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Biomedical subjects

V Shah

Publications and source records attributed to V Shah.

At least 91 records · Page 5Linked to original sources
PubMed1997

Liver sinusoidal endothelial cells are responsible for nitric oxide modulation of resistance in the hepatic sinusoids.

The mechanisms that regulate vascular resistance in the liver are an area of active investigation. Previously, we have shown that nitric oxide (NO) modulates hepatic vascular tone in the normal rat liver. In this study, the production of NO is examined in further detail by isolating sinusoidal endothelial cells (SEC) from the rat liver. Endothelial NO synthase (eNOS) was present in SEC based on Western blotting and confocal immunofluorescence microscopy. Exposure of SEC to flow increased the release of NO. To investigate the relevance of these in vitro findings to the intact liver, we modified an in situ perfusion system to allow for direct measurement of NO release from the hepatic vasculature. NO was released from the hepatic vasculature in a time-dependent manner, and administration of N-monomethyl-L-arginine reduced NO release and increased portal pressure. Immunostaining of intact liver demonstrated eNOS localization to endothelial cells lining the hepatic sinusoids. These findings demonstrate that SEC in vitro and in vivo express eNOS and produce NO basally, and increase their production in response to flow. Additionally, an increase in portal pressure concomitant with the blockade of NO release directly demonstrates that endogenous endothelial-derived NO modulates portal pressure.

Animals↗
PubMed1997

Structure of active chromatin: isolation and characterization of transcriptionally active chromatin from rat liver.

Rat liver nuclei were isolated in low-ionic-strength buffer in the absence of bi- and multi-valent cations. Digestion of these nuclei by endogenous nuclease, micrococcal nuclease and DNase I revealed that a minor chromatin fraction was preferentially digested into poly- and oligo-nucleosomes. Southern blot hybridization with various active gene probes confirmed that these chromatin fragments represent coding and 5' upstream regions of transcriptionally active chromatin. Active chromatin fragments were released selectively into the medium, with inactive chromatin remaining inside the nuclei, under the above ionic conditions. The inclusion of bivalent cations during the digestion of nuclei reversed the solubility behaviour of active chromatin. Rearrangement and exchange of histone H1 between chromatin fragments was prevented by using low-salt conditions in all steps in the absence of bivalent cations. All histones, including H1, were present in stoichiometric amounts in this active chromatin fraction. Active nucleosomes showed a lower electrophoretic mobility than bulk nucleosomes in an acrylamide/agarose composite gel in the absence of Mg2+, but were selectively bound to the gel in the presence of this ion.

Animals↗
PubMed1997

Charge and size selectivity of proteinuria in children with idiopathic nephrotic syndrome.

Experimental studies have pointed to charge selectivity as an important determinant of glomerular permeability to macromolecules. Loss of glomerular basement membrane (GBM) polyanion has been proposed as a cause of the selective proteinuria in minimal change nephrotic syndrome (MCNS). However, the presence of less-anionic albumin in urine than plasma from MCNS and focal and segmental glomerulosclerosis (FSGS) patients has been interpreted both as evidence for partial maintenance of charge selectivity and for involvement of other pathogenic mechanisms. The exact role of charge selectivity in the pathogenesis of nephrotic proteinuria remains controversial. We have examined the clearance of endogenous proteins of differing size and charge in children with idiopathic nephrotic syndrome (NS). Chromatofocusing was used to determine the isoelectric points (pIs) of albumins in paired plasma and urine samples from patients with FSGS (n = 6) and MCNS (n = 6). Charge selectivity was assessed by comparing the pIs of the fractions with the highest albumin concentration (model pI) in plasma and urine. The difference between the modal pIs was defined as the delta modal pI. Charge selectivity was also assessed from the albumin/transferrin and IgG4/IgG1 clearance ratios; size selectivity from the IgG1/albumin and IgG1/transferrin as well as the IgG4/albumin and IgG4/transferrin clearances. In children with FSGS, the mean (+/-SD) delta modal pI was -0.05 +/- 0.16, and in MCNS -0.05 +/- 0.11. Neither value differed significantly from zero. The albumin/transferrin clearance ratio showed no significant difference between FSGS and MCNS, but the IgG4/IgG1 clearance ratio was significantly higher in MCNS (P < 0.05). Size selectivity was significantly reduced in FSGS compared with MCNS (for IgG1/transferrin P < 0.01 and for IgG1/albumin P < 0.05). For IgG4/transferrin and IgG4/albumin, P was < 0.05. In conclusion, there was no evidence for residual charge selectivity in idiopathic NS associated with either MCNS or FSGS during nephrotic-range proteinuria. There was a significant loss of GBM size selectivity in children with FSGS with heavy proteinuria compared with children with MCNS with heavy proteinuria.

