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Biomedical subjects

L Smith

Publications and source records attributed to L Smith.

At least 289 records · Page 16Linked to original sources
PubMed1995

The invasive management of angina: issues for consumers and commissioners.

OBJECTIVE: To review, from the purchaser's perspective, the current state of knowledge of techniques for investigation and treating coronary artery disease. The study was based on evidence from past and continuing randomised controlled trials (RCTs). CRITERIA FOR INCLUSION OF REPORTS: Articles listed on Medline (1990-3) with the keywords coronary disease, angina, and unstable angina (combined with surgery, economics, therapy, or drug therapy) and percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass grafting (CABG) were included. Articles published before 1990 were obtained from two comprehensive literature reviews published by the Rand organisation in 1991 and from the papers obtained using the Medline search. A hand search of relevant journals published between July 1993 and June 1994 was also undertaken. Results from more recently published RCTs are included. RESULTS: CABG provides improved angina relief compared with drug treatment and may prolong life in patients with more severe illness. PTCA is also better than drug treatment, but less so than CABG, and its cost advantages over CABG decrease with time. Repeat intervention for return of symptoms is more frequently required after PTCA, but increasing numbers of patients are also undergoing second and third repeat CABG for graft occlusion in the years after the original operation. Newer PTCA techniques are not, as yet, fully evaluated. One technique, atherectomy, has been shown to be no more effective, and more expensive, than conventional balloon angioplasty. In the short term intracoronary stents reduce the problems associated with vessel occlusion after PTCA and therefore reduce the need for further intervention. PTCA should not be performed without ready access to cardiothoracic support. There is an increasing trend towards the development of coronary catheterisation units at peripheral sites. This may lead to increasing, inappropriate use of this investigation in suboptimal circumstances. CONCLUSIONS: Ischaemic heart disease is an important cause of morbidity and mortality and invasive management techniques are developing rapidly; some service expansion is occurring without trial evidence. More research is required to determine the optimum balance of PTCA, CABG, and angiography and population requirements for these procedures. In the meantime, in the absence of firm long term evidence of the superior cost effectiveness of PTCA compared with CABG, the rapid expansion of this procedure should be limited. Patients should be fully informed of the benefits and disadvantages of CABG and PTCA, where either procedure is indicated, to enable them to make fully informed choices.

Angioplasty, Balloon, Coronary↗
PubMed1995

Nonlinear behaviour of human motoneurons.

When ramp-and-hold currents are injected into a motoneuron of an anesthetized cat, the motoneuron responds with a high initial firing rate (dynamic phase), which then adapts to a lower steady-state firing rate. The firing rates during the dynamic and the steady-state phases are linearly related to the rate of change and the magnitude of the injected current, respectively. In human subjects, where inputs to the motoneurons are not accessible, force parameters are used to describe motoneuron behaviour. Population responses of human motoneurons, measured in terms of gross electromyographic (EMG) activity, increase linearly with the magnitude and the rate of change of force. No study has attempted to examine the question of linearity of single motor units during the dynamic as well as the steady-state phases. The following study recorded single motor unit and EMG activities simultaneously from the flexor carpi radialis muscle in human subjects completing ramp-and-hold force trajectories. Although the results confirmed the linear relationship between EMG activities and the rate and magnitude of the force, a nonlinear activity pattern was observed between the single motor unit firing and the force parameters, suggesting that recruitment must be responsible for the linear behaviour of EMG activity. Comparisons of different background activity levels on the firing patterns of a given motor unit, as well as comparisons of two simultaneously recorded units, further supported nonlinear response patterns of single motor units.

Adult↗
PubMed1995

Phorbol esters downregulate expression of the sodium/calcium exchanger in renal epithelial cells.

