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Biomedical subjects

D Shaw

Publications and source records attributed to D Shaw.

At least 181 records · Page 10Linked to original sources

Short-term effects of calcium antagonists on hemodynamics and cyclosporine pharmacokinetics in heart-transplant and kidney-transplant patients.

Effects of two calcium antagonists on hemodynamics and on cyclosporine pharmacokinetics were studied in eight transplant patients (four heart-transplant and four kidney-transplant patients) by use of a single-blind, randomized, crossover, and placebo-controlled design. Patients received, at least 1 week apart, either 90 mg diltiazem, 20 mg nifedipine (in tablet form), or placebo, given 1 hour before cyclosporine. Cyclosporine and its main metabolite (metabolite 17) were measured in plasma (separated at 25 degrees C) by use of HPLC. Both calcium antagonists tended to increase absorption rate and elimination rate, but none of the pharmacokinetic parameters of cyclosporine were significantly altered. Moreover, the area under the curve of plasma concentrations of metabolite 17 did not change. On the other hand, both nifedipine and diltiazem significantly altered the hemodynamics, but to a different extent in the two groups of patients. The heart-transplant patients showed larger decreases in systolic and diastolic blood pressure than the kidney-transplant patients after administration of both nifedipine and diltiazem, but they showed smaller increases in cardiac index and heart rate with nifedipine. In contrast, diltiazem caused small decreases in heart rate and cardiac index in heart-transplant patients and small increases in heart rate and cardiac index in kidney-transplant patients. We conclude that a single dose of either nifedipine or diltiazem does not affect, to a clinically significant extent, the pharmacokinetics of cyclosporine. In addition, heart-transplant patients show different hemodynamic responses to these two calcium antagonists than the responses shown by kidney-transplant patients, probably because of cardiac denervation.

Absorption↗

Exercise responses in patients treated for pulmonary tuberculosis by thoracoplasty.

Twenty eight subjects (mean age 64 years) who had been treated for tuberculosis by thoracoplasty in the past performed an increasing work rate exercise test, from which maximum oxygen consumption (VO2max), ventilation and heart rate were measured. VO2max was significantly lower than predicted, being 0.75 l/min in 17 subjects, 1.0 l/min in 10, and 1.5 l/min in one. Only one subject achieved a heart rate of 85% of the predicted maximum. The ratio of heart rate to oxygen consumption (HR/VO2) and heart rate at standard interpolated submaximal levels of oxygen uptake at 0.75 l/min (heart rate 0.75) and 1.0 l/min (heart rate 1.0) were normal. VO2max correlated with ventilation at maximal exercise (VE max) (r = 0.87) and FEV1 (r = 0.47). It did not correlate with resting arterial oxygen or carbon dioxide tensions, FEV1, maximum inspiratory pressure, angle of scoliosis, or number of ribs resected. The relation between ventilation and oxygen consumption (VE/VO2) and VE at the submaximal levels of oxygen consumption of 0.75 l/min (VE 0.75) and 1.0 l/min (VE 1.0) were normal. In 10 subjects a plateau of breathing frequency (fmax) was reached, after which the increase in ventilation was achieved by a further increase in tidal volume (VT). These subjects showed significantly lower values for the forced expiratory ratio, VO2max, and VEmax than those with a normal relation between tidal volume and breathing frequency. VEmax was correlated with FEV1 (r = 0.61), FVC (r = 0.46), maximum VT (r = 0.55), change in VT (r = 0.52), fmax (r = 0.56), and change in breathing frequency (r = 0.72). These results indicate that exercise in patients treated for tuberculosis by thoracoplasty is limited by ventilatory capacity and that this is due to a reduction in both dynamic lung volumes and respiratory frequency.

Aged↗

Concordance of creatine kinase-MB activity and mass.

The recent availability of monoclonal antibodies that are highly specific for creatine kinase (CK; EC 2.7.3.2) MB isoenzyme should allow for the development of rapid, sensitive, and specific assays of CK-MB mass and activity. However, the relationship between the mass concentration of CK-MB and its activity in plasma has previously been thought by some to be variable. To determine the extent to which discrepancies of potential clinical significance might arise between measurements of activity and mass in plasma, we compared CK-MB activity and concentration in 1298 samples obtained from 226 patients admitted to the cardiac-care unit. CK-MB activity concentration was determined with an immunoadsorption assay, and mass concentration was measured by an automated "sandwich" assay (Magic Lite; Ciba Corning Diagnostics). Both of these assays are based on specific monoclonal antibodies for CK-MB. Values obtained with these assays correlated well (r = 0.94). Normal and abnormal values with the two assays were concordant in 96% of the samples. In all but three instances, differences occurred late after myocardial infarction and were characterized by minimal increases as determined by one method vs values at the upper limit of normal as determined with the other. Thus, measurements of CK-MB mass and activity concentrations in plasma with assays based on these specific monoclonal antibodies are comparable for the detection or exclusion of acute myocardial infarction.

