Search PubMed⌕ Search

Biomedical subjects

S Shah

Publications and source records attributed to S Shah.

At least 55 records · Page 3Linked to original sources
PubMed2003

Magnetic resonance imaging, Down's syndrome and Alzheimer's disease: research and clinical implications.

BACKGROUND: The diagnosis of Alzheimer's disease (AD) remains at times difficult to make using available neuropsychological measures. Neuro-imaging is a relatively new form of detecting the changes associated with dementia. The present study investigated the role of magnetic resonance imaging (MRI) in diagnosing AD in adults with Down's syndrome (DS). METHODS: Subjects with DS and Alzheimer-type dementia were matched to non-demented controls with DS. Magnetic resonance imaging findings (i.e. volumetric and two-dimensional scans) were compared between the two groups in order to show a relationship between the changes of AD and structural MRI abnormalities. RESULTS: Specific structural abnormalities which are seen in non-intellectually disabled subjects with dementia are also found in individuals with both DS and AD. However, such findings cannot be used to diagnose clinical AD with good accuracy in adults with DS. A number of practical issues of patient compliance and over-sedation are demonstrated by the findings. CONCLUSIONS: Magnetic resonance imaging has an important but limited role to play in the management of AD in the population with DS. If intravenous sedation is used, medical support is essential to prevent a serious mishap.

Adult↗
PubMed2003

Cross-sectional survey of the extent and indicators of hepatitis C virus infection in Houston Department of Health and Human Services' sexually transmitted disease clinics.

To evaluate the prevalence and indicators of hepatitis C virus (HCV) infection in Houston and determine the effectiveness of targeted HCV screening in sexually transmitted disease (STD) clinics. We performed a cross-sectional survey in low-risk and high-risk groups in Houston. This included a blinded survey of HCV conducted in 1010 STD clinic clients having serological syphilis tests, and 1885 multi-speciality group practice patients having metabolic blood work. This was followed with a targeted hepatitis C survey of 822 high-risk clients from STD clinics. The seroprevalence of hepatitis C infection in the blinded survey was 3.9% (95% CI 3.0-4.8) in the multi-speciality group and 5.0% (95% CI 3.7-6.3) in the STD clinics. Prevalence of hepatitis C infection among targeted STD clinic clients was significantly higher at 15.3% (95% CI 12.7-17.7). Risk factors that correlated with HCV infection after logistic regression included: injection drug use (OR = 10, 95% CI = 3.4-30.3), heroin use (OR = 6.6, 95% CI = 2.2-20.5), non-transfusion/ transplantation blood exposure (OR = 3.0, 95% CI = 1.3-6.9), sharing equipment to snort drugs (OR = 2.5, 95% CI 1.2-5.4), and age above 25 years (OR = 51, 95% CI = 9-47). This study demonstrates that targeting clients in STD clinics for known risk behaviours is an effective way to identify cases of HCV infection. STD clinics allow access to clients with both drug use and sexual risk behaviours and are a useful location for targeting hepatitis C screening and prevention efforts.

Adolescent↗
PubMed2003

Evaluation of standardized versus individualized total parenteral nutrition regime for neonates less than 33 weeks gestation.

OBJECTIVE: To evaluate the difference in nutrient intakes and biochemical responses in newborn infants <33 weeks gestation who received standardized versus individualized total parenteral nutrition (TPN) regimes. METHOD: Comparison of nutrient intakes and daily biochemical responses in newborn infants <33 weeks gestation who received standardized regime versus those who received individualized TPN regimes from day 2 to day 7 of life. RESULTS: Twenty-seven infants in the standardized TPN group and 31 infants in the individualized TPN group were compared. There were no statistically significant differences (P > 0.05) between the two groups in gestation, birthweight, Clinical Risk Index for Babies scores, daily TPN volume intake and biochemical responses. Infants in the standardized TPN group received less sodium (P < 0.01) and no potassium on day 2 as required, more protein (P < 0.02) every day, and more calcium and phosphate (P < 0.02 from day 4). CONCLUSION: There were no significant clinical and statistical differences in biochemical responses in newborn infants <33 weeks gestation who received standardized versus individualized TPN regimes during the first week of life. The economic cost of TPN provision using standardized TPN formulation was approximately 30% lower.

Cost-Benefit Analysis↗
PubMed2003

Use of a paper disposable cup as a spacer is effective for the first-aid management of asthma.

