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Biomedical subjects

D Thomas

Publications and source records attributed to D Thomas.

At least 757 records · Page 42Linked to original sources
PubMed1986

Effect of glutaraldehyde on haemoglobin: oxidation-reduction potentials and stability.

Glutaraldehyde is a reagent widely used for the cross-linking of haemoglobin for use as a blood substitute. Most of the previous studies were limited to oxygen binding equilibria of the glutaraldehyde-modified haemoglobin. This paper concerns the impact of glutaraldehyde on oxidation-reduction equilibria, autoxidation kinetics and stability towards heat and urea of haemoglobin cross-linked in the oxy, deoxy and ferri states. The oxidation-reduction potentials and homotropic effects were reduced; however, the oxidation Bohr effect was not significantly different when compared with native haemoglobin. Haemoglobin immobilized in the oxy or ferri state exhibited a lower redox potential than when immobilized in the deoxy state. The autoxidation rates were increased after cross-linking, particularly at basic pH. Cross-linking stabilizes ferrihaemoglobin better than oxy or deoxyhaemoglobin against thermal- and urea-induced denaturation. Glutaraldehyde cross-linking does not stabilize haemoglobin against urea-denaturation. The experimental results were interpreted as indicating a chemical modification of the protein without 'conformation freezing' and by an opening of the haem pocket to the aqueous solvent.

Aldehydes↗
PubMed1986

Inactivation of 3 alpha-hydroxysteroid dehydrogenase by superoxide radicals. Modification of histidine and cysteine residues causes the conformational change.

3 alpha-Hydroxysteroid dehydrogenase (EC 1.1.1.50) from Pseudomonas testosterone was inactivated by superoxide radicals generated by the aerobic xanthine oxidase reaction. Superoxide dismutase, NAD+, bovine serum albumin and histidine and cysteine as free amino acids partially protected the enzyme from inactivation. NADH-binding properties were determined by fluorescence spectroscopy, and no variation was found between native enzyme and the unmodified fraction of the partly inactivated one. The fluorescence emission maximum for the completely inactivated enzyme was shifted 10 nm to a longer wavelength when compared with the native one, and it seems possible that the modification of histidine and cysteine residues by superoxide radicals causes the conformational change of the enzyme and the consequent loss of catalytic activity.

3-Hydroxysteroid Dehydrogenases↗
PubMed1986

Cyclophosphamide versus ifosfamide: preliminary report of a randomized phase II trial in adult soft tissue sarcomas.

One hundred and seventy-one patients with advanced soft tissue sarcoma entered a randomized crossover phase II study comparing cyclophosphamide (CYCLO) with a new analogue, ifosfamide (IFOS), both administered as 24 h i.v. infusions every 3 weeks. The doses used were CYCLO 1.5 g/m2 and IFOS 5 g/m2, with provision for dose escalation. All patients received mesna 400 mg/m2 as an i.v. bolus 4 hourly X 9 doses, commencing at the start of the oxazophosphorine infusion. Patients who had received previous chemotherapy were eligible provided this did not include a classical alkylating agent. There were 22 patients who were ineligible, and response could not be evaluated in 12 additional patients. IFOS produced two complete and ten partial remissions, for an overall response rate of 18%. CYCLO was significantly (P = 0.04) less active, producing one complete and five partial remissions, an overall response rate of 9%. Stabilization of disease was similar in both arms (27% and 24% respectively), but fewer patients showed progression on IFOS. The response rate was higher (20% vs 5%) for patients who had not received previous chemotherapy, and also for female compared with male patients (21% vs 5%). When only patients who had not received previous chemotherapy were considered, the respective response rates for IFOS and CYCLO were 24% and 15%. There were no responses in previously treated patients receiving CYCLO. There were four partial responses in 33 patients crossing from CYCLO to IFOS, but no responses in 18 patients receiving CYCLO after IFOS. Leucopenia was significantly more pronounced (P = 0.0004) with CYCLO, both after the first course and throughout treatment, although the incidence of severe infections, 6%, was the same in both arms. Nausea and vomiting were more severe with IFOS (P = 0.022), but other toxicities were mild. Grade 1 or 2 bladder (haematuria) or renal (rise in serum creatinine) toxicity was slightly more frequent with IFOS (7 vs 3 patients) and was a reason for stopping treatment for one patient in each arm. Three episodes of mild to moderate drowsiness after IFOS were reported, but no severe encephalopathy. A higher response rate with less myelosuppression suggests that IFOS may have advantages over CYCLO in combination with such active agents as adriamycin.

Adolescent↗
PubMed1986

Intertest variability of echocardiographic and chest X-ray measurements: implications for decision making in patients with aortic regurgitation.

