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Biomedical subjects

M Thompson

Publications and source records attributed to M Thompson.

At least 19 recordsLinked to original sources

Enhancement of the thermal and storage stability of urease by covalent attachment to phospholipid-bound silica.

Urease was immobilized directly on silanized silica surfaces carrying alkyl moieties with terminal carboxylic groups. The enzyme was also covalently attached to phospholipid-bound silanized silica surfaces through the terminal carboxyl moiety on the sn-2 acyl chain of the lipid. The surfaces were characterized by X-ray photoelectron spectroscopy and ellipsometry. The activity of the immobilized urease was determined by UV spectrophotometry using a urea/bromocresol purple substrate. The enzymic activity decreases exponentially upon storage under dry solid conditions for 1 week or upon heating to 100 degrees C in the case of the silane/enzyme surfaces. On the other hand, the enzyme immobilized on phospholipid-carrying silica surfaces retained its entire original activity under dry storage or heat treatment conditions. Such immobilized urease systems could find extensive applicability in the design of in vivo dialysis equipment or for on-line monitoring of urea.

Enzyme Stability

Outcome and complications of prolonged intraaortic balloon counterpulsation in cardiac patients.

The risks and benefits of prolonged intraaortic balloon support for the management of refractory congestive heart failure and ischemia were studied in patients with end-stage heart disease who needed support for greater than or equal to 5 days. Fifty-two insertions were performed by the percutaneous femoral route in 49 patients. The duration of insertion ranged from 5 to 46 days (mean 11.3). Clinical outcome including hemodynamic parameters and complications were recorded. Mean systemic arterial pressure did not change with balloon insertion (74 +/- 19 vs 76 +/- 11 mm Hg; p = not significant). Both the mean pulmonary artery and pulmonary arterial wedge pressures decreased (33 +/- 8 to 26 +/- 9 mm Hg [p less than 0.01], and 25 +/- 8 to 17 +/- 6 mm Hg [p less than 0.01], respectively). Over time, both parameters tended to increase, but remained significantly less than those before insertion. Cardiac index increased from 1.6 +/- 0.4 to 2.2 +/- 0.5 liters/min/m2 on insertion and continued to increase to 2.7 +/- 0.5 liters/min/m2 (p less than 0.01) before removal. Definite balloon catheter infection developed in 7 patients, and hemorrhage occurred in an additional 7. Eleven patients had vascular compromise, with loss of pulse in 6, thrombosis of the femoral artery in 1, and pseudoaneurysm in 2. Lacerated femoral artery occurred in 1 patient, and mesenteric artery thrombosis in another. Twenty patients died from progressive heart failure and multiorgan system failure, and 19 survived to receive left ventricular assist device and heart transplantation. Only 10 patients were weaned off the balloon. In conclusion, prolonged intraaortic balloon pump support may be successfully used in end-stage heart disease.

Adolescent

A 31P-NMR spin-lattice relaxation and 31P[1H] nuclear Overhauser effect study of sonicated small unilamellar phosphatidylcholine vesicles.

The motional properties of the inner and outer monolayer headgroups of egg phosphatidylcholine (PC) small unilamellar vesicles (SUV) were investigated by 31P-NMR temperature-dependent spin-lattice relaxation time constant (T1) and 31P[1H] nuclear Overhauser effect (NOE) analyses. Three different aspects of the dynamics of PC headgroups were investigated using the T1 analysis. First, differences in the dynamics of the headgroup region of both surfaces of the SUV were measured after application of a chemical shift reagent, PrCl3, to either the extra- or intravesicular volumes. Second, the ability of the T1 experiment to resolve the different motional states was evaluated in the absence of shift reagent. Third, comparison between correlation times obtained from a resonance frequency dependent 31P[1H] NOE analysis allowed a determination of the applicability of a simplified motional model to describe phosphorus dipolar relaxation. Temperature-dependent 31P-NMR T1 values obtained for the individual monolayers at 81.0 and 162.0 MHz were modelled assuming that phosphorus undergoes both a dipolar and an anisotropic chemical shielding relaxation mechanism, each being described by the same correlation time, tau. At 162.0 MHz, the position of the T1 minimum for the inner monolayer was 9 degrees higher than that of the outer region, indicating a higher level of motional restriction for the inner leaflet, in agreement with 31P[1H] NOE measurements. The 162.0 MHz T1 profile of the combined SUV monolayers exhibited a smooth minimum located at the midpoint of the monolayer minima positions, effectively masking the presence of the individual surfaces. 31P[1H] NOE results obtained at 32.3, 81.0 and 162.0 MHz did not agree with those predicted from a simple dipolar relaxation model. These results suggest a T1-temperature method can neither discriminate two or more closely related motional time scales in a heterogeneous environment (such as incorporation of protein into lipid bilayers) nor allow accurate determination of the correlation time at the position of the minimum when the dipolar relaxation rate makes a significant contribution to the overall rate.