Creatine Kinase↗

Maternal mortality in British Columbia in 1971-86.

We reviewed the 56 maternal deaths in British Columbia in 1971-78 and 1979-86 identified through the provincial Ministry of Health and compared the findings with data for the two preceding 8-year periods. The maternal death rate, defined as the number of deaths directly or indirectly related to pregnancy or delivery per 100,000 live births, decreased from 42 in 1955-62 to 5 in 1979-86. In the same interval the number of direct obstetric deaths decreased from 100 to 10 and the number of indirect deaths from 29 to 8. The number of deaths due to abortion decreased from 32 to 1. There was no change in the number of deaths among North American Indians. There was also no change in the number of deaths due to hypertension, most of which were avoidable; these findings have stimulated intensive teaching efforts to increase recognition and improve management of the problem. Review of maternal deaths can help identify deficiencies in the quality of care and can direct measures aimed at further reducing the maternal death rate.

British Columbia↗

Comparison of three Glasgow multifactor prognostic scoring systems in acute pancreatitis.

Modifications have been proposed in an attempt to improve the clinical value of the original nine-factor Glasgow prognostic scoring system for acute pancreatitis. These include the omission of age or serum transaminase, reducing the factors to eight. Debate exists as to which system should be employed. Assessment of the individual factors in 198 attacks of acute pancreatitis treated conventionally revealed that only serum transaminase did not differ significantly between mild and severe outcome groups. Multivariate analysis demonstrated four factors (Pa,O2, white cell count, lactic dehydrogenase, and urea) with independent significance in predicting severity, while serum glucose, albumin and transaminase were least useful. Findings were similar when considering only patients with gallstone aetiology. The reduction of the prognostic factors to eight by the omission of either age or transaminase improved the predictive value of the scoring system, both when considering all attacks and those of gallstone aetiology alone. We suggest that serum transaminase should be omitted because: it shows no significant difference between mild and severe outcome groups, while age has prognostic significance; the system has greater sensitivity than if age is omitted; and the number of factors requiring emergency laboratory measurement for immediate prognostication is reduced by one.

Acute Disease↗

Segregation of linked probes to myotonic dystrophy in a family demonstrating that 152 and APOC2 are on the same side of DM on 19q.

The two markers most closely linked to the myotonic dystrophy (DM) locus on chromosome 19 are the gene that codes for apolipoprotein CII (APOC2) and the anonymous probe D19S19 (LDR152). Both of these markers show tight linkage to DM, with maximum lod scores of greater than 20 at recombination fractions of less than 0.05. We have identified, in a family in which DM segregates, an affected individual where a meiotic recombination event has occurred in which both of these linked markers have crossed over with the gene defect. This demonstrates that APOC2 and D19S19 are probably on the same side of DM.

Chromosome Mapping↗

The effects of hemispatial and asymmetrically focused attention on dichotic listening with normal and learning-disabled children.

The effects of hemispatial and focused attention were examined with 50 normal and learning-disabled children to determine the extent of these two attentional strategies influenced perceptual laterality as reflected by the dichotic listening right-ear advantage (REA). Twenty-five normal children (8 females, 17 males, mean age 9.10 yr) matched with 25 learning-disabled children (8 females, 17 males, mean age 10.1 yr) were administered a dichotic consonant-vowel (CV) and consonant-vowel-consonant (CVC) syllable task. The two types of stimuli were compared across focused attention (free report, focused left, focused right) and hemispatial (central, left hemispace, right hemispace) conditions implemented independently and in systematic combinations. A four-factorial analysis of variance (groups x stimuli x conditions x ears) resulted in a significant REA for normal children across all attentional conditions whereas learning-disabled did not produce a consistent REA across all attentional conditions, and in several instances, produced equivalent left and right hemisphere processing. Right hemispatial orientation increased the magnitude of the REA (i.e., left hemisphere processing) for both groups, whereas left hemispatial orientation increased the magnitude of the left ear report (i.e., right hemisphere processing) only in learning-disabled subjects. Focused attention to the right ear also increased left hemisphere efficiency for both groups of children; however, focused attention to the left ear produced symmetrical functioning by learning-disabled subjects. Congruent combinations of focused attention and hemispatial orientation were not found to enhance the REA beyond its magnitude when each strategy was assessed independently. When focused attention and hemispatial conditions were employed in opposing directions, normal children were more susceptible to the "rightward" direction regardless of the strategy whereas learning-disabled subjects were more susceptible to the "verbal" nature of the strategy. Higher overall processing performance was exhibited for CVC stimuli when compared to CV stimuli. These findings lend support to the hypothesis that hemispatial and asymmetrically focused attention strategies interact with structural mechanisms in producing the observed REA in dichotic listening and do so differentially for normal and learning-disabled children.

Adolescent↗

Effect of commercial immunoglobulin G preparation on human monocyte Fc-receptor dependent binding of antibody coated platelets.

