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Biomedical subjects

D Evans

Publications and source records attributed to D Evans.

At least 109 records · Page 6Linked to original sources

Validation of antroduodenal motility measurements made by echo-planar magnetic resonance imaging.

Echo planar imaging, a development of magnetic resonance imaging, can produce snapshot images of the stomach and antroduodenal segment in as little as 64 msec and can be more useful than conventional techniques when assessing motility. The aim of this study was to compare antroduodenal motility measured by simultaneous perfused tube manometry and echo planar imaging. Ten volunteers were studied following the ingestion of 500 mL water or 500 mL porridge. Antroduodenal images, with acquisition times of 130 msec, were taken at 3-sec intervals, synchronized with motility traces and presented as a split-screen video. This allowed direct visual comparison of gastric wall movement and motility to be made. Contractions were confined to either the stomach or the duodenum or propagated across the antroduodenal segment. Over 4550 images were available for analysis. A larger number of propagated contractions were recorded with echo planar imaging in both water (P = 0.03) and food (P = 0.02) groups, whereas manometry detected a greater number of isolated duodenal pressure waves (P = 0.005). The contraction rate for water and food studies was similar, but direct visualization indicated that the manometric technique under-detected propagated events. The ability of echo planar imaging to record antroduodenal contractile activity provides a new insight into the role of occlusive and nonocclusive contractions during gastric emptying.

Adolescent↗

Developing strategies to control schistosomiasis morbidity in nonenrolled school-age children: experience from Egypt.

Schistosomiasis is a major health problem in school-age children in much of the tropical world. They harbour the most intense infections for both Schistosoma mansoni and S. haematobium. In Egypt, the Ministry of Health and Population (MOHP) has implemented a successful school-based treatment programme in which children are screened and those found to be infected treated with praziquantel. High nonenrolment rates in some rural areas have a negative impact on the coverage of this programme and on its ability to reduce transmission in the community. The main aim of our study was to introduce and test a simple intervention to extend treatment to nonenrolled children using the routine MOHP schistosomiasis treatment programme. Twenty villages or ezbas in Tamia district, Fayoum governorate, with 8 schools and 1901 nonenrolled children were targeted. 88.5% of nonenrolled children attended schools to avail themselves of treatment. Coverage rates were significantly higher for girls (P < 0.001). These results are important for countries where schistosomiasis is endemic. They suggest that offering interventions in schools may not only improve the health of school attendees but also be an affordable way of extending services to out-of-school children.

Adolescent↗

How long to wait for a response to clozapine: a comparison of time course of response to clozapine and conventional antipsychotic medication in refractory schizophrenia.

This study compared the time course to clinical improvement with clozapine and with conventional antipsychotic medications. A double-blind trial compared clozapine and haloperidol in patients with schizophrenia who were refractory to conventional antipsychotic medication and were hospitalized for 30 to 364 days at 15 Veteran Affairs medical centers during the year before study entry. Patients in the original study were randomly assigned to haloperidol or clozapine and followed for 12 months, at maximum tolerable doses. Patients who completed a full year of treatment with clozapine (n = 122), or with either haloperidol or another conventional antipsychotic medication (n = 123) and who also completed the 9- or 12-month assessment were included. Response to treatment was defined as 20 percent improvement on standard scales of symptoms and quality of life at the latter of the 9- or 12-month interviews. More patients assigned to clozapine achieved 20 percent improvement in symptoms at each followup. Among patients who did not improve at 6 weeks, 3 months, or 6 months, there were no significant differences between clozapine and comparison patients in outcomes at 1 year. Among patients who did improve, maintenance of that improvement also did not differ between the groups at 1 year on symptom measures. Maintenance of improvement in quality of life at 1 year was significantly greater for clozapine patients who had improved at 6 months (p < 0.04). Significant differential symptom response to clozapine occurred exclusively during the first 6 weeks of treatment.

Adult↗

Crystallization and preliminary X-ray diffraction analysis of a biologically active fragment of CD55.