Magnetic Resonance Spectroscopy

The size dependence of cholate-dialyzed vesicles on phosphatidylcholine concentration.

The size dependence of vesicles prepared by dialysis of cholate from phosphatidylcholine (PC) dispersions has been investigated as a function of lipid concentration (at a constant applied lipid: detergent molar ratio of 0.7). Gel filtration of dialyzed samples produced a symmetrical profile shape, although quasielastic laser light scattering analysis of the fractions revealed an asymmetrical range of sizes about the peak for solutions containing elevated lipid concentrations. Vesicle diameters increased by approximately 20 nm for PC concentrations ranging from 10 to a maximum of 45 mg/ml. This was attributed to mixed micelle sizes being proportional to lipid concentration, since the diameters of vesicles produced from dialysis are determined by mixed micelle sizes. Before commencement of dialysis, mixed micelle sizes are proportional to lipid concentration and, although dialysis causes an increase in mixed micelle sizes, the phase ratios attained are larger for solutions containing elevated lipid concentrations.

Cholic Acid

Stimulation by voluntary exercise of adrenal glucocorticoid secretion in mature female hamsters.

The possibility that habitual voluntary running induces a chronic change in adrenal glucocorticoid synthesis and secretion was examined in freely running mature female hamsters, in whom this behavior accelerates growth, reduces body fat levels, and elevates core temperature. Hamsters were free to run on horizontal discs or in vertical wheels between 32 and 80 days, in 14L:10D or in 10L:14D photoperiods, and at the end of this period, corticosterone and cortisol steroidogenesis and serial plasma corticosterone concentrations during day and night were used as measures of the chronic stimulation of adrenal cortical activity. Habitual voluntary running significantly increased steroidogenesis of both glucocorticoids and plasma corticosterone concentrations and alone accounted for all the variance in enhanced synthesis and secretion of corticosterone. Acute exercise and/or the nocturnal phase of circadian period enhanced the chronic stimulatory effects of exercise on cortisol. Despite its voluntary and apparently stress-free nature, running induces chronic increases in basal glucocorticoid secretion in mature female hamsters. Putative oversecretion of corticotropin releasing factor in freely running hamsters could account for increased steroidogenesis, acceleration of growth, reduced body fat levels, and core temperature elevation.

Adrenal Cortex

Inhibition of acute TCDD toxicity by treatment with anti-tumor necrosis factor antibody or dexamethasone.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) acute toxicity is characterized in part by a wasting syndrome with depletion of adipose tissue. Tumor necrosis factor (TNF) induces a similar response during chronic infection. The similarities of these toxic effects led to a hypothesis that TNF plays a role in TCDD acute toxicity. To test this hypothesis pharmacologic doses of an antibody specific for murine TNF and the potent anti-inflammatory agent Dexamethasone (DEX) were used to inhibit TCDD toxicity in mice. TNF antibody treatment resulted in a 54% reduction in TCDD-mediated mortality while DEX treatment, a glucocorticoid agonist that inhibits transcription of TNF, reduced mortality by 92%. Cyp 1A1 induction, the most commonly measured TCDD-mediated response, was not blocked by DEX, demonstrating separation of this biochemical effect from acute toxic responses to TCDD. These data suggest that TCDD-mediated changes in the TNF pathway may be an important mechanism for acute TCDD toxicity.

Animals

Study of retinal dystrophy in RCS rats: a comparison of Mg-ATP dependent light scattering activity and ERG b-wave.

