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Biomedical subjects

M Thomas

Publications and source records attributed to M Thomas.

At least 649 records · Page 36Linked to original sources
PubMed1991

Unusual presentations of duodenal tuberculosis.

Gastrointestinal tuberculosis is still rampant in underdeveloped countries and can mimic other gastrointestinal (GI) disorders. Herein we report four cases of isolated proximal duodenal tuberculosis, without involvement of other parts of the GI tract. The clinical presentation in three of them resembled that of peptic ulcer disease, and one had features of gastric outlet obstruction. On investigation, one of these patients had a pyeloduodenal fistula. The limitations of clinical evaluation, radiology, and endoscopy are stressed, and the value of surgical biopsy is highlighted.

Adult↗
PubMed1990

Inflammatory lipid mediator generation elicited by viable hemolysin-forming Escherichia coli in lung vasculature.

Escherichia coli hemolysin, a transmembrane pore-forming exotoxin, is considered an important virulence factor for E. coli-related extraintestinal infections and sepsis. The possible significance of hemolysin liberation for induction of inflammatory lipid mediators was investigated in isolated rabbit lungs infused with viable bacteria (concentration range, 10(4)-10(7)/ml). Hemolysin-secreting E. coli (E. coli-Hly+), but not an E. coli strain that releases an inactive form of the exotoxin, induced marked lung leukotriene (LT) generation with predominance of cysteinyl LTs. Eicosanoid synthesis was not inhibited in the presence of plasma with toxin-neutralizing capacity. Pre-application of 2 x 10(8) human granulocytes, which sequestered in the lung microvasculature, caused a severalfold increase in leukotriene generation in response to E. coli-Hly+ challenge both in the absence and presence of plasma. Data are presented indicating neutrophil-endothelial cell cooperation in arachidonic acid lipoxygenase metabolism as an underlying mechanism. We conclude that liberation of hemolysin from viable E. coli induces marked lipid mediator generation in lung vasculature, which is potentiated in the presence of neutrophil sequestration and may contribute to microcirculatory disturbances during the course of severe infections.

Animals↗
PubMed1990

Refractory and relapsing Hodgkin's disease: role of high-dose chemotherapy with bone marrow transplantation.

Thirty percent of adult patients with Hodgkin's disease fail primary treatment or relapse after treatment. Whereas overall mortality for Hodgkin's disease is about 20%, half the patients who relapse will die. Among patients with refractory or relapsing disease, about a third can be rescued by conventional salvage treatment. Unfortunately, except for patients with late relapse, remission after conventional salvage treatment is generally not of long duration. However, durable complete remissions can now be achieved in nearly a third of patients with refractory or relapsing disease by means of very aggressive (myeloablative) chemotherapy with consecutive autologous bone marrow transplantation (aBMT). The rate of durable complete remissions seems to be even higher if previous exposure to chemotherapeutic agents is not in excess of two different treatment protocols (optimal timing of aBMT) and if responsiveness to cytotoxic drugs is preserved (low degree of drug resistance). Bone marrow transplantation should be restricted to patients whose resulting long-term prognosis justifies such radical treatment. Reflecting ongoing clinical therapy-studies, in particular in Germany, the role of bone marrow transplantation in a general concept of salvage treatment should be pointed out. Patients should be considered candidates if they fail alternating primary chemotherapy or develop an early relapse after this treatment, but still show responsiveness to chemotherapeutic agents.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Sex steroid hormone modulation of NADPH pathways in MCF-7 cells.

