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Biomedical subjects

S Thomas

Publications and source records attributed to S Thomas.

At least 145 records · Page 8Linked to original sources

Antithrombin inhibits lipopolysaccharide-induced tissue factor and interleukin-6 production by mononuclear cells, human umbilical vein endothelial cells, and whole blood.

OBJECTIVE: To investigate the effects of antithrombin on lipopolysaccharide (LPS)-induced tissue factor and interleukin-6 (IL-6) production in three different in vitro cellular systems: whole blood, human umbilical vein endothelial cells, and mononuclear cells. DESIGN AND SETTING: Laboratory in vitro study of the effects of antithrombin on procoagulant activity and cytokine release by LPS-stimulated endothelial and peripheral blood cells. SUBJECTS: In vitro whole blood, isolated human umbilical vein endothelial cell, and mononuclear cell cultures. INTERVENTIONS: Addition of antithrombin to LPS-treated whole blood, human umbilical vein endothelial cells, and mononuclear cells. MEASUREMENT AND MAIN RESULTS: Citrated whole blood, isolated human umbilical vein endothelial cells, or mononuclear cells were stimulated with LPS for 4-6 hrs in the presence or absence of antithrombin. Tissue factor activity was estimated by a tissue factor-dependent clotting or chromogenic assay and IL-6 was measured by specific ELISA. Antithrombin was found to inhibit tissue factor and IL-6 production in all three systems in a dose-dependent manner (0-40 IU/mL). Flow-through fractions of immunoadsorbed antithrombin concentrate were found to be ineffective. Five different batches of the same antithrombin concentrate were tested and the inhibitory activity was found to be consistent throughout all batches. Up to 40 microM of recombinant hirudin, a specific thrombin inhibitor, did not inhibit the production of tissue factor or IL-6 in either of the three cell systems, suggesting that the observed inhibition by antithrombin was not due solely to its ability to inhibit thrombin. CONCLUSIONS: Apart from the inhibition of thrombin and other activated clotting factors, antithrombin may also down-regulate the cellular expression of proinflammatory cytokines. Consequently, antithrombin concentrates may have value in the treatment of sepsis-induced disseminated intravascular coagulation.

Antithrombins↗

Outcomes of cleft care in Western Australia: a pilot study.

The purpose of this study was to compare outcomes and delivery of cleft care in Western Australia with the average standard of care in the United Kingdom (UK). This was achieved through a cross-sectional study involving children born with unilateral cleft lip and palate between April 1983 and March 1985 (12 year olds) or between April 1990 and March 1992 (5 year olds). A total of 38 children born with unilateral cleft lip and palate were under the care of the cleft team based at Perth's Princess Margaret Hospital. Dental arch relations, facial skeletal pattern, speech, hearing, success of alveolar bone grafting and dental health were measured. It was found that fewer Princess Margaret Hospital children in both age cohorts had revision surgery and speech therapy compared with the UK average. The facial skeletal pattern, speech, hearing and alveolar bone grafting outcomes from Princess Margaret Hospital were similar to the UK at age 12. Seventeen per cent of the Princess Margaret Hospital 12 year olds had a poor dental arch relationship compared with 39 per cent in the UK. In the 5 year olds, most outcomes in Princess Margaret Hospital patients appeared better than the UK with lower residual treatment needs. While it is difficult to draw firm conclusions because of the small numbers involved, this study indicates standards need to be set and determined for Australia.

Bone Transplantation↗

Secreted variant of nucleoside diphosphate kinase from the intracellular parasitic nematode Trichinella spiralis.

The molecular components involved in the survival of the parasitic nematode Trichinella spiralis in an intracellular environment are poorly characterized. Here we demonstrate that infective larvae secrete a nucleoside diphosphate kinase when maintained in vitro. The secreted enzyme forms a phosphohistidine intermediate and shows broad specificity in that it readily accepts gamma-phosphate from both ATP and GTP and donates it to all nucleoside and deoxynucleoside diphosphate acceptors tested. The enzyme was partially purified from culture medium by ATP affinity chromatography and identified as a 17-kDa protein by autophosphorylation and reactivity with an antibody to a plant-derived homologue. Secreted nucleoside diphosphate kinases have previously been identified only in prokaryotic organisms, all of them bacterial pathogens. The identification of a secreted variant of this enzyme from a multicellular eukaryote is very unusual and is suggestive of a role in modulating host cell function.

Animals↗

Diversity of Streptococcus salivarius ptsH mutants that can be isolated in the presence of 2-deoxyglucose and galactose and characterization of two mutants synthesizing reduced levels of HPr, a phosphocarrier of the phosphoenolpyruvate:sugar phosphotransferase system.

