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S Nag

Publications and source records attributed to S Nag.

At least 19 recordsLinked to original sources
PubMed2007

All-cause and cardiovascular mortality in diabetic subjects increases significantly with reduced estimated glomerular filtration rate (eGFR): 10 years' data from the South Tees Diabetes Mortality study.

AIMS: To investigate the association between estimated glomerular filtration rate (eGFR) and total and cardiovascular mortality in a population-based cohort of diabetic subjects. METHODS: A longitudinal study using a population-based district diabetes register comprising 3288 subjects in South Tees, UK. The eGFR was calculated using the Modification of Diet in Renal Disease (MDRD) study equation. Patients were stratified by baseline eGFR into five stages as per the National Kidney Foundation guidelines: Stage 1, eGFR > 90; Stage 2, eGFR 60-89; Stage 3, eGFR 30-59; Stage 4, eGFR 15-29; and Stage 5, eGFR < 15 ml/min per 1.73 m(2). Main outcome was all-cause and cardiovascular mortality between 1 January 1994 and 31 July 2004. RESULTS: At baseline, mean age (58.4 years) differed between groups. Persons with lower eGFR were older (P < 0.001). Thirty-six percent (n = 1193, males 56%) had died by 10 years (cardiovascular cause in 60%). Median follow-up was 10.5 years amounting to 28 342 person years. Stages 4 and 5 (eGFR <or= 29 ml/min per 1.73 m(2)) were amalgamated for mortality analysis. Total and cardiovascular mortality increased with reduced eGFR. Adjusted hazard ratios (HR) [95% confidence interval (CI)] for all-cause mortality comparing groups 2 and 3, and 4 and 5 combined with group 1 were 1.28 (1.02, 1.60), 2.58 (2.05, 3.25) and 6.42 (4.25, 9.71), respectively. Adjusted HRs (95% CI) for mortality due to circulatory disease comparing groups 2 and 3, and 4 and 5 combined with group 1 were 1.50 (1.10, 2.06), 3.32 (2.41, 4.58) and 7.99 (4.69, 13.62), respectively. CONCLUSIONS: In diabetic subjects, mortality increases significantly with reduced GFR. Low eGFR identifies patients at high risk of cardiovascular mortality who should be targeted for aggressive risk factor modification.

Diabetes Mellitus, Type 2↗
PubMed2006

A novel combinatorial approach for understanding microstructural evolution and its relationship to mechanical properties in metallic biomaterials.

The new generation of metallic biomaterials for prosthesis implantation (orthopedic and dental) typically have a Ti base with fully biocompatible alloying additions such as Nb, Ta, Zr, Mo, Fe and Sn. While the binary Ti-Ta and the ternary Ti-Nb-Ta systems are promising, the large composition space afforded by these systems offers tremendous scope in terms of alloy design via optimization of alloy composition and thermomechanical treatment. In the present paper a novel combinatorial approach has been developed for rapidly exploring the microstructural evolution and microstructure-microhardness (or elastic modulus) relationships in these systems. Using directed laser deposition, compositionally graded alloy samples have been fabricated and subsequently heat-treated to affect different microstructures in terms of the volume fraction and distribution of the alpha phase in the beta matrix as a function of composition. Subsequently, composition-specific indentation-based hardness and modulus information has been obtained from these graded samples, and the resulting data have been used to develop relationships between the composition, microstructure and mechanical properties. Such rapid combinatorial assessments can be very useful in optimizing not only the alloy composition but also the desired microstructure for achieving the best combination of properties for specific orthopedic or dental applications.

Alloys↗
PubMed2006

Activation of alpha2-adrenoceptors in the trigeminal region produces sex-specific modulation of nociception in the rat.

