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Biomedical subjects

J Bell

Publications and source records attributed to J Bell.

At least 469 records · Page 26Linked to original sources

Asthma and panic disorder.

OBJECTIVE: To compare asthma attacks with panic attacks and identify discriminating symptoms. DESIGN: Survey, case-control study. SETTING: Tertiary care centers. PATIENTS: Convenience sample of 71 patients with panic disorder, with or without agoraphobia, and without medical illnesses; and 71 patients with asthma, cohort-matched from 407 patients to be demographically similar to the panic disorder sample. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Asthma Symptom Checklist. RESULTS: Clusters of symptoms reflecting panic-fear and hyperventilation-hypocapnia were more strongly endorsed by subjects with panic disorder, whereas airway obstruction symptom clusters were more strongly descriptive of asthma attacks (all P < .05). Three symptoms differentiated the groups with sensitivity greater than 0.90 and specificity greater than 0.70: wheezing, mucous congestion, and coughing, all being present significantly more among asthma attacks than panic attacks. CONCLUSION: Knowledge of what symptoms discriminate asthma attacks from panic attacks may help physicians identify each type of attack in individuals who experience both.

Adult↗

The impact of prenatal diagnosis on the occurrence of chromosome abnormalities.

From the public health point of view, several formal attempts have been made to measure the impact of prenatal diagnosis (PND) on the incidence of Down's Syndrome (DS), but the results have varied widely. The impact of PND (reduction in the birth rate of chromosomally abnormal neonates) is related to utilization rates but quantitative estimates of this have not been established. In a three-year (1981-1983) total population study from Queensland, Australia, we present results to measure the impact of a voluntary PND programme on the birth incidence of DS, and also other chromosomally abnormal births. Utilization rates for the PND service were 15.5 per cent in that population of mothers 35 years and over. Numbers and rates of all cases of chromosomal abnormalities are presented, subclassified by type of diagnosis--either by PND or by clinical diagnosis after birth. For the total population, 7.3 per cent of cases of DS were detected prenatally, and 15.4 per cent of all chromosome abnormalities. (A method for measuring the impact of PND is described.) Using this in conjunction with our demographic data, we estimate that with a 15 per cent utilization rate of PND by older mothers, 14 per cent of DS births can be prevented in this age group, or a 5 per cent overall reduction can be achieved if mothers of all ages are considered. One index--the ratio of the percentage of DS births which are preventable compared with the population utilization rates of PND--has potential for widespread use. Queensland data for this ratio is 0.34, a figure consistent with that from other studies. Thus a 3.5 per cent drop in the overall DS birth rate may be expected for each 10 per cent increase in the utilization rates of PND for mothers of 35 years and over. A diagram is presented which may serve as a model for improved data collection and better impact estimates in the future.

Adult↗

The influence of patient smoking status on therapeutic decisions.

STUDY OBJECTIVE: To assess the effect of patient smoking status on internists' inclinations to recommend certain types of therapy for conditions that are and conditions that are not related to smoking. DESIGN, SETTING, AND PARTICIPANTS: Five hundred ninety-eight internists identified systematically from the Directory of Medical Specialists (first entry on each page of text) were asked to complete a questionnaire about how their treatment decisions for five therapies differed as a function of patient smoking status. RESULTS: The responses of the 320 internists who completed and returned the questionnaire showed that smoking status had little effect on physicians' inclinations to recommend herniorrhaphy, hemodialysis, or bronchodilator therapy. However, physicians were considerably less inclined to recommend coronary artery bypass grafting or peripheral arterial surgery to patients who smoked. Reduced efficacy and greater risk of therapy were the most frequent reasons given for the observed decrease. Reduced entitlement by smokers to complex therapies for smoking-related diseases and the withholding of therapy as a bargaining tool to induce smokers to quit were also cited as reasons. CONCLUSIONS: Some internists believe they are less likely to recommend complex therapies for smoking-related diseases to patients who continue to smoke. Some of this decrease may be attributable to the notion that smokers are less entitled to complex therapies or that withholding therapies is a permissible way to influence patients to adopt more healthful lifestyles. Whether these physician attitudes reflect actual practice is yet to be shown.

