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Biomedical subjects

V Shah

Publications and source records attributed to V Shah.

At least 55 records · Page 3Linked to original sources

Correlation of the local distribution of topically applied substances inside the stratum corneum determined by tape-stripping to differences in bioavailability.

Tape-stripping and optical spectroscopy are used as a suitable combined method to determine the horny layer profile. Firstly, typical ultraviolet filter substances are used as active substances which are fixed inside the horny layer. Secondly, clobetasol propionate was applied topically in two formulations, Temovate Cream and Temovate and Emollient. The measured changes in the local distribution of the drug inside stratum corneum reflect the observed differences in the biological response visualized as blanching. The concentration of the drug in deeper parts of the horny layer proposes the existence of a small channel available for the percutaneous absorption. The observed low intensity blanching is correlated to the follicle orifices of the skin. After application of Temovate and Emollient, a lateral spreading of the drug must be taken into account.

Administration, Topical↗

Selective screening for neonatal galactosemia: an alternative approach.

UNLABELLED: No universal consensus exists for population-based neonatal screening for galactosemia. In our institution, selective screening for classical galactosemia is carried out on infants under 2 wk of age and those with symptoms suggestive of this disorder. Eighteen cases were diagnosed from 25,099 tests done; 17 were symptomatic at the time of diagnosis. CONCLUSION: We suggest that improved clinical vigilance and selective screening would identify most infants with severe galactosemia as early as a population-based program.

Biomarkers↗

Desmoplastic astrocytoma of infancy--a case report.

Desmoplastic cerebral astrocytoma of infancy (DCAI) is a rare tumor which shows spindle cells embedded in an extremely desmoplastic stroma. We describe a case of DCAI seen in the frontoparietal region of brain in a three-month-old infant. Microscopically classic histology of DCAI was seen. On immunohistochemistty the tumor showed strong Vimentin, S-100 and Glial Fibrillary Acidic Protein (GFAP) positivity. The brain adjacent to the tumor-showed multi-cystic transformation and the tumor formed a solid area in the wall of this cystic structure. This adjacent brain showed mild disarray of architecture and gliosis. Three months after surgery this infant was alive and well.

Astrocytoma↗

Direct interaction between endothelial nitric-oxide synthase and dynamin-2. Implications for nitric-oxide synthase function.

Endothelial nitric-oxide synthase (eNOS) is regulated in part through specific protein interactions. Dynamin-2 is a large GTPase residing within similar membrane compartments as eNOS. Here we show that dynamin-2 binds directly with eNOS thereby augmenting eNOS activity. Double label confocal immunofluorescence demonstrates colocalization of eNOS and dynamin in both Clone 9 cells cotransfected with green fluorescent protein-dynamin and eNOS, as well as in bovine aortic endothelial cells (BAEC) expressing both proteins endogenously, predominantly in a Golgi membrane distribution. Immunoprecipitation of eNOS from BAEC lysate coprecipitates dynamin and, conversely, immunoprecipitation of dynamin coprecipitates eNOS. Additionally, the calcium ionophore, a reagent that promotes nitric oxide release, enhances coprecipitation of dynamin with eNOS in BAEC, suggesting the interaction between the proteins can be regulated by intracellular signals. In vitro studies demonstrate that glutathione S-transferase (GST)-dynamin-2 quantitatively precipitates both purified recombinant eNOS protein as well as in vitro transcribed (35)S-labeled eNOS from solution indicating a direct interaction between the proteins in vitro. Scatchard analysis of binding studies demonstrates an equilibrium dissociation constant (K(d)) of 27.6 nm. Incubation of purified recombinant eNOS protein with GST-dynamin-2 significantly increases eNOS activity as does overexpression of dynamin-2 in ECV 304 cells stably transfected with eNOS-green fluorescent protein. These studies demonstrate a direct protein-protein interaction between eNOS and dynamin-2, thereby identifying a new NOS-associated protein and providing a novel function for dynamin. These events may have relevance for eNOS regulation and trafficking within vascular endothelium.