OBJECTIVE: There are many settings in which a spacer device is not available for the administration of bronchodilator. Therefore, we tested whether a paper disposable cup is as effective as a commercially produced spacer to administer bronchodilator. METHODOLOGY: Randomised controlled trial. 50 subjects aged 16-50 years who had wheeze and a greater than 10% decrease in FEV1 after histamine inhalation test (HIT). Subjects were randomised to either the 150 ml paper disposable cup group (CUP) or the commercially produced spacer group (SPACER). Twenty minutes after 400 microg salbutamol was administered FEV1 was measured. The recovery index measured post-bronchodilator FEV1 as a percentage of baseline FEV1. Also, analysis of covariance tested whether recovery of FEV1 was related to the magnitude of the fall following the HIT. RESULTS: There were no statistically significant differences between CUP and SPACER groups in any characteristics. There was no difference for the recovery index (t48=1.14, P=0.26). Regression analyses showed that the relation between the magnitude of the fall in FEV1 during the HIT and the percent recovery was not different between the CUP and SPACER groups (t=-1.2, P<0.23). CONCLUSIONS: A paper disposable cup was effective for the reversal of mild to moderate bronchoconstriction. Therefore, a paper disposable cup can be used for the first-aid management of asthma when there is concern about cross-infection and a commercially produced spacer is not available.

Adolescent↗
PubMed2003

Minimal access surgery for hydatid cyst disease: laparoscopic, thoracoscopic, and retroperitoneoscopic approach.

Surgery has remained the mainstay for the treatment of hydatid cyst. The rapid development of laparoscopic techniques has encouraged surgeons to replicate principles of conventional hydatid surgery using a minimally invasive approach. Several reports have confirmed the feasibility of laparoscopic hepatic hydatid surgery. We report the use of a laparoscopic approach for cysts located in the liver, lung, and retroperitoneum. Fifteen patients with hydatid cysts, including one patient with a recurrent cyst, of various organs, including the liver, lung, and retroperitoneum, were operated on laparoscopically. Sixteen hydatid cysts were drained in a total of 15 patients. The mean operative time was 84 +/- 6 minutes (60-125 minutes). The mean duration of the hospital stay was 2.3 days (1-6 days). The mean cyst diameter was 9.2 cm (6.4-13.5 cm). No conversions to open surgery were required. One complication, a trocar-induced bowel perforation, occurred, and there was no mortality. During 3 to 44 months (mean, 27 months) of follow-up, no recurrences developed. Minimal access surgery is a safe, effective, and viable option for the management of selected patients with hydatid cysts in various locations, such as the liver, lung, and retroperitoneum.

Adolescent↗
PubMed2002

Enhanced calcium signaling to bradykinin in airway smooth muscle from hyperresponsive inbred rats.

Inbred Fischer 344 rats display airway hyperresponsiveness (AHR) in vivo compared with the normoresponsive Lewis strain. Fischer AHR has been linked with increased airway smooth muscle (ASM) contraction ex vivo and enhanced ASM cell intracellular Ca(2+) mobilization in response to serotonin compared with Lewis. To determine the generality of this association, we tested whether bradykinin (BK) also stimulates greater contraction of Fischer airways and greater Ca(2+) mobilization in Fischer ASM cells. Explants of Fischer intraparenchymal airways constricted faster and to a greater degree in response to BK than Lewis airways. BK also evoked higher Ca(2+) transients in Fischer than in Lewis ASM cells. ASM cell B(2) receptor expression was similar between the two strains. BK activated both phosphatidylinositide-specific phospholipase C (PI-PLC) and phosphatidylcholine-specific PLC to mobilize Ca(2+) in Fischer and Lewis ASM cells. PI-PLC activity, as measured by inositol polyphosphate accumulation, was similar in the two strains. PKC inhibition with GF109203X, Go6973, or Go6983 attenuated BK-mediated Ca(2+) transients in Fischer cells, whereas GF109203X potentiated while Go6976 and Go6983 did not affect Ca(2+) transients in Lewis cells. Enhanced Ca(2+) mobilization in ASM cells can arise from variations in PKC and may be an important component of nonspecific, innate AHR.

Animals↗
PubMed2002

Is there a dose response relationship for clodronate in the treatment of tumour induced hypercalcaemia?

Eighty-six patients with tumour induced hypercalcaemia were randomised to 600, 900, 1200 or 1500 mg of intravenous clodronate, according to post hydration serum calcium levels. Sixty-seven were evaluable for response. The overall response rate was 49.3% (95% CI: 36.8-61.8) with no significant difference in response rates, i.e. achievement of normocalcaemia at days 6-9 (corrected serum calcium < or =2.6 mmol l(-1)) across all groups.