Adolescent↗
PubMed1997

Low-dose vancomycin prophylaxis reduces coagulase-negative staphylococcal bacteraemia in very low birthweight infants.

Very low birthweight (VLBW) infants undergoing neonatal intensive care are at risk of infection with coagulase-negative staphylococci (CONS). This study investigates the efficacy of twice daily, 1 h infusions of vancomycin (5 mg kg) in reducing CONS infection in VLBW infants receiving parenteral nutrition. Of 72 infants in the study, 37 were randomized to vancomycin and 35 to the control group. Clinical variables and mortality were similar in both groups. In the vancomycin group, 11 infants had one or more episodes of CONS bacteraemia compared with 17 in the control group. Two babies in the treatment group had more than one episode of CONS bacteraemia, compared with nine in the control group (P = 0.02). There were 13 episodes of CONS bacteraemia in the vancomycin group compared with 29 in the control group. When only positive blood-cultures associated with a rise in C-reactive protein were considered, there were six episodes of CONS bacteraemia in the vancomycin group compared with 18 in the control group. Similarly there were five infants with one or more CONS infections compared with 11 in controls and one with more than one episode compared with six in the control group (P = 0.05). Prophylaxis with intermittent low-dose vancomycin infusions may help reduce recurrent CONS bacteraemia in VLBW infants receiving parenteral nutrition.

Anti-Bacterial Agents↗
PubMed1997

Nitric oxide synthase inhibitors and hypertension in children and adolescents.

OBJECTIVE: To establish the role played by the circulating nitric oxide synthase inhibitors N(G)-monomethyl-L-arginine (L-NMMA), asymmetrical dimethyl arginine (ADMA) and symmetric dimethyl arginine (SDMA) and its association with hypertension of children and adolescents. DESIGN: We measured plasma concentrations of L-NMMA, ADMA and SDMA in 38 hypertensives (median age 7.7 years) and in nine healthy normotensive controls (median age 8.2 years) using high-performance liquid chromatography. In addition, their plasma renin activity was determined. The subjects' glomerular filtration rates were calculated from plasma creatinine and height measurements. To determine the vasoactive potency of the arginine analogues, concentration-response curves were plotted for the responses in isolated endothelium-intact and endothelium-denuded mouse aortic rings that had been pre-contracted by administration of a threshold concentration of phenylephrine. RESULTS: Plasma ADMA and SDMA concentrations in members of the hypertensive group [0.23 +/- 0.03 and 1.37 +/- 0.06 micromol/l, respectively (means +/- SEM)] were significantly higher than those in members of the control group (ADMA 0.10 +/- 0.01 micromol/l and SDMA 1.18 +/- 0.06 micromol/l). Plasma concentrations of L-NMMA were similar in members of the hypertensive (0.21 +/- 0.01 micromol/l) and control (0.18 +/- 0.02 micromol/l) groups. The glomerular filtration rate of the hypertensive group was below normal [70.4 +/- 5.4 ml/min per 1.73 m2 (mean +/- SEM)] and was significantly associated with elevated plasma concentrations of ADMA (r = -0.77, P < 0.001), SDMA (r = -0.38, P = 0.02) and L-NMMA (r = 0.35, P = 0.03). Higher plasma ADMA concentrations were associated with a lower plasma renin activity (r = -0.36, P = 0.04). The vasoactive potencies of ADMA (concentration for half-maximal effect with the endothelium intact 25.4 +/- 7.1 micromol/l) and L-NMMA (concentration for half-maximal effect with the endothelium intact 8.2 +/- 2.9 micromol/l) was significantly (P < 0.05) greater than that of SDMA. Both ADMA and L-NMMA (at 3 micromol/l concentrations) initiated a significant vasocontractile response from baseline (P = 0.03 and P < 0.001, respectively). These effects were absent after the endothelium had been removed. SDMA had no effect. CONCLUSIONS: Plasma ADMA and SDMA levels are increased in hypertensive children. By inference from in-vitro data, ADMA appears to attain sufficient concentrations to produce a significant change in vascular tone and hence might play a role in the pathophysiology of childhood hypertension.