A comparative study using the techniques of ERG to measure the b-wave and light scattering relaxation spectrophotometry (LSRS) to determine the dynamic behavior Mg-ATP dependent processes in the rod photoreceptors of pigmented control and dystrophic RCS rats has been carried out. LSRS results, based exclusively on photoreceptor rod outer segment dynamics, suggest a progressive failure in the dark and light-induced Mg-ATP dependent processes as a function of age. The dark signal amplitude in the dystrophic rats decreases to about 50% of the control by 5 weeks post-natal; the light-induced signal has decreased by 30% in the same period. The ERG b-wave results indicate that the differences in the amplitude and the time required to attain the peak amplitude become increasingly pronounced between the control and dystrophic groups of rats again as a function of age. By 10 weeks of age, the intensity of light required to obtain a b-wave with a amplitude of 100 microM is 10(3) greater in the dystrophic RCS rats. Similarly, the time to achieve this peak increases in the dystrophs with age. These results indicate that the retinal dystrophy in the RCS rat affects the activity of the rod photoreceptor cells.

Adenosine Triphosphate

Strategies for increasing response behavior of 1- and 2-year-old children during visual reinforcement audiometry (VRA).

This study investigated strategies for increasing the number of responses that can be obtained from young children during visual reinforcement audiometry. Subjects included normal 1- and 2-yr-old children. Responses before habituation were studied as a function of age, reinforcer conditions, and test sessions. It was found that: (1) using two reinforcers led to more responses before habituation than use of a single reinforcer; (2) after habituation in test session 1 and a 10-min break, most 1-yr-olds demonstrated a minimum of five additional responses in test session 2; and (3) 2-yr-olds habituated more rapidly than 1-yr-olds.

Acoustic Impedance Tests

Alteration of endocrine parameters in premenopausal women with breast cancer during long-term adjuvant therapy with tamoxifen as the single agent.

Tamoxifen is used to treat selected patients at each stage of breast cancer. Although most clinical experience has been obtained with postmenopausal women, increasing numbers of premenopausal women will be treated with 5 or more years of adjuvant tamoxifen therapy following surgery. Indeed, the proposed use of tamoxifen to prevent breast cancer in high-risk women could result in its extended use during the childbearing years. We have monitored the changes in circulating hormone levels from the ovary and pituitary gland in premenopausal (41-47 years old) women with stage I or II breast cancer during adjuvant therapy with tamoxifen as the single agent for 4-72 months following a mastectomy. Each patient (total eight) continued to menstruate, and ovulation occurred. Circulating levels of luteinizing hormone and follicle-stimulating hormone (except in one woman) remained in the normal range (determined in 12 regularly menstruating women in a control group). The levels of estradiol, estrone, and progesterone were elevated onefold to threefold. Prolactin levels decreased by 30%-40%, but the levels of sex hormone binding-globulin were unaffected. These data demonstrate that premenopausal women taking tamoxifen are potentially at risk for pregnancy and must be counseled about barrier contraception. Furthermore, the impact of many years of ovarian stimulation by tamoxifen must be evaluated, especially in women with node-negative disease or in healthy women in whom tamoxifen is used to prevent breast cancer.

Adult

Optical properties of normal, diseased, and laser photocoagulated myocardium at the Nd: YAG wavelength.

Laser photocoagulation of the myocardium effectively destroys arrhythmogenic foci. The purpose of this study was 1) to compare the optical properties of canine myocardium before and after photocoagulation, 2) to compare the canine model with clinical cases by measuring the optical properties of human myocardium, and 3) to assess the optical properties of human myocardial scar and epicardial fat tissue. Measured optical properties were the absorption coefficient, mu a; scattering coefficient, mu s; and scattering anisotropy factor, g. Optical measurements were performed at 1064 nm wavelength on thin plane parallel tissue slices using the integrating sphere method with glass hemispheres on either side of the sample. The study showed 1) an increase of the scattering coefficient by 40% and a two- to threefold increase in reduced scattering coefficient as a result of photocoagulation; 2) that the mu a (0.035 +/- 0.024 mm-1) and mu s (17.9 +/- 3.8 mm-1) of human myocardium were not significantly different from mu a (0.043 +/- 0.021 mm-1) and mu s (17.3 +/- 2.2 mm-1) of canine myocardium, whereas the human g (0.964 +/- 0.005) was slightly different from the canine g (0.974 +/- 0.008); and 3) that the mu a (0.021 +/- 0.016 mm-1) of epicardial fat and mu s (13.8 +/- 1.1 mm-1) of myocardial scar were significantly lower than those of normal myocardium. A dynamic model of laser-tissue interaction incorporating these changes and inhomogeneities is necessary to better describe light distribution during laser photocoagulation.

