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Biomedical subjects

S Mehta

Publications and source records attributed to S Mehta.

At least 19 recordsLinked to original sources

Ab initio thermodynamics and phase diagram of solid magnesium: a comparison of the LDA and GGA.

The finite temperature density functional theory and quasiharmonic lattice dynamics have been used to compute numerous thermodynamic properties of hexagonal close packed magnesium using both the local density approximation (LDA) and the generalized gradient approximation (GGA) for the exchange-correlation potential. Generally, it is found that there exist only minor differences between the LDA and GGA computed properties, with both giving good agreement with experiment. The hcp-bcc phase boundary has also been computed and is found to be in agreement with experimental observation. Again, only slight differences are found between the LDA and GGA.

Journal Article↗

Systematic review: Cyclo-oxygenase-2 in human oesophageal adenocarcinogenesis.

BACKGROUND: Published in vitro and animal in vivo studies have demonstrated that cyclo-oxygenase-2 plays an important role during oesophageal adenocarcinogenesis. However, the extent to which these studies are directly relevant to events in the human lower oesophagus is questionable. AIM: To perform a systematic review of all available human studies that have evaluated levels of cyclo-oxygenase-2 expression during the progression from Barrett's metaplasia to oesophageal adenocarcinoma. METHODS: A literature search was performed to identify all studies which qualitatively or quantitatively assessed cyclo-oxygenase-2 protein or gene expression in either Barrett's, dysplastic or adenocarcinoma tissue in humans. RESULTS: A total of 27 studies met the inclusion criteria. There was general agreement that cyclo-oxygenase-2 was either absent or very weakly expressed in normal oesophageal squamous mucosa, but considerable disagreement regarding the presence of cyclo-oxygenase-2 in Barrett's and low-grade dysplasia. All studies agreed that high-grade dysplasia and adenocarcinoma expressed cyclo-oxygenase-2 to some extent although levels varied considerably between tissue samples. CONCLUSIONS: There is conflicting evidence in the literature for cyclo-oxygenase-2 playing an important role in early oesophageal adenocarcinogenesis. Other non-cyclo-oxygenase-2 targets may account for the epidemiological data supporting the use of non-steroidal anti-inflammatory drugs in the chemoprevention of oesophageal adenocarcinoma.

Adenocarcinoma↗

The AIDS pandemic: a catalyst for women's rights.

The rates of HIV infection among women are rising at a higher rate than among men. After citing the reasons for women's vulnerability, this report argues the potential role of gynecologists and obstetricians through integration of HIV/AIDS into sexual and reproductive health services to strengthen the response to the epidemic.

Disease Outbreaks↗

Analysis of speech-related variance in rapid event-related fMRI using a time-aware acquisition system.

Speech production introduces signal changes in fMRI data that can mimic or mask the task-induced BOLD response. Rapid event-related designs with variable ISIs address these concerns by minimizing the correlation of task and speech-related signal changes without sacrificing efficiency; however, the increase in residual variance due to speech still decreases statistical power and must be explicitly addressed primarily through post-processing techniques. We investigated the timing, magnitude, and location of speech-related variance in an overt picture naming fMRI study with a rapid event-related design, using a data acquisition system that time-stamped image acquisitions, speech, and a pneumatic belt signal on the same clock. Using a spectral subtraction algorithm to remove scanner gradient noise from recorded speech, we related the timing of speech, stimulus presentation, chest wall movement, and image acquisition. We explored the relationship of an extended speech event time course and respiration on signal variance by performing a series of voxelwise regression analyses. Our results demonstrate that these effects are spatially heterogeneous, but their anatomic locations converge across subjects. Affected locations included basal areas (orbitofrontal, mesial temporal, brainstem), areas adjacent to CSF spaces, and lateral frontal areas. If left unmodeled, speech-related variance can result in regional detection bias that affects some areas critically implicated in language function. The results establish the feasibility of detecting and mitigating speech-related variance in rapid event-related fMRI experiments with single word utterances. They further demonstrate the utility of precise timing information about speech and respiration for this purpose.

Adult↗

Effects of macrophage inducible nitric oxide synthase in murine septic lung injury.

Inducible nitric oxide synthase (iNOS) contributes importantly to septic pulmonary protein leak in mice with septic acute lung injury (ALI). However, the role of alveolar macrophage (AM) iNOS in septic ALI is not known. Thus we assessed the specific effects of AM iNOS in murine septic ALI through selective AM depletion (via intratracheal instillation of clodronate liposomes) and subsequent AM reconstitution (via intratracheal instillation of donor iNOS+/+ or iNOS-/- AM). Sepsis was induced by cecal ligation and perforation, and ALI was assessed at 4 h: protein leak by the Evans blue (EB) dye method, neutrophil infiltration via myeloperoxidase (MPO) activity, and pulmonary iNOS mRNA expression via RT-PCR. In iNOS+/+ mice, AM depletion attenuated the sepsis-induced increases in pulmonary microvascular protein leak (0.3 +/- 0.1 vs. 1.4 +/- 0.1 microg EB.g lung(-1).min(-1); P < 0.05) and MPO activity (37 +/- 4 vs. 67 +/- 8 U/g lung; P < 0.05) compared with that shown in non-AM-depleted mice. In AM-depleted iNOS+/+ mice, septic pulmonary protein leak was restored by AM reconstitution with iNOS+/+ AM (0.9 +/- 0.3 microg EB.g lung(-1).min(-1)) but not with iNOS-/- donor AM. In iNOS-/- mice, sepsis did not induce pulmonary protein leak or iNOS mRNA expression, despite increased pulmonary MPO activity. However, AM depletion in iNOS-/- mice and subsequent reconstitution with iNOS+/+ donor AM resulted in significant sepsis-induced pulmonary protein leak and iNOS expression. Septic pulmonary MPO levels were similar in all AM-reconstituted groups. Thus septic pulmonary protein leak is absolutely dependent on the presence of functional AM and specifically on iNOS in AM. AM iNOS-dependent pulmonary protein leak was not mediated through changes in pulmonary neutrophil influx.