Echocardiograms and chest X-ray examinations are commonly employed for serial measurements of left ventricular size and function in patients with chronic aortic insufficiency and often support or even determine therapeutic decisions. This study was undertaken to assess the intertest variability of these measurements made from M-mode echocardiograms and X-ray films performed 3 months apart without intervening clinical or therapeutic changes in 22 patients with significant but asymptomatic aortic insufficiency. End-diastolic and end-systolic dimensions, fractional shortening and cardiothoracic ratios were measured by the same reader, with the initial and 3 month tests being read both independently and together for comparison. The mean values for the initial and 3 month studies were similar, but the intertest variability was substantial, especially when the two tests were read independently. The 95% prediction limits are approximately 50% smaller when the serial studies are read together for comparison. The coefficient of variation for end-diastolic and end-systolic dimensions was 6.1 and 10.1%, respectively, and that for fractional shortening was 17.1%. These findings translate into 95% level prediction limits exceeding +/- 8 mm for left ventricular dimensions and 0.12 for fractional shortening; changes on serial evaluations would have to exceed these values to be considered with a high degree of certainty to represent more than random variability. Although this variability may reflect a number of biologic and technical factors, it emphasizes the need to be cautious in making decisions based solely on changes between two tests, particularly if they are not evaluated together.

Adult↗
PubMed1986

Dissipative structures in a two-cell system: Numerical and experimental approaches.

It has been shown that the coupling between the photoreduction of the oxidized form of dichloroindophenol (an artificial electron acceptor) by thylakoids and the incident light intensity can lead to the appearance of multiple steady states when the system is operated under open conditions. In the present work, a numerical study and experimental evidence are presented on the occurrence of dissipative structures in an arrangement of two continuously stirred tank reactors with mutual mass exchange of dichloroindophenol through an inert membrane. The stable spatial structures are generated by the creation of transient internal and external asymmetries. A nontrivial hysteresis effect between symmetric and asymmetric stable steady states has been observed.

Journal Article↗
PubMed1986

Comparison of infusions of alfentanil or pethidine for sedation of ventilated patients on the ITU.

Sedation was studied in 30 patients requiring overnight ventilation in the intensive therapy unit (ITU). Patients received an infusion of either alfentanil or pethidine, supplemented with midazolam. The infusion rates were adjusted to provide optimal sedation as judged by a nurse, and measurements were made of quality of sedation, recovery and serum cortisol concentration. In addition, blood concentrations of alfentanil were measured to permit pharmacokinetic and pharmacodynamic analysis. Satisfactory sedation was achieved in both groups. The required infusion rate for alfentanil was between 0.4 and 0.5 micrograms kg-1 min-1. Recovery was good in both groups, apart from one patient in the alfentanil group, in whom recovery was greatly prolonged and alfentanil pharmacokinetics were abnormal. A difference was found in the metabolic response to surgery between the two groups, the response in the alfentanil group being significantly less marked.

Aged↗
PubMed1986

Spontaneous coronary artery dissection: case report and evidence for a defect in collagen metabolism.

Spontaneous coronary artery dissection is a rare disease with a higher prevalence in women, especially in the post-partum state. In one case, we attempted to relate this pathology to a disorder in collagen metabolism. A 32-year-old woman presented two episodes of myocardial infarction, 2 and 4 months after delivery which were shown to be due to two consecutive coronary artery dissections on coronary angiogram. Collagen metabolism was investigated in skin fibroblast cultures derived from the patient, and in control fibroblast cultures. After protein labelling in culture, total protein and collagen synthesis were determined. Quantification of procollagen synthesized in cell cultures and their rate of conversion into collagen were determined both in the culture media and a cell layer extract by DEAE cellulose chromatography. The results showed a reduced total collagen synthesis in the cultures of the patient in comparison with control cultures. The ratio between type I and III procollagen was not altered. The rate of conversion of procollagen into collagen was higher in the pathological cultures than in control cultures. Impaired collagen synthesis due perhaps to a change in hormonal equilibrium in the post-partum state might therefore have been responsible for coronary artery dissection.

Adult↗
PubMed1986

Percutaneous coronary angioplasty of a left anterior descending artery implanted on a Dacron coronary prosthesis on an aortic conduit.

Certain surgical techniques may make it difficult to catheterize the coronary ostia and perform percutaneous coronary angioplasty. We report the case of a 48 year old patient who developed unstable angina four years after a Bentall's procedure with reimplantation of the coronary arteries on a Dacron coronary prosthesis. The anginal pain was related to very severe stenosis of the proximal segment of the left anterior descending artery. The difficulties encountered during the dilatation procedure were due to: (a) the ectopic position of the ostium of the prosthesis on the anterior aortic wall; (b) the forces exerted on the aortic prosthesis wall and on the valvular prosthesis during positioning of the guiding catheter which were poorly tolerated and induced a vagal reaction; (c) the direction taken by the distal tip of the guiding catheter, perpendicular to the wall of the aortic prosthesis; (d) the sinuosity of the arterial trajectory: the left coronary segment of the coronary prosthesis was directed towards the left circumflex artery rather than towards the left anterior descending artery. Coronary angioplasty succeeded after relatively complex technical procedures: special guiding catheter, unusual intra-aortic manoeuvres for positioning the guiding catheter, dilatation catheter change on a 3-metre long guide wire in order to cross the stenotic segment; this was performed with a super low-profiled dilatation catheter. There were no complications and anginal pain disappeared.

