Acute zolpidem overdose leading to coma and respiratory failure.
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Biomedical subjects
Publications and source records attributed to N Sharma.
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Alpha-synuclein, a protein in which two mutations have been identified that cause autosomal dominant Parkinson's disease, is thought to serve as a nidus for the development of a Lewy body. We hypothesized that alpha-synuclein would display different intra- and intermolecular associations in Lewy bodies than it does in its normal intracellular compartments. Using sensitive fluorescence resonance energy transfer (FRET) techniques, we found evidence that alpha-synuclein is more compact and in closer association with other alpha-synuclein molecules in Lewy bodies than it is in the neuropil. In addition, we found evidence of a close, direct intermolecular interaction between the N terminus of alpha-synuclein and ubiquitin. These observations provide support for the hypothesis that in Lewy bodies alpha-synuclein adopts an altered three-dimensional structure and undergoes N-terminal ubiquitination.
PURPOSE: To report the reduction in postpenetrating keratoplasty astigmatism with the use of the microkeratome to create a lamellar corneal flap as the first stage in a two-step laser in situ keratomileusis. METHODS: The hansatome microkeratome was used to create a lamellar corneal flap in a 24-year-old man with a net corneal astigmatism of 7.3 diopters, 2 years after penetrating keratoplasty. No laser ablation was performed. RESULTS: The net corneal astigmatism reduced to 3.9 diopters at 1 month and 2.3 diopters at 3 months of follow-up, without any laser ablation. CONCLUSION: Laser in situ keratomileusis may be performed as a two-stage procedure, because the lamellar corneal flap alone may reduce postpenetrating keratoplasty astigmatism.
TorsinA, a novel protein in which a mutation causes dominant, early onset torsion dystonia, may serve as a chaperone for misfolded proteins that require refolding or degradation. It has been hypothesized that misfolded alpha-synuclein, a protein in which two mutations cause autosomal dominantly inherited Parkinson's disease, serves as a nidus for the development of a Lewy body. We hypothesized that torsinA plays a role in the cellular processing of alpha-synuclein. We demonstrate that anti-torsin antibodies stain Lewy bodies and Lewy neurites in the substantia nigra and cortex. Using sensitive fluorescent resonance energy transfer (FRET) techniques, we find evidence of a close association between torsinA and alpha-synuclein in Lewy bodies.
Dihydroxyacetone phosphate reductase (DHAP reductase) was purified to apparent electrophoretic homogeneity with about 24% recovery from immature seeds of Brassica campestris using (NH(4))(2)SO(4) fractionation, affinity chromatography, gel filtration and adsorption chromatography. The purified enzyme with molecular mass of about 62 kDa was a dimer with subunit molecular mass of 32 kDa. The enzyme exhibited maximum activity at pH 7.5 and was highly specific for NADH and DHAP. Typical Michaelis-Menten kinetics was obtained for both the substrates with K(m) values of 3.3 and 26.6 &mgr;M for NADH and DHAP, respectively. The enzyme did not require any metal ion for its activity. Rather, the activity was inhibited by Na(+), K(+), Mn(2+), Mg(2+,) and Ca(2+). ATP and fructose-1,6-P(2) inhibited the enzyme non-competitively with respect to DHAP with K(i) values of 0.96 and 1.3 mM, respectively. Substrate interaction kinetics and product inhibition studies were consistent with compulsory-ordered bi-bi reaction mechanism with NADH being the first substrate to bind and NAD being the last product to dissociate. Based on the properties discussed here, it appears that the enzyme probably functions for the production of glycerol-3-P from DHAP.
