"Hot cross bun" sign in two patients with multiple system atrophy-cerebellar.
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Female↗
Biomedical subjects
S Singh
Publications and source records attributed to S Singh.
Differential gene expression during apoptosis induced by a serum factor: role of mitochondrial F0-F1 ATP synthase complex.
The number of genes that are up regulated or down regulated during apoptosis is large and still increasing. In an attempt to characterize differential gene expression during serum factor induced apoptosis in AK-5 cells (a rat histiocytoma), we found subunit 6 and subunit 8 of the transmembrane proton channel and subunit alpha of the catalytic core of the mitochondrial F(0)-F(1) ATP synthase complex to be up regulated during apoptosis. The increase in the expression levels of these subunits was concomitant with a transient increase in the intracellular ATP levels, suggesting that the increase in cellular ATP content is a result of the increase in the expression of ATP synthase subunits' gene and de novo protein synthesis. Depleting the cellular ATP levels with oligomycin inhibited apoptosis significantly, pointing to the requirement of ATP during apoptosis. Caspase 1 and caspase 3 activity and the loss of mitochondrial membrane potential were also inhibited by oligomycin during apoptosis in these cells, suggesting that the oligomycin induced inhibition of apoptosis could be due to inhibition of caspase activity and inhibition of mitochondrial depolarization. However, cytochrome C release during apoptosis was found to be completely independent of intracellular ATP content. Besides the ATP synthase complex genes, other mitochondrial genes like cytochrome C oxidase subunit II and III also showed elevated levels of expression during apoptosis. This kind of a mitochondrial gene expression profile suggests that in AK-5 cells, these genes are upregulated in a time-linked manner to ensure sufficient intracellular ATP levels and an efficient functioning of the mitochondrial respiratory chain for successful completion of the apoptotic pathway.
Adenosine Triphosphate↗
Rational selection of structurally diverse natural product scaffolds with favorable ADME properties for drug discovery.
Natural product analogs are significant sources for therapeutic agents. To capitalize efficiently on the effective features of naturally occurring substances, a natural product-based library production platform has been devised at Aurigene for drug lead discovery. This approach combines the attractive biological and physicochemical properties of natural product scaffolds, provided by eons of natural selection, with the chemical diversity available from parallel synthetic methods. Virtual property analysis, using computational methods described here, guides the selection of a set of natural product scaffolds that are both structurally diverse and likely to have favorable pharmacokinetic properties. The experimental characterization of several in vitro ADME properties of twenty of these scaffolds, and of a small set of designed congeners based upon one scaffold, is also described. These data confirm that most of the scaffolds and the designed library members have properties favorable to their utilization for creating libraries of lead-like molecules.
Alkaloids↗
Post-cesarean section acute colonic pseudo-obstruction with spontaneous perforation.
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Adult↗
Superficial radial nerve damage due to Kirschner wiring of the radius.
For displaced fractures of the radius, the use of Kirschner wires (K Wires) is accepted practice either alone or to supplement external fixation. Complications related to K wires include infection, migration and damage to tendons and nerves. We set out to investigate to incidence of superficial radial nerve damage due to radial styloid K wires. Injury to the sensory branch of the superficial radial nerve was seen in eight (20%) out of the 40 patients. K wiring is a popular technique to help maintain anatomic reduction of distal radial fractures. It has the advantage of being a semi-closed procedure, which is simple to perform. However, the morbidity of nerve damage is often underestimated and can be avoided.
Bone Wires↗
Adaptogenic activity of glyco-peptido-lipid fraction from the alcoholic extract of Trichopus zeylanicus Gaerten (part II).
Anti-stress activity was carried out on glyco-peptido-lipid (AF) fraction from the alcoholic extract of Trichopus zeylanicus Gaerten and demonstrated against a battery of tests in rats and mice. AF exhibited significant anti-stress activity in dose-related manners in all the parameters studied against different models used to induce non-specific stress viz physical and chemically. The major parameters studied were immobilization induced gastric ulceration, adjuvant-induced trauma (Stress); humoral antibody synthesis in normal and immuno-suppressed mice and delayed type of hypersensitivity (DTH) reaction, chemically stress-induced alteration in hepatic function and anti-oxidant activity. The extract of Withania somnifera root (a commercial preparation available locally, Dabur India ltd.) was used to compare the results. In the safety evaluation study the maximum tolerance dose (MTD) and oral LD50 were found to be more than 3000 mg/kg, with no signs of abnormalities or any mortality observed for 15 days period under observation after single dose of drug administration. Feeding behaviour and fecal output were normal.