Adolescent↗
PubMed1997

Nitric oxide activity in childhood hypertension.

OBJECTIVES: To investigate nitric oxide (NO) activity in childhood hypertension using nitrite and nitrate (NOx) concentrations in plasma as an index of nitric oxide generation. DESIGN: Cross sectional study. SETTING: Tertiary care paediatric centre and district general hospitals in the UK. PATIENTS: Children attending the above centre for treatment of hypertension. The control subjects were normotensive healthy children attending district general hospitals for minor medical and surgical disorders. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Plasma (P) and urinary (U) NOx concentrations, blood pressure, and glomerular filtration rate. RESULTS: Sixteen normal children (mean age 6.9 years), 13 children with renovascular hypertension (mean age 7.8 years), and 25 children with hypertension associated with renal parenchymal disease (mean age 10.7 years) were studied. Mean (SD) PNOx values of children with hypertension with renovascular disease (15.3 (11.4) mumol/l) and renal parenchymal disease (18.3 (11.4) mumol/l) were significantly above that of normal children (11.9 (5.9) mumol/l) after accounting for age and glomerular filtration rate influences. Higher concentrations of PNOx in normal children were associated with younger age, but not in the children with hypertension. Higher PNOx concentrations were also associated with a lower glomerular filtration rate in normal children and children with hypertension with renal parenchymal disease, but not in the children with hypertension with renovascular disease. UNOx excretion expressed as a ratio against urine creatinine (Ucreat) excretion was not statistically different among the study groups. CONCLUSIONS: PNOx is increased in children with hypertension even after statistical elimination of the glomerular filtration rate and age influences. This suggests a normal or increased NO synthase activity in childhood hypertension in contrast with adults with hypertension in whom it is described as reduced.

Biomarkers↗
PubMed1997

Immunology of liver transplantation: clinical management aspects.

Orthotopic liver transplantation has developed into the treatment of choice for many patients who develop complications of end-stage liver disease. With improvements in surgical technique and overall survival since the inception of liver grafting, a major consideration in the longterm care of liver transplant patients has become the management of allograft rejection and immunosuppressive therapy. With an increasing number of patients having undergone successful transplantation in the community, practicing gastroenterologists will likely be called upon more frequently to render care to these patients. In this article, the immunobiology of transplantation and rejection is discussed with an emphasis placed on the T-cell-major histocompatibility complex interaction, cytokine stimulation, and adhesion molecule binding. Commonly used immunosuppressive medications and promising ones for the future are reviewed. Also, clinical aspects of the short- and long-term management of immunosuppression are explored.

Graft Rejection↗
PubMed1997

Salivary excretion of endogenous proteins in nephrotic syndrome in children.

Size and charge selectivity of capillary permeability in the salivary glands of nephrotic children were investigated by measuring salivary excretion of endogenous plasma proteins of different size and charge. We examined 10 children with steroid-sensitive nephrotic syndrome (SSNS) in relapse and subsequent remission, 11 with steroid-resistant nephrotic syndrome, and 11 healthy children (controls). Albumin [mol. wt. 66 kilodaltons (kDa), isoelectric point (pI) 4.9] was measured by radio-immunoassay, transferrin (mol. wt. 77 kDa, pI 5.9) and immunoglobulins IgG1 (mol. wt. 150 kDa, pI 7-9) and IgG4 (mol. wt. 150 kDa, pI < 6) by enzyme-linked immunoabsorbent assay. In saliva, no significant differences were found between the four groups of children for any of the four proteins. Also, the saliva/plasma ratios of the four proteins were not different among the four groups. From these data, we conclude that in subjects with SSNS in relapse, neither size nor charge selectivity of salivary gland capillary permeability are affected.

