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Biomedical subjects

S Thomas

Publications and source records attributed to S Thomas.

At least 235 records · Page 13Linked to original sources
PubMed1999

Effects of L-carnitine on leukocyte function and viability in hemodialysis patients: A double-blind randomized trial.

Excess morbidity and mortality among long-term hemodialysis patients because of infectious complications is partly caused by an impairment of cellular immune defense. We hypothesized this impairment is related to an abnormal carnitine metabolism also present in these patients. In a double-blind, randomized, placebo-controlled trial, we investigated the effect of L-carnitine on phagocytic function and viability of blood leukocytes in 17 patients undergoing maintenance hemodialysis. After an observation period of 1 month, the patients received either 10 mg/kg of L-carnitine or placebo intravenously at the end of each hemodialysis session over a period of 4 months. Leukocyte oxidative metabolism was measured by means of luminol-enhanced chemiluminescence and superoxide generation after stimulation with Staphylococcus aureus or phorbol myristate acetate. Killing capacity and phagocytosis of radiolabeled staphylococci were determined. A lactate dehydrogenase (LDH) release test was applied to assess cell viability. We were unable to show an effect of L-carnitine on phagocytic function and viability in vivo. Several clinical parameters were observed during the trial. No statistically significant differences concerning dialysis-related morbidity, anemia, or reduction of blood urea nitrogen and creatinine levels were detected. Additionally, we tested the effect of L-carnitine on phagocytic function after in vitro incubation of blood leukocytes, which also showed no changes. LDH release was decreased, indicating an improved viability of these cells. The latter results were found after in vitro incubation of cells, but could not be confirmed in vivo. In summary, we could not show beneficial effects of L-carnitine administration in hemodialysis patients for the dosage and duration of treatment stated, either on phagocytic function and viability or on the clinical and biochemical parameters observed.

Adult↗
PubMed1999

The anti-microbial activity of maggot secretions: results of a preliminary study.

The ability of larval secretions to kill or prevent the growth of a range of potentially pathogenic bacteria was investigated in a preliminary laboratory study. Marked anti-microbial activity was detected against Streptococcus A and B and Staphylococcus aureus. Some activity was also detected against Pseudomonas sp. and a clinical isolate of a resistant strain of S. aureus (MRSA). No evidence of inhibition was recorded against Enterococcus or the Gram-negative bacteria Escherichia coli and Proteus. These findings are consistent with clinical observations made by us and others that larvae of the common greenbottle are able to combat clinical infections in a variety of wound types including those caused by antibiotic-resistant strains of bacteria.

Animals↗
PubMed1999

Transmyocardial laser revascularisation has no beneficial effect on high energy phosphates and lactate content during acute myocardial ischaemia in pigs.

OBJECTIVE: Transmyocardial laser revascularisation (TMLR) is used to treat endstage coronary heart disease. There is evidence that angina is significantly reduced after TMLR. However, the precise mechanism by which symptoms disappear remains unknown. The objective of the present study was to examine the potential effects of TMLR on high-energy phosphates and myocardial perfusion in an acute ischaemic model. METHOD: Five male landrace pigs (42 +/- 1.8 kg) had TMLR of the anterolateral wall of the left ventricle using a 1000 W CO2 laser (PLC, USA). Thereafter the anterior descending coronary artery was occluded with a tourniquet. After 90 min of ischaemia, drill-biopsies were taken from ischaemic and non-ischaemic areas as well as from laser channels. The specimens were snap-frozen in liquid nitrogen. Subsequently, methylene blue was injected into the left atrium to study tissue distribution. The hearts were excised and the patency of channels was examined visually. RESULTS: Coronary artery occlusion resulted in immediate blue discoloration in both TMLR and control areas. There was no subendocardial methylene blue staining around laser channels. Inspection of hearts showed occlusion of laser channels due to thrombus formation at both endo- and epicardial levels. ATP-metabolites significantly increased in ischaemic areas compared to non-ischaemic areas. Furthermore there was significant upregulation of purine-content in ischaemic regions even in areas with laser channels. CONCLUSIONS: In our acute model there was early occlusion of the channels after TMLR. We suggest that clinical improvement after this procedure is not due to increased myocardial oxygen delivery, since high energy phosphate levels and lactate content remained unchanged.

Acute Disease↗
PubMed1999

Early postnatal dexamethasone increases the risk of focal small bowel perforation in extremely low birth weight infants.

