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Biomedical subjects

M Thompson

Publications and source records attributed to M Thompson.

At least 55 records · Page 3Linked to original sources
PubMed1994

Didanosine compared with continuation of zidovudine in HIV-infected patients with signs of clinical deterioration while receiving zidovudine. A randomized, double-blind clinical trial. The Bristol-Myers Squibb AI454-010 Study Group.

OBJECTIVE: To determine the benefits of switching to didanosine compared with continuing zidovudine among patients infected with human immunodeficiency virus (HIV) who have previously used zidovudine and have signs of clinical deterioration. DESIGN: Randomized, double-blind, two-armed, parallel, comparative clinical trial with a blinded, compassionate crossover provision at 12 weeks. SETTING: Outpatient clinics at 19 tertiary care medical centers. PATIENTS: 312 patients infected with HIV who had received zidovudine for 6 months or more, had CD4 cell counts of 300/mm3 or less, and had signs of clinical deterioration within 12 weeks before study entry. INTERVENTION: Peroral didanosine tablets (600 mg/d adjusted for weight, "high dose") or zidovudine capsules (600 mg/d). MEASUREMENTS: Primary study end points were death, a new acquired immunodeficiency syndrome (AIDS)--defining event, or the combination of two new or recurrent HIV-related diagnoses with a 50% decrease in CD4 cells. RESULTS: Switching to didanosine was associated with fewer end points than continuing zidovudine (relative risk [RR] for zidovudine:didanosine = 1.5; 95% Cl, 1.1 to 2.0). This benefit was consistent across subgroups of patients with either AIDS-related complex or AIDS and was most apparent among those with a CD4 count at entry of 100/mm3 or more (RR = 2.2; Cl, 1.1 to 4.4). CONCLUSIONS: This study shows a positive treatment effect for switching from zidovudine to didanosine among patients with either AIDS-related complex or AIDS and validates the common practice of using clinical signs or a decrease in the CD4 count as an indication for changing therapy.

AIDS-Related Complex↗
PubMed1994

Ultrasonic characterization of myocardial photocoagulation lesion size in vivo during Nd:YAG laser irradiation.

Endocardial coagulation lesions were created using transcatheter continuous-wave Nd:YAG laser irradiation. Ultrasound monitoring of thermal lesion dimensions was performed using 7.5-MHz and 10-MHz transducers directly from the epicardial surface in short-axis configuration (group A) or through the chest wall (group B). A total of 33 lesions were created in 10 dogs at energy levels ranging from 300 J to 1000 J. Mean histological lesion width (HW) compared with ultrasonically determined mean width (UW) showed that the differences (mean +/- standard deviation) in group A (UW - HW) was = 1.14 +/- 0.8 mm, which was not statistically significantly different from zero. In group B, (UW - HW) = 2.04 mm +/- 0.7 mm (p < .05), which was statistically significantly different from zero. Mean histological depth (HD) differentially related to ultrasound mean depth (UD) for group A and B combined showed (UD - HD) = -0.19 mm +/- 0.46 mm, not statistically significantly different from zero. The frequency distribution for width in group A showed magnitude of UW-HW > 3 mm in 32% of cases. In group B magnitude of UW-HW > 3 mm in 15%, whereas ultrasound width was larger than histology in 75% of the cases. For depth, magnitude of UD-HD > 3 mm in 15% of cases. With further refinement of the technique, ultrasonic tissue characterization may become a useful adjunct to monitoring lesion dimensions during transcatheter laser photocoagulation.

Animals↗
PubMed1994

Early responses of the liver of B6C3F1 mice to the hepatocarcinogen oxazepam.

Oxazepam has recently been shown to induce hepatocarcinogenicity in B6C3F1 mice. Due to the widespread human exposure to this anxiolytic compound and other structurally similar benzodiazepines, we conducted toxicity and cell proliferation studies on oxazepam to determine possible mechanisms whereby this nonmutagenic chemical may have exerted a carcinogenic effect. Male B6C3F1 mice (10 per dose-time group) received diets containing oxazepam at 0, 25, 125, 2500, and 5000 ppm. Mice were treated for 15, 30, 45, or 90 days, at which time they were evaluated for feed consumption, liver/body weight ratios, clinical pathology, serum oxazepam levels, and histopathology of the liver. During the final 7 days before sacrifice, the mice were exposed to BrDU via osmotic minipump to quantify hepatocellular replicative DNA synthesis. Few effects were observed resulting from chronic exposure to oxazepam other than statistically significant, dose-related increases in liver/body weight ratios. Replicative DNA synthesis was significantly increased in a dose-related manner at the 15-day time point in the 125, 2500, and 5000 ppm dose groups, and attained levels of four- to five-fold above control levels which returned to control levels by 30 days. The lack of significant toxicity, sustained increased liver/body weight ratios, and the rapid and transient induction of replicative DNA synthesis are similar to the effects reported for exposure to another widely used therapeutic agent shown to be a nongenotoxic carcinogen, phenobarbital.

