Biomedical subjects

A Heath

Publications and source records attributed to A Heath.

At least 37 records · Page 2Linked to original sources

PubMed2000

A double-blind, randomized, placebo-controlled dose-ranging study to evaluate the efficacy of alosetron in the treatment of irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome is a common gastrointestinal disorder characterized by abdominal pain and discomfort and altered bowel habit. Antagonism at the 5-HT3 receptor may be of benefit in the treatment of irritable bowel syndrome. AIMS: To evaluate the effect of 12 weeks of treatment with alosetron, a 5-HT3 receptor antagonist at doses of 0.1 mg b.d., 0.5 mg b.d. and 2 mg b.d. in irritable bowel syndrome patients. METHODS: A double-blind, placebo-controlled, parallel-group study with a 2-week screening and a 12-week treatment period was conducted. A total of 462 patients (335 female) recorded details of the severity of their abdominal pain, and bowel function daily on a diary card throughout the study. At monthly clinic visits patients recorded the severity of their abdominal pain/discomfort and diarrhoea on a visual analogue scale. RESULTS: In the total population and in the female subpopulation (but not in males) alosetron 2 mg b.d. significantly increased the proportion of pain-free days and decreased the visual analogue scale score for diarrhoea compared with placebo. Alosetron at doses of 0.5 mg b.d. and 2 mg b.d. led to a significant hardening of stool, and a reduction in stool frequency in the total population. CONCLUSION: Alosetron at a dose of 2 mg b.d. is an effective treatment for female patients with irritable bowel syndrome.

Adolescent↗

PubMed2000

Calibration of HCV working reagents for NAT assays against the HCV international standard. The Collaborative Study Group.

BACKGROUND AND OBJECTIVES: Five HCV RNA reference reagents, the Paul Ehrlich Institut (PEI) reference 75, the National Institute for Biological Standards and Control (NIBSC) reagent 96/586, the Central Laboratory of the Netherlands Red Cross Blood Transfusion Service (CLB) Pelispy HCV RNA run control S2001, the Istituto Superiore di Sanità (ISS) reagent 0498 and the CBER panel member No. 1, were calibrated against the WHO International Standard, 96/790. MATERIALS AND METHODS: The reference materials were calibrated in a collaborative study organised by NIBSC. Nineteen laboratories, using a range of qualitative and quantitative assays returned results. RESULTS: The concentrations of the reagents were: 25,000 IU/ml for the PEI material, 710 IU/ml for the NIBSC material 96/586, 1,000 IU/ml for the CLB material, 1,700 IU/ml for the ISS material 0498 and 250 IU/ml for the CBER panel member No. 1. CONCLUSIONS: The calibration of these five reference reagents for HCV RNA nucleic acid amplification technology (NAT) assays enables them to be used for standardisation and validation of assays. Such calibrants are essential for meeting the requirements of the European Medicinal Evaluation Agency (EMEA) for the testing of plasma pools and donations for HCV RNA for the release of blood products and the PEI requirements for the release testing of erythrocyte and thrombocyte concentrates.

Calibration↗

PubMed1999

Ophthalmomyiasis and nasal myiasis in New Zealand: a case series.

We report three cases of ophthalmomyiasis in New Zealand, due to the larvae of Oestrus ovis. All three patients reported eye injury caused by a fly. The larvae were removed from the conjunctival sac without difficulty under local anaesthesia. Presenting ocular symptoms of foreign body sensation, irritation, redness and photophobia all resolved swiftly. Topical antibiotic and steroid eye drops were administered. All three patients also developed nasal symptoms such as sneezing, nasal discharge and epistaxis. Otolaryngology follow-up demonstrated nasal myiasis in two patients which was treated with nasal decongestants. In addition, all three patients were treated with ivermectin (Mectizan).

Adolescent↗

PubMed1999

Sociodemographic and health status characteristics with prostate cancer screening in a national cohort of middle-aged male veterans.

OBJECTIVES: To characterize variables associated with obtaining prostate cancer screening in a nonclinical, nationally distributed, middle-aged male population. METHODS: Telephone interviews were administered to 2652 individual members of the Vietnam Era Twin Registry in 1992 and 1995. Dependent variables were self-report measures of having had a digital rectal examination (DRE) and/or a prostate-specific antigen (PSA) test in the past 5 years. Independent variables were current measures of age, household income, education, race, insurance, source of care, and lifetime measures of physical condition, psychiatric illness, and alcohol and nicotine dependence. RESULTS: Thirty-five percent of the sample reported having had a PSA and DRE within the past 5 years. Prevalence of obtaining either a PSA or DRE varied with age, income, education, and race. Subjects with a regular source of care, a regular physician, and health insurance reported higher rates of having had a DRE or PSA and DRE. Persons with a physical or psychiatric illness reported more screening. A multiple regression model revealed that having a regular source of care, having a regular physician, physical illness, psychiatric illness, minority status, higher income, and age predicted having had some form of screening. CONCLUSIONS: A substantial portion of middle-aged men have had both a PSA and DRE performed at least once in the preceding 5 years. It may be possible to further improve prostate cancer screening participation by directing educational programs at men who are not in contact with the healthcare system. If the PSA and DRE screening guidelines that are finally adopted discourage screening among low-risk men younger than age 50, educational programs that emphasize age screening criteria may be warranted.