Crystals have been grown of two of the domains of CD55. This is the first report of crystallization of a short consensus repeat (SCR) domain containing protein. CD55 is a widely expressed polymorphic glycoprotein, which functions as a complement regulator by inhibiting assembly and promoting destruction of C3 and C5 convertases. As a key regulator of complement, CD55 is implicated in the hyperacute rejection of xenografts from pigs into primates. It is also commonly hijacked as a receptor by viruses (e.g. medically important echoviruses and coxsackieviruses) and bacterial pathogens (e.g. certain pathogenic strains of Escherichia coli). Here, crystallization of a virus-binding fragment expressed in yeast, consisting of two of the four extracellular SCR domains of CD55, is reported. The recombinant domains have been crystallized in 30% polyethylene glycol (PEG), 0.2 M sodium acetate, 0.1 M sodium acetate trihydrate pH 4.6 using the sitting-drop vapour-diffusion method. Two crystal forms are observed (orthorhombic and monoclinic) and a native data set to 1.65 A resolution has been collected from the monoclinic form at the Synchrotron Radiation Source, Daresbury, UK.

CD55 Antigens↗

A comparison of laser Doppler flowmetry with other methods of assessing the vitality of traumatised anterior teeth.

Laser Doppler flowmetry is a non-invasive electrooptical technique which allows the semi-quantitative recording of pulpal blood flow. This study aimed to determine the reliability (measured as the sensitivity and specificity) of laser Doppler flowmetry as a method of assessing the vitality of traumatised anterior teeth, and to compare it with standard pulpal diagnostic tests. Recordings of pulpal blood flow were taken from 67 non-vital anterior teeth (55 patients), where the pulpal status was confirmed by pulpectomy. For comparison, recordings were also taken from 84 vital anterior teeth (84 patients). Analysis of the recordings allowed diagnostic criteria to be developed which gave the technique a sensitivity and specificity of 1.0 for this sample. None of the other standard pulpal diagnostic methods tested was as reliable. This was usually due to low sensitivities, which ranged between 0.92 for sensibility testing with ethyl chloride down to 0.36 for periapical radiolucency and 0.16 for a history of pain. Laser Doppler flowmetry was found to be a reliable method of assessing the pulpal status of traumatised anterior teeth, although it is technique-sensitive and time-consuming to use.

Adolescent↗

Acute health effects of the Sea Empress oil spill.

STUDY OBJECTIVE: To investigate whether residents in the vicinity of the Sea Empress tanker spill suffered an increase in self reported physical and psychological symptoms, which might be attributable to exposure to crude oil. DESIGN: Retrospective cohort study; postal questionnaire including demographic details, a symptom checklist, beliefs about health effects of oil and the Hospital Anxiety and Depression and SF-36 mental health scales. SETTING: Populations living in four coastal towns on the exposed south Pembrokeshire coast and two control towns on the unexposed north coast. PATIENTS: 539 exposed and 550 unexposed people sampled at random from the family health services authority age-sex register who completed questionnaires. MAIN RESULTS: Adjusted odds ratios for self reported physical symptoms; scores on the Hospital Anxiety and Depression and SF-36 mental health scales, in 1089 people who responded out of a possible 1585 (69%). CONCLUSIONS: Living in areas exposed to the crude oil spillage was significantly associated with higher anxiety and depression scores, worse mental health; and self reported headache (odds ratio = 2.35, 95% CI 1.56, 3.55), sore eyes (odds ratio = 1.96, 95% CI 1.06, 3.62), and sore throat (odds ratio = 1.70, 95% CI 1.12, 2.60) after adjusting for age, sex, smoking status, anxiety, and the belief that oil had affected health. People living in exposed areas reported higher rates of physical and psychological symptoms than control areas. Symptoms significantly associated with exposure after adjustment for anxiety and health beliefs were those expected from the known toxicological effect of oil, suggesting a direct health effect on the exposed population.

Adult↗

Airway epithelial tight junctions and binding and cytotoxicity of Pseudomonas aeruginosa.

