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Biomedical subjects

L Shaw

Publications and source records attributed to L Shaw.

At least 145 records · Page 8Linked to original sources

Prognostic value of a treadmill exercise score in outpatients with suspected coronary artery disease.

BACKGROUND: The treadmill exercise test identifies patients with different degrees of risk of death from cardiovascular events. We devised a prognostic score, based on the results of treadmill exercise testing, that accurately predicts outcome among inpatients referred for cardiac catheterization. This study was designed to determine whether this score could also accurately predict prognosis in unselected outpatients. METHODS: We prospectively studied 613 consecutive outpatients with suspected coronary disease who were referred for exercise testing between 1983 and 1985. Follow-up was 98 percent complete at four years. The treadmill score was calculated as follows: duration of exercise in minutes--(5 x the maximal ST-segment deviation during or after exercise, in millimeters)--(4 x the treadmill angina index). The numerical treadmill angina index was 0 for no angina, 1 for nonlimiting angina, and 2 for exercise-limiting angina. Treadmill scores ranged from -25 (indicating the highest risk) to +15 (indicating the lowest risk). RESULTS: Predicted outcomes for the outpatients, based on their treadmill scores, agreed closely with the observed outcomes. The score accurately separated patients who subsequently died from those who lived for four years (area under the receiver-operating-characteristic curve = 0.849). The treadmill score was a better discriminator than the clinical data and was even more useful for outpatients than it had been for inpatients. Approximately two thirds of the outpatients had treadmill scores indicating low risk (greater than or equal to +5), reflecting longer exercise times and little or no ST-segment deviation, and their four-year survival rate was 99 percent (average annual mortality rate, 0.25 percent). Four percent of the outpatients had scores indicating high risk (less than -10), reflecting shorter exercise times and more severe ST-segment deviation; their four-year survival rate was 79 percent (average annual mortality rate, 5 percent). CONCLUSIONS: The treadmill score is a useful and valid tool that can help clinicians determine prognosis and decide whether to refer outpatients with suspected coronary disease for cardiac catheterization. In this study, it was a better predictor of outcome than the clinical assessment.

Adult↗

Immunofluorescent labeling using covalently linked anti-phycoerythrin antibodies and phycoerythrin polymers.

We have developed methods for covalently attaching anti-phycoerythrin (PE) MAbs to other antibodies, and for using PE or polymers of PE in conjunction with these conjugates to rapidly produce specific, high intensity fluorescent labeling of antigens. The performance of these systems was examined on the surface of microspheres and on the cell surface. The noncovalent means by which PE is incorporated into the label complex in this method makes it possible to use crude algal homogenate successfully as a source of PE in immunofluorescence assays. The intensity of labeling achieved using this method is comparable to, or in some cases better than, that obtained using a direct PE conjugate. With the aim of amplifying the intensity of fluorescence obtained, we produced two types of covalently linked complexes. These were an anti-PE MAb, designated PE6, linked to itself (i.e., PE6-PE6), and PE linked to itself (i.e., PE-PE). When used in a two-stage procedure in place of monomeric PE alone, these complexes increased the intensity of fluorescence obtained on the surface of microspheres by more than fourfold. On the cell surface, the performance of this system varied from one antigen to the next but in most cases was restricted to, at best, a 60% increase in the intensity of fluorescence and in many cases only about a 30% increase.

Antibodies, Monoclonal↗

CMP-N-acetylneuraminic acid hydroxylase activity determines the wheat germ agglutinin-binding phenotype in two mutants of the lymphoma cell line MDAY-D2.