Angina Pectoris↗

Mechanism of enhancement by fucoidan and CNBr-fibrinogen digest of the activation of glu-plasminogen by tissue plasminogen activator.

The interactions of fucoidan with human glutamic type plasminogen (Glu-Plg), porcine pancreatic elastase digested plasminogen fractions and two chain tissue plasminogen activator t-PA) were investigated using fucoidan-Sepharose affinity chromatography. The results showed a high degree of affinity between fucoidan-Sepharose and Glu-Plg or PlgK(1-3) but not with PlgK4 or mini-Plg. Fucoidan-Sepharose also showed a high affinity for t-PA, which was largely reversed by 0.002 M 6-aminohexanoic acid (6-AH). The addition of fucoidan and CNBr-fibrinogen digest (CNBr-Fbg) gave the highest enhancement of the in vitro activation of Glu-Plg by t-PA in the presence of 0.002 M 6-AH. The results of affinity chromatography and enhancement studies suggested a template mechanism, since increasing the concentrations of any one of the two cofactors reversed the enhancement. Enzyme kinetic studies, using double reciprocal plots, showed that the addition of fucoidan-6-AH increased Kcat by 7-fold without affecting Km and addition of CNBr-Fbg lowered Km by 5-fold without significantly affecting Kcat while addition of the two cofactors lowered Km by 16-fold without significantly affecting Kcat. The enhancement by fucoidan-6-AH or by CNBr-Fbg of the in vitro activation of Glu-Plg by t-PA was reversed by plasminogen activator inhibitor 1 (PAI-1). Fucoidan-Sepharose affinity chromatography revealed that the binding of PAI-1 with fucoidan may be responsible for the reversal of the enhancement by fucoidan-6-AH.

Chromatography, Affinity↗

Effects of prenatal cocaine exposure on behavior during the early postnatal period.

Offspring of Sprague-Dawley dams injected SC with 40 mg/kg/3 cc cocaine HCl daily from gestational days 8-20, pair-fed dams injected with the vehicle alone and nontreated control dams were examined behaviorally during the early postnatal period. No significant differences were observed among the treatment conditions in maternal weight gain during pregnancy, duration of pregnancy, or number of live male and female pups/litter. Offspring body weights at birth and weaning, physical maturation and reflex development were not significantly affected by prenatal cocaine exposure. In contrast, neonates exposed prenatally to cocaine were observed to exhibit significant deficits in learning of an odor/milk association that nontreated offspring learned and retained for a 24 hr period. On postnatal day 12, cocaine offspring exhibited an increase in locomotor activity and attenuated wall climbing precipitated by footshock, in the absence of any alteration in sensitivity to footshock. Given that wall climbing has been previously shown to be strongly related to levels of catecholamine activity at this age, these data suggest the possibility that there may be some attenuation in catecholaminergic function in pups exposed gestationally to cocaine. The results of this study provide evidence that prenatal cocaine exposure may have an impact upon behavioral and cognitive function even during the early postnatal period. More work is needed to fully characterize the range of alterations observed and the neural mechanisms underlying these early exposure effects.

Animals↗

Examination of the potential structure of human salivary cystatins based on computer modelling.