In streptococci, HPr, a phosphocarrier of the phosphoenolpyruvate:sugar phosphotransferase transport system (PTS), undergoes multiple posttranslational chemical modifications resulting in the formation of HPr(His approximately P), HPr(Ser-P), and HPr(Ser-P)(His approximately P), whose cellular concentrations vary with growth conditions. Distinct physiological functions are associated with specific forms of HPr. We do not know, however, the cellular thresholds below which these forms become unable to fulfill their functions and to what extent modifications in the cellular concentrations of the different forms of HPr modify cellular physiology. In this study, we present a glimpse of the diversity of Streptococcus salivarius ptsH mutants that can be isolated by positive selection on a solid medium containing 2-deoxyglucose and galactose and identify 13 amino acids that are essential for HPr to properly accomplish its physiological functions. We also report the characterization of two S. salivarius mutants that produced approximately two- and threefoldless HPr and enzyme I (EI) respectively. The data indicated that (i) a reduction in the synthesis of HPr due to a mutation in the Shine-Dalgarno sequence of ptsH reduced ptsI expression; (ii) a threefold reduction in EI and HPr cellular levels did not affect PTS transport capacity; (iii) a twofold reduction in HPr synthesis was sufficient to reduce the rate at which cells metabolized PTS sugars, increase generation times on PTS sugars and to a lesser extent on non-PTS sugars, and impede the exclusion of non-PTS sugars by PTS sugars; (iv) a threefold reduction in HPr synthesis caused a strong derepression of the genes coding for alpha-galactosidase, beta-galactosidase, and galactokinase when the cells were grown at the expense of a PTS sugar but did not affect the synthesis of alpha-galactosidase when cells were grown at the expense of lactose, a noninducing non-PTS sugar; and (v) no correlation was found between the magnitude of enzyme derepression and the cellular levels of HPr(Ser-P).

Bacterial Proteins↗

Intraoperative glove perforation--single versus double gloving in protection against skin contamination.

Surgeons have the highest risk of contact with patients' blood and body fluids, and breaches in gloving material may expose operating room staff to risk of infections. This prospective randomised study was done to assess the effectiveness of the practice of double gloving compared with single gloving in decreasing finger contamination during surgery. In 66 consecutive surgical procedures studied, preoperative skin abrasions were detected on the hands of 17.4% of the surgeons. In the double gloving pattern, 32 glove perforations were observed, of which 22 were in the outer glove and 10 in the inner glove. Only four outer glove perforations had matching inner glove perforations, thus indicating that in 82% of cases when the outer glove is perforated the inner glove will protect the surgeon's hand from contamination. The presence of visible skin contamination was also higher in perforation with the single gloving pattern (42.1%) than with the double gloving pattern (22.7%). An overwhelming majority of glove perforations (83.3%) went unnoticed. Double gloving was accepted by the majority of surgeons, especially with repeated use. It is recommended that double gloves are used routinely in all surgical procedures in view of the significantly higher protection it provides.

Equipment Failure↗

Genomic organization and refined mapping of the human nuclear corepressor 2 (NCOR2)/ silencing mediator of retinoid and thyroid hormone receptor (SMRT) gene on chromosome 12q24.3.

The human nuclear co-repressor 2 (N-CoR2) gene (NCOR2, previously called silencing mediator for retinoid and thyroid hormone receptor SMRT) is recruited to nuclear and non-nuclear receptors in a large repressing complex containing also N-CoR1, mSin3 and HDACs. This large complex represses transcription in absence of ligand. Herein we report the high- resolution and refined mapping of NCOR2 at the boundary of sub-bands 12q24.23 and 12q24.31, and its intron/exon structure. The gene contains 45 exons. This information should allow further study of potential NCOR2 genomic alteration in some subsets of malignancies.

Chromosome Banding↗

Chloride conductance and genetic background modulate the cystic fibrosis phenotype of Delta F508 homozygous twins and siblings.

To investigate the impact of chloride (Cl(-)) permeability, mediated by residual activity of the cystic fibrosis transmembrane conductance regulator (CFTR) or by other Cl(-) channels, on the manifestations of cystic fibrosis (CF), we determined Cl(-) transport properties of the respiratory and intestinal tracts in Delta F508 homozygous twins and siblings. In the majority of patients, cAMP and/or Ca(2+)-regulated Cl(-) conductance was detected in the airways and intestine. Our finding of cAMP-mediated Cl(-) conductance suggests that, in vivo, at least some Delta F508 CFTR can reach the plasma membrane and affect Cl(-) permeability. In respiratory tissue, the expression of basal CFTR-mediated Cl(-) conductance, demonstrated by 30% of Delta F508 homozygotes, was identified as a positive predictor of milder CF disease. In intestinal tissue, 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid-insensitive (DIDS-insensitive) Cl(-) secretion, which is indicative of functional CFTR channels, correlated with a milder phenotype, whereas DIDS-sensitive Cl(-) secretion was observed mainly in more severely affected patients. The more concordant Cl(-) secretory patterns within monozygous twins compared with dizygous pairs imply that genes other than CFTR significantly influence the manifestation of the basic defect.