Hormonal modulation of glucose-6-phosphate dehydrogenase (G6PD) and of utilization pathways of NADPH generated by G6PD was studied in the MCF-7 human breast cancer cell line, using a quantitative cytochemical method. Our results show that G6PD is increased by 17 beta-estradiol (estradiol) and synthetic progestin (promegestone R5020). The synthetic antiestrogen tamoxifen has no effect on G6PD activity. When it is present in the medium with estradiol, tamoxifen can oppose the stimulatory effect of estradiol on G6PD activity. Mifepristone (RU 38486) has no effect on G6PD activity, but it inhibits the R5020 stimulation of G6PD activity. After MCF-7 pretreatment with estradiol, there is a much stronger stimulation of G6PD activity by R5020. When we studied the effect of the steroid on the two utilization pathways of NADPH generated by G6PD activity, we observed that, in the cells treated with estradiol, there is an increase in reducing equivalents generated by G6PD activity which only affects the NADPH2 pathway, and that there is cell growth stimulation. When tamoxifen is present in the medium, we found no effect on the NADPH utilization pathways, nor on cell growth. In the presence of R5020, the NADPH2 pathway activity is increased but, under our experimental conditions, there was no effect on cell growth. On the other hand, even though RU 38486 is without effect on total G6PD activity, it does cause a modification in the distribution of reducing equivalents: the NADPH2 pathway activity is decreased, while the NADPH1 pathway is stimulated.

Breast Neoplasms↗
PubMed1990

Human uncoupling protein gene: structure, comparison with rat gene, and assignment to the long arm of chromosome 4.

The uncoupling protein (UCP) gene encodes a unique mammalian mitochondrial proton carrier that induces heat production in brown adipocytes. Human UCP gene was isolated and its organization analyzed. A comparison was made with rat UCP gene. Human UCP gene spans 13 Kb and contains a transcribed region that covers 9 Kb of the human genome. All of the exons were also sequenced except the extreme end of the 3' untranslated region. Two Kb DNA upstream the TATA box were also sequenced. This region contains several fragments that are highly homologous to the gene of rat UCP. Neither CCAAT sequence nor Sp 1 binding motif were detected. Human UCP gene is split into six exons. The complete amino acid sequence of the protein was determined. Human UCP has 305 amino acids and a molecular weight of 32,786. It has no N-terminal targeting sequence. It is 79% homologous to rat UCP both at nucleotidic and amino acid levels. The primary structure of UCP is significantly homologous to the primary structure of the human T1 ADP/ATP carrier, particularly in the C-terminal extremity, which is supposed to contain a nucleotide-binding site in both proteins. Human UCP gene is single type, as it is in rodents. Two genomic fragments were used to detect a 1.9 Kb mRNA in human perirenal brown adipose tissue. Using in situ hybridization, UCP gene was assigned in humans to chromosome 4 in q31. Interestingly, the T1 gene encoding the heart-skeletal muscle ADP/ATP carrier has recently been shown to be on the same chromosome (Li et al. Biol Chem 264:13998, 1989).

Amino Acid Sequence↗
PubMed1990

Myocardial oxygen supply in coronary artery disease.

In patients with coronary artery disease investigated during cardiac catheterisation, myocardial blood flow and myocardial oxygen consumption were significantly decreased as compared to control patients without signs of coronary artery disease. At the same time left ventricular function was impaired. In addition to regional contraction abnormalities observed in 77% of the patients, mean heart index and mean left ventricular work were diminished and mean enddiastolic pressure elevated. Among the coronary artery disease group, patients with normal blood pressure had a significantly higher left ventricular enddiastolic pressure than patients with hypertension.

Coronary Circulation↗
PubMed1990

The novel 21-aminosteroid U-74006F attenuates cerebral oedema and improves survival after brain injury in the rat.

The present study evaluated the effect of the non-glucocorticoid 21-aminosteroid U74006F on the development of regional cerebral oedema after lateral fluid-percussion (FP) brain injury in the rat. Male Sprague-Dawley rats (n = 20) were anaesthetized and subjected to lateral FP brain injury of moderate severity (2.5-2.6 atmospheres). Fifteen minutes after brain injury, animals randomly received an i.v. bolus of either U74006F (3 mg/kg, n = 11) followed by a second bolus (3 mg/kg) at 3 hours vs buffered saline vehicle (equal volume, n = 9). At 48 hours postinjury, animals were sacrificed and brains tissue assayed for water content using wet weight/dry weight methodology. Administration of U74006F significantly attenuated the increase in water content observed in control animals in the ipsilateral hippocampus (adjacent to the site of maximal injury, p less than 0.05). Administration of U74006F also significantly reduced post-injury mortality from 28% in control animals to zero in treated animals (p less than 0.001). These results suggest that lipid peroxidation may be involved in the pathophysiological sequelae of brain injury and that 21-aminosteroids may be beneficial in the treatment of brain injury.