Animals↗
PubMed1994

Phospholipases and melatonin signal transduction in the ovine pars tuberalis.

The potential role of phospholipases in mediating melatonin-dependent inhibition of adenylyl cyclase was investigated in pars tuberalis (PT) cultures. The phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) stimulated the release of choline metabolites and increased the transphosphatidylation reaction. The calcium ionophore A23187 stimulated the release of arachidonic acid from cultures. These observations demonstrate phospholipase A and D activities within PT. Phosphatidic acid inhibited forskolin-stimulated production of cyclic AMP both in PT cells and in membrane preparations. This indicates that melatonin could inhibit adenylyl cyclase by increasing phosphatidic acid levels through activation of cellular phospholipases. Melatonin did not stimulate the release of arachidonic acid or choline from PT cultures, nor did it increase intracellular levels of hydrophobic second messengers or stimulate transphosphatidylation. Therefore melatonin does not stimulate phospholipase A and D pathways in PT cells. However, these pathways are present in the PT and their activation could potentially modulate the cellular actions of melatonin.

Adenylyl Cyclases↗
PubMed1994

Behaviour problems and pre-school intellectual attainment: the associations of hyperactivity and conduct problems.

The relationship between behaviour problems and intelligence was examined in a sample of 106 three-year-old boys and girls selected for the presence of either conduct problems or hyperactivity. Parents' reports of hyperactivity, but not conduct problems, were negatively related to IQ scores for both boys and girls. There was a significant sex difference in the association between conduct problems and IQ. For girls IQ was positively correlated with conduct problems. The implications of the results for existing models of the relationship between behavioural deviance and cognitive functioning in childhood is discussed.

Aggression↗
PubMed1994

Radiotracer studies of cystic fibrosis transmembrane conductance regulator expressed in Xenopus oocytes.

We measured fluxes of radiotracers in Xenopus oocytes expressing the cystic fibrosis transmembrane conductance regulator (CFTR). Addition of adenosine 3',5'-cyclic monophosphate (cAMP)-elevating agents [forskolin and 3-isobutyl-1-methylxanthine (I/F)] led to large increases in uptake of 36Cl, 125I, and 82Br into oocytes expressing wild-type CFTR or delta F508 CFTR but not sham-injected oocytes. I/F also stimulated halide efflux from CFTR and delta F508 oocytes in the sequence Cl > Br > I. cAMP-induced increases in 36Cl efflux from delta F508 oocytes were approximately 20% of those in CFTR oocytes. Increases in halide efflux were blocked by diphenylamine-2-carboxylic acid but not by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid. The phorbol ester, phorbol 12-myristate 13-acetate, also stimulated 36Cl efflux from CFTR oocytes. ATP uptakes into CFTR and sham oocytes were similar, and both were reduced by I/F. However, ATP uptake into I/F-treated CFTR oocytes was slightly greater (approximately 40%) than into I/F-treated sham oocytes. Urea uptake into CFTR and sham oocytes was similar and in both cases was increased by I/F. However, the I/F-induced increase in urea uptake into CFTR oocytes was significantly greater than for sham oocytes. I/F stimulated formate uptake into CFTR oocytes but not into sham oocytes. Fluxes of 22Na, 86Rb, 35SO4, 32PO4, and mannitol were unaltered by expression and activation of CFTR.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1994

The effects of bundling on infant temperature.

