Are the Health of the Nation's targets attainable? Postal survey of general practitioner's views.
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Attitude of Health Personnel↗
Biomedical subjects
H Smith
Publications and source records attributed to H Smith.
Cloning and characterization of a microsomal aminopeptidase from the intestine of the nematode Haemonchus contortus.
In order to characterise the integral membrane glycoprotein H11 from the intestinal microvilli of the nematode Haemonchus contortus, cDNA libraries prepared using mRNA from adult worms from the UK and Australia were immunoscreened with anti-H11 sera. Antibodies affinity purified on the protein expressed by insert DNA (295 bp) of a positive clone from a UK library bound specifically to H11. A longer clone (948 bp) was obtained from the Australian library by hybridisation. Using a primer based on sequence common to these, a polymerase chain reaction product of 3.3 kb was generated from cDNA from UK H. contortus. The sequences from the UK and Australian nematodes were essentially identical over the 929 bp region in which both were represented. All three cloned DNAs hybridised to mRNA of about 3.5 kb. Analysis of the deduced amino acid sequence, which showed 32% identity with those of mammalian microsomal aminopeptidases, indicated that H11 has a short N-terminal cytoplasmic tail, a single transmembrane region and a long extracellular region with putative N-linked glycosylation sites and the HEXXHXW motif characteristic of microsomal aminopeptidases. Microsomal aminopeptidase activity co-purifies with H11. It is inhibited by bestatin, phenanthroline and amastatin. The recombinant protein has been expressed in active form in insect cells.
Amino Acid Sequence↗
Mutagenicity of the atmospheric transformation products 2-nitrofluoranthene and 2-nitrodibenzopyranone in Salmonella and human cell forward mutation assays.
The mutagenicity of the atmospheric transformation products 2-nitrofluoranthene (2-NF) and 2-nitrodibenzopyranone (2-NDBP), as well as a related isomer 3-nitrodibenzopyranone (3-NDBP), was measured in quantitative forward mutation assays with bacteria (Salmonella typhimurium TM677) and in two metabolically competent human cell lines (MCL-5 and h1A1v2) that differ in their complement of cytochrome P450s and microsomal epoxide hydrolase. 2-NF was a potent mutagen in Salmonella TM677 both in the absence and presence of rat liver postmitochondrial supernatant (PMS). 2-NDBP was non-mutagenic in the absence of PMS, but was mutagenic in its presence. The converse result was obtained for 3-NDBP. The mutagenic potency series in Salmonella in the absence of PMS, expressed as the minimum detectable mutagen concentration (MDMC) in nmol/ml, was: 2-NF, 2.5; 3-NDBP, 16.9; and 2-NDBP, > 415. With PMS, the potency series was: 2-NF, 1.2; 2-NDBP, 15.1; 3-NDBP, 208. Neither 2-NDBP nor 3-NDBP were mutagenic at the tk locus in MCL-5 or h1A1v2 cells at up to 200 nmol/ml. 2-NF was also inactive in MCL-5 cells, but was a potent mutagen in h1A1v2 cells with an MDMC of 0.02 nmol/ml. Cytochrome P450 CYP1A1, present constitutively only in h1A1v2 cells, was implicated in 2-NF activation because mutagenicity was reduced by 55-80% when alpha-naphthoflavone (ANF) was present during incubation. The lack of mutagenicity in MCL-5 cells was attributed to the inability of 2-NF to induce CYP1A1 activity in this cell line. These data indicate a primary role for ring oxidation in 2-NF activation. Previous emphasis placed upon 2-NDBP as a major mutagen in ambient air may need to be modified in view of the negative results for this compound in the human cell assays and in the absence of PMS in Salmonella TM677. However, these findings support the concern that 2-NF may be a risk to human health.
Air Pollutants↗
Refinement of the NMR solution structure of the gamma-carboxyglutamic acid domain of coagulation factor IX using molecular dynamics simulation with initial Ca2+ positions determined by a genetic algorithm.
A genetic algorithm (GA) successfully identified the calcium positions in the crystal structure of bovine prothrombin fragment 1 bound with calcium ions (bf1/Ca). The same protocol was then used to determine the calcium positions in a closely related fragment, the Gla domain of coagulation factor IX, the structure of which had previously been determined by NMR spectroscopy in the presence of calcium ions. The most frequently occurring low-energy structure found by GA was used as the starting structure for a molecular dynamics refinement. The molecular dynamics simulation was performed using explicit water and the Particle-Mesh Ewald method to accommodate the long-range electrostatic forces. While the overall conformation of the NMR structure was preserved, significant refinement is apparent when comparing the simulation average structure with its NMR precursor in terms of the N-terminal (Tyr1-N) network, the total number of hydrogen bonds, the calcium ion coordinations, and the compactness of the structure. It is likely that the placement of calcium ions in the protein is critical for refinement. The calcium ions apparently induce structural changes during the course of the simulation that result in a more compact structure.