Adult↗
PubMed2002

Indomethacin lowers the threshold thermal exposure for hyperthermic radiosensitization and heat-shock inhibition of ionizing radiation-induced activation of NF-kappaB.

PURPOSE: It is well established that salicylate and several other non-steroidal anti-inflammatory agents (NSAID), including indomethacin, can activate the heat-shock response, albeit at high concentrations. This is significant since heat shock significantly alters the cellular cytotoxic response to ionizing radiation (IR). It was previously shown that heat shock, as well as NSAIDs, inhibits IR-induced activation of NF-kappaB and that NF-kappaB protects against IR-induced cytotoxicity. Hence, it is hypothesized that pretreatment with indomethacin before heating will lower the temperature and heating times required to inhibit the activation of NF-kappaB and induce significant hyperthermic radiosensitization. MATERIALS AND METHODS: Experiments were performed in HeLa cell lines and the DNA-binding activity was determined by EMSA. Cellular radiosensitivity was determined by clonogenic assay. RESULTS: HeLa cells pretreated with indomethacin showed a decrease in the temperature-time combination necessary to inhibit IR-induction of NF-kappaB DNA binding. In addition, clonogenic cell survival assays using identical conditions showed an indomethacin dose-dependent enhancement of hyperthermic radiosensitization. Thus, similar concentrations of indomethacin both lowered the threshold thermal exposure to inhibit activation of NF-kappaB DNA-binding and increased the sensitivity of tumour cells to hyperthermic radiosensitization-induced cytotoxicity. In HeLa cells treated with N-alpha-tosylphenylalanyl-chloromethyl ketone (TPCK), a serine protease inhibitor that blocks activation of NF-kappaB, an increase in radiosensitivity was observed. Interestingly, no additional cell killing was observed when heat shock was added to cells treated with TPCK before IR, suggesting a possible common cytotoxic pathway. CONCLUSIONS: The results demonstrate that indomethacin lowers the temperature-time conbination necessary to induce several physiological processes associated with the heat-shock response. Furthermore, NSAID may be potential adjuvants in improving the clinical effectiveness of hyperthermia in radiation therapy.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2002

SF-1, DAX-1, and acd: molecular determinants of adrenocortical growth and steroidogenesis.

The formation of the adrenal cortex in humans is notable for the presence of two discrete zones, the fetal zone (FZ) which regresses soon after birth and the definitive zone (DZ) which gives rise to the classic steroidogenic zones of the adult cortex. Mice possess an analogous structure to the FZ referred to as the X-zone (XZ) which regresses at puberty in the male and during the first pregnancy in the female. Similar to the human FZ in X-linked Congenital Adrenal Hypoplasia caused by loss of function mutations in DAX-1 (Dosage-sensitive sex reversal-Adrenal hypoplasia congenita critical region on the X chromosome), the mouse XZ does not regress when DAX-1 is mutated. Only in humans with DAX-1 mutations, however, is the DZ small and hypofunctional. Patients and mice with SF-1 mutations have complete adrenal aplasia with absence of both the DZ and FZ/XZ. Lastly, the phenotype of the Autosomal Recessive Adrenocortical Dysplasia (acd) mouse is strikingly similar to human Miniature Adult Congenital Adrenal Hypoplasia, lacking an XZ/FZ and possessing a dysfunctional DZ. Current work has addressed the regulation of SF-1 and DAX-1 dependent adrenocortical growth and steroidogenesis in vivo utilizing mouse models of simple and combined SF-1 and DAX-1 deficiency. In addition, the model of compensatory adrenal growth in SF-1 haplo-insufficient mice has been applied to evaluate the potential role of SF-1 in adrenocortical proliferation. Additional efforts aim to positionally clone the acd gene, predicated on the hypothesis that it is a critical component of the adrenal developmental cascade.

Adrenal Cortex↗
PubMed2002

Bladder dysfunction in acute transverse myelitis: magnetic resonance imaging and neurophysiological and urodynamic correlations.

