Domiciliary thrombolysis by general practitioners.
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Biomedical subjects
Publications and source records attributed to G Gordon.
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OBJECTIVE: To determine whether magnesium administration is effective in reducing postoperative morbidity and mortality after cardiac surgery. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: A tertiary acute-care 500-bed university teaching hospital. PATIENTS: Over a 6-month period, 100 patients electively scheduled for cardiac surgery involving cardiopulmonary bypass were studied. INTERVENTIONS: Fifty patients were randomized to receive an intravenous infusion of magnesium chloride, 2 g, and 50 patients received placebo intraoperatively after the termination of cardiopulmonary bypass. RESULTS: Magnesium-treated patients had a significantly decreased frequency (P < .04) of postoperative ventricular dysrhythmias (eight [16%] of 50) compared with placebo-treated patients (17 [34%] of 50). Patients who were normomagnesemic postoperatively had new supraventricular dysrhythmias less frequently (P < .03) than patients who were hypomagnesemic postoperatively (eight [17%] of 48 vs 19 [37%] of 52). Compared with placebo-treated patients, magnesium-treated patients had significantly higher (P < .02) postoperative cardiac indices in the intensive care unit (2.8 +/- 0.1 vs 2.5 +/- 0.1 L/min per m2). Patients with postoperative total and ultrafilterable hypomagnesemia had postoperative ventricular dysrhythmias (P < .04) and required prolonged mechanical ventilatory support (P < .01) more frequently than patients without postoperative hypomagnesemia. CONCLUSIONS: Total and ultrafilterable hypomagnesemia are prevalent findings in cardiac surgery patients, and postoperative hypomagnesemia is strongly associated with clinically important morbidity. Magnesium administration decreased the frequency of postoperative ventricular dysrhythmias and increased the stroke volume and thereby cardiac index in the early postoperative period.
Extracellular records were made from single identified lemniscal neurons of the cell-cluster regions of the cuneate and gracile nuclei, and of the lateral cervical nucleus, in pentobarbitone-anaesthetized cats. Forepaw, hind paw or face regions of the contralateral Sm I cortex were identified by recording through an inserted microelectrode which was then used for stimulation. The effect of a double cortical shock or train of shocks was usually inhibition: occasionally facilitation was observed, or mixed effects with facilitation preceding inhibition. Effects were seen in about half the cells studied in all three nuclei. Some cells of the lateral cervical nucleus were strongly excited, an effect not seen in the other nuclei. No component of these responses depended on suprathreshold stimulus intensities. Some lateral cervical cells were studied after deafferentiation by section of the dorsolateral spinal white matter; the same pattern of effects was seen. With an upper stimulus limit of 200 microA, cuneate but not gracile cells were affected from the cortical forepaw region, and gracile but not cuneate cells from the hind paw region. With threshold stimuli in an identified part of the forepaw cortical representation it was clear that cuneate cells with cutaneous receptive fields in corresponding parts of the forepaw had the lowest thresholds (minimum 6 microA). Threshold rose steeply with distance across the paw, suggesting quite sharp focusing of corticofugal effects in this system. When using similar procedures with the lateral cervical nucleus, with an upper limit of 200 microA, stimulation of forelimb cortex, or of facial cortex, affected both neurons with forelimb and those with hind limb fields.(ABSTRACT TRUNCATED AT 250 WORDS)
To detect the presence in adipose tissue of peptides known to affect tissue growth and to investigate potential regional differences, epididymal and perirenal adipose tissue depots from male Sprague-Dawley rats were separated into adipocyte and stroma-vascular fractions by collagenase digestion, sequential centrifugation and filtration. Identity and integrity of the fractions were demonstrated by light and electron microscopy, while dose-response curves for angiotensin-converting enzyme (ACE) were performed, revealing maintained functional capacity of the stroma-vascular fraction. ACE, atrial natriuretic peptide (ANP), and transforming growth factor-alpha (TGF-alpha) concentrations were significantly greater in epididymal than perirenal stroma-vascular tissue. Adipocyte fractions from both depots contained significant concentrations of ANP and TGF-alpha. There was no detectable ACE in the adipocyte fractions, indicating that no contaminating stromal-vascular cells were present in these fractions. These data show significant concentrations of peptides with effects on growth in subfractions of adipose tissue and demonstrate regional differences in concentrations between fat depots.
