Biomedical subjects
Publications and source records attributed to M Thompson.
Belfast has many of the social problems common in major British cities: soaring unemployment, teenage crime, joy-riding, high levels of teenage pregnancy, drug and alcohol abuse. In Belfast, these problems are further complicated by the political and religious divide which affects virtually every area of society. Maura Thompson reports on a unique health visitor-led initiative working with teenage girls.
Explore the source record for details and available documents.
The study describes the indications and results of combined liver/kidney transplantation in eight patients suffering from end-stage hepato-renal diseases. The causes of primary renal failure were hyperoxaluria type I (2/8), diabetic nephropathy (2/8), glomerulonephritis (2/8), congenital pyelonephritis (1/8), and polycystic kidneys (1/8). Only five of these patients were on chronic dialysis prior to transplantation. The indication for kidney transplantation in the other three patients was low GFR (< 20 mL/min) and the anticipation of further deterioration of the renal function after liver transplantation as a result of cyclosporine toxicity. The end-stage liver diseases were chronic active hepatitis (4/8) and alcoholic cirrhosis (2/8). There was no evidence for liver failure in two patients undergoing combined transplants for primary hyperoxaluria. The 1-year patient survival rate is 75 per cent, and at that time, kidney and liver function were found to be within normal range. In conclusion, excellent long-term patient survival, as well as kidney and liver graft function, can be achieved in patients suffering from complex end-stage disease of both organs who undergo combined liver and kidney transplantation.
We report a technique which allows for the direct molecular analysis of single whole murine hemopoietic colonies by pulsed field gel electrophoresis (PFGE). Murine bone marrow cells were plated out in semi-solid agarose and gave rise to macroscopic colonies after 11 days in culture. Single colonies were excised from the agarose using a sterile blade and embedded without further manipulation in molten low-melting-temperature agarose. The leucocyte DNA contained within the agarose plug was subjected to restriction enzyme digestion and PFGE. Sufficient high molecular weight DNA is afforded by this method to achieve a hybridization signal with a single copy probe. This method will make PFGE directly applicable to the clonal analysis of chromosomal aberrations in hemopoietic stem and progenitor cells.
We have presented 73 patients (48 adults and 25 children) with microbiologically documented M. bovis infections identified over the 12-year period from 1980 through 1991. Epidemiologic investigation of these patients revealed that the majority (80%) were of Hispanic origin. The non-Hispanic patients either had traveled extensively outside the United States, were born in the United States during its endemic period or in other countries with endemic bovine tuberculosis, or were exposed to a close relative with a positive PPD and known exposure to M. bovis. For Hispanic patients, the presence of reactivation disease in adults and primary disease in children indicate that this mycobacterium remains endemic in Mexican beef and dairy herds, a position supported by United States monitoring of Mexican cattle transferred across the border. Our review of the historical and contemporary efforts to eradicate this animal and human pathogen from the livestock industry in the United States and abroad shows that the implementation of similar methods could be effective in Mexico. The detailed presentations of selected patients and summaries of the clinical manifestations in the remainder of our 73 patients reveal striking similarities to historical accounts and to more contemporary studies of reactivated disease in England. Although M. bovis infections are still expressed predominantly in extrapulmonary sites (cervical and mesenteric nodes, the peritoneum, and the GU tract), as many as 50% of adult patients will present only with pulmonary disease. Underlying immunosuppressive disorders were particularly prominent in adults with extrapulmonary disease. For example, HIV positive patients accounted for 12 of 48 adults and 1 adolescent patient in our series. Overall, M. bovis infections accounted for almost 3% of all tuberculous disease reported in San Diego County during the study period. The intrinsic resistance of M. bovis to PZA could threaten the response of patients with bovine tuberculosis to the short-course chemotherapeutic regimens now recommended by the CDC and the American Thoracic Society. We strongly recommend continued surveillance for this forgotten pathogen because the importation of Mexican cattle, the migration of Hispanic immigrants from border areas to the United States interior, and the persistence of extrapulmonary disease in immunocompetent and HIV-infected United States citizens assure its persistence in this country.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Explore the source record for details and available documents.
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.
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)
Explore the source record for details and available documents.