The dominant glycosylation mutants of MDAY-D2 mouse lymphoma cells, designated class 2 (D33W25 and D34W25) were selected for their resistance to the toxic effects of wheat germ agglutinin (WGA) and shown to express elevated levels of Neu5Gc. In accordance with this, the activity of CMP-Neu5Ac hydroxylase was found to be substantially higher in the mutant cells. The hydroxylase in the D33W25 mutant cells exhibited kinetic properties identical to those of the same enzyme from mouse liver. Growth rate experiments in vivo and in vitro, where the mutant cells grew more slowly at low cell densities in serum-free medium and also formed slower growing tumours in syngeneic mice, indicate that CMP-Neu5Ac hydroxylase expression may be associated with altered growth of the mutant cells.

Cell Division↗

GnRH-induced gonadotrophin secretion in ovariectomized Booroola ewes with hypothalamic-pituitary disconnection.

To test whether the F gene-specific differences in the plasma concentrations of FSH and LH are due to differences in the pituitary responsiveness to exogenous GnRH, ovariectomized Booroola ewes with hypothalamic-pituitary disconnection (HPD-ovx) were treated with GnRH (250 ng i.v.) once every 2 h for up to 5 weeks. In Exp. 1, jugular venous blood was collected once weekly from 13 FF and 14 ++ HPD-ovx ewes for 6 weeks before GnRH treatment and every 2nd, 3rd or 6th day for 5 weeks during treatment. In Exp. 2, jugular venous blood was collected from another 8 FF and 7 ++ HPD-ovx ewes at 5- or 10-min intervals over 4 GnRH pulses (250 ng i.v. once every 2 h) on 3 separate occasions after the animals had been subjected to the GnRH pulse regimen for approximately 7 days beforehand. Also in Exp. 2, the animals were extensively sampled around a larger (10 micrograms) i.v. injection of GnRH and the pituitary FSH and LH contents assessed after the animals had been re-exposed to the once every 2 h GnRH (250 ng i.v.) pulse regimen for several days following the larger GnRH bolus. In Exp. 3 the distributions of mean plasma concentrations of FSH and LH in individual GnRH-treated HPD-ovx ewes were compared with those in ovariectomized and ovary-intact FF and ++ ewes. During the 6 weeks before GnRH treatment (Exp. 1), the plasma concentrations of FSH (approximately 1 ng/ml) and LH (less than or equal to 0.8 ng/ml) were not different between the genotypes. After GnRH treatment both the mean FSH and LH concentrations increased significantly (P less than 0.01) above basal values after 2 days with F gene-specific differences being noted for FSH but not LH (FSH; FF greater than ++; P less than 0.05). Thereafter, the mean FSH but not LH concentrations increased at a faster rate in FF than in ++ ewes with the overall mean FSH concentrations between the genotypes being significantly different (P less than 0.05). In Exp. 2 considerable between-animal variation in the pulsatile pattern of FSH but not LH concentrations was seen in ewes of both genotypes during GnRH treatment. The overall mean FSH concentrations were higher in FF than in ++ ewes (P less than 0.05) and the mean FSH response to each GnRH pulse was significantly higher in FF than in ++ ewes (P less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Realizing information technology benefits.

The Regional Medical Center at Memphis--the oldest hospital in Tennessee--acknowledged that information technology is a critical key to the pursuit of medical and managerial excellence. By outsourcing much of the center's computing and telecommunications needs, the MED's CEO, Lucy Shaw, feels she has maximized information technology benefits to her institution with maximum cost control.

Computer Communication Networks↗

The effectiveness of differing dental health education programmes in improving the oral health of adults with mental handicaps attending Birmingham adult training centres.

There are few published data available relating to dental health in adults with handicaps, or to the effectiveness of dental health education in this group. The present study involved 382 people attending four different adult training centres in Birmingham, UK. Following baseline examinations all participants were given oral hygiene instruction and a scale and polish. Each of the centres was then randomly allocated to one of the four treatment regimens. No specific treatment was provided for the control group; daily supervised toothbrushing was carried out by the participants in the other three groups, with the addition of a three-monthly scale and polish and reinforcement of oral hygiene instruction in group 3 and one-monthly input in group 4. The participants were re-examined after three months and then at six-monthly intervals until 24 months after the baseline examination. The results showed that those people left to their own devices to carry out toothbrushing at home following instruction were not achieving an acceptable standard. Those who were reminded, encouraged and motivated by the adult training centre staff were obviously capable of better standards of oral care. The input of an experienced dental hygienist on a regular basis improved the periodontal condition considerably. Although there were significant differences between the groups throughout the study, particularly in the presence of calculus, the differences between the one-monthly and three-monthly hygienist input were not clinically very apparent after two years, and therefore a one-monthly input would be difficult to justify on a cost benefit basis.