OBJECTIVE: To determine whether bundling elevates rectal and/or skin temperature of young infants. DESIGN: Randomized, prospective study stratified by age. SETTING: Clinical Studies Center at a teaching hospital in Los Angeles. PATIENTS: Sixty-four well, full-term infants (ages 11 to 95 days). INTERVENTIONS: Control infants (n = 28) were dressed in a disposable diaper and terry coveralls. Bundled infants (n = 36) were dressed as control infants, plus a cap, a receiving blanket, and a thermal blanket. All infants were monitored in an open crib (room temperature 72 degrees to 75 degrees F). Rectal and skin (anterior mid-lower leg) temperatures and infant states were measured at 5-minute intervals from time 0 to 60 minutes and at 62 and 65 minutes. RESULTS: The mean skin temperature of bundled infants increased by 2.67 degrees C/hr; mean rectal temperature increased by 0.06 degrees C/hr. The mean skin temperature of nonbundled infants increased by 1.5 degrees C/hr; mean rectal temperature decreased by less than 0.01 degree C/hr. Comparing bundled infants to nonbundled controls, there was a significant rise in skin temperature (P = .0001) but not in rectal temperature (P > .05, Wilcoxon rank sum test). The study had a power > 98% to detect a rise of .5 degrees C in rectal temperature over 60 minutes. The 95% confidence interval for the change in rectal temperature in bundled infants was -0.03 to +0.15 degrees C. CONCLUSIONS: Bundling a healthy infant in a temperate external environment causes an increase in skin temperature, but not in rectal temperature. Elevated rectal temperatures should therefore, rarely if every be attributed to bundling.

Body Temperature↗
PubMed1994

Endotoxin-induced cytokine gene expression and excretion in the liver.

Peptide mediators, including tumor necrosis factor-alpha, interleukin 1 and interleukin-6, are associated with many chronic inflammatory diseases and septic shock. As such, considerable information has been collected by means of study of cytokine secretion from isolated cells or plasma cytokines during septic shock or inflammatory disorders. In this investigation, we used semiquantitative polymerase chain reaction analysis and a recently developed liver slice model to examine the characteristics of cytokine profiles that occur in the liver, the main organ involved in endotoxemia, after lipopolysaccharide challenge. Tumor necrosis factor-alpha, interleukin-1 alpha and interleukin-6 were rapidly secreted after in vivo LPS exposure or when added in vitro to rodent or human liver slice samples. This increase was associated with increased cytokine-specific mRNA transcripts. Kinetic analysis revealed that most tumor necrosis factor-alpha is released from the liver within 1 hr of lipopolysaccharide challenge, whereas interleukin-1 alpha and interleukin-6 continued to be produced for the entire culture period. Addition of monoclonal antibodies against tumor necrosis factor-alpha or interleukin-1 alpha to the culture partly inhibited interleukin-6 secretion, indicating that interleukin-1 alpha and tumor necrosis factor-alpha help mediate and sustain interleukin-6 synthesis. Depletion of hepatic sinusoidal macrophages (Kupffer cells) by a liposome-mediated macrophage "suicide" technique indicated that almost all of the secreted interleukin-1 alpha and tumor necrosis factor-alpha originate from these cells, whereas interleukin-6 secretion might also include other cell types. This study supports and extends previous findings and allows for a more rational approach to developing effective therapies against chronic inflammatory diseases and septic shock.

Alanine Transaminase↗
PubMed1993

Cloning and sequencing of the cyclodiene insecticide resistance gene from the yellow fever mosquito Aedes aegypti. Conservation of the gene and resistance associated mutation with Drosophila.

In order to examine the conservation of the mechanism of cyclodiene insecticide resistance between species we cloned a cDNA from the yellow fever mosquito Aedes aegypti homologous to the resistance gene Rdl in Drosophila. In D. melanogaster, resistance to cyclodienes and picrotoxinin is caused by a single amino acid substitution (alanine to serine) in the putative channel lining of a gamma-aminobutyic acid gated chloride ion channel. We report that the mosquito gene not only shows high homology to that of Drosophila but also that resistant strains display substitution of the same amino acid. The significance of this result in relation to the evolution of pesticide resistance, the use of Drosophila as a model insect for resistance studies and the potential use of this gene as a selectable marker in the genetic transformation of non-Drosophilids is discussed.

Aedes↗
PubMed1993

Planned sexual behaviour of young Australian visitors to Thailand.

OBJECTIVE: To research the knowledge of AIDS and other sexually transmitted diseases among young Australian tourists to Thailand, and their intended sexual behaviour. DESIGN AND SETTING: A cross-sectional survey by anonymous, self-administered questionnaire, of persons seeking pre-travel medical advice in private clinics in five Australian cities. PARTICIPANTS: 213 consecutive patients travelling to Thailand without a spouse or partner. RESULTS: Only 34% of the sample reported a definite intention not to have sex in Thailand. Regarding choice of potential partners: 24.5% more men than women said they would have sex with a Thai national; 13.7% of men said they would have sex with a "bar girl"; and 21.7% more women than men said they would choose a fellow Australian traveller. Eighty-two per cent of the sample reported that they would use condoms 100% of the time, and there was no significant difference between the number of men and women who expressed this intention. CONCLUSIONS: Although not obviously "sex tourists", many young Australian travellers are likely to have sex while visiting Thailand. These data have important implications for education and prevention programs to control the spread of human immunodeficiency virus (HIV) and other sexually transmitted diseases.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Neodymium:YAG contact laser photocoagulation of the in vivo canine epicardium: dosimetry, effects of various lasing modes, and histology.