The role of tight junctions in the binding and cytoxicity of Pseudomonas aeruginosa to apical or basolateral membranes of lung airway epithelial cells was tested with fluorescence microscopy on living cells. Binding of noncytotoxic P. aeruginosa strain O1 was assessed with P. aeruginosa that expressed green fluorescent protein. Binding of cytotoxic P. aeruginosa strain 6206 was assessed with FITC-labeled P. aeruginosa; cytotoxicity was determined from nuclear uptake of the impermeant dye propidium iodide. The role of direct contact of P. aeruginosa to epithelial cells was tested with filters with small (0.45-micrometer) or large (2.0-micrometer) pores. High transepithelial resistance (R(t)) Calu-3 and cultured bovine tracheal monolayers (R(t) > 1,000 Omega. cm(2)) bound P. aeruginosa very infrequently (<1 P. aeruginosa/100 cells) at the apical membrane, but P. aeruginosa bound frequently to cells near "free edges" at holes, wounds, islands, and perimeters; cytotoxicity required direct interaction with basolateral membranes. Wounded high R(t) epithelia showed increased P. aeruginosa binding and cytotoxicity at the free edges because basolateral membranes were accessible to P. aeruginosa, and dead and living cells near the wound bound P. aeruginosa similarly. Compared with high R(t) epithelia, low R(t) CFT1 (R(t) = 100-200 Omega. cm(2)) and EGTA-treated Calu-3 monolayers were 25 times more susceptible to P. aeruginosa binding throughout the monolayer. Cytotoxicity to CFT1 cells (throughout the confluent monolayer, not only at the free edge) occurred after a shorter delay (0.25 vs. 2.0 h) and then five times faster than to Calu-3 cells, indicating that the time course of P. aeruginosa cytotoxicity may be limited by the rate of gaining access through tight junctions and that this occurred faster in low R(t) than in high R(t) airway epithelia. Cytotoxicity appeared to occur in a sequential process that led first to a loss of fura 2 and a later uptake of propidium iodide. P. aeruginosa bound three times more frequently to regions between cells (tight junctions?) than to cell membranes of low R(t) CFT1 cells.

Animals↗

Self-regulating childhood asthma: a developmental model of family change.

This article tests a model of self-regulatory development in which families' cognitive beliefs and behavioral skills for managing asthma symptoms emerge in four successive phases: asthma symptom avoidance, asthma acceptance, asthma compliance, and asthma self-regulation. Confirmatory factor analyses revealed that the hypothesized multiphase model provided the best factorial fit for phase items. Subsequent Guttman analyses of the families' phase scores revealed a high degree of sequential ordering. Finally, trend analyses of family phase differences revealed a significant negative linear relation with measures of asthma severity and a significant positive linear relation with physician care and concern measures, asthma regulatory measures, and beliefs in Western biomedical practices. Despite receiving primary care for asthma at a major metropolitan university hospital, 83% of the sample were classified as precompliant. The phase model of asthma self-regulatory development offers a qualitative approach for investigating the psychological determinants of asthma self-regulatory behavior.

Adaptation, Psychological↗

The shrinking renal replacement therapy "break-even" point.

BACKGROUND: This study examines the current cost of live donor (LD) transplantation at our institution, and compares it with that of dialysis. METHODS: The study population consisted of 184 consecutive adult recipients of laparoscopically procured LD kidney transplants. Cost-containment measures instituted during this series included elimination of routine postoperative antilymphocyte induction and an accelerated discharge clinical pathway with planned discharge of the recipient on postoperative day (POD) 2. Costs of the transplants to Medicare were estimated from hospital charges, readmission rates, and immunosuppressant usage. These were compared with published costs of dialysis to Medicare in terms of a fiscal transplant-dialysis break-even point. RESULTS: Kaplan-Meier patient and graft survival rates at 1 year were 97 and 93%, respectively. Among patients followed for at least 90 days and treated with no induction and either cyclosporine-mycophenolate mofetil or tacrolimus-mycophenolate mofetil, acute rejection rates were low (27.6 and 13.9%, respectively). In the last 124 patients, 32.3% were discharged by POD 3 and 71.8% by POD 6, with corresponding mean transplant hospital charges (excluding organ acquisition) of $11,873 and $17,350, respectively. The 30-day readmission rate for patients discharged on the accelerated pathway by POD 3 was only 16%. The least expensive subgroup in the present study (30% of patients) was that of patients discharged by POD 6 and not readmitted during the first year; the break-even point with dialysis costs was calculated as 1.7 years after the transplant. CONCLUSIONS: The cost of LD transplants can be safely reduced by elimination of routine postoperative anti-lymphocyte immune induction and by an early discharge clinical pathway. Uncomplicated LD kidney transplants, meaning those with a short length of stay in the hospital after transplantation and no need for readmission within the first year, accrue savings over dialysis within 2 years.