1-Carboxyglutamic Acid↗
Medical care costs and quality of life after randomization to coronary angioplasty or coronary bypass surgery. Bypass Angioplasty Revascularization Investigation (BARI) Investigators.
BACKGROUND: Randomized trials comparing coronary angioplasty with bypass surgery in patients with multivessel coronary disease have shown no significant differences in overall rates of death and myocardial infarction. We compared quality of life, employment, and medical care costs during five years of follow-up among patients treated with angioplasty or bypass surgery. METHODS: A total of 934 of the 1829 patients enrolled in the randomized Bypass Angioplasty Revascularization Investigation participated in this study. Detailed data on quality of life were collected annually, and economic data were collected quarterly. RESULTS: During the first three years of follow-up, functional-status scores on the Duke Activity Status Index, which measures the ability to perform common activities of daily living, improved more in patients assigned to surgery than in those assigned to angioplasty (P<0.05). Other measures of quality of life improved equally in both groups throughout the follow-up period. Patients in the angioplasty group returned to work five weeks sooner than did patients in the surgery group (P<0.001). The initial mean cost of angioplasty was 65 percent that of surgery ($21,113 vs. $32,347, P<0.001), but after five years the total medical cost of angioplasty was 95 percent that of surgery ($56,225 vs. $58,889), a difference of $2,664 (P = 0.047). The five-year cost of angioplasty was significantly lower than that of surgery among patients with two-vessel disease ($52,930 vs. $58,498, P<0.05), but not among patients with three-vessel disease ($60,918 vs. $59,430). After five years of follow-up, surgery had an overall cost-effectiveness ratio of $26,117 per year of life added, but unacceptable ratios of $100,000 or more per year of life added could not be excluded (P=0.13). Surgery appeared particularly cost effective in treating diabetic patients because of their significantly improved survival. CONCLUSIONS: In patients with multivessel coronary disease, coronary-artery bypass surgery is associated with a better quality of life for three years than coronary angioplasty, after the initial morbidity caused by the procedure. Coronary angioplasty has a lower five-year cost than bypass surgery only in patients with two-vessel coronary disease.
Angioplasty, Balloon, Coronary↗
A PCR-based non-radioactive X-chromosome inactivation assay for genetic counseling in X-linked primary immunodeficiencies.
The Wiskott-Aldrich syndrome (WAS), X-linked severe combined immunodeficiency (SCIDX1), and X-linked agammaglobulinemia (XLA) are severe congenital immunodeficiencies with X-linked inheritance. Although rare, they are all associated with severe infections from early in life, and high morbidity and mortality. Female carriers of these diseases can be identified by a non-random pattern of X-chromosomal inactivation in cell lineages targeted by each gene defect. For patients with WAS, SCIDX1 or XLA, the demonstration of non random X-Chromosome inactivation in their mothers can be used to confirm clinical diagnosis. Furthermore, analysis of X-Chromosome inactivation in at risk females allows preconceptional carrier detection, thus representing an important aid in genetic counseling. For each disease we established a PCR-based, non radioactive assay at the human androgen receptor (HUMARA) locus, that allows analysis of X-Chromosome inactivation in the affected cell types and in tissue specific controls to exclude the issue of skewed X-chromosomal inactivation. In our study, 50 females with a known family history of XLA [19], WAS [18], and SCIDX1 [13],were examined. A carrier status was established in 19 females (7 XLA, 6 WAS, 6 SCIDX1) and excluded in 29 ( 11 XLA, 11 WAS, 7 SCIDX1). Only in 2 cases (4%) the assay was not informative.
Cell Lineage↗
Vaccination against Haemonchus contortus with denatured forms of the protective antigen H11.
As part of a systematic examination of the protective epitopes on H11, groups of sheep were vaccinated with preparations of purified H11 used untreated (group A), or progressively denatured (linearized) by incubation with sodium dodecyl sulphate (SDS) (group B) or by boiling with SDS in the presence of dithiothreitol (group C). All the sheep developed antibodies which bound to the untreated H11. When challenged with 10,000 infective larvae of Haemonchus contortus the mean levels of protection relative to the mean values for adjuvant controls were 99.8%, 85% and 79% for faecal egg counts and 95%, 79% and 54% for worm burden at post-mortem for groups A, B and C respectively. The H11-specific antibodies inhibited the microsomal aminopeptidase activity of H11 in vitro up to 80%. The levels of inhibition by sera from individual animals correlated with levels of protection with r2, of 0.69-0.87.