Adolescent↗
PubMed1996

15-year follow-up of renin and blood pressure in reflux nephropathy.

BACKGROUND: Beginning in 1978 a cohort of patients with reflux nephropathy first seen at a London Childrens hospital have had 5-yearly follow-ups. This is the fourth (15-year) report from that series. METHODS: Of the original 100 normotensive children with reflux nephropathy 78 were traced for the 15-year study in 1994. Five patients were excluded because of nephrectomy, ten for other reasons, and eight refused to take part, leaving 55. 26 were on oral contraceptives. Supine blood pressure and plasma renin activity (PRA) were measured, and daily sodium excretion was assessed on a sample of overnight urine. FINDINGS: Of the 55 patients (15 male, 40 female, median age 27 years, range 20-31), five had systolic and two had diastolic hypertension. Compared with the 10-year (1988) follow-up there was no change in blood pressure standard deviation scores (SDS) in this cohort. PRA showed an increasing dissociation from controls after 15 years of age and was significantly above that of controls by age 25. Exclusion of the patients on oral contraceptives did not significantly alter the results. The PRA values in 1988 were not individually predictive of the development of hypertension over the ensuing 5 years. INTERPRETATION: Previously, in the long-term study of reflux nephropathy, blood pressure SDS had progressively increased with age. By 15 years blood pressure had levelled out and the PRA, though raised, did not predict the development of hypertension. Oral contraceptive use did not significantly modify the results.

Adolescent↗
PubMed1996

Tubular proteinuria in reflux nephropathy: post ureteric re-implantation.

We studied urine protein excretion in 55 adults with reflux nephropathy (median age 26.9 years) who had had normal blood pressure, renal function and ureteric reimplantation in childhood. Urine retinol binding protein (RBP), N-acetyl-beta-D-glucosaminidase (NAG), albumin, bacteriuria, systolic blood pressure, glomerular filtration rate (GFR), peripheral plasma renin activity (PRA) and the degree of renal scarring were measured in each subject; 20 had bilateral and 35 unilateral renal scarring; 5 were hypertensive and none were in renal failure. Urinary NAG and RBP excretions were significantly greater in the study group than in 34 healthy controls (median age 29.7 years). Within the study group, NAG excretion significantly correlated with PRA (P = 0.02). RBP excretion correlated with PRA, systolic blood pressure and the laterality (bilateral vs. unilateral) of scarring (P < 0.01). Urinary albumin excretion correlated with systolic blood pressure (P = 0.03). We conclude that increased urinary protein, especially NAG and RBP excretion, occur late after ureteric re-implantation in reflux nephropathy independent of GFR. Its association with PRA supports the concept of segmental perfusion and filtration as an important mechanism that may explain the above findings.

Acetylglucosaminidase↗
PubMed1996

Role of endothelium in the abnormal response of mesenteric vessels in rats with portal hypertension and liver cirrhosis.

BACKGROUND & AIMS: Previous studies have shown that nitric oxide synthesis inhibition corrects the hyporesponsiveness to vasoconstrictors present in the mesenteric vascular bed of portal-hypertensive rats. The origin of this elevated NO production, whether endothelial or muscular, is unknown. The aim of this study was to evaluate the role of vascular endothelium in the hyporesponsiveness to methoxamine (MTX) in the mesenteric vascular bed of portal vein-ligated (PVL) and cirrhotic rats. METHODS: Endothelial denudation was achieved using a combined treatment of cholic acid and distilled water. RESULTS: Compared with the respective control groups, PVL rats showed a reduced vascular response to MTX. Similar results were obtained in cirrhotic animals. The presence of ascites was associated with a more severe reduction in the response to MTX. Removal of the endothelium completely corrected the vascular hyporesponsiveness of PVL, cirrhotic nonascitic, and ascitic animals. In these experiments, acetylcholine-mediated vasodilation was practically absent whereas that of sodium nitroprusside was potentiated, which indicates a successful elimination of the endothelium and the preservation of smooth muscle function. Immunostaining for NO synthase isoforms revealed the presence of endothelial NO synthase protein in healthy and PVL rats exclusively in the endothelium. CONCLUSIONS: The mesenteric vascular hyporesponsiveness to MTX present in these models of liver diseases and portal hypertension is solely due to endothelium-dependent factors.