Animals↗

Non-mosaic trisomy 22: a report of 2 cases.

Non-mosaic trisomy 22 is a common cause of first trimester miscarriage and has a livebirth incidence of 1 in 30,000-50,000. Consequently there is a paucity of information for counselling parents. Detection in the second trimester is rare. It is commonly associated with severe growth retardation and multiple structural abnormalities. Oligohydramnios is frequently seen and can make detection of other abnormalities difficult. The outlook is uniformly poor and survival beyond the first trimester may present management dilemmas. A thorough fetal assessment including high-resolution cytogenetics with or without FISH is required for counselling. Careful plans for intrapartum and neonatal management may be necessary. The recurrence risk is thought to be low but information is very limited as there have been no reported cases of recurrence. We present two case of non-mosaic trisomy 22 including the first to be diagnosed subsequent to investigation for a high serum screening Down's risk.

Abnormalities, Multiple↗

Anticoagulation in pulmonary arterial hypertension: a qualitative systematic review.

Thrombotic arteriopathy has been implicated in the pathophysiology of pulmonary arterial hypertension (PAH). However, the role of anticoagulants in the treatment of PAH is uncertain. Through a qualitative systematic review of epidemiological studies, the effectiveness of anticoagulation therapy with warfarin on survival was evaluated in patients with PAH. MEDLINE (1966 to November 2005), EMBASE (1966 to November 2005), bibliographies of included studies and published reviews were searched without language restriction. Epidemiological studies evaluating the effectiveness of warfarin in PAH were included. Studies had to report mortality as an outcome. Seven observational studies evaluating the effectiveness of warfarin comprising 488 patients were identified. Five studies support the effectiveness of anticoagulation therapy, whereas two do not. Data from observational studies suggest that anticoagulation therapy may be an effective intervention in pulmonary arterial hypertension. However, given the methodological limitations and the small number of existing observational studies, a randomised controlled trial is needed in order to definitively address this important clinical issue.

Anticoagulants↗

Prospective randomized trial of laparoscopic gastrojejunostomy versus duodenal stenting for malignant gastric outflow obstruction.

BACKGROUND: We prospectively compared laparoscopic gastrojejunostomy with duodenal stenting as a means of palliating malignant gastric outflow obstruction. METHODS: A total of 27 patients with malignant gastric outflow obstruction were randomized to either laparoscopic gastrojejunostomy (LGJ) or duodenal stenting (DS) over a 3-year period. RESULTS: Thirteen patients underwent successful LGJ and 10 had successful DS. Eight patients had complications after LGJ, but none had complications after DS. Patients who underwent LGJ had a significant increase in visual analog pain score at day 1 (p = 0.05), and also had a longer hospital stay compared to those who underwent DS (11.4 vs. 5.2 days, p = 0.02). After DS, patients experienced an improvement in physical health at 1 month as measured using the Short Form-36 (SF-36) questionnaire (p < 0.01). There was no change following LGJ. CONCLUSION: Duodenal stenting is a safe means of palliating malignant gastric outflow obstruction. It offers significant advantages for patients compared with minimal-access surgery.

Aged↗

Systematic review: the chemoprevention of oesophageal adenocarcinoma.

The incidence of oesophageal adenocarcinoma is increasing in the UK faster than any other malignancy. Despite its relatively poor prognosis and the limited success of existing treatments, there is enthusiasm that chemopreventive agents might be able to stem the transition from normal squamous epithelium to adenocarcinoma. We discuss gastro-oesophageal reflux as the main risk factor for the development of Barrett's metaplasia, the only known precursor of oesophageal adenocarcinoma. Treatment options for reflux disease are considered with regard to their effects on cancer risk. Recent advances in the molecular and cell biology of Barrett's are outlined, and potential targets for chemoprevention examined. Available treatments for reflux disease have not convincingly altered the likelihood of cancer development. Epidemiological and animal studies support the use of non-steroidal anti-inflammatory drugs as potential chemopreventive agents. Dietary agents, however, have a more favourable side-effect profile and may prove to be an attractive alternative, although more work is needed to fully explore this prospect.

Adenocarcinoma↗

Changes in functional gastrointestinal symptoms as a result of antireflux surgery.