Sex-related differences in the sensitivity to pain and in the response to analgesics have been reported including higher perceptual responses to experimentally induced pain and the higher prevalence of many pain syndromes in women compared with men. This study examines whether alpha2-adrenoceptor-mediated antinociceptive effects are reduced by estrogen which could account for the sex-related differences in pain perception and modulation. Clonidine, an alpha2-adrenoceptor agonist, has been shown to inhibit noxious stimulus-evoked nociceptive behavior as well as the responses of nociceptive neurons in the medullary dorsal horn. Intracisternal microinjection of clonidine (7 microg/5 microl) through the implanted PE-10 cannulae dorsal to the trigeminal region in male, ovariectomized (OVX), and diestrous (DiE) Sprague-Dawley rats produced a strong antinociceptive effect on N-methyl-D-aspartic acid (NMDA)-induced nociceptive scratching behavior and heat-induced face withdrawal nociceptive tests. However, it failed to produce any inhibition in the estradiol-treated ovariectomized (OVX+E) group regardless of the dose of estradiol (1, 10 or 100 microg/100 microl sesame oil) or in the proestrous (ProE) group. Further, clonidine produced dose-dependent effects in male and OVX groups but not in the OVX+E group on the NMDA-induced nociceptive behavior. Finally, the effect of clonidine was reversed by yohimbine, an alpha2-adrenoceptor antagonist, in male and OVX groups on thermal nociceptive test. These results lead us to conclude that activation of alpha2-adrenoceptors produces sex-specific, estrogen dependent modulation of nociception in the trigeminal region of the rat. A decreased alpha2-adrenoceptor-mediated inhibition could be one of the factors responsible for the higher prevalence of pain syndromes in females.

Adrenergic alpha-2 Receptor Agonists↗
PubMed2006

Laser-deposited Ti-Nb-Zr-Ta orthopedic alloys.

The complex quaternary Ti-35Nb-7Zr-5Ta orthopedic alloy has been successfully deposited from a powder feedstock consisting of a blend of elemental titanium, niobium, zirconium, and tantalum powders, using the laser engineered net-shaping (LENStrade mark) process. In the as laser-deposited form, these alloys exhibit a substantially higher tensile strength as compared with more conventionally processed counterparts of similar composition, while maintaining excellent ductility and a low modulus. Furthermore, the as-deposited alloys appear to exhibit a <001> texture, with a substantially large number of grains of the beta phase aligning one of their <001> axes nearly normal to the substrate or parallel to the growth direction. The microstructure of the as-deposited as well as tensile-tested alloys have been characterized in detail using scanning electron microscopy (SEM), orientation microscopy (OM), and transmission electron microscopy (TEM). Formation of a high density of shear bands, possibly arising from slip localization due to precipitates of the omega phase in the beta matrix, is clearly evident in the tensile-tested sample. The enhanced tensile strength and low modulus in these laser-deposited alloys coupled with the ability to form near-net shape components makes LENS an attractive processing technology for orthopedic implants.

Alloys↗
PubMed2005

Comparison of microstructural evolution in Ti-Mo-Zr-Fe and Ti-15Mo biocompatible alloys.

The microstructural evolution and attendant strengthening mechanisms in two biocompatible alloy systems, the binary Ti-15Mo and the quaternary Ti-13Mo-7Zr-3Fe (TMZF), have been compared and contrasted in this paper. In the homogenized condition, while the Ti-15Mo alloy exhibited a single phase microstructure consisting of large beta grains, the TMZF alloy exhibited a microstructure consisting primarily of a beta matrix with grain boundary alpha precipitates and a low volume fraction of intra-granular alpha precipitates. On ageing the homogenized alloys at 600 degrees C for 4 h, both alloys exhibited the precipitation of refined scale secondary alpha precipitates homogeneously in the beta matrix. However, while the hardness of the TMZF alloy marginally increased, that of the Ti-15Mo alloy decreased substantially as a result of the ageing treatment. In order to understand this difference in the mechanical properties after ageing, TEM studies have been carried out on both alloys in the homogenized and homogenized plus aged conditions. The results indicate that the omega precipitates dissolve on ageing in case of the Ti-15Mo alloy, consequently leading to a substantial decrease in the hardness. In contrast, the omega precipitates do not dissolve on ageing in the TMZF alloy and the precipitation of the fine scale secondary alpha leads to increased hardness.

Alloys↗
PubMed2004

Estrogen attenuates antinociception produced by stimulation of Kölliker-Fuse nucleus in the rat.