UNLABELLED: Neodymium:YAG laser photocoagulation (LPC) is an investigational technique for the treatment of drug-resistant postinfarction ventricular tachycardia that requires cardiopulmonary bypass and open heart surgery. The purpose of this experimental study was to evaluate the feasibility of contact epicardial LPC to reach subepicardial, deep myocardial, and subendocardial regions without ventriculotomy and to analyze the dose-response relationships of this new technology. In 24 open-chest, closed heart dogs, a total of 219 epicardial laser lesions were generated under sterile conditions. Laser source was a continuous wave 1064 nm Nd:YAG; the delivery system consisted of a 400 mu bare quartz fiber fed into an 8F electrode catheter in direct contact with the epicardial surface. Laser variables were power at 10-15-20 W; lasing time, 6-12-18-24 s; lasing mode, continuous and pulse-pause; fiber mode, optical fiber tip inside and extending out from the electrode catheter. Hearts were harvested at 1 week. Histologic measurements included lesion surface diameter, internal diameter, and depth. RESULTS: Significant linear correlation was found between the total delivered energy and all measured lesion parameters. Transmural lesions were found at energy levels of 270-480 J. Maximum depth measured up to 1.68 cm; at high energies, it was limited by myocardial thickness only. At constant energy levels, power and lasing time did not independently affect lesion dimensions; lasing mode and fiber mode had statistically significant but minor effects. Laser lesions were homogeneous and sharply demarcated without epicardial crater or endocardial thrombus formation. Endocardial surface cooling by circulating blood and the presence of epicardial vessels resulted in modifications in lesion morphology. In 29 out of 74 grossly transmural lesions, there was a 0.082 +/- 0.127 cm thin surviving subendocardium. Forty-five coagulation lesions were truly transmural with no surviving myocardial strands. In conclusion, contact epicardial LPC can result in deep, transmural myocardial coagulation lesions. Lesion dimensions can be adequately controlled by total delivered energy. Closed heart epicardial Nd:YAG laser photocoagulation could become a new, less invasive surgical technique for the treatment of drug-resistant ventricular tachycardia.

Aluminum Silicates↗
PubMed1993

Surface modification of the biomedical polymer poly(ethylene terephthalate).

X-ray photoelectron spectroscopy was used to characterize modified surfaces of a biomedically important polymer, poly(ethylene terephthalate). Several modification schemes were investigated and direct silanization with 3-aminopropyltriethoxysilane was found to be the optimum procedure, resulting in an aminated surface. Surface coverage of up to 100% was achieved with retention of the polymeric structural integrity. Further activation of the silanized surface was accomplished with two cross-linkers, glutaraldehyde and sebacoyl chloride. A simple biomolecule, L-cysteine, was successfully immobilized onto a surface pre-treated with 3-aminopropyltriethoxysilane and glutaraldehyde, with a coverage of 42%.

Biocompatible Materials↗
PubMed1993

Conservation of cyclodiene insecticide resistance-associated mutations in insects.

Cyclodiene insecticide resistance has accounted for over 60% of reported cases of insecticide resistance. In Drosophila melanogaster resistance is associated with a single base pair substitution in the GABA receptor/chloride ion channel gene Rdl. This substitution predicts the replacement of an alanine with a serine in the second membrane spanning domain, the region thought to line the chloride ion channel pore. Here we report, via the use of degenerate primers in the polymerase chain reaction, that precisely the same substitution is present in three pests from three different insect orders: the house fly (Diptera), red flour beetle (Coleoptera) and American cockroach (Dictyoptera). This finding suggests that there are a limited number of mutations that can confer resistance to cyclodienes, putative channel blockers, while still maintaining adequate chloride ion channel function. The conservation of the resistance-associated mutation between Drosophila and pest insects directly validates the approach of using this insect as a model system for isolating and studying resistance genes. The importance of single base pair substitutions in the evolution of pesticide resistance and in the design of molecular monitoring techniques is discussed.

Animals↗