The cystatin family of proteins exists in both excreted and intracellular forms, and appears to be involved in protective and regulatory roles, inhibiting a variety of bacterial, viral and intracellular proteases. The amino acid sequences of several human forms of cystatin are known, but currently only the structure of chicken cystatin (approx. 40% homologous to the human forms) has been experimentally determined. The objective of this study was to use the X-ray coordinates of chicken cystatin to construct computer models of the structures of three human salivary forms (SN, S and SA). These structures were energy-minimized and subjected to dynamic simulations. The resultant structures were compared to determine conformational differences. Global root mean square deviations between equivalent atoms ranged from 1.4 A to 3.9 A. The closest structural similarity to chicken cystatin involved cystatin SN, which also showed the highest (68%) functional sequence homology. Local secondary structure was examined in more detail. In comparisons of alpha-carbon position the third beta-strand (77% functional sequence conservation) and its preceding loop (60% conserved) showed the highest structural conservation in S, while beta-strand 4 showed the highest structural conservation in SN and SA. Throughout their structures, SN and SA were more structurally similar to chicken cystatin than to salivary cystatin S. There are two regions of conserved, negatively charged residues in the salivary cystatins, which appear to be spaced so that they are capable of interaction with hydroxypatite. It is concluded that not only does structural modelling by analogy provide detailed models of salivary cystatins that can be tested by future experimentation, but also that examination of the models has revealed potential sites of interaction with hydroxyapatite.

Amino Acid Sequence↗

Stress and body shape: stress-induced cortisol secretion is consistently greater among women with central fat.

OBJECTIVE: Excessive central fat puts one at greater risk of disease. In animal studies, stress-induced cortisol secretion has been shown to increase central fat. The objective of this study was to assess whether women with central fat distribution (as indicated by a high waist-to-hip ratio [WHR]), across a range of body mass indexes, display consistently heightened cortisol reactivity to repeated laboratory stressors. METHODS: Fifty-nine healthy premenopausal women, 30 with a high WHR and 29 with a low WHR, were exposed to consecutive laboratory sessions over 4 days (three stress sessions and one rest session). During these sessions, cortisol and psychological responses were assessed. RESULTS: Women with a high WHR evaluated the laboratory challenges as more threatening, performed more poorly on them, and reported more chronic stress. These women secreted significantly more cortisol during the first stress session than women with a low WHR. Furthermore, lean women with a high WHR lacked habituation to stress in that they continued to secrete significantly more cortisol in response to now familiar challenges (days 2 and 3) than lean women with a low WHR. CONCLUSIONS: Central fat distribution is related to greater psychological vulnerability to stress and cortisol reactivity. This may be especially true among lean women, who did not habituate to repeated stress. The current cross-sectional findings support the hypothesis that stress-induced cortisol secretion may contribute to central fat and demonstrate a link between psychological stress and risk for disease.

Adaptation, Psychological↗

Cardiac function assessed by gated heart pool studies in an alcohol clinic population: a preliminary study.

The nuclear gated heart pool scan was used to assess the left ventricular ejection fraction (LVEF) in 19 patients attending the Drug and Alcohol Unit for treatment of their alcoholism. Eighteen of the patients were asymptomatic and had no signs of cardiac impairment. In 14 subjects (13 asymptomatic), the LVEF was subnormal. Repeat studies were performed in 10 of the subjects following a period of 4-9 months of reduced intake of alcohol or abstinence. The LVEF improved in four subjects, remained unchanged in four, and actually decreased in two others despite a reduction in reported alcohol intake.

Adult↗

Genetics of inflammatory bowel disease. A personal view on progress and prospects.

Clinical, epidemiological and molecular data reported in the last 5 years have provided strong evidence that genetic factors are important in susceptibility to both Crohn's disease and ulcerative colitis. The model of disease inheritance which best fits the epidemiological data is that Crohn's disease and ulcerative colitis are related polygenic diseases. However, genetic heterogeneity is likely to be extensive, and may well underlie the variability in clinical presentation associated with inflammatory bowel disease. Considerable progress has already been made in identifying potential disease susceptibility loci using the technique of genome-wide scanning. There is optimism that international collaborative studies will allow fine mapping of the loci implicated on chromosomes 16 and 12. The identification of novel susceptibility genes has become a realistic goal for investigators. Once this has been achieved, there are likely to be immediate clinical benefits, both in understanding disease pathophysiology, and in disease management.

Colitis, Ulcerative↗

Prostaglandins PGE2 and PGF2 alpha in human fetal lung: immunohistochemistry and release from organ culture.

