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Biomedical subjects

V Sharma

Publications and source records attributed to V Sharma.

At least 55 records · Page 3Linked to original sources

Detecting disorder in spatial vision.

In normal foveal vision, visual space is accurately mapped from retina to cortex. However, the normal periphery, and the central field of strabismic amblyopes have elevated position discrimination thresholds, which have often been ascribed to increased 'intrinsic' spatial disorder. In the present study we evaluated the sensitivity of the human visual system (both normal and amblyopic) to spatial disorder, and asked whether there is increased 'intrinsic' topographical disorder in the amblyopic visual system. Specifically, we measured thresholds for detecting disorder (two-dimensional Gaussian position perturbations) either in a horizontal string of N equally spaced samples (Gabor patches), or in a ring of equally spaced samples over a wide range of feature separations. We also estimated both the 'equivalent intrinsic spatial disorder' and sampling efficiency using an equivalent noise approach. Our results suggest that both thresholds for detecting disorder, and equivalent intrinsic disorder depend strongly on separation, and are modestly increased in strabismic amblyopes. Strabismic amblyopes also show markedly reduced sampling efficiency. However, neither amblyopic nor peripheral vision performs like ideal or human observers with added separation-independent positional noise. Rather, the strong separation dependence suggests that the 'equivalent intrinsic disorder' may not reflect topographic disorder at all, but rather may reflect an abnormality in the amblyopes' Weber relationship.

Adolescent↗

A note on suicidal deterioration with recovered memory treatment.

BACKGROUND: Many patients who have been told they have Multiple Personality/Dissociative Identity Disorder (MPD/DID) seem to have deteriorated clinically after being so diagnosed. We report here the results of a survey of suicide attempts in patients diagnosed as having MPD and a comparison group hospitalized with a mood disorder. METHODS: Twenty individuals who had been diagnosed as having MPD, had developed false memories, and had relinquished them, were surveyed with respect to suicide attempts before and after the diagnosis. Twelve of those approached agreed to provide data and were compared with 12 patients from an in-patient mood disorders unit, matched for age and sex. RESULTS: In the MPD group more patients attempted suicide after being diagnosed than before and they made more separate attempts at suicide than before. The reverse was true in the comparison group with patients and suicide attempts before and after hospitalization. Comparing the numbers of attempts in the groups before diagnosis/hospitalization and afterward Chi(2)=20.177, DF=1, P<0.001. LIMITATIONS AND CONCLUSIONS: Both samples were highly selected, and the comparison group does not provide an exact control. Nevertheless, the results support a trend in the literature that finds the diagnosis of multiple personality disorder and the use of recovered memory treatment are harmful.

Adult↗

Novel gallium(III) complexes transported by MDR1 P-glycoprotein: potential PET imaging agents for probing P-glycoprotein-mediated transport activity in vivo.

BACKGROUND: Multidrug resistance (MDR) mediated by expression of MDR1 P-glycoprotein (Pgp) represents one of the best characterized barriers to chemotherapy in cancer patients. Positron emission tomography (PET) agents for analysis of Pgp-mediated drug transport activity in vivo would enable noninvasive assessment of chemotherapeutic regimens and MDR gene therapy. RESULTS: Candidate Schiff-base phenolic gallium(III) complexes were synthesized from their heptadentate precursors and gallium(III)acetylacetonate. Crystal structures demonstrated a hexacoordinated central gallium with overall trans-pseudo-octahedral geometry. Radiolabeled (67)Ga-complexes were obtained in high purity and screened in drug-sensitive (Pgp(-)) and MDR (Pgp(+)) tumor cells. Compared with control, lead compound 6. demonstrated antagonist-reversible 55-fold lower accumulation in Pgp-expressing MDR cells. Futhermore, compared with wild-type control, quantitative pharmacokinetic analysis showed markedly increased penetration and retention of 6. in brain and liver tissues of mdr1a/b((-/-)) gene disrupted mice, correctly mapping Pgp-mediated transport activity at the capillary blood-brain barrier and hepatocellular biliary cannalicular surface in vivo. CONCLUSIONS: These results indicate that gallium(III) complex 6. is recognized by MDR1 Pgp as an avid transport substrate, thereby providing a useful scaffold to generate (68)Ga radiopharmaceuticals for molecular imaging of Pgp transport activity in tumors and tissues in vivo using PET.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Structure-function modeling of the interactions of N-alkyl-N-hydroxyanilines with rat hepatic aryl sulfotransferase IV.