Animals

Electrophysiologic characteristics of manifest and latent retrograde conduction in dogs.

Atrioventricular (AV) nodal reentry requires intact retrograde ventriculoatrial (VA) conduction. The purpose of this study was to assess the contribution of various pacing and pharmacologic techniques to uncover VA conduction during apparent unidirectional VA block, and to evaluate the role of several biologic and electrophysiologic factors in concealment of retrograde conduction. Forty healthy dogs underwent catheter-electrophysiologic studies of AV and VA conduction. Group I (20 animals) had intact VA conduction. Group II (six animals) had VA dissociation with ventricular pacing initiated during sinus rhythm, but the presence of VA conduction was confirmed by isoproterenol infusion or by premature ventricular stimulation. In group III (14 animals), the above techniques failed to uncover VA conduction. Eight of 14 group III animals underwent thoracotomy and crushing or freezing of the sinoatrial (SA) node. Ventricular pacing initiated during sinus standstill was associated with 1:1 VA conduction in each experiment. VA conduction time and retrograde Wenckebach cycle length, both in the baseline state and during isoproterenol infusion, were significantly longer in the eight animals in group III than in those in group I. Age, gender, weight, breed, sinus cycle length, and anterograde AV conduction properties were not significantly different between groups I, II, and III. The data suggest that (1) in normal dogs, complete unidirectional VA block probably does not exist; (2) in the presence of anterograde input to the AV node, even sophisticated pacing and pharmacologic maneuvers may fail to uncover the presence of VA conduction; (3) although anterograde input is essential for concealment of VA conduction, the phenomenon is more closely associated with depressed retrograde than with anterograde AV nodal characteristics.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

The red cell distribution width in sickle cell disease--is it of clinical value?

The red cell distribution width (RDW) has been studied during the clinical steady state in 1121 patients with homozygous sickle cell (SS) disease, 344 with sickle cell-haemoglobin C (SC) disease, 68 with sickle cell-beta+ thalassaemia, 49 with sickle cell beta 0 thalassaemia and in 130 control subjects with a normal (AA) genotype. The mean RDW was moderately increased in S beta + thalassaemia and SC disease and markedly increased in S beta 0 thalassaemia and SS disease. In SS, SC and S beta 0 thalassaemia genotypes, lower RDW values occurred in females and with alpha thalassaemia. The RDW correlated negatively with total haemoglobin, mean cell haemoglobin concentration, mean cell volume, and fetal haemoglobin (HbF) and positively with reticulocyte count in SS disease. A low RDW was associated with higher weight and less frequent dactylitis, painful crisis, acute chest syndrome, acute splenic sequestration, and hospital admissions. A low RDW in SS disease is consistent with a high total haemoglobin, high HbF, low reticulocyte count, alpha thalassaemia, and a more mild clinical course.

Adolescent

Treatment of refractory peptic ulcer with omeprazole or continued H2 receptor antagonists: a controlled clinical trial.