Animals↗
Steroid sparing in renal transplantation with tacrolimus and mycophenolate mofetil: three-year results.
Although renal transplantation with a 7-day steroid-sparing regimen, tacrolimus and mycophenolate, is associated with good short-term outcomes, late allograft dysfunction and failure remain concerns. In this study 101 consecutive patients underwent renal transplantation using this immunosuppressive regimen. In addition, anti-CD25 monoclonal antibody was used in 25 high-risk patients (regrafts, two-antigen human leukocyte antigen (HLA)-DR mismatch or sensitized with anti-HLA panel reactivity >30%). After a median follow-up of 39 months (range 29 to 49), overall patient survival is 98%, with two cardiac deaths. Three other graft losses occurred, one each to early venous thrombosis, polyoma viral nephropathy, and late rejection due to noncompliance. Therefore, overall graft survival is 95%. The acute rejection rate at 6 and 12 months was 19% (no rejection occurred between months 6 and 12). Late rejection was uncommon, with only two further episodes beyond 12 months. Mean creatinine at 12 months was 144 micromol/L and mean estimated glomerular filtration rate (GFR) of 55 mL/min. Graft function was stable at 3 years with a mean creatinine of 142 micromol/L and mean estimated GFR 56 mL/min. During the study, five patients developed posttransplant diabetes mellitus (two cases beyond 12 months). Tissue-invasive cytomegalovirus disease and BK viral nephropathy each occurred in three patients, with all episodes in the first 12 months. Mean weight gain is 3.3 kg and mean blood pressure is 135/81 on an average of 1.5 antihypertensive agents. This steroid-avoidance regimen is associated with excellent medium-term patient and graft outcomes and a low incidence of side effects.
Antibodies, Monoclonal↗
Tacrolimus monitoring in renal transplantation: a comparison between high-performance liquid chromatography and immunoassay.
It is recommended that specific methods of tacrolimus monitoring rather than immunoassays, which overestimate tacrolimus levels, should be used in transplant recipients. Direct comparison of these techniques, however, has not been conducted in renal transplantation. In this study, 40 renal transplant recipients with tacrolimus monitoring by microparticle enzyme immunoassay (MEIA; target trough level 10 to 15 ng/mL) were compared with 40 patients monitored by high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS; target trough level 8 to 13 ng/mL). All patients received anti CD25 antibody induction and mycophenolate mofetil in a steroid-sparing protocol. No differences were seen between MEIA and HPLC-MS groups in patient demographics. All patients were followed for 6 months. Patient survival was 100% in both groups; graft survival was 100% in the MEIA group and 97.5% in the HPLC-MS group. The groups did not differ in the number of dose changes required in the first 6 months or in the number of patients displaying tacrolimus levels within target range at 3 and 6 months. Delayed graft function occurred in 14 patients in the MEIA group and 12 patients in the HPLC-MS group (P = NS). Biopsy-proven acute rejection occurred in four patients in the MEIA group and one patient in the HPLC-MS group (P < .2). No differences were seen for the following parameters at 3 or 6 months: biopsy-proven tacrolimus nephrotoxicity, serum creatinine or estimated creatinine clearance, systolic or diastolic blood pressure, cholesterol, cytomegalovirus disease, posttransplant diabetes, or tremor. This study suggests that renal transplantation with HPLC-MS monitoring of tacrolimus is safe and effective.
Blood Pressure↗
Thyroid hormone dysregulation in intrauterine growth retardation associated with maternal malnutrition and/or anemia.
Data on the effect of maternal malnutrition and/or anemia on thyroid hormone regulation in human fetuses are scarce, and would be of great importance in examining the relevance of Barker's hypothesis, which proposes adaptation of fetuses to undernutrition leading to permanent metabolic and endocrine changes that form the basis of adult diseases. To examine the quantitative variations in thyroid hormone profile of neonates born to malnourished and/or anemic mothers, we quantitated the T3, T4, rT3 and TSH levels in cord blood of neonates and maternal blood of their corresponding mothers that are malnourished and/or anemic. Further, we classified neonates born to each of these groups of mothers into Small for Gestational Age (SGA) or Appropriate for Gestational Age (AGA) based on the intrauterine growth curve for our population, and examined the thyroid hormone profile in these neonates. Our results show that firstly, the effects of malnutrition or anemia on thyroid hormone profile are distinct, secondly, significantly higher levels of cord blood T4 and correspondingly lower levels of T3 and rT3 are observed in the neonates born to anemic and malnourished mothers and thirdly, decreases in cord blood T3 levels were observed in Small for Gestational Age neonates born to anemic mothers. These observations lead us to speculate that alterations in the pituitary-thyroid function result in beneficial adaptations to the hostile intrauterine environment in malnutrition related growth retardation and anemia.