Aminopeptidases↗
Nicotiana plumbaginifolia hlg mutants have a mutation in a PHYB-type phytochrome gene: they have elongated hypocotyls in red light, but are not elongated as adult plants.
Two new allelic mutants of Nicotiana plumbaginifolia have been isolated which display a hypocotyl which is long (hlg) when seedlings are grown in continuous white light (W). This can be accounted for by the decreased response to red light (R) of the hypocotyl elongation rate in these mutants. Responses to other wavelengths are unaffected in the mutants. When grown in white light, mature hlg mutants are not elongated with respect to the wild-type; they also bolt and flower later. The shade-avoidance responses to red/far red ratio (R:FR) are intact in these mutants. Both mutants are deficient in phyB-like polypeptide that is immunodetectable in the wild-type; both have wild-type levels of a phyA-like polypeptide. These alleles are inherited in a partially dominant manner, and correspond to single-base missense mutations in a gene highly homologous to N. tabacum PHYB, which codes for a phytochrome B-type photoreceptor. One allele, hlg-1, has an introduced amino acid substitution; this may define a residue essential for phytochrome protein stability. The other allele, hlg-2, has a stop codon introduced C-terminal to the chromophore binding domain. As these phyB mutants are unaffected in shade-avoidance responses, but deficient in perception of R, it is concluded that the phyB absent in these mutants is responsible for R perception in the N. plumbaginifolia seedling, but is not a R:FR sensor in light-grown plants.
Amino Acid Sequence↗
An evaluation of dipstick-dot immunoassay in the detection of antibodies to HIV-1 and 2 in Zimbabwe.
There is a need, in many developing countries, for simple and inexpensive HIV serology tests for use at the district level of health care. The Programme for Appropriate Technology in Health has developed a simple dipstick ELISA to detect antibodies to HIV-1 and 2, at a cost considerably lower than current ELISAs, which requires no specialized washing or reading equipment. In order to evaluate this dipstick under local conditions we used a panel of 546 sera selected from frozen stocks maintained by the Zimbabwe AIDS Prevention Project in Harare, Zimbabwe. Prior to storage, the sera had been tested by Abbott recombinant peptide HIV-1 and 2 ELISA and Enzygnost synthetic peptide HIV-1 and 2 ELISA. The panel included sera that were positive by both (including symptomatics and asymptomatics), negative by both, and sera showing discrepant test results. The panel was not representative of a "normal' batch of sera in Zimbabwe, and in particular included an abnormally high number of sera showing discrepant results. Thawed sera were retested using the Abbott recombinant peptide HIV-1 and 2 ELISA and concurrently with the synthetic peptide ICL-Dipstick ELISA. Both the sensitivity and specificity of the ICL Dipstick exceeded 99% when using sera that were positive or negative in all 3 plate ELISAs as the gold standard. When using sera that gave discrepant results between the two pre-storage ELISAs, most results with the ICL Dipstick concurred with findings from other test systems, including Western blot and p24 antigen detection. Considering the accuracy, low cost and case of operation of the ICL Dipstick ELISA, this test can be recommended for use for the rapid detection of antibodies to HIV at district level in developing countries.
Enzyme-Linked Immunosorbent Assay↗
Preventive care for patients following myocardial infarction. The Wessex Research Network (WReN).
OBJECTIVE: We aimed to assess general practice care for patients following a myocardial infarction (MI). METHOD: A structured review was carried out of general practice records of patients identified from hospital administration data. A total of 266 survivors following MI were identified from the discharge data of 13 hospitals in Southern England and registered with 71 GPs belonging to the Wessex Research Network. Median time since hospital discharge was 2.1 years. The main outcome measures were the provision of appropriate preventive care, including cardiac rehabilitation, drug therapy, and lifestyle advice for modifiable risk factors. RESULTS: Basic care was provided to nearly all patients; 253 (95.1%, 95% Cl 91.8-97.4) had blood pressure documented after their MI, 216 of 234 patients eligible for aspirin (92.3%; 88.1-95.4) had been recommended treatment, and the provision of advice on smoking cessation was documented for 27 of 33 continuing smokers (81.8%; 64.5-93.0). However, only 73 of 236 patients eligible to attend a structured rehabilitation programme (30.9%; 25.0-36.8) were documented as having received rehabilitation. Of 89 patients with heart failure following MI, 33 (37.1%; 27.1-48.0) had no record of having been offered treatment with an ACE inhibitor. Total cholesterol measurement was documented for only 144 patients (54.1%; 48.1-60.1). We estimate that there is still the potential to prevent between 4 and 9 deaths in this group of 266 surviving patients in the next 2 years by further improving the quality of follow-up care. CONCLUSIONS: Preventive care in patients with proven ischaemic heart disease in general practice remains haphazard, even among doctors enthusiastic to participate in research and to audit their quality of care. As general practitioners we should ensure that we are providing high quality preventive care to patients with clinical disease before we focus on the even more demanding task of primary prevention.