This study examined the in vitro effect of a commercial immunoglobulin preparation on human monocytes and the Fc-receptor dependent binding of antibody coated platelets. Monocytes were exposed to Sandoglobulin in vitro and subsequently examined for membrane surface bound IgG. Dramatic increments of surface IgG were found which were maximal with 18 h exposure and somewhat higher at 4 degrees C than 37 degrees C. Ultracentrifugations of Sandoglobulin immediately prior to monocyte exposure reduced the monocyte membrane IgG by 75%. The 18 h exposure at 37 degrees C produced dramatic impairment of monocyte Fc-receptor binding of IgG coated platelets (P less than 0.001) while exposure for 18 h at 4 degrees C produced a modest impairment of Fc-receptor function. These studies indicate that Sandoglobulin contains IgG aggregates which are able to firmly bind to the monocyte surface in a time and temperature dependent fashion. The dramatic impairment of Fc-receptor function at 37 degrees C and not at 4 degrees C suggests that Fc-receptor modulation, as well as competitive inhibition/steric hindrance, contribute to impairment of monocyte Fc-receptor function.

Antigen-Antibody Reactions↗

Prognostic markers in acute pancreatitis: can pancreatic necrosis be predicted?

The value of six prognostic markers was assessed prospectively in 198 attacks of acute pancreatitis with specific attention to their ability to predict pancreatic necrosis. The Imrie Prognostic Score (IPS) was recorded within 48 h of diagnosis. The serum C-reactive protein (CRP) alpha 1 antiprotease (A1AP), alpha 2 macroglobulin (A2M), amylase and white cell count (WCC) were measured on days 1, 3 and 7. When comparing all severe clinical outcomes to mile outcomes, serum CRP concentrations were higher on all three days (P less than 0.02, less than 0.001, less than 0.001), A1AP concentrations were higher on day 3 (P less than 0.05), A2M concentrations were lower on day 7 (P less than 0.01) and WCC was higher on all three days (P less than 0.001, less than 0.001, less than 0.001). Serum amylase concentrations showed no significant differences. None of the measured parameters were helpful in distinguishing patients who subsequently developed pancreatic necrosis from patients who had other severe outcomes. Multivariate analysis revealed that the initial IPS showed greatest independent significance in predicting severe outcome followed by the WCC (days 1 and 7) and CRP (day 3). CRP and WCC may be clinically useful predictors of severe outcome to supplement the initial IPS. These methods are unlikely to distinguish pancreatic necrosis from other severe outcomes, but they may supplement clinical judgment in selecting a high risk group of patients for contrast enhanced computed tomography.

Acute Disease↗

Simple test of intestinal calcium absorption measured by stable strontium.

A clinical test of intestinal calcium absorption has been developed using non-radioactive stable strontium as a calcium tracer. In nine elderly subjects there was a close correlation between the fractional absorption of strontium and radioactive calcium (45Ca) during a five hour period after the simultaneous oral administration of the two tracers. Comparable precision was achieved with each tracer in six subjects in whom the test was repeated after two weeks. The effect of food on strontium absorption was examined in a further 33 normal subjects (age 21-60 years), and the administration of the strontium with a standard breakfast was shown to reduce the variance at individual time points. A simplified test in which serum strontium concentration was measured four hours after the oral dose given with a standard breakfast was adopted as the routine procedure. The normal range (mean (2 SD], established over 97 tests in 53 patients, was 7.0-18.0% of the dose in the extracellular fluid. A further 30 patients with possible disorders of calcium absorption (10 with primary hyperparathyroidism and 20 with coeliac disease) were studied by this standard test. In both groups of patients the mean four hour strontium values were significantly different from normal. This standard strontium absorption test allows assessment of calcium absorption with sufficient sensitivity and precision to have a wide application in clinical practice.

Adult↗

Five year results of a randomized trial of adjuvant 5-fluorouracil and levamisole in colorectal cancer.

Following curative surgery for colorectal cancer 141 patients were randomized to receive a 6 month course of 5-fluorouracil (5FU) with or without postoperative levamisole or supportive treatment only. The patients have been followed up for a minimum of 5 years and 52 per cent of patients in the control group, 44 per cent of the 5FU group and 32 per cent of the 5FU/levamisole group have died of tumour recurrence. This represents a significant survival advantage in the patients receiving levamisole, even when other patient and tumour factors are allowed for.

Adult↗

Acquired immune deficiency syndrome: psychological impact on health personnel.

Eight nurses and four physicians involved in the care of an acquired immune deficiency syndrome (AIDS) patient and a matched, non-AIDS patient responded to three self-report measures that assessed the psychological distress associated with working with each patient. While working with the AIDS patient the physicians and nurses experienced increased anxiety, greater interference in nonwork activities, more frequent negative ruminations, and more negative perceptions regarding the AIDS patient's behavior than they did with the non-AIDS patient. Because of the fears and concerns engendered in medical personnel when providing care to AIDS patients, psychological and educational interventions are needed to reduce staff's discomfort and thereby facilitate optimal care of AIDS patients.

Acquired Immunodeficiency Syndrome↗