Animals↗

Venepuncture versus heel lance for blood sampling in term neonates.

BACKGROUND: Heel lance has been the conventional method of blood sampling in neonates for screening tests. Neonates undergoing this procedure experience pain. Despite various studies evaluating the role of pharmacological and non-pharmacological interventions to date, there are no effective and practical methods to alleviate pain from heel lance. OBJECTIVES: To determine whether venepuncture or heel lance is less painful and more effective for blood sampling in term neonates. SEARCH STRATEGY: Systematic search in accordance with Cochrane Neonatal Collaborative Review Group. All randomized controlled trials which compared pain response to venepuncture vs. heel lance were searched using MEDLINE, Embase, CINAHL, the Cochrane Library, reference lists of identified trials and personal files. No language restrictions were applied. SELECTION CRITERIA: Randomized controlled trials which compared pain response to venepuncture vs. heel lance were selected for this review. DATA COLLECTION AND ANALYSIS: Data regarding the primary outcome of pain response to venepuncture vs. heel lance as assessed by validated pain measures were abstracted. Secondary outcomes including the need of repeat blood sampling, bruising/hematoma at local site, and parental perception of their own anxiety and infant's pain were also abstracted. All data were analysed using Revman 3.1. When possible, meta-analysis was done using relative risk (RR) and event rate difference (ERD), along with their 95% confidence intervals (CI). If ERD was significant, number needed to treat (NNT) was calculated. MAIN RESULTS: Two trials were eligible for inclusion in the review. One study using Neonatal Infant Pain Scale (NIPS) and one study using Neonatal Facial Action Coding System (NFCS) and cry duration showed statistically significantly lower pain scores for venepuncture as compared to heel lance. In one study, maternal anxiety was noted to be higher in the venepuncture group as compared to heel lance group prior to the procedure; however, after observing the procedure, mothers rated their infant's pain to be lower in the venepuncture group. A meta-analysis was performed on the need for at least one additional skin puncture to obtain the required amount of blood using venepuncture as compared to heel lance. The relative risk for requiring more than one skin puncture for venepuncture versus heel lance was 0.19 [95% confidence interval (CI) 0.10, 0.38]. The risk difference was -53% (95% CI -66%, -40%). The number needed to treat (NNT) to avoid one repeat skin puncture was 1.9 (95% CI 1.5, 2.5). REVIEWER'S CONCLUSIONS: Venepuncture, when performed by a trained phlebotomist, appears to be the method of choice for blood sampling in term neonates. For each two venepunctures instead of heel lance, the need for one additional skin puncture can be avoided. In view of the promising results derived from small studies with some methodological limitations, further well designed randomized controlled trials need to be conducted. The interventions should be compared in settings where several individuals perform the venepuncture and/or the heel lance.

Blood Specimen Collection↗

Erythromycin for feeding intolerance in preterm infants.

BACKGROUND: Functional immaturity of gastointestinal motility predisposes preterm infants to feeding intolerance. Motilin, a gastrointestinal peptide, stimulates propagative contractile activity during phase III of the migratory motor complex in the interdigestive state. Erythromycin (EM) is a motilin agonist with prokinetic effect at low doses (1-3mg/kg). OBJECTIVES: To evaluate the effectiveness of EM in promoting gastrointestinal motility in preterm infants with feeding intolerance and assess clinically significant adverse effects associated with its use. SEARCH STRATEGY: Systematic literature search in accordance with the Cochrane Neonatal Collaborative Review Group search strategy. Randomized and quasi-randomized controlled trials of EM use, at any dose, in preterm infants to promote gastrointestinal motility were identified by searching MEDLINE, EMBASE, CINAHL, the Cochrane Library, reference lists of published studies, personal files, and abstracts published in Pediatric Research. SELECTION CRITERIA: Randomized controlled trials of oral or intravenous EM use at dose range of 3 to 12 mg/kg/day in preterm infants less than or equal to 36 weeks gestational age with feeding tolerance were included in this review. DATA COLLECTION AND ANALYSIS: Data regarding the primary clinical outcome of days to achieve full enteral feeding were compared among studies. Data on secondary outcomes including adverse effects associated with the use of EM (diarrhea, nosocomial infections, cardiac arrhythmias, or theophylline toxicity), duration of parenteral nutrition, weight gain, incidence of necrotizing enterocolitis (NEC), hypertrophic pyloric stenosis, and length of hospital stay were assessed. MAIN RESULTS: Two randomized controlled studies of EM use in preterm infants for improving gastrointestinal motility were identified. Since both studies involved preterm infants treated with EM at dose >12mg/kg/day at commencement of feeding, they did not meet inclusion criteria defined a priori for this review. There was no statistically significant difference in the incidence of NEC (RR 0.59, 95%CI 0.11, 3.01; RD -0.021, 95%CI -0. 087, 0.045). No statistically significant difference was noted in days to achieve full enteral feeds, length of hospital stay, and adverse events between groups. REVIEWER'S CONCLUSIONS: EM at antimicrobial doses may not be effective in preterm infants with feeding intolerance. Further studies are needed to determine whether EM in lower doses is effective as a prokinetic agent in such infants.