Adult↗

Quality assurance. A project on patient waiting times at appointment in an orthodontic department.

A quality assurance project to establish patient waiting time at appointments was undertaken over a four-week period during the spring of 1989. The Orthodontic Department was selected as one of two departments in the Birmingham General Hospital/Birmingham Dental Hospital unit site that was to participate in the programme initiated at the District Health Authority management level. Patient waiting periods for a total of 142 clinical sessions were assessed. Fifty per cent of patients were kept waiting and 50 per cent were seen either earlier or at their appointed time. The mean period of time that patients were kept waiting past their appointment time was 9.4 min (+/- 10.9). On clinics for which patients arrived late the mean time that they were kept waiting increased to a mean of 18.9 min (+/- 9.1). Data from 92 patient questionnaires established that they considered a reasonable mean time of waiting to be 16.1 min (+/- 7.9). Five recommendations were proposed as a result of this quality assurance initiative and their implementation is discussed.

Appointments and Schedules↗

Estimating the likelihood of severe coronary artery disease.

PURPOSE: To determine which clinical characteristics obtained by a physician during an initial clinical examination are important for estimating the likelihood of severe coronary artery disease, and to determine whether estimates based on these characteristics remain valid when applied prospectively and in different patient groups. PATIENTS AND METHODS: We examined clinical characteristics predictive of severe disease in 6,435 consecutive symptomatic patients referred for suspected coronary artery disease between 1969 and 1983. RESULTS: Eleven of 23 characteristics were important for estimating the likelihood of severe coronary artery disease. A model using these characteristics accurately estimated the likelihood of severe disease in an independent sample of 2,342 patients referred since 1983. The model also accurately estimated the prevalence of severe disease in large series of patients reported in the literature. CONCLUSIONS: These findings suggest that the clinician's initial evaluation can identify patients at high or low risk of anatomically severe coronary artery disease. Cost-conscious quality care is encouraged by identifying patients at higher risk for severe coronary artery disease who are most likely to benefit from further evaluation.

Adult↗

A study on the regulation of N-glycoloylneuraminic acid biosynthesis and utilization in rat and mouse liver.

The relative contribution of N-glycoloyl-beta-D-neuraminic acid (Neu5Gc) to total sialic acids expressed in mouse and rat liver glycoconjugates was found to be 95% and 11%, respectively. This considerable difference in sialic acid composition made these two tissues suitable models for a comparative investigation into the regulation of Neu5Gc biosynthesis and utilization. An examination of the CMP-glycoside specificity of Golgi-associated sialyltransferases using CMP-N-acetyl-beta-D-neuraminic acid (CMP-Neu5Ac) and CMP-Neu5Gc revealed no significant tissue-dependent differences. The Golgi membrane CMP-sialic acid transport system from rat liver did, however, exhibit a slightly higher internalisation rate for CMP-Neu5Ac, though no preferential affinity for this sugar nucleotide over CMP-Neu5Gc was observed. In experiments, where Golgi membrane preparations were incubated with an equimolar mixture of labelled CMP-Neu5Ac and CMP-Neu5Gc, no significant tissue-dependent differences in [14C]sialic acid composition were observed, either in the luminal soluble sialic acid fraction or in the precipitable sialic acid fraction, results which are consistent with the above observations. From this experiment, evidence was also obtained for the presence of a Golgi-lumen-associated CMP--sialic acid hydrolase which exhibited no apparent specificity for either CMP-Neu5Ac or CMP-Neu5Gc. The specific activity of the CMP-Neu5Ac hydroxylase, the enzyme responsible for the biosynthesis of Neu5Gc, was found to be 28-fold greater in high-speed supernatants of mouse liver than of rat liver. No hydroxylase activity was detected in the Golgi membrane preparations. It is therefore proposed that the cytoplasmic ratio of CMP-Neu5Ac and CMP-Neu5Gc produced by the hydroxylase, remains largely unmodified after CMP-glycoside uptake into the Golgi apparatus and transfer on to growing glycoconjugate glycan chains. The close relationship between the total sialic acid composition and the sialic acid pattern in the CMP-glycoside pools of the tissues lends considerable weight to this hypothesis.