Angina Pectoris↗
PubMed1986

Triazolam premedication. A comparison with lorazepam and placebo in gynaecological patients.

A randomised, double blind study, of 58 female patients undergoing laparoscopic investigation was carried out to compare triazolam 0.25 mg, lorazepam 2 mg, or placebo as oral premedication. Each patient was assessed by only one of the authors both pre- and postoperatively with regard to anxiolysis, sedation and rapidity of recovery. Triazolam and lorazepam were each associated with a significant reduction in anxiety compared to the initial assessment, whereas placebo had no anxiolytic effect. Sixty minutes after premedication, patients who had received triazolam were significantly more sleepy than patients given placebo or lorazepam. Two hours after the operation, the patients who had had triazolam or lorazepam were significantly more sleepy than those who received placebo. However, at 6 hours postoperatively there was no difference between triazolam and placebo, whilst those who had been given lorazepam were still significantly more sleepy than those given placebo. Triazolam appears to offer advantages over either lorazepam or placebo in patients who require rapid recovery, sedation and reduction in pre-operative anxiety.

Adolescent↗
PubMed1986

Plasmid inheritability and biomass production: comparison between free and immobilized cell cultures of Escherichia coli BZ18(pTG201) without selection pressure.

Maintenance of the plasmid pTG201 in Escherichia coli BZ18 was studied for both free and immobilized cells during chemostat culture, in the absence of the antibiotic against which resistance was plasmid encoded. Electron microscopic observations of immobilized proliferant cells within carrageenan gel beads showed high cell concentrations and growth into distinct cavities. The plasmid which coded for the catechol 2,3-dioxygenase activity was stably maintained during 80 generations in the case of immobilized cells. A theoretical analysis founded on the compartmentalization resulting from the immobilized growth conditions was described. However, the model still showed a plasmid stability inferior to that determined experimentally. Hypotheses dealing with physiological changes of immobilized cells were presented. In addition, the high cell concentrations obtained in the outer 50 microns of the carrageenan gel beads gave a biomass productivity within this useful volume which was 20 times higher than in free-cell cultures.

Bacteriological Techniques↗
PubMed1986

Helical structure of Bordetella pertussis fimbriae.

The helical structures of Bordetella pertussis fimbriae of serotypes 2 and 6 were determined by optical diffraction analysis of electron micrographs of negatively stained paracrystalline bundles of purified fimbriae. The fimbrial structure is based on an axial repeat of 13 nm that contains five repeating units in two complete turns of a single-start helix. This structure was confirmed by direct measurements of mass per unit length for individual fimbriae performed by dark-field scanning transmission electron microscopy of unstained specimens. These data further established that the helically repeating unit is a monomer of fimbrial protein (Mr congruent to 22,000 for type 2 and Mr congruent to 21,500 for type 6). Radial density profiles calculated from the scanning transmission electron micrographs showed that the fimbria has peak density at its center, i.e., no axial channel, consistent with the results of conventional negative-staining electron microscopy. The radial profile gives an outermost diameter of approximately 7.5 nm, although the peripheral density is, on average, diffuse, allowing sufficient intercalation between adjacent fimbriae to give a center-to-center spacing of approximately 5.5 nm in the paracrystals. Despite serological and biochemical differences between type 2 and type 6 fimbriae, the packing arrangements of their fimbrial subunits are identical. From this observation, we infer that the respective subunits may have in common conserved regions whose packing dictates the helical geometry of the fimbria. It is plausible that a similar mechanism may underlie the phenomenon of phase variations in other systems of bacterial fimbriae.

Bordetella pertussis↗
PubMed1986

Duchenne muscular dystrophy in one of monozygotic twin girls.

Monozygotic twin girls are reported, one of whom has the typical clinical features of Duchenne muscular dystrophy despite a normal female karyotype. Although certain features of the biopsy were atypical, the clinical diagnosis was supported by persistent markedly raised blood creatine kinase levels and findings typical of DMD on electromyography and magnetic resonance spectroscopy. Analysis of an X linked DNA polymorphism in 16 independent somatic cell hybrids made between cells derived from each girl and a mouse line suggest that in one twin only the maternal X chromosome is active, whereas in the other the active X was paternally derived. More data are needed to exclude sampling error. These preliminary experimental results support the hypothesis that both girls are heterozygous for Duchenne muscular dystrophy. X inactivation, by chance, resulted in two contrasting cell masses with different active X chromosomes. This segregation was followed by, and may even have resulted in, twinning into a female pair, one normal and one with the full clinical features of the disease.