Anti-Bacterial Agents↗

Early administration of inhaled corticosteroids for preventing chronic lung disease in ventilated very low birth weight preterm neonates.

BACKGROUND: Chronic lung disease remains a common complication amongst preterm infants. There is increasing evidence that inflammation play an important role in the pathogenesis of CLD. Due to their strong anti-inflammatory properties corticosteroids is an attractive intervention strategy. However, there are growing concerns regarding short and long term effects of systemic corticosteroids. Theoretically, administration of inhaled corticosteroids may allow for beneficial effects on the pulmonary system with a lower risk of undesirable systemic side effects. OBJECTIVES: To determine the impact of inhaled corticosteroids administered to ventilated very low birth weight preterm neonates in the first two weeks of life for the prevention of chronic lung disease(CLD). SEARCH STRATEGY: Systematic search in accordance with Cochrane Neonatal Review Group. Randomized and quasi-randomized trials were identified by searching MEDLINE, Embase, CINAHL, the Cochrane Library, reference lists of published trials and abstracts published in Pediatric Research. SELECTION CRITERIA: Randomized controlled trials of inhaled corticosteroid therapy initiated within the first 2 weeks of life in ventilated preterm infants with birth weight 1500 grams or less were included in this review. DATA COLLECTION AND ANALYSIS: Data regarding clinical outcomes including chronic lung disease at 28 days or 36 weeks corrected gestational age (CGA), mortality, combined outcome of death or CLD at 28 days of age and at 36 weeks CGA, the need for systemic corticosteroids, failure to extubate within 14 days and adverse effects of corticosteroids were evaluated. All data were analyzed using Revman 3.1. When possible, meta-analysis was performed using relative risk (RR), risk difference (RD), along with their 95% confidence intervals (CI). If RD was significant, number needed to treat (NNT) was calculated. MAIN RESULTS: Eight trials assessing the impact of inhaled corticosteroid for the prevention of CLD were identified. The study by Kovacs 1998 was excluded as investigators evaluated the impact of a combination of systemic and inhaled corticosteroid for prevention of CLD. Seven trials qualified for inclusion in this review but data from two of these studies are awaiting assessment. Thus, the present review includes data analyses based on five qualifying trials. There was no statistically significant effect of inhaled steroids on CLD either at 28 days or at 36 weeks CGA, when analyzed either for all randomized infants or amongst survivors. No statistically significant differences were noted for mortality or for the combined outcome of mortality and CLD either at 28 days of age or at 36 weeks CGA. The meta-analysis supports a reduction in the need for systemic steroids, RR 0.78 (95% CI 0.62, 0.99), RD -0. 097 (95% CI -0.187, -0.008); however statistical heterogeneity was noted. The number needed to treat (NNT) to reduce the need for systemic steroid was 10 (95% CI 5.3, 125). There were no statistically significant differences in adverse events between groups. REVIEWER'S CONCLUSIONS: There is no evidence from the trials reviewed that early administration (in the first 2 weeks of life) of inhaled steroids to ventilated preterm neonates was effective in reducing the incidence of CLD. There was a reduction in the need for systemic steroids. Although this difference was statistically significant, there was significant heterogeneity between studies and the upper limit of the 95% CI for this outcome was very close to no effect. Currently, use of inhaled steroids in this population cannot be recommended. Studies are needed to identify the risk/benefit ratio of different delivery techniques and dosing schedules for the administration of these medications. Studies need to address both the short-term and long-term benefits and adverse effects of inhaled steroids with particular attention to neurodevelopmental outcome.