In male albino mice, the petroleum ether extract of the leaves of Mentha arvensis L., at the doses 10 and 20 mg/mouse per day for 20, 40 and 60 days, when administered orally, showed a dose and duration dependent reduction in the number of offspring of the treated male mated with normal females. Negative fertility was observed in both dose regimens after 60 days of treatment. The body weight and libido of the treated ammals remain unaffected. However, a significant decrease in the weight of the testis, epididymis, cauda epididymal sperm count, motility, viability and normal morphology of the spermatozoa was observed. The levels of serum protein, bilirubin, GOT, GPT and acid phosphatase, blood urea and haematological indices were unaltered throughout the course of investigation. All the altered parameters were reversible following withdrawal of treatment. The results suggest that the petroleum ether extract of the leaves of M. arvensis possess reversible antifertility property without adverse toxicity in male mice.
BACKGROUND: Skin cancer screening has the potential to detect early precancerous lesions and may ultimately be important in reducing melanoma mortality. The purpose of this study was to evaluate the ability of trained nurse practitioners to accurately identify suspicious lesions in a clinical setting. METHODS: We identified five nurse practitioners who had no previous experience in evaluating skin lesions. Each nurse practitioner participated in a training program for skin cancer detection consisting of a workshop, clinical apprenticeship, and didactic lectures. RESULTS: Evaluation of nurse practitioner competency involved three assessments. First, the nurse practitioner's ability to distinguish benign and malignant lesions was assessed using clinical color slides. The sensitivity of all five nurse practitioners to refer benign and malignant lesions for dermatologic follow-up based on the slides was 100%, whereas the specificity ranged from 53% to 100%. Second, each nurse practitioner evaluated approximately 25 different patients along with a single dermatologist. The nurse practitioner's ability to correctly refer patients with suspicious lesions for dermatologic follow-up was determined based on the dermatologist's assessment of need for referral. Results suggested a referral sensitivity and specificity ranging from 67% to 100% and 62% to 100%, respectively. In the final clinical assessment, 30 patients were independently examined by two dermatologists and four nurse practitioners. Using the consensus clinical diagnosis of the dermatologists as the gold standard, the nurse practitioner's sensitivity for detecting significant skin cancer lesions ranged from 50% to 100% and the detection specificity was 99% to 100%. CONCLUSIONS: These preliminary results have important implications for skin cancer screening efforts and suggest that nurse practitioners can be trained to accurately identify and triage suspicious lesions.
PURPOSE: To evaluate the technique of silicone oil removal through a posterior capsulorhexis combined with phacoemulsification and intraocular lens (IOL) implantation. SETTING: Dr. Rajendra Prasad Center for Ophthalmic Sciences, New Delhi, India. METHODS: Fifteen eyes of 15 patients had phacoemulsification with removal of silicone oil, which had been used for intraocular tamponade after a previous pars plana vitrectomy. Eyes with a stable retina were included in the series. In all eyes, the silicone oil was removed through a planned posterior capsulorhexis after phacoemulsification. The parameters evaluated were the primary diagnosis, duration between silicone oil instillation and phacoemulsification, type of cataract, preoperative and postoperative best corrected visual acuities (BCVAs), and complications such as frequency of retinal redetachment and secondary cataract. RESULTS: Vitreoretinal surgery with silicone oil instillation was performed for rhegmatogenous-tractional detachment resulting from Eales' disease in 6 eyes and from proliferative diabetic retinopathy in 2 eyes, for primary rhegmatogenous retinal detachment in 6 eyes, and for traumatic rhegmatogenous detachment in 1 eye. The mean duration between the silicone oil instillation and phacoemulsification was 7.5 months +/- 3.8 (SD). Fourteen eyes had posterior subcapsular cataract, and 10 had nuclear sclerosis. Preoperative BCVA was worse than 6/60 in all eyes. The BCVA was 6/60 or better in 9 eyes after a minimum follow-up of 6 months. Two eyes had choroidal detachment in the early postoperative period. No eye had vitreous hemorrhage, retinal redetachment, secondary cataract, clinically significant endothelial decompensation or macular edema, or a dislocated IOL. CONCLUSION: The results indicate that silicone oil removal through a posterior capsulorhexis during phacoemulsification is a viable option and can be performed in selected cases of cataract with previous silicone oil instillation and a stable retina.