Although previous investigations have clearly shown that N-hydroxy arylamines and N-hydroxy heterocyclic amines are substrates for sulfotransferases, relatively little is known about which structural features of the N-hydroxy arylamines are important for sulfation to occur. The purpose of this investigation was to determine the extent to which secondary N-alkyl-N-hydroxy arylamines interact with aryl sulfotransferase (AST) IV (also known as tyrosine-ester sulfotransferase or ST1A1) and to evaluate these interactions using molecular modeling techniques. AST IV is a major cytosolic sulfotransferase in the rat, and it catalyzes the sulfation of various phenols, benzylic alcohols, arylhydroxamic acids, oximes, and primary N-hydroxy arylamines. In this study, three secondary N-hydroxy arylamines, N-hydroxy-N-methylaniline, N-ethyl-N-hydroxyaniline, and N-hydroxy-N-n-propylaniline, were found to be substrates for the purified rat hepatic AST IV. However, when the N-alkyl substituent was an n-butyl group (i.e., N-n-butyl-N-hydroxyaniline), the interaction with the enzyme changed from that of a substrate to competitive inhibition. This change in specificity was further explored through the construction and use of a model for AST IV based on mouse estrogen sulfotransferase, an enzyme whose crystal structure has been previously determined to high resolution. Molecular modeling techniques were used to dock each of the above N-hydroxy arylamines into the active site of the homology model of AST IV and determine optimum ligand geometries. The results of these experiments indicated that steric constraints on the orientation of binding of secondary N-alkyl-N-hydroxy arylamines at the active site of AST IV play a significant role in determining the nature of the interaction of the enzyme with these compounds.

Aminophenols↗

The influence of supernumerary embryos on the clinical outcome of IVF cycles.

PURPOSE: To assess the influence of the presence of quality supernumerary embryos on the clinical outcome and risk of multiple conception in patients having their first in vitro fertilization (IVF) cycle. METHODS: Retrospective cohort study of 1448 women having their first IVF treatment cycle who received 4004 embryos where at least six embryos were available for transfer treated in an Assisted Conception Unit based in a large teaching hospital. RESULTS: The replacement of three rather than two embryos to women under 35 years who had good-quality supernumerary embryos resulted in a higher twin (12.5 vs. 11.9%) and triplet birth rates (2.1 vs. 0%), without significantly improving the clinical pregnancy (50.5 vs. 45.2%) or total live birth rates (38.9 vs. 35.7%). In the absence of quality spare embryos, these women who had three rather than two embryos replaced had a significantly higher clinical pregnancy rate (39.3 vs. 28.8%; P = 0.04), total live birth (32.7 vs. 19.4%; P = 0.02) and singleton birth rate per cycle (20.8 vs. 14.4%; P = 0.04), without significantly influencing the multiple birth rate. In women over 35 years, the replacement of three instead of two embryos in the presence or absence of quality supernumerary embryos led to a significant improvement in clinical outcome, without being associated with a concurrent increase in the multiple birth rate. Women in both age groups who had either two or three embryos replaced in the presence of quality supernumerary embryos had a notably better clinical outcome compared with their counterparts who had the same number of embryos replaced, but with no quality embryos to spare. CONCLUSIONS: The presence of good-quality supernumerary embryos can be used as a reference to determine the optimal number of embryos to transfer and as an indicator of the probability of success of an individual couple in a given cycle. Optimal pregnancy rates and simultaneous reduction of multiple gestation can be achieved with a flexible embryo replacement policy that is based on embryo quality, maternal age, and the presence or absence of surplus quality embryos.

Adult↗

Role of linkage specific 9-O-acetylated sialoglycoconjugates in activation of the alternate complement pathway in mammalian erythrocytes.

Substitution of the -OH group at C-9 of sialic acid by an O-acetyl ester has been suggested to modify various biological phenomena that are regulated by sialic acids. Amongst them, enhancement of erythrocyte lysis by 9-O-acetylated sialic acid determinants through modulation of the alternate pathway of complement has been extensively studied on murine erythrocytes [1]. A variable expression of linkage specific 9-O-acetylated sialoglycoconjugates as defined by the lectinogenic epitope of Achatinin-H namely 9-O-acetylated sialic acid alpha2-->6Gal NAc was identified on rabbit, guinea pig, hamster, rat, mouse and human erythrocytes. This differential expression of linkage specific 9-O-acetylated sialoglycoconjugates strongly correlated with the susceptibility of mammalian erythrocytes to lysis by the alternate pathway of complement. Additionally, low levels of antibodies directed against O-acetylated sialic acids in these mammalian species suggested that these constitutively present determinants have low immunogenicity. Taken together, our results indicate that complement mediated hemolysis depends not simply upon the extent of surface 9-O-acetylated sialic acids present but more importantly upon the specific linkage.