Administration, Inhalation↗

Renal amyloidosis following tuberculosis.

Amyloidosis, either primary or secondary, may be defined as a group of chronic infiltrative disorders that have in common a beta-pleated sheet configuration on X-ray diffraction examination, a fine fibrillar nonbranching appearance on electron microscopy and an apple-green birefringence when examined under polarised light after staining with Congo-red. Renal amyloidosis is a rare entity in the pediatric age group and is almost always secondary in nature, related to chronic infections and inflammatory conditions. It occurs 2-7 years after a chronic inflammatory process; however an onset as early as 9 months of life is known. The diagnosis of amyloidosis is suspected on the basis of clinical features and is established by obtaining an appropriate tissue biopsy and demonstrating amyloid with appropriate stains. All the tissues obtained must be stained with Congo-red stain which is the singlemost useful diagnostic test to define amyloidosis. In order to differentiate the primary from secondary variety, the deposits may be treated with potassium permanganate before Congo-red staining. In secondary amyloidosis, the green birefringence seen under polarized light is abolished. Therapeutic approaches include specific measures to reduce the amyloid deposition and general measures to relieve symptoms related to involvement of specific organs. The prognosis in renal amyloidosis is relatively poor, with a median survival of 9-13 months in primary amyloidosis complicated by renal involvement, and more than 50 months in secondary amyloidosis. We have reported a case of secondary amyloidosis following tuberculosis and have discussed the clinical features, diagnosis and management of amyloidosis.

Amyloidosis↗

Degradation of polycyclic aromatic hydrocarbons by the copper(II)-hydrogen peroxide system.

A non-enzymic system containing CuSO4 (10 mmol/L) and hydrogen peroxide (100 mmol/L) was used for the degradation of three polycyclic aromatic hydrocarbons: phenanthrene, fluoranthene, and pyrene (all at 10 mmol/L). The system degraded the compounds rapidly and efficiently. After 1 d at room temperature, more than 80% of pyrene, phenanthrene, and fluoranthene disappeared. Several products are formed during the reaction including a black precipitate.

Biodegradation, Environmental↗

Characterization of the extracellular polysaccharide produced by a marine cyanobacterium, Cyanothece sp. ATCC 51142, and its exploitation toward metal removal from solutions.

Cyanobacterium, Cyanothece sp. ATCC 51142 produces an exopolysaccharide at a high level. Physical analysis of the exopolysaccharide (EPS), such as nuclear magnetic resonance, infrared spectrum, were done to determine its possible structure. Thermal gravimetric analysis, differential scanning calorimeter, and differential thermal analysis of the polymer were done to find out the thermal behavior. Calcium content within the sample was found out. Some of the physicochemical properties, such as relative viscosity, specific viscosity, and intrinsic viscosity of the EPS were studied under different conditions. The phenomenon of gel formation by the EPS was investigated for its potential application in metal removal from solutions.

Calcium↗

Neonatal escherichia coli infections: concerns regarding resistance to current therapy.