We tested the hypothesis that the gastric H+/K+ adenosine triphosphatase inhibitor, omeprazole, because of its different mode of action and pronounced inhibitory effect on gastric acid secretion, may be more effective in peptic ulcer that is refractory to histamine H2 receptor antagonist treatment than continuing the same therapy. Altogether 107 patients (duodenal ulcer, n = 88; prepyloric ulcer, n = 14; gastric ulcer, n = 3; mixed sites, n = 2) with refractory peptic ulcer - that is ulcer unhealed after at least two months' treatment with cimetidine 0.8 g or 1 g daily or with ranitidine 0.3 g daily - were randomly allocated to receive either omeprazole 40 mg daily (n = 54) or to continue treatment with the same H2 receptor antagonist and at the same dose (n = 53) for up to eight weeks. The patients in the two treatment groups were well matched demographically. Healing by 'intent to treat' analysis was as follows: at four weeks, omeprazole 46 of 54 (85%), H2 receptor antagonist 18 of 53 (34%) (p less than 0.0001); and at eight weeks, 52 of 54 (96%) and 30 of 53 (57%) respectively (p less than 0.0001). One patient was lost to follow up but of the 22 patients whose ulcers were shown to be unhealed at endoscopy after receiving continued H2 receptor antagonist treatment, 21 healed in four to eight weeks when changed to omeprazole. Daytime epigastric pain cleared at four weeks in 43 of 47 (91%) patients on omeprazole and in 32 of 46 (70%) on H2 receptor antagonists (p=0.01) and relief of all dyspeptic symptoms occurred in 39 of 47 (83%) and 23 of 45 (51%) (p=0.0009) patients respectively. Adverse events occurred in 11 of 54 (20%) patients on omeprazole and in 12 of 35 (34%) on cimetidine but in none on ranitidine. The events were mild and none required treatment withdrawal. The commonest event in patients on omeprazole was loose stools or diarrhoea (n=5). Omeprazole was significantly better than continued H2 receptor antagonist treatment for the short term management of refractory peptic ulcer as judged by healing rate and pain relief, and it was safe.

Cimetidine

Intracellular signalling in the ovine pars tuberalis: an investigation using aluminium fluoride and melatonin.

The effect of aluminium fluoride (AlF4-) has been studied on inositol phosphate accumulation, calcium mobilization, cyclic AMP production and [2-125I]iodomelatonin binding in ovine pars tuberalis cells. These cells have high-affinity receptors for, and respond to, melatonin through inhibition of forskolin-stimulated adenylate cyclase. In the presence of 10 mM LiCl, AlF4- stimulated the net accumulation of inositol monophosphate and inositol bisphosphate. Consistent with these findings, AlF4- increased intracellular calcium; although this response was attenuated in calcium-depleted medium, indicating that the calcium response comprises both intracellular and extracellular components. Melatonin was ineffective on either basal or AlF4(-)-stimulated turnover of inositol phosphates. In concordance with the inositol phosphate response, melatonin had no effect on either the AlF4(-)-stimulated or the basal calcium levels. AlF4- blocked the increase in cyclic AMP stimulation by 1 microM forskolin, being as effective as melatonin, achieving approximately 90% inhibition. AlF4- also attenuated the binding of [2-125I]iodomelatonin to ovine pars tuberalis membranes by 15%. At the concentration used, these results are consistent with the interpretation that AlF4- activates many G protein-mediated responses, and thus imply that the inhibitory pathway for cyclic AMP predominates over the stimulatory arm, whereas there can only be a stimulatory pathway linked to phosphoinositide metabolism in ovine pars tuberalis cells.

Aluminum

Gastric ulcer healing: a comparison of enprostil versus ranitidine.

Enprostil is a synthetic prostaglandin E2 analogue with gastric antisecretory and mucosal protective properties. We compared the effects of enprostil and ranitidine on the healing of gastric ulcers and the subsequent relapse rates over 6 months. Patients (N = 156) were recruited for a double-blind study from 12 centers in Europe; 71 were randomly assigned to oral treatment with 35 micrograms enprostil twice daily and 85 to 150 mg ranitidine twice daily for up to 8 weeks. Both groups were of similar demography; their healing rates were also similar. Cumulative intent-to-treat healing rates were at 4 weeks enprostil 48%, ranitidine 41%: at 6 weeks enprostil 65%, ranitidine 68%; and at 8 weeks enprostil 72%, ranitidine 80%. Of those patients who met all protocol criteria and completed treatment, and were endoscoped at the prescribed times, healing rates were at 4 weeks enprostil 55%, ranitidine 54%, at 6 weeks enprostil 75%, ranitidine 84%; and at 8 weeks enprostil 80%, ranitidine 90%. Relief of pain was rapid and similar in both groups. The incidence of adverse events was low and similar in the two groups. The treatment-free relapse rate at 6 months was enprostil 64%, ranitidine 49%; the median times to relapse were 169 and 203 days, respectively. Enprostil and ranitidine appear to be equally effective in healing gastric ulcers.

Antacids