Animals↗

An off-line digital system for reproducible interpretation of the exercise ECG.

Exercise electrocardiograms of 20 patients were analyzed using a customized software exercise electrocardiographic program and compared to measurements made by two cardiologists performing independent interpretations. The computerized program requires identification of the PQ junction, J point, and tracing of the ST-segment in three consecutive beats. The proportion of variance for J point, and ST 80 measurements was 0.93 and 0.90, respectively, when the same electrocardiogram was processed twice and analyzed by two separate cardiologists. The same 20 exercise electrocardiograms were analyzed by two other experienced cardiologists without computerized measurements. The proportion of variance was less at 0.73 and 0.76 for the J point and ST 80 measurements, respectively. The average amount of time required for the cardiologist to over read the computerized measurements was 2.7 +/- 1.5 minutes per ECG as compared to 20.7 +/- 11 minutes for the cardiologists who did not have computer-assisted measurements (p less than 0.0001). Thus, off-line computerized exercise electrocardiographic interpretation is highly reproducible, accurate, time-sparing for cardiologist over read function, and suitable for use in large-scale clinical trials.

Coronary Disease↗

A simple technique for removal of mottling, opacities and pigmentation from enamel.

Mottling of teeth can have significant psychological impact on patients--particularly on adolescents, who may be subjected to much unkind teasing. A number of procedures have been suggested for removal of mottling and stains. The authors describe a simple and quick technique using a paste of hydrochloric acid and pumice, and on the basis of their clinical and laboratory experience suggest it as a treatment of first choice.

Adolescent↗

The oral health in different groups of adults with mental handicaps attending Birmingham (UK) adult training centres.

The policies of normalisation and integration into the community of people with mental handicap have significant implications for dental care. Before dental services can be planned, the extent of the problem needs to be identified. A total of 382 people with mental handicap living in the community and attending day centres was examined; 52 of these people were edentulous. The mean age of the dentate adults was 30.9 years and the mean DMFT was 9.59. This was low in comparison with data available from national studies but when component parts of the DMF were evaluated it was apparent that far less restorative care had been received by the adults with mental handicap. There were also significant differences in the mean DMFT between mentally handicapped people who had additional handicaps; the mean DMFT for people with Down's syndrome was 10.95, whilst those mentally handicapped people who also had epilepsy had a mean DMFT of 11.19. The oral hygiene and periodontal condition was also poor and there were significant differences between the sub-groups. However, despite people with Down's syndrome having lower levels of plaque, they showed evidence of greater periodontal destruction. When resources are allocated, consideration should be given to raising the oral health of adults with mental handicap up to at least the same level as that of the rest of the population.

Adult↗

Detection of CMP-N-acetylneuraminic acid hydroxylase activity in fractionated mouse liver.