OBJECTIVE: We observed two clusters of spontaneous pneumoperitoneums in extremely low birth weight infants during the use of a protocol for early dexamethasone prophylaxis (EDP) for bronchopulmonary dysplasia from 1996 to 1997. During surgery, focal small bowel perforation (FSBP) was found in eight of nine cases. A retrospective study was designed to identify risk factors for FSBP in these extremely low birth weight infants. METHODS: A case-controlled analysis was performed using all infants born weighing < 1001 gm and admitted to the University of Washington Medical Center Neonatal Intensive Care Unit during a 13-month period. A total of 51 infants were identified and divided into groups based on treatment or not with dexamethasone and indomethacin. These cohorts were homogeneous for gestational age, birth weight, and perinatal stability. Relative risk and confidence intervals were calculated for each of the comparisons. Routine pathology was performed on all surgical specimens and additional sections were cut and stained for further study. RESULTS: Infants who received EDP had a relative risk of perforation that was 12.3 times that of untreated infants. Those treated with indomethacin had a risk that was comparable with that for infants who did not receive indomethacin. Infants who received both EDP and indomethacin tended to have higher rates of pneumoperitoneum than infants who received EDP alone but comprised a cohort too small for valid analysis. The pathology of surgical specimens revealed FSBP with segmental loss of the muscularis externa. There was no evidence of fungal or bacterial infection in any of the surgical specimens. CONCLUSION: These findings implicate EDP, but not indomethacin, as a significant risk factor for FSBP.

Anti-Inflammatory Agents↗
PubMed1999

Relation between indoor and outdoor exposure to fine particles near a busy arterial road.

Various studies on indoor and outdoor particulate matter in the urban environment in the vicinity of busy arterial roads in the centre of the subtropical city of Brisbane have indicated that the revised United States Environmental Protection Agency National Ambient Air Quality Standards (US EPA NAAQS) for Particulate matter PM2.5 could be exceeded not only outdoors but also indoors. The aim of this work was to investigate outdoor exposure to submicrometer particles and their relationship with indoor exposure in a hypothetical office building located in the vicinity of a busy arterial road. The outdoor exposure values and trends were measured in terms of particle number in the submicrometer size range and were then recalculated to represent mass concentration trends. The results of this study indicate that exposure to PM0.7 particles in ambient air close to a busy road often exceeds the levels of the annual and 24-hour US EPA NAAQS PM2.5 standards. It is likely that exposure to PM2.5 is even higher, and may significantly exceed these standards.

Air Pollution, Indoor↗
PubMed1999

Contribution of individual subunits to the multimeric P2X(2) receptor: estimates based on methanethiosulfonate block at T336C.

P2X receptors are membrane proteins that incorporate a cation-selective ion channel that can be opened by the binding of extracellular ATP. They associate as hetero- and homo-multimers of currently unknown stoichiometry. In this study, we have used Xenopus laevis oocytes to express rat P2X(2) receptor subunits, which carry a cysteine mutation at position 336. ATP-induced currents at this mutant receptor subunit were blocked by more than 90% when exposed to [2-(trimethylammonium) ethyl] methanethiosulfonate (MTSET), whereas currents from wild-type subunits were not affected. To compare mutant and wild-type channel expression, we introduced an epitope in their extracellular domains and found for both channels a similar linear relationship between antibody binding and currents induced by ATP. To study the contribution of the individual subunits to the block by MTSET, we coinjected different mixtures of wild-type and mutant-encoding mRNAs. We found that the inhibition by MTSET depended linearly on the proportion of mutant subunits, which was clearly contrary to the hypothesis that a single mutant subunit could act in a dominant fashion. Subsequent concatenation of wild-type and mutant-encoding cDNAs resulted in an inhibition by MTSET that also depended linearly on the number of mutant subunits and was independent of the position of the mutant subunit, as long as only two or three P2X(2) subunits were joined. With four or six subunits joined, however, the inhibition by MTSET became strongly position-dependent. The present results show that a "per-subunit" channel block causes the blocking effects of MTSET and they suggest that not four but maximally three subunits actively participate in the channel formation.

Animals↗
PubMed1999

Phenotypic consequences resulting from a methionine-to-valine substitution at position 48 in the HPr protein of Streptococcus salivarius.