UNLABELLED: Currently recommended antibiotic treatment of suspected neonatal sepsis is ampicillin and an aminoglycoside. Recently, we observed increasing ampicillin and gentamicin resistance in strains of Escherichia coli isolated from neonates at our institution. We therefore reviewed clinical and laboratory records of all neonates with systemic infection, hospitalized from 1994 through 1998, from whom E. coli was isolated from blood and/or cerebrospinal fluid. The influence of perinatal variables (e.g. rupture of foetal membranes > 24h, group B Streptococcus (GBS) colonization, urinary tract infection during pregnancy and the use of antepartum and/or intrapartum antibiotics), and neonatal variables (e.g. gestational age, age at onset of sepsis (early: < or = 72 h, late: >72 h), number of E. coli septic recurrences, and associated underlying medical and/or surgical conditions) on antimicrobial susceptibilities of invasive E. coli isolates was studied. Twenty-three neonates with invasive E. coli infection were identified; most [19 (83%)] presented as late-onset sepsis (LOS). Ampicillin-resistant E. coli were isolated in 75% and 53% of neonates in the early- and late-onset groups, respectively. Gentamicin resistance was found in 50% of early-onset sepsis (EOS) isolates compared with 16% in the late-onset group. Isolates from two neonates with EOS were resistant to both ampicillin and gentamicin. One neonate with EOS and three with LOS had recurrent E. coli sepsis; all isolates were ampicillin-resistant and one was gentamicin-resistant. All these neonates were initially treated with ampicillin and gentamicin. Both groups had associated underlying medical and/or surgical conditions (50% early-onset, 47% late-onset). Maternal GBS colonization occurred in 2 (50%) versus 3 (16%) of EOS and LOS cases, respectively. All GBS colonized women received intrapartum ampicillin prior to delivery. CONCLUSIONS: Ampicillin and gentamicin resistance is emerging in neonatal E. coli isolates from invasive infection. Current- empiric management of neonatal sepsis requires re-evaluation given changing antimicrobial susceptibilities.

Ampicillin↗

Functional interdependence and colocalization of endothelial nitric oxide synthase and heat shock protein 90 in cerebral arteries.

Heat shock protein 90 (HSP90), an essential component of several signal transduction systems, participates in the activation of endothelial nitric oxide synthase (eNOS) in cells. The objective of the current study was to determine if HSP90 and eNOS were functionally interdependent and colocalized in the cerebral circulation. The authors used isometric force recording, cyclic 3'5'-guanosine monophosphate (cGMP) radioimmunoassay (RIA), and immunogold electron microscopy (EM) to study canine basilar artery. They found that geldanamycin (0.1 to 10 microg/mL), a selective HSP90 inhibitor, caused concentration-dependent contractions in arterial rings (n = 6 dogs). Contractions to geldanamycin were unaffected by a cyclooxygenase inhibitor, indomethacin (10 micromol/L; P < 0.05, n = 6). Functional evidence for interaction between HSP90 and nitric oxide (NO)-mediated signaling included observations that the contractile effect of geldanamycin was the following: (1) endothelium-dependent, (2) abolished by Ng-nitro-L-arginine methylester (L-NAME; 0.3 mmol/L), and (3) non-additive with the contractile effect of this NOS inhibitor (P < 0.01, n = 6 for each). Furthermore, RIA showed significant reduction in cGMP levels in arteries treated with geldanamycin (3 microg/mL; P < 0.02, n = 8), whereas immunogold EM demonstrated areas of colocalization of HSP90 and eNOS selectively in the cytoplasm of endothelial cells. The current findings suggest that in cerebral arteries, endothelial HSP90 plays an important role in modulation of basal NO-mediated signaling. This interaction may be particularly important in stress-induced up-regulation of HSP90 with subsequent alteration of vasomotor function.

Animals↗

Dislodgement of the locking cap from the AO unreamed intramedullary nail: a case report.

We report on the dislodgement of the proximal locking cap from an AO solid femoral intramedullary nail with spiral blade. The pathologic femoral fracture subsequently went on to heal, and the spiral blade did not back out of the femoral neck. Meticulous intraoperative attention to detail is required to select the correct offset for the proximal cap, because the turning moments of the hip abductor muscles are sufficient to unscrew a prominent cap.

Bone Nails↗

Gene transfer of recombinant endothelial nitric oxide synthase to liver in vivo and in vitro.

