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Biomedical subjects

R Sharma

Publications and source records attributed to R Sharma.

At least 199 records · Page 11Linked to original sources

Transforming growth factor-beta1 increases albumin permeability of isolated rat glomeruli via hydroxyl radicals.

BACKGROUND: Transforming growth factor-beta1 (TGF-beta1) is a multifunctional cytokine. Glomerular cells and tubular epithelial cells secrete and respond to TGF-beta1. A close association between elevated levels of TGF-beta1 and the development of glomerulonephritis, glomerulosclerosis, and tubular hypertrophy has been documented. The role of TGF-beta1 in proteinuria is not well understood. METHODS: Isolated rat glomeruli were incubated in medium alone or with TGF-beta1 (1 to 10 ng/mL) and TGF-beta1 + 200 U/mL of superoxide dismutase (SOD) or 1 mmol/L of dimethylthiourea (DMTU) scavengers of superoxide and hydroxyl radicals, respectively, for up to 60 minutes at 37 degrees C. Glomerular albumin permeability (Palb) was calculated from the volumetric response of glomeruli to an oncotic gradient using videomicroscopy. RESULTS: One or 2.5 ng/mL of TGF-beta1 had no effect on Palb (0.18 +/- 0.08, N = 17; 0.18 +/- 0. 079, N = 20 vs. control 0.00 +/- 0.06, N = 25), whereas 5 or 10 ng/mL of TGF-beta1 caused a significant increase in Palb (0.31 +/- 0. 09, N = 20; 0.33 +/- 0.06, N = 23) within 15 minutes. The effect of 10 ng/mL of TGF-beta1 on Palb increased further after 30, 45, or 60 minutes of incubation (0.43 +/- 0.06, N = 24; 0.53 +/- 0.06, N = 25; 0.74 +/- 0.075, N = 21). The TGF-beta1-induced increase in Palb (0. 75 +/- 0.065, N = 15) was blocked by SOD (0.07 +/- 0.14 N = 15) or by DMTU (0.04 +/- 0.13, N = 15). Incubation of glomeruli with the carrier medium (4N HCl) in which TGF-beta1 is dissolved and SOD or DMTU alone did not affect Palb. CONCLUSION: Elevated levels of TGF-beta1 derived from glomerular or extraglomerular sources are capable of increasing glomerular Palb via superoxide and hydroxyl radicals and may lead to proteinuria in vivo.

Animals↗

Multicentre dose-ranging study on the efficacy of USPIO ferumoxtran-10 for liver MR imaging.

AIM: A dose ranging multicentre phase-II clinical trial was conducted to evaluate the efficacy of ultrasmall superparamagnetic iron oxide (USPIO) ferumoxtran-10 for magnetic resonance (MR) imaging of focal hepatic lesions. MATERIAL AND METHODS: Ninety-nine patients with focal liver lesions received USPIO at a dose of 0.8 (n = 35), 1.1 (n = 32), or 1.7 (n = 32) mg Fe/kg. Liver MR imaging was performed before and after USPIO with T1-weighted and T2-weighted pulse sequences. Images were analysed by two independent readers for additional information (lesion detection, exclusion, characterization and patient management). Signal intensity (SI) based quantitative measurements were also taken. RESULTS: Post-contrast medium MR imaging showed additional information in 71/97 patients (73%) for reader one and 83/96 patients (86%) for reader two. The results with all three doses were statistically significant (P < 0.05). Signal intensity analysis revealed that all three doses increased liver SI on T1-weighted images and decreased liver SI on T2-weighted images. On T2-weighted images metastases increased in contrast relative to normal hepatic parenchyma whereas haemangiomas decreased in contrast. On T2-weighted images there was statistically improved efficacy at the intermediate dose, which did not improve at the highest dose. CONCLUSION: Ultrasmall superparamagnetic iron oxide was an effective contrast agent for liver MR imaging at all doses and a dose of 1.1 mg Fe/kg was recommended for future clinical trials.

Adult↗

Validity and reliability of three generic outcome measures for hand disorders.

This is an assessment of three different outcome measures for the hand: the Hand Clinic Questionnaire (HCQ); the Patient Evaluation Measure (PEM); and the Hand Outcome Survey Sheet (HOSS). Each measure has been tested for its reliability and validity. The results suggest that the PEM and the HCQ are comparably consistent but the PEM is more reproducible. Both the PEM and HOSS are valid questionnaires. The PEM is suitable for use in an outpatient clinic and as a postal questionnaire. The HOSS may be used for research or audit especially when the injury has been measured using the Hand Injury Severity Score.

Adolescent↗

Perinatal lethal form of Gaucher's disease presenting with hemosiderosis.