AIMS: To evaluate micturition abnormalities in acute transverse myelitis and correlate these with evoked potentials, magnetic resonance imaging (MRI), and urodynamic findings. SETTING: Tertiary care teaching hospital. PATIENTS: 18 patients with acute transverse myelitis, aged 4-50 years; 15 had paraparesis and three quadriparesis. METHODS: Patients with acute transverse myelitis had a neurological evaluation and tibial somatosensory and motor evoked potential studies in the lower limbs. Spinal MRI was carried out using a 1.5 T scanner. Urodynamic studies were done using Dantec UD 5500 equipment. Neurological outcome was determined on the basis of Barthel index score at six months as poor, partial, or complete. In some patients, urodynamic studies were repeated at six and 12 months. RESULTS: Spinal MRI in 14 of the 18 patients revealed T2 hyperintense signal changes extending for at least three spinal segments in 13; one patient had normal MRI. In the acute stage, 17 patients had a history of urinary retention and one had urge incontinence. On follow up at six months two patients regained normal voiding, retention persisted in six, and storage symptoms developed in 10, of whom five also had emptying difficulties. Urodynamic studies showed an areflexic or hypocontractile bladder in 10, detrusor hyperreflexia with poor compliance in two, and detrusor sphincter dyssynergia in three. Early abnormal urodynamic findings commonly persisted at the six and 12 months examinations. Persistent abnormalities included detrusor hyperreflexia, dyssynergia, and areflexic bladder. The urodynamic abnormalities correlated with muscle tone and reflex changes but not with sensory or motor evoked potentials, muscle power, MRI signal changes, sensory level, or six months outcome. CONCLUSIONS: Bladder dysfunction is common in acute transverse myelitis and may be the only sequel. Urodynamic study is helpful in evaluating the bladder dysfunction and also in its management.

Adolescent↗
PubMed2001

Novel vertebrate nucleoporins Nup133 and Nup160 play a role in mRNA export.

RNA undergoing nuclear export first encounters the basket of the nuclear pore. Two basket proteins, Nup98 and Nup153, are essential for mRNA export, but their molecular partners within the pore are largely unknown. Because the mechanism of RNA export will be in question as long as significant vertebrate pore proteins remain undiscovered, we set out to find their partners. Fragments of Nup98 and Nup153 were used for pulldown experiments from Xenopus egg extracts, which contain abundant disassembled nuclear pores. Strikingly, Nup98 and Nup153 each bound the same four large proteins. Purification and sequence analysis revealed that two are the known vertebrate nucleoporins, Nup96 and Nup107, whereas two mapped to ORFs of unknown function. The genes encoding the novel proteins were cloned, and antibodies were produced. Immunofluorescence reveals them to be new nucleoporins, designated Nup160 and Nup133, which are accessible on the basket side of the pore. Nucleoporins Nup160, Nup133, Nup107, and Nup96 exist as a complex in Xenopus egg extracts and in assembled pores, now termed the Nup160 complex. Sec13 is prominent in Nup98 and Nup153 pulldowns, and we find it to be a member of the Nup160 complex. We have mapped the sites that are required for binding the Nup160 subcomplex, and have found that in Nup98, the binding site is used to tether Nup98 to the nucleus; in Nup153, the binding site targets Nup153 to the nuclear pore. With transfection and in vivo transport assays, we find that specific Nup160 and Nup133 fragments block poly[A]+ RNA export, but not protein import or export. These results demonstrate that two novel vertebrate nucleoporins, Nup160 and Nup133, not only interact with Nup98 and Nup153, but themselves play a role in mRNA export.

Active Transport, Cell Nucleus↗
PubMed2001

Two double-blind placebo-controlled pilot studies of eicosapentaenoic acid in the treatment of schizophrenia.

Evidence that the metabolism of phospholipids and polyunsaturated fatty acids (PUFA) is abnormal in schizophrenia provided the rationale for intervention studies using PUFA supplementation. An initial open label study indicating efficacy for n-3 PUFA in schizophrenia led to two small double-blind pilot studies. The first study was designed to distinguish between the possible effects of two different n-3 PUFA: eicosapentaenoic acid (EPA) and docohexaenoic acid (DHA). Forty-five schizophrenic patients on stable antipsychotic medication who were still symptomatic were treated with either EPA, DHA or placebo for 3 months. Improvement on EPA measured by the Positive and Negative Syndrome Scale (PANSS) was statistically superior to both DHA and placebo using changes in percentage scores on the total PANSS. EPA was significantly superior to DHA for positive symptoms using ANOVA for repeated measures. In the second placebo-controlled study, EPA was used as a sole treatment, though the use of antipsychotic drugs was still permitted if this was clinically imperative. By the end of the study, all 12 patients on placebo, but only eight out of 14 patients on EPA, were taking antipsychotic drugs. Despite this, patients taking EPA had significantly lower scores on the PANSS rating scale by the end of the study. It is concluded that EPA may represent a new treatment approach to schizophrenia, and this requires investigation by large-scale placebo-controlled trials.

Adult↗
PubMed2001

Ku80 is required for addition of N nucleotides to V(D)J recombination junctions by terminal deoxynucleotidyl transferase.