The Na+/Ca2+ exchanger (NCE) contributes to Ca2+ reabsorption by connecting tubules of the nephron. A line of renal epithelial cells from monkey kidney (LLC-MK2) was used to investigate the regulation of NCE expression. After the activation of protein kinase C (PKC) by phorbol myristate acetate (PMA), NCE activity decreased exponentially by 75% in 48 h (half time approximately 19 h). PMA decreased NCE mRNA by 85% in 24 h. The decrease in NCE transcript preceded the downregulation of NCE activity. NCE protein was quantified with a monoclonal antibody to cardiac NCE. PMA decreased the binding of 3H-labeled antibody to cell sonicates by 40% in 24 h. Immunoblots show that PMA produced a marked and extended increase in membrane-associated PKC-alpha, although PMA depleted total PKC-alpha by 65% in 24 h. In vivo 32P labeling of myristolated alanine-rich C kinase substrate, a specific PKC substrate, confirmed that PMA produced a rapid and extended activation of PKC. 4 alpha-PMA, a stereoisomer of PMA that neither binds nor activates PKC, had no effect on NCE activity or transcript. These findings indicate that activation of PKC with phorbol esters downregulates NCE mRNA, protein, and activity in renal epithelial cells.

Animals↗
PubMed1995

Activation of adenylyl cyclase downregulates sodium/calcium exchanger of arterial myocytes.

Chronic elevation of adenosine 3',5'-cyclic monophosphate (cAMP) is known to inhibit the proliferation of cultured vascular smooth muscle cells. The present findings show that the activation of adenylyl cyclase with forskolin decreased Na+/Ca2+ exchanger (NCX) mRNA and activity. Fetal bovine serum restored NCX transcript and activity. The changes in NCX transcript preceded the changes in NCX activity. Incubation of low-passage immortalized myocytes with forskolin plus 3-isobutyl-1-methylxanthine (IBMX), which inhibits cAMP phosphodiesterase, decreased NCX mRNA by 60% in 6 h and 80% in 24 h. After a 6-h lag, forskolin plus IBMX decreased NCX activity almost linearly to 20% of control at 40 h. 1,9-Dideoxyforskolin, which does not activate adenylyl cyclase, had no effect on NCX mRNA or activity. Forskolin plus IBMX decreased the c-Myc transcript, an immediate-early gene whose expression correlates with cell proliferation, but had no effect on plasma membrane Ca(2+)-ATPase transcripts. Removal of forskolin plus IBMX and addition of fetal bovine serum increased NCX and c-Myc transcripts seven- to eightfold in 6 h and restored NCX activity in 24 h. Inhibition of protein or RNA synthesis by cycloheximide or actinomycin D, respectively, prevented the increase in NCX mRNA. In contrast to blocking NCX induction, cycloheximide potentiated c-Myc induction by serum. Transcription factors that regulate myocyte growth may mediate the opposing influences of serum and forskolin on NCX mRNA and activity.

1-Methyl-3-isobutylxanthine↗
PubMed1995

ATSDR evaluation of health effects of chemicals. II. Mirex and chlordecone: health effects, toxicokinetics, human exposure, and environmental fate.

This document provides public health officials, physicians, toxicologists, and other interested individuals and groups with an overall perspective of the toxicology of mirex and chlordecone. It contains descriptions and evaluations of toxicological studies and epidemiological investigations and provides conclusions, where possible, on the relevance of toxicity and toxicokinetic data to public health. Additional substances will be profiled in a series of manuscripts to follow.

Administration, Cutaneous↗
PubMed1995

Pregnancy associated alpha-glycoprotein (SP-III) in Nigerian pregnant women.

Pregnancy associated protein (SP-III) was measured by rocket electroimmunoassay in the sera of Nigerian women with normal and abnormal singleton pregnancy. A tendency to increases of SP-III levels with advancing gestational age was observed. SP-III may contribute to immunosuppression in preventing anti-allograft responsiveness and levels may also reflect the effect of infections since SP-III is also leucocyte derived. Values in PET and anaemia in pregnancy were similar to values in normal pregnant women.

Adolescent↗
PubMed1995

High prevalence of serological markers of autoimmunity in patients with chronic hepatitis C.