Acetylation↗

Undercounting features and missing features: evidence for a high-level deficit in strabismic amblyopia.

Abnormal visual development in strabismic amblyopia drastically affects visual perception and properties of neurons in primary visual cortex (V1). To test the notion that amblyopia also has consequences for higher visual areas, we asked humans with amblyopia to count briefly presented features. Using the amblyopic eye, strabismic amblyopes counted inaccurately, markedly underestimating the number of features. This inaccuracy was not due to low-level considerations (blur, visibility, crowding, undersampling or topographical jitter), as they also underestimated the number of features missing from a uniform grid. Rather, counting deficits in strabismic amblyopes reflected a higher-level limitation in the number of features the amblyopic visual system can individuate.

Adult↗

Structure of isocitrate lyase, a persistence factor of Mycobacterium tuberculosis.

Isocitrate lyase (ICL) plays a pivotal role in the persistence of Mycobacterium tuberculosis in mice by sustaining intracellular infection in inflammatory macrophages. The enzyme allows net carbon gain by diverting acetyl-CoA from beta-oxidation of fatty acids into the glyoxylate shunt pathway. Given its potential as a drug target against persistent infections, we solved its structure without ligand and in complex with two inhibitors. Covalent modification of an active site residue, Cys 191, by the inhibitor 3-bromopyruvate traps the enzyme in a catalytic conformation with the active site completely inaccessible to solvent. The structure of a C191S mutant of the enzyme with the inhibitor 3-nitropropionate provides further insight into the reaction mechanism.

Amino Acid Substitution↗

Human B-cell lines constitutively express and secrete interleukin-16.

Interleukin-16 (IL-16), produced by activated CD8+ T lymphocytes, is inhibitory to human immunodeficiency virus-1 (HIV-1) replication. In an attempt to determine whether human B cells express and secrete IL-16, a wide panel of B-cell lines derived from patients with acquired immune deficiency syndrome (AIDS)-associated B-cell lymphomas (AABCL) (n = 5) and from non-AABCLs (n = 8) were studied. Using reverse transcription-polymerase chain reaction (RT-PCR) analysis, we were able to observe ubiquitous expression of IL-16 mRNA. Kinetic studies on constitutive mRNA turnover and secretion for IL-16 suggests that the optimum expression is at 24 hr. Interestingly, we report, for the first time, IL-16 secretion by human B-cell lines.

B-Lymphocytes↗

Cost-effective post-exposure prevention of poison ivy dermatitis.

BACKGROUND: Poison ivy (toxicodendron) dermatitis is the most common allergic contact dermatitis in the USA. No studies have shown an effect of washing after a short period of time for the prevention of binding of urushiol to the skin. Objective To evaluate the efficacy of three different modes of postcontact prevention using a surfactant (Dial ultra dishwashing soap), an oil-removing compound (Goop), and chemical inactivation (a commercial product Tecnu). METHODS: A consented, unsponsored, volunteer experimental study on medical students from the University of Missouri School of Medicine, Kansas City. Each subject served as his/her own control, comparing four 2.5-cm exposed squares on the inner aspect of the forearm, three of which were treated and one untreated. RESULTS: Comparisons between the different agents were nonsignificant with P > 0.05. Each treatment, however, was significantly improved over the untreated control. CONCLUSIONS: Our study showed 70%, 61.8%, and 56. 4% protection with Tecnu, Goop, and Dial, respectively, when compared to the positive control, or to the possible maximum response, with a cost per ounce (in a local drug and automotive store) of $1.25, $0.07, and $0.07, respectively, for a decrease in protection that is nonsignificant.

Adult↗

Late esophageal toxicity using a combination of external beam radiation, intraluminal brachytherapy and 5-fluorouracil infusion in carcinoma of the esophagus.

One hundred patients with potentially curable squamous cell carcinoma of the esophagus were treated using a combination of external beam radiation, medium-dose intraluminal brachytherapy (ILBT), and 5-fluorouracil infusion (as a radiosensitizer) from January 1990 to December 1993. The main objective was to determine late toxicity and optimization of the dose of intraluminal radiation. All patients had external radiation of 50 Gy over 5 1/2 weeks, followed by ILBT of 20 Gy for 50 patients (group 1) and 15 Gy for a subsequent 50 patients (group 2), using a dose rate of 315-330 cGy/h with the prescription at 1 cm off axis. The 5-fluorouracil infusion was 500 mg/m2 administered 12 h prior to ILBT. The treatment-related complications among groups 1 and 2 were strictures 24% vs. 8% (p = 0.029), ulceration 30% vs. 28% (p = 0.8), and tracheoesophageal fistulae 12% for both groups. The overall survival for groups 1 and 2 was 8% and 23% at 5 years. The development of life-threatening complications is a major concern and extreme caution is urged before selecting patients for a combination of ILBT and 5-fluorouracil treatment.