The finding that N-glycoloylneuraminic acid (Neu5Gc) in pig submandibular gland is synthesized by hydroxylation of the sugar nucleotide CMP-Neu5Ac [Shaw & Schauer (1988) Biol. Chem. Hoppe-Seyler 369, 477-486] prompted us to investigate further the biosynthesis of this sialic acid in mouse liver. Free [14C]Neu5Ac, CMP-[14C]Neu5Ac and [14C]Neu5Ac glycosidically bound by Gal alpha 2-3- and Gal alpha 2-6-GlcNAc beta 1-4 linkages to fetuin were employed as potential substrates in experiments with fractionated mouse liver homogenates. The only substrate to be hydroxylated was the CMP-Neu5Ac glycoside. The product of the reaction was identified by chemical and enzymic methods as CMP-Neu5Gc. All of the CMP-Neu5Ac hydroxylase activity was detected in the high-speed supernatant fraction. The hydroxylase required a reduced nicotinamide nucleotide [NAD(P)H] coenzyme and molecular oxygen for activity. Furthermore, the activity of this enzyme was enhanced by exogenously added Fe2+ or Fe3+ ions, all other metal salts tested having a negligible or inhibitory influence. This hydroxylase is therefore tentatively classified as a monooxygenase. The cofactor requirement and CMP-Neu5Ac substrate specificity are identical to those of the enzyme in high-speed supernatants of pig submandibular gland, suggesting that this is a common route of Neu5Gc biosynthesis. The relevance of these results to the regulation of Neu5Gc expression in sialoglycoconjugates is discussed.

Animals↗

Prognostic value of intravenous dipyridamole thallium scintigraphy after an acute myocardial ischemic event.

Seventy-seven patients recovering from an acute coronary event were studied by intravenous dipyridamole thallium scintigraphy to evaluate the prognostic value and safety of the test in this patient subset. Forty-four patients (58%) had unstable angina and 33 (42%) had an acute myocardial infarction. One death occurred within 24 hours of testing. Sixty-eight patients were followed for an average of 12 months; 25, 31 and 23% had a fixed, reversible or combined thallium defect on their predischarge thallium scan. During follow-up, 10 patients died or had a nonfatal myocardial infarction; in each case, a reversible or combined myocardial thallium defect was present. Univariate analysis of 17 clinical, scintigraphic and angiographic variables showed that a reversible thallium defect and the angiographically determined extent of coronary artery disease were predictors of future cardiac events. The extent of coronary disease and global left ventricular ejection fraction were predictors of subsequent reinfarction or death. Logistic regression analyses revealed that a reversible thallium defect (p less than 0.001) and the extent of coronary disease (p less than 0.009) were the only significant predictors of a cardiac event. When death or reinfarction were the outcome variables, the extent of coronary disease (p less than 0.02) and left ventricular ejection fraction (p less than 0.06) were the only variables selected. Thus, intravenous dipyridamole thallium scintigraphy after an acute coronary ischemic syndrome is a useful and relatively safe noninvasive test to predict subsequent cardiac events.

Aged↗

Transport of CMP-N-glycoloylneuraminic acid into mouse liver Golgi vesicles.

CMP-Neu5Gc has been shown to be transported into mouse liver Golgi vesicles by a specific carrier the characteristics of which were investigated in detail. In the system employed, CMP-Neu5Gc enters the Golgi vesicles within 2 min; transport was saturable with high concentrations of the sugar-nucleotide and was dependent on temperature. A kinetic analysis gave an apparent Km of 1.3 microM and a maximal transport velocity of 335 pmol/mg protein per min. Almost identical values were obtained with CMP-Neu5Ac, under the same incubation conditions. Furthermore, the uptake of CMP-Neu5Gc was inhibited by CMP-Neu5Ac, a substrate analogue. Conversely, the uptake of CMP-Neu5Ac was inhibited by CMP-Neu5Gc to the same extent, leading to the conclusion that the transport of CMP-Neu5Ac and CMP-Neu5Gc is mediated by the same carrier molecule. This transport system for CMP-Neu5Gc involves both CMP and CMP-Neu5Gc since intravesicular CMP induced the entry of external CMP-Neu5Gc.

Animals↗