A term infant with hydrops fetalis presented with hypotonia, massive splenomegaly, renal failure, and severe hyperferritinemia. Multiple organ failure, myoclonus, and opisthotonus ensued and she died at 15 days of age. High rounded forehead, large open fontanel, and a small recessed chin led to initial premortem diagnosis of Zellweger syndrome, but her plasma profile of long chain fatty acid was normal. Her subsequent clinical course and findings of postmortem examinations were consistent with perinatal lethal form of Gaucher's disease (PLGD). The diagnosis was confirmed by deficiency of enzyme beta-glucocerebrosidase in white blood cells and in cultured fibroblasts. In addition to the crossover features of Zellweger phenotype, this infant exhibited a number of unusual features including, severe hyperferritinemia, rapid progression of splenomegaly, and absence of icthyosis.

Fatal Outcome↗

Severe pain confounds neuropsychological test performance.

There is little information on the effect of pain on neuropsychological test performance. We have undertaken this study to explore which tests are affected by pain, the magnitude of these changes, and other confounders of neuropsychological performance in a population of patients having spine surgery. Twenty-four elderly English speaking Caucasian patients (age > 60 years) were enrolled pre-operatively in this Institutional Review Board approved study. Pain scores using an 11-point Numeric Pain Intensity scale and performance on a neuropsychological battery (Controlled Oral Word Association, Rey Complex Figure, Trails A and B) were assessed at two times, before and one day after surgery. Scores were calculated using the standard algorithms and change scores were calculated by subtracting the baseline from follow-up scores. After surgery, performance on the Rey Complex Figure ( r = -0.577, p = 0.004) and Trails Part A (r = 0.527, p = 0.01) declined with increasing post-operative pain scores. Women reported higher pain scores post-operatively than men (p = 0.046), and performed worse than men for change in performance on Trails Part A (p = 0.027). These data suggest that pain can influence performance on certain cognitive tests, and that some gender differences in these effects may occur. Interpretation of performance measures should take into account possible effects of pain, although our understanding of pain effects and ability to predict them in individual people, currently are quite limited.

Aged↗

Correction of cubitus varus by French or dome osteotomy: a comparative study.

BACKGROUND: The purpose of this study was to compare the outcomes of two different techniques of supracondylar osteotomy, French osteotomy and dome osteotomy, for the correction of posttraumatic cubitus varus. METHODS: A comparative randomized study was undertaken of 25 patients (average age 10 years) with an established posttraumatic cubitus varus deformity (mean time from injury to corrective osteotomy, 1.7 years). Patients were followed-up with for 1 year, and carrying angle, Baumann's angle, and internal rotation deformity were measured. Postoperative complications were assessed. RESULTS: A significant (p < 0.01) correction of carrying angle and Baumann's angle was achieved with both techniques, with no statistically significant differences between them. Although internal rotation deformity was corrected by both techniques, the correction was significantly greater with the dome osteotomy (p < 0.01). However, the persistence of internal rotation did not seem to affect the final outcome. There was a higher incidence of postoperative complications in the dome osteotomy group, including infection (1), inadequate correction (1), nerve palsy (1), loss of motion (5), and circulatory compromise (1). CONCLUSION: The dome osteotomy is technically more difficult than the French osteotomy and has a higher incidence of complications. We suggest that the French osteotomy be used for the correction of cubitus varus after supracondylar fractures of the elbow in children.

Adolescent↗

Evaluation of the urological complications of living related renal transplantation at a single center during the last 10 years: impact of the Double-J* stent.

PURPOSE: We evaluated the impact of the routine use of Double-J stents for decreasing urological complications in living related renal transplantation at a single center during the last 10 years. MATERIALS AND METHODS: Our 3-phase longitudinal study included 670 consecutive living related renal transplants from 1989 to 1998. In phase 1 from 1989 to 1993 a stent was introduced as and when required in only 15 of 170 patients. In phase 2 from January 1994 to April 1995 we randomized 57 and 43 cases to stenting and no stenting, respectively. The stent was removed after 4 weeks. In phase 3 from May 1995 to December 1998 all patients received a stent, which was removed 10 to 14 days just before discharge home. We reviewed urological complications at various time frames to determine the impact of routine Double-J stenting on decreasing urological complications. RESULTS: In phase 1 the major ureteral complication rate was 8.8%, which decreased to 3% in phase 2 when half of our cases were stented. In phase 3 there was only 1 ureteral complication (0.04%) in 400 patients, of whom all received a stent. The overall ureteral complication rate in nonstented and stented cases was 8.5% (18 of 213) and 0.22% (1 of 457). There was no difference in urological complications or stent related problems whether the stent was removed at 4 or 2 weeks. However, stent removal at 2 weeks eliminated the possibility of a forgotten stent, avoided repeat hospitalization for stent removal and decreased the cost. Routine stenting was cost-effective and almost eliminated urological complications. CONCLUSIONS: Routine Double-J stenting prevents ureteral complications. Early removal at 2 weeks is advisable. The short duration of stenting is effective and saves the cost of repeat hospitalization at a later date.