Adult↗
Caffeine intake in relation to the risk of primary cardiac arrest.
We conducted a population-based case-control study in King County, WA, to evaluate the association between usual caffeine intake and primary cardiac arrest. We identified primary cardiac arrest cases (N = 362) without a history of clinical heart disease or major comorbidity through paramedic incident reports during the period 1988-1994. We identified controls (N = 581), individually matched to cases on age (+/-7 years) and gender and meeting the same general health criteria, through random digit dialing. We interviewed the spouses of cases and controls to obtain information on usual caffeine intake from coffee, tea, and cola during the prior year. After adjusting for cigarette smoking and other risk factors, we observed little association between daily consumption of the caffeine equivalent of fewer than 5 cups per day of drip coffee (< 687 mg per day) and primary cardiac arrest. High usual caffeine consumption (> or = 687 mg per day) was associated with a modestly elevated risk of primary cardiac arrest [odds ratio = 1.44; 95% confidence interval (CI) = 0.82-2.53]. The elevated risk associated with high caffeine consumption appeared to be restricted to never-smokers (odds ratio for > or = 687 mg per day = 3.2; 95% CI = 1.3-8.1).
Adult↗
Hepatitis C virus antibodies in systemic lupus erythematosus.
To determine the prevalence and significance of serum antibody to hepatitis C virus (HCV) in patients with systemic lupus erythematosus (SLE), we measured serum antibodies to HCV by enzyme-linked immunosorbent (ELISA) and by Abbott MATRIX Immunoblot assays in 42 patients with SLE, a condition associated with hypergammaglobulinemia. We used the polymerase chain reaction (PCR) to identify patients with HCV viremia. Five of 42 (11.9%) patients were seropositive for anti-HCV by ELISA; of these only two were positive by PCR; only one of three patients seropositive by Immunoblot assay was also positive by PCR. Both ELISA and the Immunoblot assays may be falsely positive for ongoing HCV infection in patients with SLE. Suspected HCV infection should be confirmed with PCR for serum HCV RNA in these patients.
False Positive Reactions↗
Antibody to Haemophilus ducreyi among trucking company workers in Kenya.
BACKGROUND AND OBJECTIVES: To determine the prevalence, correlates, and incidence of Haemophilus ducreyi antibodies, a cohort of East African trucking company employees was evaluated. STUDY DESIGN: Human immunodeficiency virus (HIV)-1-seronegative men working in six trucking companies in Mombasa, Kenya, were evaluated with a questionnaire and serologic testing for antibodies to H. ducreyi and other sexually transmitted pathogens. Men who were initially H. ducreyi seronegative were retested at 1 year of follow-up. RESULTS: The H. ducreyi seroprevalence among 501 men at enrollment was 26.5%. Seropositivity was significantly associated with older age, married status, years of active sex life, number of sex partners in the past year, history of unprotected sex with a prostitute in the past year, and history of alcohol intake (all P values < 0.01). Occupational travel for more than 14 days per month was also significantly associated with H. ducreyi seropositivity (odds ratio [OR] 2.1, 95% confidence interval [CI] 1.3-3.2). Using multivariate analysis, H. ducreyi seropositivity was independently associated with age, married status, history of sex with a prostitute, and history of alcohol intake. Presence of H. ducreyi antibodies was significantly associated with seropositivity to the other major genital ulcerative pathogens, Treponema pallidum (OR 4.3, 95% CI 2.2-8.3), herpes simplex virus type 2 (OR 4.9, 95% CI 2.0-11.5), and Chlamydia trachomatis (OR 3.2, 95% CI 1.5-6.9). These associations remained significant after adjusting for demographic and exposure variables. The incidence of seroconversion to H. ducreyi antibodies was 3.6 per 100 person years. CONCLUSIONS: Serologic evidence of H. ducreyi infection was common among male trucking company employees. H. ducreyi seropositivity is an objective marker of high-risk behavior and is associated with serologic evidence of other ulcerative sexually transmitted diseases.