Anemia↗
"It isn't just consultants that need a BSc": student experiences of an Intercalated BSc in primary health care.
More medical schools are moving towards a compulsory intercalated BSc. These courses have not traditionally been aimed at those students interested in general practice and have tended to have limited clinical relevance. This paper explores the perceptions of students who undertook a BSc in primary health care using qualitative methodology comprising semi-structured interviews with students just before completion of their course. Interviews were undertaken with 24 of the 26 students who started the course over a 4-year period. All the students have finished the course and have graduated with good honours degrees. Students refine existing skills and develop new, relevant skills for medicine. The students discussed the prestige (or lack) of a BSc in this field and how the course has impacted on their career decisions. A Primary Health Care BSc such as this appears to give students an in depth and to some, a positive view of general practice and primary care. The course allowed students to develop a more critical approach to medicine and enabled them to develop skills in addition to those acquired from their undergraduate medicine course. They perceived that these skills will serve them throughout their career in whatever branch of medicine they choose.
Attitude of Health Personnel↗
Tumor necrosis factor-alpha levels in patients with HIV with wasting in South Asia.
Tumor necrosis factor (TNF)-alpha is thought to play an important role in wasting; but TNF-alpha levels have not been consistently found to be high in AIDS wasting. We conducted this study to determine any correlation between TNF-alpha levels and wasting in HIV-positive patients in a developing country. TNF-alpha levels were measured in four groups of patients: Group 1, HIV/AIDS with wasting (n = 25); group 2, HIV/AIDS without wasting (n = 47); group 3, HIV-negative patients with tuberculosis with wasting (n = 25); and group 4, healthy controls (n = 25). Wasting was defined as a body bass index (BMI) </=16.0 kg/m(2). TNF-alpha was measured by a solid-phase sandwich enzyme linked immunosorbent assay (ELISA) kit. The mean BMI in HIV-positive patients with wasting (group 1) and without wasting (group 2) was 15.192 +/- 1.142 and 19.507 +/- 2.457, respectively, while group 3 and 4 had a BMI of 14.878 +/- 3.234 and 21.862 +/- 2.763 kg/m(2). The mean TNF-alpha level in group 1 was 50.864 +/- 99.13 pg/mL and 43.39 +/- 66.372 pg/mL in group 2. There was no significant difference between the two groups. TNF-alpha was significantly higher in the HIV/AIDS groups (group 1 and 2) compared to the tuberculosis group (10.74 +/- 7.854) and healthy controls (5.846 +/- 3.40) at p = 0.01. TNF-alpha was significantly (p = 0.002) higher in symptomatic patients compared to asymptomatic patients (16.03 +/- 7.61 versus 64.70 +/- 98.70). In conclusion, TNF-alpha levels were higher in HIV patients, regardless of the presence of wasting, compared to normal healthy controls of patients with tuberculosis with wasting.
Adolescent↗
Simultaneous determination of vincristine, vinblastine, catharanthine, and vindoline in leaves of catharanthus roseus by high-performance liquid chromatography.
A simple reversed-phase liquid chromatographic method is developed for the simultaneous quantitation of the anticancerous drugs vincristine, vinblastine, and their precursors catharanthine and vindoline using a Merck Chromolith Performance reversed-phase high-performance liquid chromatography column. A better resolution is obtained in comparison with available particulate-type C18 columns. The column provides good reproducibility and peak symmetry. Chromatography is carried isocratically with a mobile phase of acetonitrile-0.1M phosphate buffer containing 0.5% glacial acetic acid (21:79, v/v; pH 3.5) at a flow rate of 1.2 mL/min and UV detection at 254 nm. Parameters such as linearity, limits of quantitation (LOQ) and detection (LOD), precision, accuracy, recovery, and robustness are studied. The method is selective and linear for alkaloid concentration in the range 0.25 microg-25 microg/mL. The LOQ and LOD are 25, 46, 56, and 32 microg/mL and 8, 14, 18, and 10 microg/mL, respectively. The results of accuracy studies are good. Values for coefficient of variation are 2.50, 1.82, 1.33, and 1.13, respectively. The percent recovery of the alkaloids was found to be 96%, 97%, 98%, and 98%, respectively. Peak purity and homogeneity of these compounds in plant extract is studied using a photodiode-array detector. This simple and rapid method of analysis is applied for the determination of these alkaloids in a large number of leaf extracts of Catharanthus roseus..