This is the first demonstration of sex-related differences in the alpha2-adrenoceptor-mediated antinociceptive effects produced by stimulation of an endogenous noradrenergic pathway. Electrical or chemical (substance P) stimulation of Kölliker-Fuse nucleus (KF, A7) is known to produce antinociception mediated by alpha2-adrenoceptors in the spinal cord. KF stimulation has also been shown to inhibit the responses of nociceptive neurons in the dorsal horn of the medulla and the spinal cord. We investigated whether KF stimulation produces sex-specific modulation of trigeminal nociception. The N-methyl-D-aspartic acid (NMDA)-induced nociceptive behavior was employed as an index of nociception. Microinjection of NMDA (2 nmol/10 microL) in the trigeminal region produced nociceptive scratching behavior that was confined to the orofacial region. Male and ovariectomized (OVX) Sprague-Dawley rats were implanted with a guide cannula dorsal to the KF nucleus and a PE-10 cannula in the trigeminal region dorsal to obex. Nociceptive testing was conducted after 5-7 days of recovery. A group of ovariectomized rats (OVX+E) was treated with estradiol benzoate 48 h prior to nociceptive testing. There were no significant differences in the number of NMDA-induced scratches or duration between the male, OVX and OVX+E groups. Microinjection of substance P (3.7 pmol/0.5 microL) in the KF significantly reduced the number of NMDA-induced scratches and their duration in male and OVX groups; these were restored to control levels by yohimbine (30 microg/15 microL), an alpha2-adrenoceptor antagonist. However, KF stimulation failed to inhibit the NMDA-induced scratching behavior in the OVX+E group. We conclude that stimulation of KF produces estrogen-dependent modulation of nociception.

Adrenergic alpha-Antagonists↗
PubMed2003

Behavioral and neurochemical characterization of transgenic mice carrying the human presenilin-1 gene with or without the leucine-to-proline mutation at codon 235.

Human presenilin-1 (PS1) mutations are associated with the incidence of familial Alzheimer's disease. The present study evaluated the behavioral and neurochemical effects of the L235P mutation (substitution of leucine by proline at codon 235) of the human PS1 gene, which has been linked to a form of early-onset Alzheimer's disease. Except for a significant increase in the production of beta-amyloid-42, the mutant mice did not show any overt signs of Alzheimer-like neuropathology in the form of plaque formation, changes in choline acetyltransferase activity, or somatostatin content in the brain. Cognitive assays indicated that the mutation did not affect the acquisition or reversal of a spatial reference memory task in the water maze or performance on a spatial working memory task. In contrast, L235P PS1 transgenic mice exhibited a significant impairment in a test of spontaneous object recognition. This dissociation is suggestive of a preferential impairment of the extrahippocampal memory system and is consistent with what has been reported in another pathological mutation (substitution of leucine by valine at codon 286) of the PS1 gene.

Alzheimer Disease↗
PubMed2002

The effects of melatonin and Ginkgo biloba extract on memory loss and choline acetyltransferase activities in the brain of rats infused intracerebroventricularly with beta-amyloid 1-40.

Intraventricular infusion of rats with beta-amyloid for 14 days resulted in memory deficit in the water maze as well as decreases in choline acetyltransferase activities and somatostatin levels in the cerebral cortex and hippocampus. These changes were not altered by daily intraperitoneal injection of 20 mg/Kg melatonin. Orally administered Ginkgo biloba extract, however, partially reversed the memory deficit and the decrease in choline actyltransferase activities in the hippocampus. The latter treatment failed to reverse the decrease in somatostatin levels. The results indicate that orally administered Ginkgo biloba extract can protect the brain against beta-amyloid from changes leading to memory deficit through its effect on the cholinergic system.

Administration, Oral↗
PubMed2001

Intraoperative planning and evaluation of permanent prostate brachytherapy: report of the American Brachytherapy Society.