Multiplane transesophageal echocardiography is a new exciting development in echocardiography. We examined the methodology and echo-anatomic correlations of multiplane transesophageal echocardiography and its clinical applications in 100 patients. We used a 5-MHz phased array multiplane (OmniPlane) transesophageal probe. In this instrument, the transducer array can be steered through 180 degrees from any transducer location. This provides a vast assembly of imaging planes, allowing for detailed visualization of all dimensions of cardiac anatomy. This report presents our observations on the echocardiographic anatomy seen in various image planes and the unique clinical potential of multiplane transesophageal echocardiography in the diagnostic assessment of cardiovascular disorders. This technique appears to provide incremental diagnostic information that enhances the interpretative ability. Less esophageal probe manipulation is required with consequent decrease in patient discomfort. We conclude that multiplane transesophageal echocardiography enhances the versatility of transesophageal examination and offers many new avenues for developments such as three-dimensional echocardiography.
The modes of action of atypical tetracyclines that do not directly inhibit bacterial protein synthesis were investigated. The analogs tested, chelocardin, anhydrotetracycline, 6-thiatetracycline, anhydrochlortetracycline, and 4-epi-anhydrochlortetracycline, were bactericidal and caused the lysis of Escherichia coli accompanied by the release of the cytoplasmic enzyme beta-galactosidase into the supernatant. Examination by electron microscopy demonstrated that cells exposed to these analogs underwent marked morphological alterations that included the formation of numerous ghosts and the appearance of cellular debris in the culture medium. Although atypical tetracyclines promoted lysis in intact organisms, they did not cause lysis of E. coli spheroplasts, indicating that the analogs do not directly destroy the cytoplasmic membrane. These agents may promote cell lysis and death by interfering with the membrane's electrochemical gradient, which in turn leads to stimulation of autolytic enzyme activity and cellular lysis. The results support recently published data which indicate that tetracyclines are divisible into two classes on the basis of their modes of action.
Information about the economic benefit of new drugs is becoming increasingly important for formulary considerations, reimbursement policies and related considerations. Although economic benefits of drugs have been analysed and reported, the economic benefits of drugs have rarely been examined in the course of randomised therapeutic trials. We designed a modular survey instrument, the Resource Utilisation Survey (RUS), to collect economic outcomes in prospective trials. A pilot test of the RUS was conducted using clinical trial methods in a study of nizatidine versus placebo in preventing ulcers induced by nonsteroidal anti-inflammatory drugs. The purpose of the pilot study was to evaluate the RUS instrument and corresponding study design issues in clinical trials for either acute or chronic diseases. With the lessons learned from the pilot study, the RUS has been used successfully in other ongoing clinical trials.
Three specific platelet-derived growth factor (PDGF) isoforms are thought to bind with differing affinities to two distinct PDGF receptors which undergo activation following dimerization. Recent evidence has been presented that marked differences exist between the ability of PDGF-AA versus PDGF-AB and PDGF-BB to stimulate alterations in second messengers in cultures of vascular smooth muscle cells (VSMC), a result which was thought to be due to low numbers of the A-type receptor in this cell type (Sachinidis, A., Locker, R., Vetter, W., Tatje, D., and Hoppe, J. (1990) J. Biol. Chem. 265, 10238-10243, 1990). In particular, PDGF-BB and PDGF-AB but not PDGF-AA could elicit alterations in cytosolic free calcium (Ca2+i). However, because these studies were performed on large cell populations using biochemical assays of PDGF activity, a minor PDGF-AA-Ca(2+)-responsive population of cells might go undetected. To test this possibility, VSMC were isolated from either thoracic or abdominal pig aorta, and alterations in Ca2+i were monitored using Multiparameter Digitized Video Microscopy following stimulation with PDGF isoforms alone, or either before or after exposure of VSMC to 5 mM EGTA. PDGF-AA-responsive cells were found to exist only in cultures of thoracic VSMC, caused oscillations in Ca2+i, represented 20% of the PDGF-BB-responsive cells, and were subsequently responsive to PDGF-BB. PDGF-BB elicited monophasic alterations in Ca2+i in both thoracic and abdominal VSMC. Prior addition of EGTA inhibited PDGF-AA but not PDGF-BB-induced alterations in Ca2+i. Addition of EGTA during PDGF-AA-induced Ca2+i oscillations inhibited subsequent oscillations in Ca2+i, while addition of EGTA at the peak of the PDGF-BB Ca2+ response resulted in a more rapid return of Ca2+i to prestimulation levels. These data suggest that regional differences in the distribution of PDGF-A- and B-type receptor exists in vivo, and that activation of the A- and B-type PDGF receptors results in distinct alterations in Ca2+i.