V(D)J recombination generates a remarkably diverse repertoire of antigen receptors through the rearrangement of germline DNA. Terminal deoxynucleotidyl transferase (TdT), a polymerase that adds random nucleotides (N regions) to recombination junctions, is a key enzyme contributing to this diversity. The current model is that TdT adds N regions during V(D)J recombination by random collision with the DNA ends, without a dependence on other cellular factors. We previously demonstrated, however, that V(D)J junctions from Ku80-deficient mice unexpectedly lack N regions, although the mechanism responsible for this effect remains undefined in the mouse system. One possibility is that junctions are formed in these mice during a stage in development when TdT is not expressed. Alternatively, Ku80 may be required for the expression, nuclear localization or enzymatic activity of TdT. Here we show that V(D)J junctions isolated from Ku80-deficient fibroblasts are devoid of N regions, as were junctions in Ku80-deficient mice. In these cells TdT protein is abundant at the time of recombination, localizes properly to the nucleus and is enzymatically active. Based on these data, we propose that TdT does not add to recombination junctions through random collision but is actively recruited to the V(D)J recombinase complex by Ku80.

Animals↗
PubMed2001

Effect of peer led programme for asthma education in adolescents: cluster randomised controlled trial.

OBJECTIVE: To determine the effect of a peer led programme for asthma education on quality of life and related morbidity in adolescents with asthma. DESIGN: Cluster randomised controlled trial. SETTING: Six high schools in rural Australia. PARTICIPANTS: 272 students with recent wheeze, recruited from a cohort of 1515 students from two school years (mean age 12.5 and 15.5 years); 251 (92.3%) completed the study. INTERVENTION: A structured education programme for peers comprising three steps (the "Triple A Program"). MAIN OUTCOME MEASURES: Quality of life, school absenteeism, asthma attacks, and lung function. RESULTS: When adjusted for year and sex, mean total quality of life scores showed significant improvement in the intervention than control group. Clinically important improvement in quality of life (>0.5 units) occurred in 25% of students with asthma in the intervention group compared with 12% in the control group (P=0.01). The number needed to treat was 8 (95% confidence interval 4.5 to 35.7). The effect of the intervention was greatest in students in year 10 and in females. Significant improvements occurred in the activities domain (41% v 28%) and in the emotions domain (39% v 19%) in males in the intervention group. School absenteeism significantly decreased in the intervention group only. Asthma attacks at school increased in the control group only. CONCLUSION: The triple A programme leads to a clinically relevant improvement in quality of life and related morbidity in students with asthma. Wider dissemination of this programme in schools could play an important part in reducing the burden of asthma in adolescents.

Absenteeism↗
PubMed2001

Successful stenting of a complex inferior vena cava stenosis using a modified sharp recanulization technique.

We describe a case of a 30-year-old male who presented with features of noncirrhotic portal hypertension, who was diagnosed to have inferior vena cava (IVC) obstruction. IVC angiogram and ultrasound study revealed a long-segment (36 mm long), chronic total thrombotic occlusion that was dilated and stented with a satisfactory end result. The unique feature of this case is a modified sharp recanulization technique involving the use of Brokenborough (septal puncture) needle and Mullin dilator to create a track in such a long, chronic total occlusion under simultaneous ultrasound and fluoroscopic guidance.

Adult↗
PubMed2001

Short-term and long-term quality of life after neck dissection.

INTRODUCTION: Quality of life (QOL) is an important outcome measure in cancer therapy. Neck dissection (ND) morbidity has been well studied, but no study has focused on the quality of life after ND specifically. METHODS: Fifty-one patients who have undergone ND completed a 6-item quality-of-life survey with a 7-point frequency and interference response scale. General QOL and comorbidity biases were evaluated with the SF-12 questionnaire and the Charlson comorbidity index. RESULTS: The following symptoms were the most commonly experienced after surgery: neck tightness (71%), numbness or burning of the ear (57%), and shoulder discomfort (53%). However, interference with daily activities was reported by only 37%, 32%, and 33% of patients with these symptoms, respectively. Within 2 years of surgery, interference with daily activities decreased to 17%, 18%, and 12%, respectively. QOL after ND was negatively associated with previous radiation, previous chemotherapy, tumor stage, and more radical neck surgery but was positively associated with time after surgery. Shoulder discomfort and neck tightness had the greatest affect on QOL. CONCLUSIONS: Our results suggest that patients should receive preoperative counseling regarding the morbidities from ND and the possible short-term and long-term impact on QOL. Further studies evaluating the relationship between primary tumor characteristics and quality of life after ND need to be undertaken.

Adult↗