Endothelial nitric oxide synthase (eNOS)-derived nitric oxide (NO) contributes to hepatic vascular homeostasis. The aim of this study was to examine whether delivery of an adenoviral vector encoding eNOS gene to liver affects vasomotor function in vivo and the mechanism of NO production in vitro. Rats were administered adenoviruses encoding beta-galactosidase (AdCMVLacZ) or eNOS (AdCMVeNOS) via tail vein injection and studied 1 wk later. In animals transduced with AdCMVLacZ, beta-galactosidase activity was increased in the liver, most prominently in hepatocytes. In AdCMVeNOS-transduced animals, eNOS protein levels and catalytic activity were significantly increased. Overexpression of eNOS diminished baseline perfusion pressure and constriction in response to the alpha(1)-agonist methoxamine in the perfused liver. Transduction of cultured hepatocytes with AdCMVeNOS resulted in the targeting of recombinant eNOS to a perinuclear distribution and binding with the NOS-activating protein heat shock protein 90. These events were associated with increased ionomycin-stimulated NO release. In summary, this is the first study to demonstrate successful delivery of the recombinant eNOS gene to liver in vivo and in vitro with ensuing NO production.

Adenoviridae↗

Mechanisms of vascular instability in a transgenic mouse model of sickle cell disease.

We investigated a transgenic mouse model of sickle cell disease, homozygous for deletion of mouse beta-globin and containing transgenes for human beta(S) and beta(S-antilles) globins linked to the transgene for human alpha-globin. In these mice, basal cGMP production in aortic rings is increased, whereas relaxation to an endothelium-dependent vasodilator, A-23187, is impaired. In contrast, aortic expression of endothelial nitric oxide synthase (NOS) is unaltered in sickle mice, whereas expression of inducible NOS is not detected in either group; plasma nitrate/nitrite concentrations and NOS activity are similar in both groups. Increased cGMP may reflect the stimulatory effect of peroxides (an activator of guanylate cyclase), because lipid peroxidation is increased in aortae and in plasma in sickle mice. Despite increased vascular cGMP levels in sickle mice, conscious systolic blood pressure is comparable to that of aged-matched controls; sickle mice, however, evince a greater rise in systolic blood pressure in response to nitro-L-arginine methyl ester, an inhibitor of NOS. Systemic concentrations of the vasoconstrictive oxidative product 8-isoprostane are increased in sickle mice. We conclude that vascular responses are altered in this transgenic sickle mouse and are accompanied by increased lipid peroxidation and production of cGMP; we suggest that oxidant-inducible vasoconstrictor systems such as isoprostanes may oppose nitric oxide-dependent and nitric oxide-independent mechanisms of vasodilatation in this transgenic sickle mouse. Destabilization of the vasoactive balance in the sickle vasculature by clinically relevant states may predispose to vasoocclusive disease.

Anemia, Sickle Cell↗

Pycnogenol protects vascular endothelial cells from beta-amyloid-induced injury.

The neuropathological hallmarks of Alzheimer's disease (AD) are senile plaques, cerebrovascular beta-amyloidosis, neurofibrillary tangles, and selective neuronal loss. Beta-amyloid (Abeta) has been shown to cause vascular damage mediated by generation of reactive oxygen species and this damage is considered an early event in the development of AD. In this study, we determined the effect of pyenogenol, a potent antioxidant phytochemical, on Abeta-induced cellular injury. Pulmonary artery endothelial cells (PAEC) were exposed to Abeta for 24 h. Cell injury was assessed by measuring cell viability with methylthiazol tetrazolium (MTT) assay, and by determining the release of intracellular lactate dehydrogenase (LDH). Lipid peroxidation products of PAEC were determined by measuring thiobarbituric acid-reactive substances (TBARS). Exposure of PAEC to Abeta resulted in a decrease in cell viability, an increase of LDH release indicating membrane damage, and an elevated level of TBARS. Preincubation of PAEC with pycnogenol significantly minimized these changes. This study demonstrated that pycnogenol can protect vascular endothelial cells from Abeta-induced injury. The data suggest that pycnogenol may be useful for the prevention and/or treatment of vascular or neurodegenerative diseases associated with Abeta toxicity.

Alzheimer Disease↗