Adolescent↗

Allosteric regulation and substrate channeling in multifunctional pyrimidine biosynthetic complexes: analysis of isolated domains and yeast-mammalian chimeric proteins.

The initial steps of pyrimidine biosynthesis in yeast and mammals are catalyzed by large multifunctional proteins of similar size, sequence and domain structure, but appreciable functional differences. The mammalian protein, CAD, has carbamyl phosphate synthetase (CPSase), aspartate transcarbamylase (ATCase) and dihydroorotase (DHOase) activities. The yeast protein, ura2, catalyzes the first two reactions and has a domain, called pDHO, which is homologous to mammalian DHOase, but is inactive. In CAD, only CPSase is regulated, whereas both CPSase and ATCase in the yeast protein are inhibited by UTP. These functional differences were explored by constructing a series of mammalian yeast chimeras. The isolated ATCase domain is catalytically active, but is not regulated. The inclusion of the yeast sequences homologous to the mammalian regulatory domain (B3) and the intervening pDHO domain did not confer regulation. Chimeric proteins in which the homologous regions of the mammalian protein were replaced by the corresponding domains of ura2 exhibited full catalytic activity, as well regulation of the CPSase, but not the ATCase, activities. The yeast B3 subdomain confers UTP sensitivity on the mammalian CPSase, suggesting that it is the locus of CPSase regulation in ura2. Taken together, these results indicate that there are regulatory site(s) in ura2. Channeling is impaired in all the chimeric complexes and completely abolished in the chimera in which the pDHO domain of yeast is replaced by the mammalian DHO domain.

Allosteric Regulation↗

Utility of the apolipoprotein E genotype in the diagnosis of Alzheimer's disease. Alzheimer's Disease Centers Consortium on Apolipoprotein E and Alzheimer's Disease.

BACKGROUND: The epsilon4 allele of the gene encoding apolipoprotein E (APOE) is strongly associated with Alzheimer's disease, but its value in the diagnosis remains uncertain. METHODS: We reviewed clinical diagnoses and diagnoses obtained at autopsy in 2188 patients referred to 1 of 26 Alzheimer's disease centers for evaluation of dementia. The sensitivity and specificity of the clinical diagnosis or the presence of an APOE epsilon4 allele were calculated, with pathologically confirmed Alzheimer's disease used as the standard. The added value of the APOE genotype was estimated with pretest and post-test probabilities from multivariate analyses to generate receiver-operating-characteristic curves plotting sensitivity against the false positive rate. RESULTS: Of the 2188 patients, 1833 were given a clinical diagnosis of Alzheimer's disease, and the diagnosis was confirmed pathologically in 1770 patients at autopsy. Sixty-two percent of patients with clinically diagnosed Alzheimer's disease, as compared with 65 percent of those with pathologically confirmed Alzheimer's disease, had at least one APOE epsilon4 allele. The sensitivity of the clinical diagnosis was 93 percent, and the specificity was 55 percent, whereas the sensitivity and specificity of the APOE epsilon4 allele were 65 and 68 percent, respectively. The addition of information about the APOE genotype increased the overall specificity to 84 percent in patients who met the clinical criteria for Alzheimer's disease, although the sensitivity decreased. The improvement in specificity remained statistically significant in the multivariate analysis after adjustment for differences in age, clinical diagnosis, sex, and center. CONCLUSIONS: APOE genotyping does not provide sufficient sensitivity or specificity to be used alone as a diagnostic test for Alzheimer's disease, but when used in combination with clinical criteria, it improves the specificity of the diagnosis.