BACKGROUND: This study identifies how functional symptoms are altered after antireflux surgery and whether there are any predictors of such change. METHODS: A total of 206 patients underwent successful laparoscopic Nissen fundoplication. A questionnaire was sent at a median of 4.3 years (range = 0.3-8.4) after fundoplication. Patients were asked to provide scores for reflux and functional symptoms that were experienced prior to surgery and at the time of the questionnaire. RESULTS: Eighty-one percent of patients responded. Scores for heartburn, regurgitation, and difficulty swallowing were felt to have significantly improved (p < 0.01). Flatulence was the only functional symptom to have significantly worsened (p < 0.01). A regression analysis incorporating prospectively collected data identified variables that were predictive of changes in functional symptoms following surgery. CONCLUSIONS: Flatulence was the only functional symptom to have worsened overall after surgery. Predictors of changes in functional symptoms may help clinicians when informing patients about gastrointestinal side effects following antireflux surgery.

Female↗

Synthesis of aryl semicarbazones as potential anticonvulsant agents.

A series of 4-ethoxyphenyl semicarbazones (1-10) have been synthesized using an appropriate synthetic route and characterized by elemental analyses and spectral data. The anticonvulsant activity of all the synthesized compounds was evaluated against maximal electroshock induced seizures (MES) and subcutaneous pentylenetetrazole (scPTZ) induced seizure models in mice. The neurotoxicity was assessed using the rotorod method. All the test compounds were administered at doses of 30, 100, and 300 mg/kg body weight and the anticonvulsant activity was noted at 0.5 and 4 h time intervals after the drug administration. Among the compounds tested, compounds except 3, 4 and 10 showed protection from seizures in both the animal models. Compounds 6 and 8 were found to increase gamma-aminobutyric acid (GABA) levels in the medulla oblongata region of the rat brain.

Animals↗

IFN-gamma enhances paclitaxel-induced apoptosis that is modulated by activation of caspases 8 and 3 with a concomitant down regulation of the AKT survival pathway in cultured human keratinocytes.

The aim of this study was to investigate the molecular effects of paclitaxel and IFN-gamma on cultured human keratinocyte cells (HaCaT) assessing the induction of both the apoptotic pathway and cell survival signals. Cellular cytotoxicity assays were performed by MTT dye assay. Caspases 8, 3 and AKT (Ser473 and Thr308 residues) were assessed by Western blot analysis. Morphological characteristics were examined by Wright stain analysis. Paclitaxel reduced keratinocyte growth in a 3-day bioassay with an effective ED(50) of 6-600 ng/ml. A large variation in ED(50) can be attributed to the asynchronous population of cells. Paclitaxel treatment induced activation of the AKT survival pathway in a time-dependent manner. The down-regulation of AKT signal was preceded by the subsequent activation of caspases 8 and 3 leading to apoptosis. These results indicate that paclitaxel activates both the PI3-K/AKT cell survival pathway followed by induction of apoptotic signals in cultured human keratinocytes. The induction of apoptosis in paclitaxel-treated cells is enhanced by coadministration of IFN-gamma. The synergistic effect of these two agents on HaCaT cells relies on a pathway involving caspases 8 and 3, with activity increasing by 48 h. Collectively, our data indicate that i) paclitaxel-induced apoptosis is enhanced by IFN-gamma; ii) the down-regulation of PI3-K/AKT survival pathway may help potentiate the apoptotic effects of paclitaxel and iii) the apoptotic signaling pathways are initiated with the activation of caspases 8 and 3 activities.

Adult↗

Seroprevalence of Chalmydia trachomatis infection amongst patients with pelvic inflammatory diseases and infertility.

Chlamydia trachomatis (C. trachomatis) is a common cause of pelvic inflammatory disease in female population. This infection can be diagnosed both by culture and serology. The present study evaluated the seroprevalence of chlamydial infection in patients with pelvic inflammatory disease (ND) and infertility and in control population of healthy normal females. The seroprevalence was found to be 82.7% in patients and 32% in controls by Enzyme Linked Immuno Sorbent Assay (ELISA) for any one or more class of antichlamydial antibodies (IgG/IgM/ IgA). The study demonstrates the importance of serology to monitor trends of chlamydial infections in women with PID and infertility.

Adult↗

Anticonvulsant and neurotoxicity evaluation of some 6-substituted benzothiazolyl-2-thiosemicarbazones.

Various 6-substituted benzothiazolyl-2-thiosemicarbazones were synthesized and screened for anticonvulsant activity in maximal electroshock induced seizure (MES) and subcutaneous pentylenetetrazole (scPTZ) induced seizure models in mice. The neurotoxicity was assessed using the rotorod method. The 6-methyl benzothiazolyl-2-thiosemicarbazones showed anticonvulsant activity in both mice i.p. and rat oral MES screen. The 6-nitro benzothiazolyl thiosemicarbazone derivative 1a emerged as the most promising one with anti-MES activity in mice i.p., rat i.p. and rat p.o. evaluations. All the compounds exhibited lesser or no neurotoxicity compared to phenytoin. The isatinimino derivatives had shown better activity when compared to the benzylidene or acetophenone derivatives.

Animals↗