Calibration↗
Prc protease promotes mucoidy in mucA mutants of Pseudomonas aeruginosa.
Mucoid strains of Pseudomonas aeruginosa that overproduce the exopolysaccharide alginate are a frequent cause of chronic respiratory infections in cystic fibrosis (CF) patients. The overproduction of alginate by these strains is often caused by mutations within mucA of the algU mucABCD gene cluster. This gene cluster encodes an extreme stress response system composed of the ECF alternative sigma factor AlgU, the anti-sigma factor MucA located in the inner membrane and the negative regulator MucB located in the periplasm. Most of the mutations in mucA found in mucoid strains cause a truncation of the C-terminal, periplasmic domain of MucA. The most significant effect of these mutations appears to be to reduce the levels of MucA. PA3257 (prc) was identified as a regulator of alginate production in P. aeruginosa through the isolation and study of mutations that partially suppressed the mucoid phenotype of a mucA22 strain. The suppressor of mucoidy (som) mutants isolated produced very little alginate when grown on LB medium, but were still mucoid when grown on Pseudomonas isolation agar. These som mutations and another previously isolated suppressor mutation were complemented by cosmids or plasmids carrying PA3257. PA3257 is predicted to encode a periplasmic protease similar to Prc or Tsp of Escherichia coli. Sequencing of prc from three strains with som suppressor mutations confirmed that each had a mutation within the prc coding region. The authors propose that Prc acts to degrade mutant forms of MucA. Additional evidence in support of this hypothesis is: (1) transcription from the AlgU-regulated algD reporter was reduced in som mutants; (2) inactivation of prc affected alginate production in mucoid strains with other mucA mutations found in CF isolates; (3) inactivation or overexpression of prc did not affect alginate production in strains with wild-type MucA.
Alginates↗
Fine needle aspiration cytology of a non-ulcerated penile lump.
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Aged↗
Granular cell tumour of the subcutis: a cytological diagnosis.
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Adult↗
The upper oesophageal sphincter.
The upper oesophageal sphincter (UOS) is a high-pressure zone comprising functional activity of three adjacent muscles together with cartilage and connective tissue. Its primary function is to allow food into the oesophagus and prevent air ingestion. However, it must also allow the reflux of material during belching or vomiting. Cricopharyngeus is the most important muscle with contributions from inferior pharyngeal constrictor and cervical oesophagus. Basal tone within the UOS is contributed to by all three muscles with asymmetry in the axial plane. Relaxation of the UOS occurs during swallowing as well as in sleep while UOS pressure rises with stress, slow oesophageal distension, intra-oesophageal acid infusion and pharyngeal stimulation with air or water. Many physiological characteristics have been attributed to UOS function following videofluoroscopic swallow examinations, manometry and electromyography but a range of normal values remains controversial and their utility uncertain. The result has been that pathological change is inconsistently characterized and management is instigated without a satisfactory evidence base. In this article, we review the anatomy, physiology and pathophysiology of the UOS along with the current opinions on investigation and treatment of UOS dysfunction.
Esophageal Sphincter, Upper↗
Cerebral venous sinus thrombosis presenting as subdural haematoma.
The authors report a 39-year-old woman who presented with intermittent, excruciating nuchal and occipital headache. Magnetic resonance imaging and magnetic resonance angiography scans showed bilateral subdural haematomas with veno-occlusive disease of the superficial and deep venous systems. There were bridging collaterals with scalp veins, bleeds from which could explain the subdural haematoma. There was acute on chronic veno-occlusive disease with an acute rise in intracranial pressure and a bleed from the vein of Galen.
Adult↗
Diagnosis of tubular colonic duplication by barium follow-through study.
Barium enema studies are considered essential for the diagnosis of tubular colonic duplication with opacification of two colons being the diagnostic sign. Yet in certain cases, barium enema apparently does not show positive findings. A case is reported in which a barium follow-through study established the complete diagnosis of duplication of colon and terminal ileum. The findings were confirmed on laparotomy.
Barium Sulfate↗