Adolescent↗

A rapid access husky voice clinic: useful in diagnosing laryngeal pathology.

A new established pilot husky voice clinic with agreed referral protocols for patients at risk of developing laryngeal malignancy was audited. Thirty-four patients were seen, 41.2 per cent having abnormal findings on flexible nasendoscopy, 29.4 per cent requiring rigid endoscopy, 38.1 per cent were discharged after the initial visit. One case of early laryngeal cancer was picked up during this period from this group of patients. The data for the remaining population in Portsmouth was examined, and a further eight cases of laryngeal cancer were diagnosed in keeping with national incidences. A rapid access clinic with agreed protocols that referring practitioners adhered to, was useful for diagnosing laryngeal cancer and should meet the requirements of the government's 14-day rule.

Adult↗

The current status of maggot therapy in wound healing.

The clinical use of sterile maggots under the brand name LarveE has increased steadily in the UK since they were introduced in the UK in late 1995. Some 50 articles have been published in the last 4 years that describe the cost-effectiveness of maggot therapy in a variety of wound types including leg ulcers, pressure ulcers and diabetic ulcers. The ability of these creatures to combat wound infection has been well documented including those caused by antibiotic-resistant strains of bacteria such as methicillin-resistant Staphylococcus aureus. No significant risks or adverse events have been linked to the use of maggots, although their presence may increase pain levels in leg ulcers associated with ischaemic disease.

Animals↗

Gays and lesbians in local races: a study of electoral viability.

Although lesbians and gays are more visible in the political arena than in the past, there is little published research on their electoral viability. This article helps to fill that void by presenting results of experimental research featuring respondents' reactions to a hypothetical candidate for a non-partisan city council seat. Sex and sexual orientation of the candidates were manipulated so that six categories were tested: a straight woman, a lesbian, a woman rumored to be lesbian, a straight man, a gay man, and a man rumored to be gay. The findings suggest that openly gay and lesbian candidates are seen as less viable than straight candidates or those rumored to be homosexual. Hence, the extent to which a candidate portrays his or her sexual orientation appears to make a difference in the chance to win elective office.

Adult↗

A qualitative systematic overview of the measurement properties of functional walk tests used in the cardiorespiratory domain.

OBJECTIVE: To perform a qualitative systematic overview of the measurement properties of the most commonly utilized walk tests in the cardiorespiratory domain: the 2-min walk test (2MWT), 6-min walk test (6MWT), 12-min walk test (12MWT), self-paced walk test (SPWT), and shuttle walk test (SWT). DATA SOURCES: MEDLINE (1966 to January 2000) and CINAHL (1982 to December 1999) electronic databases were searched. Bibliographies of the retrieved articles were reviewed. STUDY SELECTION: Clinical trials and observational studies were included if they reported data on the validity, reliability, interpretability, or responsiveness of the 2MWT, 6MWT, 12MWT, SPWT, or SWT. Only studies conducted on patients with cardiac and/or respiratory involvement were included. RESULTS: Fifty-two studies examining measurement properties of the various walk tests were found: 5 studies on the 2MWT, 29 studies on the 6MWT, 13 studies on the 12MWT, 6 studies on the SPWT, and 4 studies on the SWT. Measurement properties were most strongly demonstrated for the 6MWT. Correlations of 6MWT distance and maximal oxygen consumption ranged from 0.51 to 0.90. A change in distance walked of at least 54 m was found to be clinically significant for the 6MWT. Reliability was shown to be optimized when the administration of walk tests was standardized and at least two practice walks were performed. Patients with increased likelihood of postoperative complications, hospitalization, and death were identified by analysis of distance walked. CONCLUSIONS: Measurement properties of the 6MWT have been the most extensively researched and established. In addition, the 6MWT is easy to administer, better tolerated, and more reflective of activities of daily living than the other walk tests. Therefore, the 6MWT is currently the test of choice when using a functional walk test for clinical or research purposes.

Adult↗

A study of waiting time for surgery in elderly patients with hip fracture and subsequent in-patient hospital stay.