Animals↗
PubMed1996

Normal levels of soluble E-selectin, soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1) decrease with age.

sE-selectin, sICAM-1, sVCAM-1 and von Willebrand factor (vWF) were assayed in 238 samples in a longitudinal study of 81 normal children from 9.5 to 15.5 years old. Multilevel modelling was used to quantify changes with age. sE-selectin, sICAM-1 and sVCAM-1 all fell significantly over the age range (by 17%, 16%, and 10%, respectively). In contrast, levels of vWF were not age-dependent. Our findings highlight the need for age-matched controls when studying cell surface adhesion molecules in disease groups, and may imply developmental changes in expression of these molecules and their shedding from the cell surface.

Adolescent↗
PubMed1996

Cystadenoma of spermatic cord resembling ovarian serous epithelial tumour of low malignant potential: immunohistochemical study suggesting Müllerian differentiation.

A cystic lesion of the spermatic cord resembling an ovarian serous epithelial tumour of low malignant potential or borderline malignancy is reported. Immunohistochemical staining and electronmicroscopic examination suggested epithelial rather than mesothelial differentiation of the cyst lining cells. There was strong positive immunohistochemical staining of cyst lining cells for CA 125, providing evidence for Müllerian differentiation. A flow cytometric analysis of nuclear DNA content revealed a diploid profile.

Aged↗
PubMed1996

Albendazole-induced pseudomembranous colitis.

We report a patient with AIDS and intestinal microsporidiosis. While undergoing treatment with albendazole, he developed worsening diarrhea with abdominal pain and fever. The diagnosis of pseudomembranous colitis was made by flexible sigmoidoscopy and a positive stool specimen for Clostridium difficile toxin. The patient's symptoms resolved with oral vancomycin and his stool C. difficile toxin became negative. Albendazole is an antibiotic that is chemically related to metronidazole. Although a few case reports link metronidazole with the development of pseudomembranous colitis, albendazole has not been associated with the development of this condition. The spectrum of antimicrobial activity of albendazole and its efficacy in the treatment of intestinal microsporidiosis are reviewed. Pathogenic mechanisms for the development of pseudomembranous colitis and the epidemiology of this condition in patients with AIDS are discussed.

AIDS-Related Opportunistic Infections↗
PubMed1996

Intravascular ultrasound for evaluation of coronary arteries.

Intravascular ultrasound (IVUS) has emerged form a research tool to an intrinsic part of modern invasive cardiology. The main reason is the capability to obtain "in vivo" histology. For the first time it is possible to base decisions not only on lumenograms but also on vessel wall assessment. The capabilities of IVUS can be divided in its (a) diagnostic and (b) intervention associated potentials. Diagnostic strength of IVUS is the ability to monitor compensatory coronary artery enlargement as a response to arteriosclerosis, to assess intermediate lesions, to reveal occult left main stem disease, and angiographycally "silent" arteriosclerosis. The intervention associated potentials of IVUS are the ability to allow optimal device selection, i.e. rotablators in calcified lesions or atherectomy devices in large plaque burden. The effects of PTCA on vessel wall morphology can be studied in great detail and the effect on luminal gain can be assessed almost on-line. Several groups showed, that the residual plaque area even after angiographycally successful PTCA lies still in the range of 60%. A significant reduction of this number may influence longterm outcome after PTCA. Minimal luminal areas and residual plaque area after PTCA seem to be an indicator of restenosis, while the presence or absence of dissections seem to be less predictive. Intravascular monitoring of stent expansion led to high-pressure stent deployment with significant increase in post-procedural luminal diameters and finally the ability to withhold anticoagulation in patients with optimal stent deployment. In the future, integrated devices, like balloons on intravascular ultrasound catheters, steerable catheters, integrated flow and pressure transducers, tissue characterization, and 0.018 "intravascular ultrasound guide-wires will further enhance the usefulness of IVUS.

Angioplasty, Balloon, Coronary↗