Adolescent↗
Differential induction of cytotoxicity and apoptosis by influenza virus strains of differing virulence.
Two influenza viruses of differing virulence, clone 7a (virulent for humans and ferrets) and A/Fiji (attenuated for both species), induced differential levels of cytotoxicity (as measured by release of lactate dehydrogenase from cells) and apoptosis (as determined by altered nuclear morphology or flow cytometry) in MDCK and U-937 cells. Clone 7a induced more apoptosis and cytotoxicity than A/Fiji, despite the fact that its infectious virus yields were similar to or less than those for A/Fiji. This indicates a greater capacity of clone 7a to induce the two phenomena. Nevertheless the replication process was clearly essential, since UV-irradiated virus induced little or no apoptosis, and apoptosis occurred as a late event post-infection. The possible relevance of these findings to destruction of host cells by influenza virus in vivo is discussed.
Animals↗
Antagonistic but complementary actions of phytochromes A and B allow seedling de-etiolation.
Using dichromatic radiation, we show that the actions of phytochromes A and B (phyA and phyB) in Arabidopsis thaliana are antagonistic in mediating red and far-red radiation effects on seedling de-etiolation and yet act in a complementary manner to regulate de-etiolation, irrespective of spectral composition. At low phytochrome photoequilibria inhibition of hypocotyl extension was strong, because of the action of a far-red high-irradiance response mediated by phyA. At high phytochrome photoequilibria inhibition of hypocotyl extension was also strong, because of the action of phyB. At intermediate photoequilibria hypocotyl inhibition was less strong. In their natural environment, this dual action will strongly retard hypocotyl growth and promote cotyledon opening and expansion both in open daylight and under dense vegetation. Overlapping action by phyA and phyB will substantially promote de-etiolation in sparse vegetation. The antagonistic and complementary actions of phyA and phyB, therefore, allow the optimum regulation of seedling growth after emergence from the soil.
Arabidopsis↗
Guarding paediatricians against allegations of assault.
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Child↗
Validation of the paediatric appropriateness evaluation protocol in British practice.
The reliability and validity of the North American paediatric appropriateness evaluation protocol (PAEP) for use in paediatric practice in Britain was tested. The protocol was applied to 418 case records of consecutive emergency admissions to three Yorkshire district general hospitals. The PAEP ratings were then compared with a clinical consensus opinion obtained from two expert panels. Altogether 32% of the admissions were rated inappropriate by the PAEP and 36% by the panels. Validity of the PAEP, as measured by agreement beyond chance with the expert panel rating, was only moderate with a kappa of 0.29 (95% confidence interval 0.11 to 0.47). The PAEP has limited validity for evaluating British paediatric practice. Utilisation review instruments developed in differing clinical cultures should be used with caution until shown to be valid for the practice setting under review.
Adolescent↗
Climate and aeroallergen levels in asthma: a 12 month prospective study.
BACKGROUND: There is evidence to suggest that changes in weather and airborne fungal spore and pollen counts may affect asthma symptoms. METHODS: The relationship between climate, airborne fungal spore, and pollen counts and peak expiratory flow rate (PEFR) and asthma symptoms was prospectively investigated in a population of mild to moderate asthmatic subjects in Blenheim, New Zealand. Subjects recorded twice daily PEFR measurements and asthma symptom scores for up to one year. Spore and pollen counts were measured two hourly and meteorological data were measured hourly. Individual, within person, multiple linear regression analyses were conducted, adjusting for auto-correlation. A random effects model was assumed for the individual regression co-efficients and weighted estimates of the mean of these coefficients were obtained by the method of maximum likelihood. RESULTS: One hundred and thirty nine asthmatic patients (60% atopic) aged 17-80 years completed the study. Of the weather variables, only temperature showed a small but consistent association with PEFR. The mean rise in PEFR for an 8.8 degrees C (2 SD) change in temperature was 0.78% (95% CI 0.44% to 1.11%), approximately 3.0 l/min. There was a weak association between days of high basidiospore counts and increased nocturnal wakening and reliever medication use. Pollen counts showed no consistent association with either PEFR or asthma symptoms. CONCLUSIONS: The results of this study suggest that the effects of weather and aeroallergens on PEFR and asthma symptoms in this population are small, and that other causes need to be sought to account for variations in asthma severity and exacerbations.
Adolescent↗