In gram-positive bacteria, the HPr protein of the phosphoenolpyruvate:sugar phosphotransferase system (PTS) can be phosphorylated on a histidine residue at position 15 (His(15)) by enzyme I (EI) of the PTS and on a serine residue at position 46 (Ser(46)) by an ATP-dependent protein kinase (His approximately P and Ser-P, respectively). We have isolated from Streptococcus salivarius ATCC 25975, by independent selection from separate cultures, two spontaneous mutants (Ga3.78 and Ga3.14) that possess a missense mutation in ptsH (the gene encoding HPr) replacing the methionine at position 48 by a valine. The mutation did not prevent the phosphorylation of HPr at His(15) by EI nor the phosphorylation at Ser(46) by the ATP-dependent HPr kinase. The levels of HPr(Ser-P) in glucose-grown cells of the parental and mutant Ga3.78 were virtually the same. However, mutant cells growing on glucose produced two- to threefold less HPr(Ser-P)(His approximately P) than the wild-type strain, while the levels of free HPr and HPr(His approximately P) were increased 18- and 3-fold, respectively. The mutants grew as well as the wild-type strain on PTS sugars (glucose, fructose, and mannose) and on the non-PTS sugars lactose and melibiose. However, the growth rate of both mutants on galactose, also a non-PTS sugar, decreased rapidly with time. The M48V substitution had only a minor effect on the repression of alpha-galactosidase, beta-galactosidase, and galactokinase by glucose, but this mutation abolished diauxie by rendering cells unable to prevent the catabolism of a non-PTS sugar (lactose, galactose, and melibiose) when glucose was available. The results suggested that the capacity of the wild-type cells to preferentially metabolize glucose over non-PTS sugars resulted mainly from inhibition of the catabolism of these secondary energy sources via a HPr-dependent mechanism. This mechanism was activated following glucose but not lactose metabolism, and it did not involve HPr(Ser-P) as the only regulatory molecule.

Alkaline Phosphatase↗
PubMed1999

Risk of myocardial infarction in young female smokers.

OBJECTIVES: To determine the extent of risk of myocardial infarction from cigarette smoking in young women, and to examine the relation of smoking with other putative risk factors. DESIGN: Community based case control study. SETTING: England, Scotland, and Wales. PATIENTS: Women (n = 448) between 16 and 44 years old with a diagnosis of incident myocardial infarction between 1 October 1993 and 16 October 1995. Controls (n = 1728) were age and general practice matched women without a diagnosis of myocardial infarction. OUTCOMES MEASURES: Odds ratios for risk of myocardial infarction associated with smoking and other risk factors. RESULTS: Odds ratios for myocardial infarction in smokers versus non-smokers showed a strong dose response, from 2.47 (95% confidence interval (CI) 1.12 to 5.45) in smokers of 1-5 cigarettes per day to 74.6 (95% CI 33.0 to 169) in smokers of >/= 40 cigarettes per day. There was no interaction of smoking with use of oral contraceptives, but there were additive risks with other clinical risk factors such as hypertension and diabetes. It is estimated that if all women aged 16-44 years were able to stop smoking, 400 cases of myocardial infarction per annum (of whom 112 would die) would be prevented. CONCLUSIONS: In young women the risk of myocardial infarction from smoking was considerable, and heavy smokers with other risk factors were especially at risk.

Adolescent↗
PubMed1999

Genetic pathway to recurrent chromosome translocations in murine lymphoma involves V(D)J recombinase.

Chromosome translocations involving antigen receptor loci are a genetic hallmark of non-Hodgkin's lymphomas in humans. Most commonly, these translocations result in juxtaposition of the immunoglobulin heavy-chain (IgH) locus with one of several cellular proto-oncogenes, leading to deregulated oncogene expression. The V(D)J recombinase, which mediates physiologic rearrangements of antigen receptor genes, may play a mechanistic role in some lymphoma translocations, although evidence is indirect. A high incidence of B-lineage lymphomas has been observed in mice with severe combined immunodeficiency (SCID) and p53-null mutations. We show that these tumors are characteristic of the pro-B-cell stage of development and that they harbor recurrent translocations involving chromosomes 12 and 15. Fluorescence in situ hybridization (FISH) shows retention of IgH sequences on the derivative chromosome 12, implying that breakpoints involve the IgH locus. Pro-B-cell lymphomas were suppressed in SCID p53(-/-) mice by a Rag-2-null mutation, demonstrating that DNA breaks generated during V(D)J recombination are required for oncogenic transformation, and suggesting that t(12;15) arise during attempted IgH rearrangement in pro-B cells. These studies indicate that the oncogenic potential inherent in antigen receptor diversification is controlled in vivo by efficient rejoining of DNA ends generated during V(D)J recombination and an intact cellular response to DNA damage.

Animals↗
PubMed1999

Leiomyosarcoma of the larynx. Case report.

Leiomyosarcoma involving the larynx is extremely rare and may be difficult to diagnose. Likewise, because of the rarity of this lesion, little information exists with regard to long-term follow-up or optimal management. Reported here is a review of the literature and a case report of a patient with leiomyosarcoma of the larynx treated by surgery alone with 5 years of follow-up.

Aged↗
PubMed1999

The effect of hydrogel dressings on maggot development.

The effect of six different hydrogels on the development of sterile larvae (Lucilia sericata) was examined in a laboratory study. Five of the products had a marked adverse effect on maggot survival but one appeared to facilitate growth of the larvae when compared to control values. These results are consistent with clinical observations that larvae may not survive well in wounds containing residues of some hydrogel dressings.

Animals↗