Brachytherapy↗

Limited contact dynamic compression in diaphyseal fractures of the humerus: good outcome in 51 patients.

We reviewed 51 plate fixations for fracture of the humeral diaphysis managed during the last 3 years. The indications for surgery included non-union, delayed union, polytrauma, neurological involvement and inadequate reduction. All the fractures were stabilized with a Limited Contact Dynamic Compression Plate (LCDC Plate). We found that this plate gave adequate rotational and vertical stability to the fracture. 48 fractures healed after median 2.5 months. Early evidence of callus formation indicated minimal compromise with the vascularity of bone which may be attributed to the undercut design of the plate, causing relatively less cortical ischemia. In addition, the plate fixation was associated with fewer complications, as compared to those reported with intramedullary nailing.

Adolescent↗

Induction of ovulation in women undergoing assisted reproductive techniques: recombinant human FSH (follitropin alpha) versus highly purified urinary FSH (urofollitropin HP).

This multicentre, open, randomized, study compared the efficacy and safety of recombinant follicle stimulating hormone (rFSH; follitropin alpha) with highly purified urinary human FSH (uFSH; urofollitropin HP) in women undergoing ovulation induction for assisted reproductive techniques. Following long down-regulation with buserelin, patients received two ampoules of 75 IU (150 IU) s.c. rFSH or highly purified uFSH for 6 days, after which the dose could be increased until they fulfilled the criteria for human chorionic gonadotrophin (HCG) administration. Of 168 patients recruited, 155 received at least one dose of FSH, and 137 received HCG [68: rFSH (85%); 69: uFSH (92%)]. Following oocyte retrieval and fertilization, up to three embryos were replaced/patient and luteal support was given. The mean number of oocytes retrieved/patient was 10.2 +/- 6.0 for rFSH patients compared with 10.8 +/- 6.1 in the uFSH group (not significant). There was a trend towards fewer ampoules used (22.3 +/- 6.5 versus 24.3 +/- 6.5), higher pregnancy (44.3 versus 41.4%) and live birth rates (33.8 versus 26.7%), as well as a lower miscarriage rate (0.0 versus 16.7%) in favour of rFSH. However, no significant differences in efficacy parameters were recorded. Ovarian hyperstimulation syndrome occurred in 8.6% and 7.9% of rFSH and uFSH patients respectively. In conclusion, this protocol was effective in inducing multiple follicular development and high numbers of oocytes were retrieved with both drugs.

Adolescent↗

Trends in the incidence of ectopic pregnancy in England and Wales from 1966 to 1996.

OBJECTIVE: To examine the incidence of ectopic pregnancy over the period 1966 to 1996. SETTING: England and Wales. DESIGN: Use of official statistics on hospital discharges, maternities, legal abortions and estimated populations of women aged 15-44 years. MAIN OUTCOME MEASURES: Incidence rates of ectopic pregnancies. RESULTS: Between 1966 to 1970 and 1994 to 1996 the recorded incidence increased 4.5-fold from 3.45 to 15.5 per 1000 maternities, 3.8-fold from 3.25 to 12.4 per 1000 pregnancies and 3.1-fold from 30.2 to 94.8 per 100,000 women aged 15-44. The rate of increase was not uniform. Incidence approximately doubled between 1966 and 1985, when the official data collection system changed. By 1989, when data from the new system became available, there had been a further almost doubling of recorded incidence. Subsequently, the upward trend appears to have continued until 1991 to 1992 and has remained stable in the last four years of the study. The trends were similar in each of three 10-year age groups. CONCLUSIONS: The recorded incidence of ectopic pregnancy has increased markedly over the last three decades. This may be partly due to artefacts of data recording and more sensitive diagnostic tests, but it is likely that the actual incidence has increased, probably due to a sexually transmitted agent.

Adolescent↗

Contact fluorescence imaging of reentry in monolayers of cultured neonatal rat ventricular myocytes.