We describe a technique of enlarging a small primary capsulorhexis. Two Sinskey hooks are introduced through the side ports. One hook is placed above the anterior capsulorhexis margin with its tip pointing down, and the other is placed beneath the anterior capsulorhexis margin with its tip pointing up. A small nick is made between the tips of the 2 hooks, and the capsulorhexis is extended with a Utrata capsulorhexis forceps. This technique does not require additional instrumentation, impart zonular stress, or disturb wound architecture or integrity.
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This paper attempts to understand the experience of menstruation in the socio-cultural context of an urban Indian slum. Observations were gathered as part of a larger study of reproductive tract infections in women in Delhi, using both qualitative and quantitative methods. The qualitative phase consisted of 52 in-depth interviews, three focus groups discussions and five key informant interviews. In the quantitative phase inferences were drawn from 380 respondents. Mean age at menarche was 13.5. Onset of menarche is associated with physical maturity and the ability to marry and reproduce. However, a culture of silence surrounds menarche, an event which took the women interviewed almost by surprise. Most were previously unaware that it would happen and the information they were given was sparse. Menstruation is associated with taboos and restrictions on work, sex, food and bathing, but the taboos observed by most of the women were avoidance of sex and not participating in religious practices; the taboo on not going into the kitchen, which had been observed in rural joint households, was not being observed after migration from rural areas due to lack of social support mechanisms. There is a clear need to provide information to young women on these subjects in ways that are acceptable to their parents, schools and the larger community, and that allow them to raise their own concerns. Education on these subjects should be envisaged as a long-term, continuous process, beginning well before menarche and continuing long after it.
The absorption and fluorescence spectra of some biologically active flavones have been studied as a function of the acidity (pH/H0) of the solution. Dissociation constants have been determined for the ground and first excited singlet states. The results are compared with those obtained from Forster-Weller calculations. The acidity constants obtained by fluorimetric titration method are in complete agreement (in most of the systems) with ground state data indicating a excited state deactivation prior to prototropic equilibration. Compared to umbelliferones, flavones are only weakly fluorescent in alkaline solution. This behaviour is explained by the small energy difference between the singlet excited state and triplet excited state giving rise to more efficient intersystem crossing. Most of the flavones studied here undergo adiabatic photodissociation in the singlet excited state indicating the formation of an exciplex or a phototautomer.
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PURPOSE: To evaluate the influence of focal aser photocoagulation on contrast sensitivity in diabetic patients with clinically significant macular oedema (CSMO). METHODS: A prospective non-comparative interventional study was performed on a group of patients with CSMO at Dr Rajendra Prasad Centre for Ophthalmic Sciences, New Delhi, a tertiary eye care centre. Thirteen diabetc patients (14 eyes) with CSMO and no history of prior photocoagulation were recruited for this study. Direct focal photocoagulation of all leaking microaneurysms was performed using an argon green laser (514 nm). A contact lens was used as a slit lamp delivery system. Evaluation of the best corrected Snellen visual acuity, contrast senstivity, slit lamp biomicroscopy, macular status on direct ophthalmoscopy and fluorescein angiography was carried out 1 month and 3 months after laser photocoagulation. RESULTS: Following direct focal laser photocoagulation, focal CSMO resolved completely in all but one eye, 4-8 weeks later, as seen on slit lamp biomicroscopy and/or fluorescein angiography. Post-treatment, visual acuity remained stationary in eight eyes, improved by one line in three eyes, by two lines in two eyes and by three lines in one eye. The mean +/- SD pretreatment and post-treatment decimal visual acuities were 0.49+/-0.30 and 0.59+/-0.28, respectively. The mean +/- SD pre-laser contrast sensitivity score was 121.3+/-83.6, which increased significantly to a mean +/- SD of 151.6+/-80.5 fo lowing direct focal photocoagulation. CONCLUSION: Focal argon laser photocoagulation in CSMO in diabetics helps in improving the contrast sensitivity and stabilizes the visual acuity. The changes in contrast sensitivity and visual acuity are independent of each other.