Biopsy↗
PubMed1986

Effect of glutaraldehyde on hemoglobin: functional aspects and Mössbauer parameters.

Glutaraldehyde is widely used for the cross-linking of hemoglobin for blood substitute research or for technological purposes. The effects of this reagent on the biochemical properties of hemoglobin were correlated with Mössbauer data. Human hemoglobin was cross-linked by glutaraldehyde as soluble polymers and insoluble particles. Effects of cross-linking on oxygen affinity, oxidation-reduction potential, autoxidation kinetics, and thermal stability were studied. Stability of cross-linked hemoglobin was specifically studied by Mössbauer spectroscopy. Oxygen affinity is increased, redox potential is decreased, autoxidation rates are increased, and stability towards thermal denaturation is increased. The regeneration of partially denatured hemoglobin by glutaraldehyde cross-linking is shown. Effects of cross-linking on biochemical properties are explained by the hypothesis of the opening of the heme pocket on the distal-histidine side and the concomitant charge transfer from the iron to the oxygen.

Aldehydes↗
PubMed1986

Respiratory survey of North American Indian children living in proximity to an aluminum smelter.

We explored the relationship of respiratory symptoms and lung function to exposure to ambient air pollution consisting of particulate and gaseous fluorides. The subjects were 253 North American Indian children 11 to 17 yr of age living on the Akwasasne reserve, which is adjacent to an aluminum smelter. Among boys, closing volume (CV/VC%) was increased in those raised closest to the smelter as opposed to those having lived most of their lives farthest from this source of air pollution. In both sexes, there was a significant linear relationship between increasing CV/VC% and the amount of fluoride contained in a spot urine sample. We conclude that exposure to fluoride air pollution in the community may be associated with abnormalities in small airways. The implication of these abnormalities for future respiratory health is unknown.

Adolescent↗
PubMed1986

Contribution of radon and radon daughters to respiratory cancer.

This article reviews studies on the contribution of radon and radon daughters to respiratory cancer and proposes recommendations for further research, particularly a national radon survey. The steady-state outdoor radon concentration averages 200 pCi/m3, and indoor levels are about 4 times higher. The primary source of radon in homes is the underlying soil; entry depends on multiple variables and reduced ventilation for energy conservation increases indoor radon levels. Occupational exposures are expressed in units of radon daughter potential energy concentration or working level (WL). Cumulative exposure is the product of the working level and the time exposed. The unit for cumulative exposure is the working level month (WLM). The occupational standard for radon exposure is 4 WLM/year, and 2 WLM/year has been suggested as a guideline for remedial action in homes. Epidemiologic studies show that miners with cumulative radon daughter exposures somewhat below 100 WLM have excess lung cancer mortality. Some 3% to 8% of miners studied have developed lung cancer attributable to radon daughters. All of the underground mining studies show an increased risk of lung cancer with radon daughter exposure. All cell types of lung cancer increased with radon exposure. If radon and smoking act in a multiplicative manner, then the risk for smokers could be 10 times that for nonsmokers. The potential risk of lung cancer appears to be between 1 and 2 per 10,000/WLM, which yields a significant number of lung cancers as some 220 million persons in the United States are exposed on average to 10 to 20 WLM/lifetime.

Carcinoma, Bronchogenic↗
PubMed1986

Contribution of metals to respiratory cancer.

This paper reviews studies on the adverse health effects of exposure to metals, using arsenic and cadmium as examples. The carcinogenic potential of arsenic has been studied in various settings. Inhalation is clearly related to the development of lung cancer in (copper) smelting and arsenical pesticide manufacturing, and also in heavily exposed wine merchants who had an additional source of exposure by ingestion. Animal studies have shown cadmium to be a lung carcinogen, while a study by Thun et al. provides the best evidence to date that cadmium inhaled as CdO particles may be a human lung carcinogen. On the basis of this latter study, EPA estimates the risk due to cadmium at 1.8 X 10(-3) cases/micrograms/m3, which results in more than 100,000 excess lung cancers (lifetime). For arsenic, the risk estimate of 4.29 cases/1,000 micrograms/m3, based on epidemiologic data also results in more than 100,000 lung cancers (lifetime). This paper reviews the bases for these estimates and presents recommendations for further research. Lung cancer risks also exist for other metals such as nickel, chromium, and beryllium. Further study is required before a definitive conclusion can be reached about the significance and magnitude of environmental exposures to metals as a cause of lung cancer.

Air Pollutants↗