Aged↗

Efficacy of meningococcal vaccine and barriers to vaccination.

CONTEXT: Use of the quadrivalent meningococcal vaccine for control of outbreaks has increased in recent years, but the efficacy of meningococcal vaccine during mass vaccination campaigns in US civilian populations has not been assessed. OBJECTIVES: To evaluate the efficacy of the quadrivalent meningococcal vaccine against serogroup C meningococcal disease in a community outbreak setting and to evaluate potentially modifiable barriers to vaccination in an area with persistent meningococcal disease following immunization. DESIGN: Matched case-control study of vaccine efficacy using cases of serogroup C meningococcal disease in persons eligible for vaccination during mass vaccination campaigns. Control patients were matched by neighborhood and age. The control group was used to identify possible barriers to vaccination. SETTING: Gregg County, Texas, population 106076, from 1993 to 1995. PARTICIPANTS: A total of 17 case patients with serogroup C meningococcal disease eligible for vaccine and 84 control patients. MAIN OUTCOME MEASURES: Vaccine efficacy and risk factors associated with nonvaccination. RESULTS: Vaccine efficacy among 2- to 29-year-olds was 85% (95% confidence interval, 27%-97%) and did not change in bivariate analyses with other risk factors that were significant in univariate analysis. Among control patients, older age was strongly associated with nonvaccination; vaccination rates for 2- to 4-year-olds, 5- to 18-year-olds, and 19- to 29-year-olds were 67%, 48%, and 20%, respectively (chi2 for linear trend, P=.01). CONCLUSIONS: The meningococcal polysaccharide vaccine was effective against serogroup C meningococcal disease in this community outbreak. Although specific barriers to vaccination were not identified, older age was a risk factor for nonvaccination in the target population of 2- to 29-year-olds. In future outbreaks, emphasis should be placed on achieving high vaccination coverage, with special efforts to vaccinate young adults.

Adolescent↗

Expression of type III hyperlipoproteinemia in patients homozygous for apolipoprotein E-2 is modulated by lipoprotein lipase and postprandial hyperinsulinemia.

Type III hyperlipoproteinemia (HLP) is a multifactorial disorder associated with homozygosity for the apolipoprotein (apo) E-2 allele. Factors which may promote the development of HLP include lipoprotein lipase (LPL) and hyperinsulinemia. These factors were investigated in eight patients with type III HLP and in nine normolipidemic controls. In vitro the interaction of apoE with LPL was analyzed in cell binding assays. All type III HLP patients showed delayed triglyceride (TG) clearance and remnant lipoprotein accumulation in an oral fat tolerance test. Normolipidemic apoE-2/2 controls revealed normal TG clearance comparable to apoE3/3 controls. HLP patients showed lower LPL activity and mass than controls. Analysis of the LPL gene revealed an Asn 291-->Ser mutation in three patients and a -93 T-G substitution combined with an Asp 9-->Asn mutation in one control subject. In addition to LPL abnormalities, postprandial hyperinsulinemia was observed in five out of eight patients. In vitro LPL compensated the defective function of apoE-2 in mediating remnant lipoprotein binding to cells. In summary, seven out of eight patients with type III HLP showed LPL abnormalities and/or postprandial hyperinsulinemia. Together with the in vitro data these findings support a coordinate effect of apoE and LPL for the manifestation of type III HLP. Hyperinsulinemia appears to be an additional factor important for disease expression.

Adult↗

To tube or not to tube: do infants and children need post-laparotomy gastric decompression?

The purpose of this study was to evaluate the role of nasogastric (NG) decompression after laparotomy in pediatric surgical practice: 94 children who underwent abdominal surgery by a single surgeon were consecutively prospectively managed without postoperative NG tubes. Patients with either bowel obstruction or intra-abdominal infection were excluded from the study. These children were compared with 94 retrospective, matched controls who were routinely managed with postoperative NG decompression by the same surgeon. Data were analyzed with regard to patient, operative, and outcome variables. There was no difference in gender, age (3.8 +/- 0.5 vs 3.5 +/- 0.4 years, P > 0.7), or postoperative complications (P > 0.8) between the two groups. However, there was a higher incidence of postoperative vomiting (22% vs 11%, P > 0.05) in the children who did not have postoperative NG decompression. Nevertheless, a significant decrease in time to first feed, first stool, and discharge was noted in the group of patients managed without NG tubes (P < 0.05). NG decompression thus need not be routinely used in the pediatric patient undergoing abdominal surgery, as there is no difference in postoperative complications and the hospital stay is shortened.