Acute retinal necrosis (ARN) syndrome usually occurs as the result of secondary reactivation of latent, previously acquired, varicella-zoster or herpes simplex virus. The authors report four patients who developed a mild form of ARN within 1 month (5 to 28 days) after the onset of chickenpox. In contrast to typical cases of ARN, these cases were less severe, with retinitis limited to two quadrants or less (three patients), no retinal detachment (four patients), minimal vitreitis (four patients), and no loss of visual acuity (four patients). Thus, ARN may occur during the course of primary varicella-zoster infection.
This paper describes a community-based agency's approach to reducing perinatal risk among populations at high medical, familial and environmental risk. Following a descriptive analysis of 96 families enrolled in a maternal outreach program, a case study illustrates how client-sensitive strategies are applied to successfully engage a traumatized population. The intensity and duration of the interventions, the extensive outreach efforts to the family and the dedication and commitment of the staff are not easily replicated but invaluable in helping providers and researchers understand to what extent the impact of severe deprivations and risk can be mediated and potential damage to the newborn prevented. The paper concludes that community-based agencies in partnership with social and clinical researchers from a tertiary care setting provide the key for developing more effective, integrated perinatal care by virtue of the critical density of hard-to-reach patients who can be followed by providers and clinical researchers.
We sought to assess occupational joint use and osteoarthritis (OA) longitudinally in a large population with multiple occupations. Subjects were members of the Framingham Heart Study cohort followed over 40 years with occupational status assessed at the beginning of the Heart Study [from Examination 1 (1948-51) through Examination 6 (1958-61)] and knee OA assessed by weight bearing knee radiograph at Examination 18 (1983-85) when mean age of subjects was 73 years. Each subject's job was characterized by its level of physical demand and whether the job was associated with knee bending. Odds ratios (OR) testing the association of job demand with OA were adjusted by logistic regression for age, body mass, knee injury history, smoking, and educational level. Men whose jobs required knee bending and at least medium physical demands had higher rates of later radiographic knee OA (at least definite osteophytes) than men whose jobs required neither (43.4 vs 26.8%; OR of OA = 2.22, 95% CI 1.38, 3.58). Rates of severe radiographic OA (osteophytes and joint space narrowing) and of bilateral radiographic OA were also significantly increased in these men. Few women had jobs requiring knee bending or that were physically demanding and these jobs were generally unassociated with later radiographic OA. Only a small number of men (n = 28) had symptomatic knee OA, and we could not confirm that it was associated with occupation in men. Thus, among men, occupations which combine knee bending and physical demands may be an important cause of radiographic OA.
The authors have presented what they believe is the only reported case of a stress fracture of the tarsal middle cuneiform bone. Stress fracture pathogenesis, as well as diagnosis and treatment, were reviewed. It has been proposed that the middle cuneiform may be subject to increased stress in the runner during the propulsive phase, as this is the midfoot bone that transmits weight proximally in the medial column. This is evident by studying the cancellous structure of the tarsal bones. The ligamentous and osseous architecture of this region also can produce a midfoot buckling when the foot is plantarflexed against resistance. Prompt diagnosis and treatment is the key in preventing the stress fracture from becoming a chronic source of discomfort.
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The osmotic coefficients phi p,Na of dilute solutions of the sodium form of some weakly acidic polymers are theoretically predicted in this work. Based on the measured value 0.73 of gamma Na, the activity coefficient of free Na+, of the completely ionized humic acid (sodium salt) in a salt-free solution, the effective interligand distance b is calculated to be 11.34 A by using Manning's counterion condensation theory [Manning, G. S. (1969) J. Chem. Phys. 51(3), 924]. The corresponding values of gamma Na (measured experimentally) and b for the completely ionized exopolymer of Pseudomonas atlantica are 0.624 and 7.57 A when cultivated at a dilution rate D = 0.015 h-1, 0.647 and 8.19 A at D = 0.025 h-1, and 0.613 and 7.29 Aat D = 0.06 h-1. For alginic acid (in the completely ionized sodium form), gamma Na = 0.40 and b = 4.71 A. The osmotic coefficients phi p,Na for the partially and the completely ionized polymers are then predicted with Manning's theory as well.