OBJECTIVE: To establish whether increased waiting time to operation in elderly patients with hip fracture significantly affects postoperative time to discharge. METHODS: Combined prospective and retrospective analysis of theatre logbooks and in-patient data to determine the type, time and date of operation and subsequent in-patient stay. SETTING: A busy district general hospital in the South East Thames Valley area with changing availability of a dedicated trauma list. PATIENTS: 441 elderly patients undergoing hip surgery between May 1995 and March 1997. MAIN OUTCOME MEASURES: Waiting time from booking of operation to surgery and length of postoperative hospital stay. RESULTS: Increased pre-operative wait for emergency hip surgery in elderly patients significantly increases postoperative stay. Roughly doubling pre-operative wait increases postoperative stay by 19% (P < 0.01).

Aged↗

Concurrent alcoholism and social anxiety disorder: a first step toward developing effective treatments.

BACKGROUND: Social anxiety disorder (also called social phobia) is an anxiety disorder in which affected individuals fear the scrutiny of others. Clinical reports suggest that individuals with social anxiety disorder often use alcohol to alleviate anxiety symptoms, a practice that leads to alcohol abuse and/or dependence in approximately 20% of affected individuals. The present study investigated whether simultaneous treatment of social phobia and alcoholism, compared with treatment of alcoholism alone, improved alcohol use and social anxiety for clients with dual diagnoses of social anxiety disorder and alcohol dependence. METHODS: The design was a two-group, randomized clinical trial that used 12 weeks of individual cognitive behavioral therapy for alcoholism only (n = 44) or concurrent treatment for both alcohol and social anxiety problems (n = 49). Outcome data were collected at the end of 12 weeks of treatment and at 3 months after the end of treatment. RESULTS: Results with intent-to-treat analyses showed that both groups improved on alcohol-related outcomes and social anxiety after treatment. With baseline scores covaried, there was a significant effect of treatment group on several drinking measures. Counter to the hypothesis, the group treated for both alcohol and social anxiety problems had worse outcomes on three of the four alcohol use indices. No treatment group effects were observed on social anxiety indices. CONCLUSIONS: Implications for the staging of treatments for coexisting social phobia and alcoholism are discussed, as well as ways that modality of treatments might impact outcomes.

Adult↗

High prevalence of microcytic anaemia in Omani children: a prospective study.

Iron deficiency is a common cause of microcytic anaemia. However, a high prevalence of haemoglobinopathies in the Arab population makes differential diagnosis difficult. This prospective study of anaemia in children attending a regional hospital in the Sultanate of Oman looked at the prevalence and causes of anaemia in 256 children, 153 in the age group 3-5 years (group A) and 103 in the age group 10-12 years (group B). Of the children studied, 45.1% in group A and 37.9% in group B were anaemic according to WHO criteria. All the anaemic children had low mean corpuscular haemoglobin and 75% showed microcytosis. Serum ferritin levels were normal and glucose-6-phosphate dehydrogenase deficiency did not contribute to the anaemia. The microcytosis and microcytic anaemia in the study population could be attributed to the alpha-thalassaemia trait which is highly prevalent in Oman. The information is of value in any country where there is a significant prevalence of alpha-thalassaemia genes because these can confound the diagnosis of iron deficiency.

Anemia, Iron-Deficiency↗

Lymphocytic hypophysitis: spontaneous resolution on MRI with progression of endocrine defect.

Lymphocytic hypophysitis is an uncommon condition that typically occurs during the last trimester of pregnancy or in the postpartum period. Presentation is of an anterior pituitary mass with varying degrees of pituitary dysfunction. We present a case in which there was dramatic resolution of the pituitary lesion on sequential MRI scanning. Despite this apparent resolution, however, the patient continues to have significant pituitary dysfunction.

Adult↗

Brain and CSF entry of the novel non-nucleoside reverse transcriptase inhibitor, GW420867X.

(S)-2-ethyl-7-fluoro-3-oxo-3, 4-dihydro-2H-quinoxaline-carboxylic acid isopropylester (GW420867X) inhibits HIV-1 reverse transcriptase and could be used for the treatment of HIV infection. This study quantified the movement of [14C]GW420867X into the CNS by means of a guinea-pig brain perfusion technique. Results indicated that [14C]GW420867X can enter the brain (Kin: 38.4+/-7.7 microl min(-1) g(-1)) and cerebrospinal fluid (CSF; Kin: 1.2+/-0.1 microl min(-1) g(-1)). Self-inhibition studies also suggested the presence of a saturable transport system for [14C]GW420867X at the blood-brain barrier (BBB). Thus [14C]GW420867X can enter the brain via the BBB and, compared with the blood-CSF barrier, this route is the predominant pathway for the brain entry of this drug. This would suggest that GW420867X is a promising drug for the treatment of HIV infection within the brain.

Animals↗