PURPOSE: The preplanned technique used for permanent prostate brachytherapy has limitations that may be overcome by intraoperative planning. The goal of the American Brachytherapy Society (ABS) project was to assess the current intraoperative planning process and explore the potential for improvement in intraoperative treatment planning (ITP). METHODS AND MATERIALS: Members of the ABS with expertise in ITP performed a literature review, reviewed their clinical experience with ITP, and explored the potential for improving the technique. RESULTS: The ABS proposes the following terminology in regard to prostate planning process: *Preplanning--Creation of a plan a few days or weeks before the implant procedure. *Intraoperative planning--Treatment planning in the operating room (OR): the patient and transrectal ultrasound probe are not moved between the volume study and the seed insertion procedure. * Intraoperative preplanning--Creation of a plan in the OR just before the implant procedure, with immediate execution of the plan. *Interactive planning--Stepwise refinement of the treatment plan using computerized dose calculations derived from image-based needle position feedback. *Dynamic dose calculation--Constant updating of dose distribution calculations using continuous deposited seed position feedback. Both intraoperative preplanning and interactive planning are currently feasible and commercially available and may help to overcome many of the limitations of the preplanning technique. Dosimetric feedback based on imaged needle positions can be used to modify the ITP. However, the dynamic changes in prostate size and shape and in seed position that occur during the implant are not yet quantifiable with current technology, and ITP does not obviate the need for postimplant dosimetric analysis. The major current limitation of ITP is the inability to localize the seeds in relation to the prostate. Dynamic dose calculation can become a reality once these issues are solved. Future advances can be expected in methods of enhancing seed identification, in imaging techniques, and in the development of better source delivery systems. Additionally, ITP should be correlated with outcome studies, using dosimetric, toxicity, and efficacy endpoints. CONCLUSION: ITP addresses many of the limitations of current permanent prostate brachytherapy and has some advantages over the preplanned technique. Further technologic advancement will be needed to achieve dynamic real-time calculation of dose distribution from implanted sources, with constant updating to allow modification of subsequent seed placement and consistent, ideal dose distribution within the target volume.

Brachytherapy↗
PubMed2001

Intraoperative high-dose-rate brachytherapy for the treatment of pediatric tumors: the Ohio State University experience.

PURPOSE: To determine whether intraoperative high-dose-rate brachytherapy (IO-HDRBT) can be used to decrease the dose of external beam radiotherapy (EBRT) in the treatment of children with soft-tissue sarcomas and, thereby, reduce morbidity without compromising local control. METHODS AND MATERIALS: From March 1992 through April 1999, 13 pediatric patients were treated with IO-HDRBT, low-dose EBRT, chemotherapy, and radical surgery at 21 sites that were not amenable to intraoperative electron beam therapy. The IO-HDRBT dose at 5 mm depth was 10 to 12.5 Gy for close margins/microscopic disease at 14 sites and 12.5 to 15 Gy for gross disease at 7 sites. The treatment volumes ranged from 4 to 96 cm(3) (mean 27). The EBRT dose was limited to 27-30 Gy in most cases to minimize growth retardation and preserve normal organ function. RESULTS: After a median follow-up of 47 months (range 12-97), 11 patients were alive and without evidence of disease (overall survival rate 85%, 4-year actuarial survival rate 77%). Of the 2 who died, 1 had Stage III pulmonary blastoma with a sacral recurrence; the other had Stage IV undifferentiated synovial sarcoma with a pulmonary recurrence. One local failure occurred in a patient with gross residual disease after incomplete resection for Stage IV pulmonary blastoma. The local control rate was 95%, and morbidity was observed in 3 patients (23%). One patient developed impaired orbital growth with mild ptosis. Another patient required orthopedic pinning of her femoral subcapital epiphysis and construction of a neobladder secondary to urethral obstruction. The third patient required reimplantation of her autotransplanted kidney secondary to chronic urinary tract infection and ureteral reflux. CONCLUSIONS: IO-HDRBT allowed for reduction in EBRT without compromising local control or disease-free survival in children with soft-tissue sarcomas. Tumor beds inaccessible to electron beam methods could be satisfactorily encompassed with IO-HDRBT techniques.

Adolescent↗
PubMed2001

The American Brachytherapy Society recommendations for high-dose-rate brachytherapy for head-and-neck carcinoma.