Child, Preschool↗

Differentiation between human and animal isolates of Cryptosporidium parvum using molecular and biological markers.

Isolates of Cryptosporidium parvum obtained from infected humans, calves and lambs were typed using arbitrary primed polymerase chain reaction (AP-PCR) and isoenzyme electrophoresis. All animal isolates tested (n = 17) showed similar profiles in AP-PCR and isoenzyme typing. In AP-PCR assays, 9 out of 15 human isolates showed a distinct "human" profile while the remaining 6 isolates showed the "animal" profile. In isoenzyme typing, 5 human isolates which had shown "human" profiles in AP-PCR demonstrated a unique isoenzyme banding pattern, while 2 isolates which had shown "animal" profiles in AP-PCR gave the "animal" banding pattern. In a murine model of infection, all four animal isolates tested were highly infective but only one of four human isolates identified as "human" type in the AP-PCR and isoenzyme typing systems was infective. The good correlation between the data from the different typing systems supports the hypothesis that there are genetically distinct human and animal populations of C. parvum.

Animals↗

Identification of a novel gene involved in pilin glycosylation in Neisseria meningitidis.

The pili of Neisseria meningitidis are a key virulence factor, being major adhesins of this capsulate organism that contribute to specificity for the human host. Recently it has been reported that meningococcal pili are post-translationally modified by the addition of an O-linked trisaccharide, Gal (beta1-4) Gal (alpha1-3) 2,4-diacetimido-2,4,6-trideoxyhexose. Using a set of random genomic sequences from N. meningitidis strain MC58, we have identified a novel gene homologous to a family of glycosyltransferases. A plasmid clone containing the gene was isolated from a genomic library of N. meningitidis strain MC58 and its nucleotide sequence determined. The clone contained a complete copy of the gene, here designated pglA (pilin glycosylation). Insertional mutations were constructed in pglA in a range of meningococcal strains with well-defined lipopolysaccharide (LPS) or pilin-linked glycan structures to determine whether pglA had a role in the biosynthesis of these molecules. There was no alteration in the phenotype of LPS from pglA mutant strains as judged by gel migration and the binding of monoclonal antibodies. In contrast, decreased gel migration of the pilin subunit molecules of pglA mutants was observed, which was similar to the migration of pilins of galE mutants of same strains, supporting the notion that pglA is a glycosyltransferase involved in the biosynthesis of the pilin-linked trisaccharide structure. The pglA mutation, like the galE mutation reported previously, had no effect on pilus-mediated adhesion to human epithelial or endothelial cells. Pilin from pglA mutants were unable to bind to monospecific antisera recognizing the Gal (beta1-4) Gal structure, suggesting that PglA is a glycosyltransferase involved in the addition of galactose of the trisaccharide substituent of pilin.

Amino Acid Sequence↗

A school-based schistosomiasis and intestinal helminthiasis control programme in Nigeria: acceptability to community members.

In a population with high prevalences in schoolchildren of infection with hookworm (32.4%), Ascaris (22.9%) and Trichuris (2.5%), visible haematuria (17.9%), micro-haematuria (17%) and proteinuria (47.3%), the knowledge about transmission of schistosomiasis and acceptability of a school-based control programme were assessed. The community perceived schistosomiasis (80.6%) and intestinal helminthiasis (66.5%) as important health problems in school-age children and most people would prefer placement of the control programme in school because it would eliminate transportation cost to the health facility. They welcomed the idea of using teachers for detection of infection and drug administration. The health staff, on the other hand, were willing to work with teachers, but emphasized that teachers should be limited to organizational and supervisory roles while they do tests and administer the drug. This view was also shared by the officials in the state ministries of health and education.

Adolescent↗