Animals↗
PubMed1990

Development of regional cerebral oedema after lateral fluid-percussion brain injury in the rat.

Most studies attempting to characterize post-traumatic oedema formation have focused on the acute postinjury period. We have recently developed a new model of lateral (parasagittal) fluidpercussion (FP) brain injury in the rat. The purpose of the present study was to characterize the temporal course of oedema formation and resolution in this experimental model of brain injury. Male Sprague-Dawley rats (n = 67) were anaesthetized and subjected to FP brain injury of moderate severity. Animals were sacrified at 1 hour, 6 hours, 24 hours, 2 days, 3 days, 5 days and 7 days after brain injury, brains removed and assayed for water content using either specific gravitimetric or wet weight/dry weight techniques. In the injured left parietal cortex, a significant increase in water content was observed by 6 hours postinjury (p less than 0.05) that persisted up to 5 days postinjury. A prolonged and significant increase in water content was also observed in the left (ipsilateral) hippocampus which began at 1 hour postinjury (p less than 0.05) and continued up to 3 days. Other regions examined showed no significant regional oedema after brain injury. These results suggest that lateral FP brain injury produces an early focus oedema that persists for a prolonged period after trauma. This model may be useful in the evaluation of novel pharmacological therapies designed to reduce cerebral oedema after brain injury.

Animals↗
PubMed1990

Effect of cortisone on cells at the bone-marrow interface.

A study of the association between the rate of proliferation of marrow fibroblast-like stromal cells (in vitro) and the rate of endosteal bone mineralization (EsMR) (in vivo) was undertaken in an osteopenic rat model. We report that 200 g male rats treated with cortisone acetate (5 mg/day for 7 days) exhibit decreases in marrow fibroblast colony-forming units (FCFU) and tetracycline-based measurements of EsMR at the level of the femoral midshaft. In cortisone-treated rats recovering for 1-3 weeks, the FCFU census and EsMR normalized during the first posttreatment week, remained at control levels after 2-3 weeks, and exhibited a relapse in the third week which signified only partial recovery. These changes were unrelated to patterns of body weight gain. The data indicate that the FCFU census can serve to index endosteal osteoblast vigor.

Animals↗
PubMed1990

Responsiveness to physicians' requests for information concerning drug interactions: a comparison of brand and generic companies.

Research-based pharmaceutical companies maintain that there are important differences between themselves and their generic competitors. Prominent among them is an alleged greater ability to provide accurate and rapid responses to requests from physicians for information about drug products. This study evaluates pharmaceutical company behavior with regard to these issues. Two drug-drug interactions were identified, along with all of the companies in Canada marketing any of the four drugs involved. Each company received a letter describing symptoms suggestive of an interaction in a patient taking its particular product and the relevant second drug. The companies were asked if they were aware of any evidence of an interaction involving the two drugs. They were also asked to provide references regarding the interaction. Responses were received from all companies contacted except one. There were no significant differences (in the hypothesized direction) between the generic and brand companies with regard to either the accuracy or promptness of the response, or the usefulness of the references cited. On the contrary, generic firms were markedly quicker to respond than were brand manufacturers. The latter were slightly more likely to acknowledge evidence of an adverse drug interaction, and to provide useful references to relevant published research.

Canada↗
PubMed1990

Rhinomanometry evaluation of the effects of pre- and post-operative SMR on exercise.

Nasal airway resistance due to uncomplicated DNS was examined in 43 patients, and the results compared with those obtained following corrective surgery. The patients were examined independently by the two authors using a strict examination protocol. Rhinomanometry was carried out pre- and post-operatively at rest and after exercise assessing the worst and the better breathing nostrils separately. The results show that both resting and post-exercise nasal resistance was reduced following septal surgery.

Adult↗