Immunohistochemical studies in human fetal lung have shown that epithelial and endothelial cells are both strongly and equally reactive for PGE2. In contrast, epithelial PGF2 alpha reactivity varied between fetuses, in some as intense as endothelial staining and in others very much less. As lung organ cultures differentiated, the intensity of PGE2 staining declined in airways and blood vessels, although it was still weakly positive at 10 days. In contrast, epithelial cells rapidly became negative for PGF2 alpha, whereas PGF2 alpha positivity was retained in blood vessels, albeit less obviously. PGF2 alpha and PGE2 were released into the media of organ cultures in decreasing amounts as cultures progressed. Amounts of released PGF2 alpha were greater by 2- to 10-fold than PGE2. Our findings suggest that the endogenous production of prostaglandins by human fetal lung in organ culture has a key role in the self-differentiation process that occurs in the absence of sera or added growth factors or hormones.

Absorption↗

Prostaglandin production and metabolism in self-differentiating human fetal lung organ culture.

PGE2 and PGF2 alpha are released into the media of human fetal lung organ cultures in decreasing amounts with time. This decline in PGs is not due to culture failure or loss of synthetic capacity, which can be stimulated by fetal bovine serum, nor is it due to increased catabolism of PGE2 to 13,14-dihydro-15-keto-PGE2 (PGEM) or of PGF2 alpha to 13,14-dihydro-15-keto-PGF2 alpha (PGFM). Immunohistochemically reactive PGs are not retained within lung cells. Antisera against methyl-moximated derivatives of PGEM or PGFM and preceded by derivatization on tissue sections of PGs by methyl-moximation not only demonstrate the localization of PGEM and PGFM in epithelial cells and blood vessels, but also show an overall decline in immunoreactivity with time. In addition electron microscopy of uncultured fetal lung removed directly after termination reveals various degrees of mitochondrial damage and in some cases plasma membrane blebs which resolve during the period in culture and as fetal lung self-differentiates. It is proposed that oxidative and mechanical stresses, occurring during termination of pregnancy or tissue preparation, result in cell damage and increased lung prostaglandin production, which, although decreasing during culture as cells recover, is sufficient to trigger terminal self-differentiation.

Cell Differentiation↗

Autologous red blood cell and platelet engulfment in hairy cell leukemia.

Seven cases of hairy cell leukemia (leukemic reticulo-endotheliosis) are presented in which peripheral blood or splenic hairy cells or both were identified engulfing autologous red blood cells or platelets. In 3 patients, approximately 5-15% of their peripheral blood hairy cells were engulfing red cells and platelets. In 2 patients, intercellular junctions were present between processes of hairy cells and were similar to processes occasionally seen connecting Langerhans cells to each other. Also, parallel tubular arrays were identified in the cytoplasm of hairy cells from 2 other patients. We conclude that autologous red blood cell and platelet engulfment is a common finding in hairy cell leukemia.

Aged↗

Quality improvement for methadone maintenance treatment.

Negative community attitudes toward heroin addicts and toward methadone treatment are the major obstacles to providing good treatment. Negative attitudes find expression in inappropriate and constricting regulation of treatment, and in inadequate resources to support programs. They contribute to the ambivalence of patients in treatment. They find expression in a variety of staff behaviors in anxiety and defensiveness about treatment, in staff ambivalence about the value of methadone, and in extreme cases, in cynical and suboptimal treatment practices. These issues are not merely theoretical barriers to quality, but have contributed to serious problems in the quality and effectiveness of treatment. Neither regulations, nor wise prescriptions as to how treatment should be delivered, is an adequate response to these problems. A systematic approach to dealing with these issues is highly desirable. External, peer-based quality improvement provides an appropriate form of accountability, while enhancing the sense of professionalism of clinical staff. Although conventional approaches to quality assurance do not ensure the delivery of good care, benchmarking approaches based on monitoring outcomes can be used to review and improve treatment.

Attitude of Health Personnel↗