The numbers, laminar position, perikaryal and dendritic morphology, and axonal trajectories of postsynaptic cells ascending the dorsal column have been studied after implantation of HRP pellets in either the dorsal columns or dorsal column nuclei after destruction of the dorsolateral fascicle on one side. Observations made throughout the spinal cord gave estimated figures of 800-1000 and 1700-2000 cells in lumbosarcal and brachial enlargements respectively on the side of the implant. The commonest type (C), centred on lamina IV, had dendritic trees greatly extended rostrocaudally and restricted mediolaterally in the lateral dorsal horn, the extension and restriction diminishing for more medial cells. Type B cells differed dramatically, with large straight dendrites in the transverse plane and large perikarya in medial lamina V. Type A cells, distinguished by both rostrocaudal and mediolateral restriction in dendritic trees, were only found medially in laminae III and IV. Outside the enlargements, in high lumbar and thoracic cord, many fewer cells were found, corresponding to Type C but with dendrites much elongated rostrocaudally and little mediolateral variation. Many small fusiform cells were found in medial lamina VI in the upper cervical cord, distinct from any of the above. A few cells were found in the cord enlargements in lamina VII of the contralateral ventral horn, with axons crossing through the ventral commissure. The axons of all cell types were tortuous, and some entered the dorsolateral fascicle before crossing into the dorsal column: collaterals were often seen but could not be followed far. A complementary study of cells with axons ascending in the dorsolateral fascicle is reported in the following paper.
Spinocervical cells were identified by retrograde labelling from implants of HRP in the dorsolateral fascicle after destruction of the dorsal columns. They lay in laminae III and IV throughout the cord in estimated numbers of 700, 450 and 1100 in lumbosacral enlargement, upper lumbar and thoracic cord, and brachial enlargement respectively. In the cord enlargements dendritic trees were mainly or exclusively developed dorsally, with rostrocaudal exceeding mediolateral spread, and a gradient across the dorsal horn, lateral cells showing this contrast most strongly. Dendritic spread was limited at the II/III laminar boundary. Transition occurred at the edge of the enlargements to a shape with extreme rostrocaudal elongation of perikarya and of dendritic trees in upper lumbar and thoracic segments. Axons of spinocervical cells ascended in the most dorsal part of the fascicle, distinguishable from the larger spinocerebellar bundle lying adjacent and ventral. The initial axonal course was tortuous, with local collateral branching, the axon sometimes travelling briefly in the dorsal column. In other experiments implants were made ipsilaterally in the dorsal column nuclei after destruction of the dorsal columns. Cells were few and relatively poorly labelled, for which the reasons are discussed. Some such cells, lying in lamina IV, were similar to spinocervical tract cells and may have projected to both lateral cervical and dorsal column nuclei. Others, at the extreme lateral edge of the mid-dorsal horn, were quite different, with dendrites greatly extended rostrocaudally and primary and higher order dendrites projecting ventrally from the perikaryon.
Thalidomide is reported to have immunosuppressive and anti-inflammatory effects which have led to its use in the treatment of a number of immune-mediated disorders including leprosy, prurigo, discoid lupus, and Behcet's disease. In addition, thalidomide has recently been used to prevent immunological rejection phenomena following skin and bone-marrow grafts. The immune responses in these conditions are thought to be cell-mediated. However, little is known about the effectiveness of thalidomide in suppressing antibody-mediated immune responses. In the present study, we have examined the effect of thalidomide in a model antibody-mediated autoimmune disorder--experimental autoimmune myasthenia gravis (EAMG). To induce EAMG, Lewis rats were immunized with acetylcholine receptor (AChR) purified from the electric organ of Torpedo californicus. Groups of rats were treated daily, either with thalidomide in excess of doses reported to prevent graft-versus-host (GVH) disease in bone-marrow-transplanted rats, or with control treatments. Our results show that thalidomide failed to inhibit AChR antibody production despite good absorption and high blood levels of the drug. This suggests that thalidomide is not likely to be generally useful in the treatment of antibody-mediated autoimmune conditions. However the selective effect of thalidomide in suppressing certain presumably cellular immune responses, while sparing antibody production, is inherently interesting, and merits further study.