nerve enlargement was found in 94% of patients, while only 24% and 3% had paraesthesia and nerve tenderness on palpation, respectively. These increased the risk of reactions only marginally. Seven subjects had abnormal tendon reflexes and seven abnormal joint position sense. In all but one case, there impairments were accompanied by abnormalities in two or more other nerve function tests and thus seemed in indicate more serve neuropathy. At diagnosis, 38% of a cohort of newly diagnosed MB leprosy patients had recent or new reactions or nerve damage at the time of intake into the study. The main risk factor for neuropathy found in this baseline analysis was the presence of skin lesions overlying nerve trunks. They increased the risk of sensory or motor impairment in the concerned nerve by 3-4 times. For some nerves, reactional signs in the lesions further increased this risk to 6-8 times the risk for those without such lesions. Patients with skin lesions overlying peripheral nerve trunks should be carefully monitored for development of sensory or motor impairment
Cytokine and protein markers of leprosy reactions in skin and nerves: baseline results for the North Indian INFIR cohort.
No full textBACKGROUND: Previous studies investigating the role of cytokines in the pathogenesis of leprosy have either been on only small numbers of patients or have not combined clinical and histological data. The INFIR Cohort study is a prospective study of 303 new multibacillary leprosy patients to identify risk factors for reaction and nerve damage. This study characterised the cellular infiltrate in skin and nerve biopsies using light microscopic and immunohistochemical techniques to identify any association of cytokine markers, nerve and cell markers with leprosy reactions. METHODOLOGY/PRINCIPAL FINDINGS: TNF-α, TGF-β and iNOS protein in skin and nerve biopsies were detected using monoclonal antibody detection immunohistochemistry techniques in 299 skin biopsies and 68 nerve biopsies taken from patients at recruitment. The tissues were stained with hematoxylin and eosin, modified Fite Faraco, CD68 macrophage cell marker and S100. CONCLUSIONS/SIGNIFICANCE: Histological analysis of the biopsies showed that 43% had borderline tuberculoid (BT) leprosy, 27% borderline lepromatous leprosy, 9% lepromatous leprosy, 13% indeterminate leprosy types and 7% had no inflammation. Forty-six percent had histological evidence of a Type 1 Reaction (T1R) and 10% of Erythema Nodosum Leprosum. TNF-α was detected in 78% of skin biopsies (181/232), iNOS in 78% and TGF-β in 94%. All three molecules were detected at higher levels in patients with BT leprosy. TNF-α was localised within macrophages and epithelioid cells in the granuloma, in the epidermis and in dermal nerves in a few cases. TNF-α, iNOS and TGF-β were all significantly associated with T1R (p<0.001). Sixty-eight nerve biopsies were analysed. CD68, TNF-α and iNOS staining were detectable in 88%, 38% and 28% of the biopsies respectively. The three cytokines TNF-α, iNOS and TGF-β detected by immunohistochemistry showed a significant association with the presence of skin reaction. This study is the first to demonstrate an association of iNOS and TGF-β with T1R
Role of glutathione-s-transferase and CYP1A1FNx012A polymorphisms in the therapy outcome of south Indian acute lymphoblastic leukemia patients
No full textAbstract
Background: Polymorphisms in the drug-metabolizing enzymes are found to be associated with the inter-individual variation in response to a particular drug. Glutathione S-transferases (GSTs) are involved in the metabolism of several anticancer drugs, including alkylating agents, anthracyclines, and cyclophosphamides. Aim: The present study is aimed to examine the association of GST and CYP1A1FNx012A polymorphisms in the susceptibility to acute lymphoblastic leukemia (ALL) and the prognostic significance. Materials and Methods: A total of 92 immunophenotyped patients and 150 cord blood controls were genotyped by PCR for GSTM1 and GSTT1, RQ-PCR allelic discrimination assay for GSTP1 and PCR-RFLP for CYP1A1FNx012A polymorphism. Results: We have previously reported the significant association of GSTM1 (null) and combined GSTP1 {(Ile/Val)/ (Val/Val)} /GSTM1 (null) genotype with the susceptibility to ALL. No significant association was observed with GSTT1 (P=0.75) and CYP1A1FNx012A (P=0.61 for +/- and P=0.86 for -/- respectively) in the susceptibility to ALL. Survival analysis was performed in 50 of the 92 patients who were followed for three years. Kaplan-Meier survival analysis for three years showed significant lower event-free survival in patients harboring GSTP1 (Ile/Val) and GSTP1 (Val/Val) (P=0.038 and 0.0001, respectively) genotype. Cox regression analysis revealed GSTP1 as an independent prognostic marker with 6-fold higher risk with Val/Val genotype (P=0.003). Conclusions: Our results show that GSTP1 (Ile/Val) polymorphism has a role in the susceptibility to ALL and also influence treatment outcome.</jats:p
Examination, Screening and Statistical Analysis with respect to Prevalent Alzheimer's Disease
No full textABSTRACT Alzheimer's disease (AD) is the most common neurodegenerative disease, caused by accumulation of abundant senile plaques and neurofibrillary tangles in certain brain regions. It is an irreversible and progressive disease that slowly destroys memory, thinking skills and, eventually the ability to perform simple day to day tasks. This project was to investigate the prevalence of Alzheimer's disease (AD) in Vellore and Chennai, India by conducting an epidemiological survey of 120 individuals from dementia club and old age homes and carrying out certain blood tests on patient's sample and comparing the results with the controls. Patient's cognitive function like orientation, registration, attention, calculation, recalling, and language were graded by minimal mental state examination (MMSE). Caregivers of the patients were interviewed to confirm the familial history and progression of the disease in the patients. The blood test results were correlated with that of MMSE. ESR, blood glucose and lithium ion concentrations were shown to be significant and presence of oxidative stress was seen in majority of the patients. Hence it is suggested that these factors can be quantified to confirm the presence or absence of disease. The in situ hybridization of blood samples of the patients yielded no result as there is no presence of amyloid-β protein, and can be avoided as a confirmatory test
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