The advent of specific antiviral therapy for chronic hepatitis C has increased the importance of establishing the correct etiology of chronic hepatitis in patients, especially because interferon alfa (IFN-alpha) has been reported to exacerbate autoimmune hepatitis (AIH), whereas corticosteroids increase viral replication in chronic hepatitis C. In our medical center, we have treated many patients with apparent chronic hepatitis C and serological or clinical evidence of autoimmunity. Our aim was to estimate the prevalence of this association and to learn whether demographic or clinical features distinguished between patients with or without autoimmune markers. We performed a retrospective review of the records of 244 unselected patients seen at the Clinics and Hospital of the University of Massachusetts between May 1991 and November 1993, who had elevated serum aminotransferases. One hundred seventeen patients had chronic hepatitis C defined by elevations of serum alanine transaminase (ALT) for at least 6 months, positive serum antibodies to hepatitis C virus (HCV; second-generation enzyme immunoassay [EIA2] or recombinant immunoblot assay [RIBA]), and absence of hepatitis B surface antigen in the serum. Records were reviewed for results of autoimmune markers in sera, including anti-nuclear antibodies (ANAs), anti-smooth muscle antibodies (SMAs), rheumatoid factor (RF), antimitochondrial antibodies (AMAs), anti-liver and kidney microsomal (LKM) antibodies, and cryoglobulins. We found a high prevalence of positivity, particularly for anti-SMAs (66%) and RF (76%) in both men and women. Forty of 41 patients tested negative for anti-LKM antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Epidermolysis bullosa simplex: a keratin 5 mutation is a fully dominant allele in epidermal cytoskeleton function.

To explore the relationship between abnormal keratin molecules, 10-nm intermediate filament (IF) organization, and epidermal fragility and blistering, we sought to determine the functional consequences of homozygosity for a dominant keratin defect. We describe a family with an autosomal dominant skin-blistering disorder, epidermolysis bullosa simplex, Koebner subtype (EBS-K), that has a novel point mutation, occurring in the keratin 5 gene (KRT5), that predicts the substitution of an evolutionarily conserved lysine by an asparagine residue (K173N). Unlike previous heterozygous mutations located within the initial segment of domain 1A of keratin molecules, K173N heterozygosity did not result in severe disease or clumping of keratin filaments. One family member was found to be homozygous for the K173N allele, having inherited it from each of her affected first-cousin parents. Despite a lack of normal keratin 5 molecules, and an effective doubling of abnormal molecules, available for heterodimerization with keratin 14 during IF formation, there were no significant differences in the clinical severity or the ultrastructural organization of the keratin IF cytoskeleton of the homozygous individual. These data demonstrate that the K173N mutation behaves as a fully dominant allele and indicate that a limited number of abnormal keratin molecules are sufficient to impair cytoskeletal function and elicit epidermal fragility and blistering.

Alleles↗
PubMed1995

A detailed analysis of the Knodell score and other histologic parameters as predictors of response to interferon therapy in chronic hepatitis C.

UNLABELLED: The Knodell score is inaccurate at predicting response to interferon alpha (IFN-alpha) therapy in patients with hepatitis C. Our aim was to see if specific histologic parameters, including iron deposition in liver biopsies, are better predictors of response to IFN-alpha than the total Knodell score. Thirty-five unselected patients were studied who had hepatitis C treated with IFN-alpha between 1990 and 1993, and pretreatment serum iron indices and liver needle biopsies performed. Biopsies were divided for light microscopy and quantitative iron determination. H&E-stained slides were graded for components I, II, III, IV, and total Knodell score. Quantitative determinations were percentage of portal triads with inflammation, piecemeal necrosis, lymphoid aggregates, and inflamed bile ducts; percentage of lobules with inflammation or acidophilic bodies; and percentage of triads with positive iron stain. Complete responders (CR) to IFN-alpha were defined by normalization of serum alanine aminotransferase (< or = 40 IU/liter), and noncomplete responders (NCR) by partial or no response. Data were analyzed statistically. CR had < 40% of triads positive for iron (P = 0.02) and lower serum ferritin (P = 0.05) and higher scores for lobular necrosis (P = 0.04). The percentage of iron-positive triads correlated only with cirrhosis. Addition of cirrhosis to percentage of iron-positive triads did not improve the predictive power of the portal iron. CR and NCR did not differ with respect to total Knodell score or any of the other individual parameters except Knodell II. CONCLUSIONS: (a) Individual features of lobular necrosis and iron staining in portal triads are better predictors of response to IFN-alpha than the total Knodell score.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Tannic acid's effect on bird antigen.