INTRODUCTION: We present a novel contact fluorescence imaging (CFI) approach to monitor transmembrane potentials in monolayers of cultured neonatal rat ventricular cells. We apply CFI to demonstrate, for the first time, long-term recordings as well as electrical induction and termination of reentrant activity in this in vitro model. METHODS AND RESULTS: CFI was performed in confluent cell monolayers stained with di-8-ANEPPS. An anatomic obstacle (6 x 0.5 mm) was created in the center of the monolayers. Reentry was induced with a premature stimulus after pacing at 2 Hz (both via field stimulation). Seven sustained (>3 min) reentrant episodes, anchored to the anatomic obstacle, were observed in three monolayers. Field stimulation (30 V/cm) was applied to successfully terminate 6 of the 7 reentries. Analysis of reentrant activity showed similarities with anatomic reentry in tissue preparations, such as reduced conduction velocity around the core, variable conduction velocity along the reentrant pathway due to wavefront curvature effects, and field-induced activation at the obstacle borders leading to reentry termination (cardioversion). CONCLUSION: This study demonstrates the feasibility of CFI for macroscopic optical mapping of transmembrane potentials in a single layer of cultured cells. Our results suggest that the monolayer cell culture model is an attractive complement to tissue models of reentry and cardioversion.

Animals↗

Thyroid hormone resistance and increased metabolic rate in the RXR-gamma-deficient mouse.

Vitamin A and retinoids affect pituitary-thyroid function through suppression of serum thyroid-stimulating hormone (TSH) levels and TSH-beta subunit gene expression. We have previously shown that retinoid X receptor-selective (RXR-selective) ligands can suppress serum TSH levels in vivo and TSH-beta promoter activity in vitro. The RXR-gamma isotype has limited tissue distribution that includes the thyrotrope cells of the anterior pituitary gland. In this study, we have performed a detailed analysis of the pituitary-thyroid function of mice lacking the gene for the RXR-gamma isotype. These mice had significantly higher serum T4 levels and TSH levels than did wild-type (WT) controls. Treatment of RXR-gamma-deficient and WT mice with T3 suppressed serum TSH and T4 levels in both groups, but RXR-gamma-deficient mice were relatively resistant to exogenous T3. RXR-gamma-deficient mice had significantly higher metabolic rates than did WT controls, suggesting that these animals have a pattern of central resistance to thyroid hormone. RXR-gamma, which is also expressed in skeletal muscle and the hypothalamus, may have a direct effect on muscle metabolism, regulation of food intake, or thyrotropin-releasing hormone levels in the hypothalamus. In conclusion, the RXR-gamma isotype appears to contribute to the regulation of serum TSH and T4 levels and to affect peripheral metabolism through regulation of the hypothalamic-pituitary-thyroid axis or through direct effects on skeletal muscle.

Animals↗

Preferred terms for users of mental health services among service providers and recipients.

OBJECTIVE: The terms used to refer to recipients of psychiatric services continue to be controversial. Terms in current use include "patient," "client," "consumer," and "survivor." In this study mental health service recipients and providers were surveyed about their preferences among these terms, and responses were analyzed to identify factors associated with various preferences. METHODS: A total of 550 service providers and 427 recipients at four sites in Ontario-two provincial psychiatric hospitals, a private mental health center, and a psychiatric unit of a general hospital-participated in a brief anonymous survey. RESULTS: Among service providers, 68.4 percent preferred the term "patient," 26.5 percent preferred "client," and.5 percent preferred "consumer." Logistic regression analysis showed that service providers' preferences were associated with age and gender. Among service recipients, 54.8 percent preferred the term "patient," 28.8 percent preferred "client," 7 percent preferred "survivor," and 2.8 percent preferred "consumer." Service recipients' preferences were associated with site, self-reported diagnosis, and employment status. CONCLUSION: The study results indicate lack of universality in preferences for terms for users of mental health services and suggest the need for dialogue about preferred terms between service providers and recipients.

Adult↗

Self-report quality of life measure for people with schizophrenia: the SQLS.

BACKGROUND: Quality of life is the subject of growing interest and investigation. AIMS: To develop and validate a short, self-report quality of life questionnaire (the Schizophrenia Quality of Life Scale, SQLS). METHOD: People with schizophrenia in Liverpool were recruited via the NHS. Items, generated from in-depth interviews, were developed into an 80-item self-report questionnaire. Data were factor analysed, and a shorter form measure was tested for reliability and validity. This measure was administered together with other self-report measures--SF-36, GHQ-12 and HADS--to assess validity. RESULTS: Data were analysed to produce a final 30-item questionnaire, comprising three scales ('psychosocial', 'motivation and energy', and 'symptoms and side-effects') addressing different SQLS dimensions. Internal consistency reliability of the scale was found to be satisfactory. There was a high level of association with relevant SF-36, GHQ-12 and HADS scores. CONCLUSIONS: The SQLS was completed within 5-10 minutes. It possesses internal reliability and construct validity, and promises to be a useful tool for the evaluation of new treatment regimes for people with schizophrenia.

Adolescent↗