Adolescent↗

Components of normal serum block the focal segmental glomerulosclerosis factor activity in vitro.

BACKGROUND: Sera from some patients with focal segmental glomerulosclerosis (FSGS) increase glomerular albumin permeability (P(alb)) in vitro. The hypothesis that a component of normal serum can protect the glomerular permeability barrier was tested using sera from FSGS patients, normal individuals, and several mammalian and avian species. METHODS: In most experiments, isolated rat glomeruli were incubated in medium containing FSGS serum known to increase P(alb) in vitro, normal serum, or both active FSGS and normal serum. In other experiments, fractions of normal serum and serum from other vertebrate species were incubated with active FSGS serum. P(alb) was calculated from glomerular capillary expansion in response to an oncotic gradient. To enrich the blocking activity, normal pooled human plasma was subjected to various biochemical manipulations. RESULTS: Normal human serum prevented the increase in P(alb) (active FSGS sera, 0.77 +/- 0.12; active FSGS sera:normal serum, 1:1 mix, 0.06 +/- 0.30, P < 0.001). Protection diminished as the concentration of normal serum was decreased. Specific fractions of human serum, including human albumin and immunoglobulin fractions, were not protective. Blocking activity was present in 80% ammonium sulfate precipitate and certain fractions from size-exclusion chromatography of normal pooled human plasma. Normal serum from each of the vertebrate species tested also prevented the increase in P(alb). Preincubation with normal serum was protective during subsequent incubation with FSGS serum, but normal serum was not protective after preincubation with FSGS serum. CONCLUSIONS: We conclude that a factor or factors in normal serum block the permeability effect of active FSGS sera. This phenomenon may account for variability in proteinuria among patients with FSGS and may explain inconsistent proteinuria following injection of FSGS sera into experimental animals. Characterization of the protective substance(s) and the mechanism by which the increase in permeability is blocked may provide insight into the pathogenesis of FSGS.

Animals↗

Pigmentation and pits at uncommon sites in a case with reticulate acropigmentation of Kitamura.

Reticulate acropigmentation of Kitamura is now reported from all over the world. Additional features are being readily recognized. Our cases had pigmentation and pits on the dorsa of the distal phalanges of the fingers and toes - the classical features - as well as widely distributed pits on the palms, palmar aspect and sides of the fingers. The involvement in our cases was more pronounced than in the previously reported ones.

Adult↗

Right ventricular dysfunction in adult severe cystic fibrosis.

STUDY OBJECTIVES: This study sought to assess the extent of impairment of cardiac function in adult patients with end-stage cystic fibrosis (CF) and to examine the relationship between cardiovascular abnormalities and the degree of hypoxemia and hypercapnia. DESIGN AND SETTING: A retrospective study in a tertiary cardiac and CF center. PARTICIPANTS AND INTERVENTIONS: A total of 103 adult patients with end-stage CF awaiting lung or heart and lung transplantation (mean age [+/- SD], 26+/-7 years; 54 men) underwent Doppler echocardiography and arterial blood gas analysis (mean PaO(2), 54+/-10 mm Hg; mean PaCO(2), 47+/-8 mm Hg). The findings were compared to those of 17 healthy control subjects (mean age, 24+/-7 years; 13 men) who had no history of cardiac or pulmonary disease. MEASUREMENTS AND RESULTS: All patients were in sinus rhythm with a mean tachycardia of 112+/-18 beats/min (control subjects, 76+/-16; p<0.0001) and had a cardiac output of 5.3 L/min (control subjects, 4.3 L/min; p<0.04). In the patient group, the left ventricular (LV) dimensions, systolic and diastolic function, and wall thickness were all within normal limits. The mean amplitude of long-axis excursion in patients was normal at the LV site, but that of the right ventricular (RV) free wall was significantly reduced as compared with control subjects (1.6+/-0.4 vs. 2.2+/-0.4 cm, respectively; p<0.001), which was found to correlate with the degree of hypoxemia (r = 0.63; p<0.02) and hypercapnia (r = -0.68; p<0.01). RV diastolic function, which was represented by the relative isovolumic relaxation time to cardiac cycle length, was longer in patients than in control subjects (8.7+/-4.8% vs. 5.0+/-3.0%, respectively; p<0.03). The pulmonary flow acceleration time (90+/-22 vs 121+/-34 ms, respectively; p<0.01) and the systolic stroke distance (7.0+/-2.2 vs. 10.5+/-1.9 cm/s(2); p<0.001) were both lower than normal. CONCLUSIONS: This study confirms the presence of significant RV systolic and diastolic dysfunction in the setting of consistent tachycardia and increased cardiac output in adult CF patients with severe disease. No specific LV abnormalities were detected in these patients.

Adolescent↗