BACKGROUND: Birds have been associated with many diseases including hypersensitivity pneumonitis and allergic diseases such as asthma and rhinitis. Bird antigen from homes of patients with hypersensitivity pneumonitis persists long after the bird is removed from the home. This may account for the persistence of symptoms, signs, and bird-specific IgG in patients with hypersensitivity pneumonitis. Tannic acid application has been effective in decreasing cat and mite allergen levels. No data have been available on tannic acid's effect on bird antigen. OBJECTIVE: It is the purpose of this study to determine whether tannic acid reduces bird antigen in the home. METHOD: Dust samples were collected from homes with bird antigen before and after application of tannic acid. Samples were assayed for bird antigen levels using a competitive inhibition ELISA. Pre- and post-bird antigen levels were compared using a paired t test to determine whether antigen was reduced significantly. RESULTS: There was not a statistical difference between bird antigen levels before and after application of tannic acid as compared by paired t test (P = .09). CONCLUSION: Tannic acid is not effective in decreasing bird antigen levels. In patients with hypersensitivity pneumonitis or allergic disease to birds, the bird should be removed from the home and environmental cleanup should be undertaken, but tannic acid application is not indicated.

Allergens↗
PubMed1995

Building consensus for nephrology nursing practice.

Building consensus for nephrology nursing practice was the theme for the American Nephrology Nurses' Association's (ANNA's) 1994 Clinical Concerns Meetings in Chicago and LaJolla, California respectively. This article emphasizes the importance of consensus building, traditional approaches to consensus conferences, and the inherent risks in conducting such a conference. Additionally, the consensus conference design and steps leading to a final working document are presented by members of the Clinical Concerns Planning Committee.

Consensus Statements as Topic↗
PubMed1995

Bronchial hyperreactivity revisited.

OBJECTIVE: The purpose of this article is to review bronchial reactivity: how it is detected, what are the clinical and pathologic correlates and what treatment modulates it. Is it a good diagnostic test for a disease such as asthma? Is it a reasonable parameter to follow in assessing disease severity and response to treatment? DATA SOURCES: Recent studies on human subjects in the English language medical literature involving bronchial hyperreactivity. In particular all studies were sought that correlated indices of inflammation obtained either by bronchoalveolar lavage or biopsy with degree of bronchial hyperresponsiveness. Pertinent studies reviewing disease association with presence of bronchial hyperreactivity were sought. All studies of treatment with inhaled corticosteroids were reviewed and those in which the subjects could be classified as having either mild or moderately severe asthma on the basis of the clinical information given were used to provide data on correlation of bronchial reactivity and disease severity. RESULTS: The relationship of bronchial reactivity and any disease state is not straightforward. It is not clear what causes hyperreactivity of the airways but there must be other factors besides inflammation as bronchial hyperreactivity can occur without microscopic evidence of inflammation. Hyperresponsiveness does not appear to be as sensitive or specific for the diagnosis of asthma as previously thought, or as closely related to the severity of asthma. Effects of treatment appear to be somewhat independent of their impact on bronchial responsiveness. CONCLUSIONS: Airway hyperresponsiveness can be found in many circumstances. Its relationship to symptom production and clinical course in any disease is not clear. Further studies are needed to elucidate the relationship between airways hyperreactivity, asthma, and other lung diseases and the factors that lead to increased bronchial reactivity.

Asthma↗
PubMed1995

The cost of monitoring glaucoma patients by community optometrists.

Glaucoma patients are currently undergoing monitoring by community based optometrists as part of a randomised controlled trial of shared care. As part of this trial, the costs of monitoring these patients by community optometrists are being calculated. Data were obtained from eight practices for the 1993-1994 financial year. The average 'full' cost of a 40 min appointment was calculated as epsilon 31.56 pounds. The average number of unbooked appointments for the month of October 1994 was 16 per practice, which equated to 12, 40 min appointments. Once the number of unbooked appointments was surpassed for each practice, an average opportunity cost of epsilon 54.00 pounds was experienced per appointment. The participating optometrists were willing to accept a minimum fee of epsilon 26.03 pounds for a small number of patient assessments but this rose to epsilon 43.16 pounds for up to 100 glaucoma patients seen per annum.

Community Health Services↗
PubMed1995

CHIME-Net, the Connecticut Health Information Network: a pilot study.

CHIME-Net is a state-wide community health information network project which uses a frame-relay approach to interfacility and internet connectivity. This is a collaborative effort among competitive institutions, which embraces technologies new to the health care industry. The experiences of implementation of the CHIME-Net pilot project are presented as a first milestone for the state-wide effort.

Community Networks↗