PURPOSE: To develop recommendations for use of high-dose-rate (HDR) brachytherapy in patients with head-and-neck cancer. METHODS: A panel consisting of members of the American Brachytherapy Society (ABS) performed a literature review, added information based upon their clinical experience, and formulated recommendations for head-and-neck HDR brachytherapy. RESULTS: The ABS recommends the use of brachytherapy as a component of the treatment of head-and-neck tumors. However, the ABS recognizes that some radiation oncologists are reluctant to employ brachytherapy in the head-and-neck region because of the complexity of the postoperative management and concerns about radiation safety. In this regard, HDR eliminates unwanted radiation exposure and thereby permits unrestricted delivery of clinical care to these brachytherapy patients. The ABS made specific recommendations for previously untreated and recurrent head-and-neck cancer patients on patient selection criteria, implant techniques, target volume definition, and HDR treatment parameters (such as time, dose, and fractionation schedules). Suggestions were provided for treatment with HDR alone and in combination with external beam radiation therapy. It should be recognized that only limited experiences exist with HDR brachytherapy in patients with head-and-neck cancers. Therefore, some of these suggested doses have not been extensively tested in clinical practice. Hence, these guidelines will be updated as significant new outcome data are available. Any clinician following these guidelines is expected to use clinical judgment to determine an individual patient's treatment. CONCLUSIONS: Little has been published in the clinical literature on HDR brachytherapy in head-and-neck cancer. Based upon the available information and the clinical experience of the panel members, general and site-specific recommendations were offered. Areas for further investigations were identified.

Brachytherapy↗
PubMed2001

The American Brachytherapy Society recommendations for brachytherapy of soft tissue sarcomas.

PURPOSE: This report presents the American Brachytherapy Society (ABS) guidelines for the use of brachytherapy for patients with soft tissue sarcoma. METHODS AND MATERIALS: Members of the ABS with expertise in soft tissue sarcoma formulated brachytherapy guidelines based upon their clinical experience and a review of the literature. The Board of Directors of the ABS approved the final report. RESULTS: Brachytherapy used alone or in combination with external beam irradiation is an established means of safely providing adjuvant local treatment after resection for soft tissue sarcomas in adults and in children. Brachytherapy options include low dose rate techniques with iridium 192 or iodine 125, fractionated high dose rate brachytherapy, or intraoperative high dose rate therapy. Recommendations are made for patient selection, techniques, dose rates, and dosages. Complications and possible interventions to minimize their occurrence and severity are reviewed. CONCLUSION: Brachytherapy represents an effective means of enhancing the therapeutic ratio, offering both biologic and dosimetric advantage in the treatment of patients with soft tissue sarcoma. The treatment approach used depends upon the institution, physician expertise, and the clinical situation. Guidelines are established for the use of brachytherapy in the treatment of soft tissue sarcomas in adults and in children. Practitioners and cooperative groups are encouraged to use these guidelines to formulate their treatment and dose-reporting policies. These guidelines will be modified, as further clinical results become available.

Adult↗
PubMed2001

The effect of age on the response of the rat brains to continuous beta-amyloid infusion.

Young (3 months old) and aging (18-21 months old) rats were infused intracerebroventricularly with beta-amyloid (1-40; 4.2 nmol) for 14 days. In both age groups, beta-amyloid led to deficits in water-maze and decreased choline acetyltransferase activity and somatostatin levels. Cortical substance P levels also decreased whereas neuropeptide Y levels remained unaltered. There were no significant age dependent differences among these neurochemicals except a decrease in hippocampal neuropeptide Y levels in the aging group. It is concluded that young and aging rat brains respond similarly to beta-amyloid infusion.

Aging↗
PubMed2001

Chronic intracerebroventricular exposure to beta-amyloid(1-40) impairs object recognition but does not affect spontaneous locomotor activity or sensorimotor gating in the rat.

This study examined the cognitive effects of chronic in vivo exposure to beta-amyloid(1-40) via the intracerebroventricular route on two distinct paradigms. The first test evaluated a form of early attentional control referred to as sensorimotor gating in which an antecedent weak prepulse stimulus modulates the reactivity to a subsequent startle-eliciting stimulus. The second test utilized the spontaneous preference for a novel object over that of a familiar one in rats as a measure of object recognition memory. We found that beta-amyloid exposure leads to a severe deficit in the object memory test but spares sensorimotor gating. Moreover, unlike the water maze deficit induced by beta-amyloid (Nag et al., in preparation), the deficit on object recognition was resistant to amelioration by systemic physostigmine treatment at a dose of 0.06 mg/kg per day intraperitoneally. The present results add to previous reports that beta-amyloid exposure can lead to deficits on hippocampal lesion sensitive tasks, suggesting that dysfunction of the rhinal cortices in addition to that of the septohippocampal system is implicated in beta-amyloid-induced behavioral impairments. It therefore lends support to the hypothesis that beta-amyloid exposure can lead to severe impairment across multiple memory systems.

Acoustic Stimulation↗