Health Status↗

PubMed1999

Complex genetic and environmental relationships between psychological distress, fatigue and immune functioning: a twin study.

BACKGROUND: Although there is considerable support for adverse relationships between states of psychological and somatic distress and immune response, there is little evidence in humans of the relative contribution of genetic and environmental factors. METHODS: This study utilized a twin methodology to examine the interplay between psychological distress, fatigue and immune function. We recorded a number of measures of distress, including conventional depression and anxiety as well as the somatic symptom of prolonged fatigue, and immune responsiveness (by delayed-type hypersensitivity skin response) in 124 normal adult twin pairs (79 monozygotic, 45 dizygotic). RESULTS: While there were strong genetic influences on the psychological distress and fatigue factors (only some of which are common to both), familial aggregation of immune responsiveness arose mainly from environmental factors shared by both members of a twin pair. Phenotypic correlations between psychological and immune measures were negligible, but multivariate genetic modelling revealed that these masked larger genetic and environmental correlations of opposite sign. Negative environmental effects of psychological distress and fatigue on immune responsiveness were countered by a positive genetic relationship between psychological distress and immune function. CONCLUSIONS: Our study suggests that current psychoneuroimmunological hypotheses in humans need to be modified to place increasing importance on the individual's genotype. In this cohort immune responsiveness varied in response to a complex interplay of genetic and environmental factors. Additionally, although psychological distress and fatigue had some shared genetic determinants, independent genetic and environmental risk factors for fatigue were also identified.

Adult↗

PubMed1999

Improvement in pain and bowel function in female irritable bowel patients with alosetron, a 5-HT3 receptor antagonist.

BACKGROUND: No currently available treatment provides consistent relief of irritable bowel syndrome. Colonic sensory and motor function are modulated partly through 5HT3-receptors. AIM: To evaluate effects of the 5HT3-receptor antagonist, alosetron, in irritable bowel syndrome. METHODS: Randomized, double-blind, placebo-controlled, dose-ranging (1, 2, 4, 8 mg b.d. alosetron), 12-week trial in 370 patients with diarrhoea-predominant or alternating constipation and diarrhoea irritable bowel syndrome. Weekly measurement of adequate relief was the key end-point; other irritable bowel syndrome symptoms were collected daily using an electronic phone system. RESULTS: Alosetron (1 mg or 2 mg b.d.) significantly (P < 0.05 vs. placebo) increased the proportion of females, but not males, reporting adequate relief. Stool consistency, frequency and percentage days with urgency improved over placebo (P < 0.05) within the first month with all doses of alosetron, and persisted throughout the trial with all doses in female patients. With 1 mg b.d. alosetron, females had improved stool consistency and urgency within the first week, and adequate relief and improved stool frequency within the first 2 weeks. There was no consistent improvement in bowel function among male patients. CONCLUSION: In female irritable bowel syndrome patients with predominant diarrhoea or alternating constipation and diarrhoea, alosetron is effective in treatment of abdominal pain and discomfort and bowel-related symptoms.

Abdominal Pain↗

PubMed1999

Application of distance geometry to 3D visualization of sequence relationships.

SUMMARY: We describe the application of distance geometry methods to the three-dimensional visualization of sequence relationships, with examples for mumps virus SH gene cDNA and prion protein sequences. Sequence-sequence distance measures may be obtained from either a multiple sequence alignment or from sets of pairwise alignments. AVAILABILITY: C/Perl code and HTML/VRML files from http://www.nibsc.ac.uk/dg3dseq/

Algorithms↗

PubMed1999

A two-component regulatory system, CsrR-CsrS, represses expression of three Streptococcus pyogenes virulence factors, hyaluronic acid capsule, streptolysin S, and pyrogenic exotoxin B.

Certain Tn916 insertions in the chromosome of an M1-type, nonmucoid Streptococcus pyogenes isolate (MGAS166) were previously shown to result in stable mucoidy with increased expression of the capsular synthetic genes. The transposon insertions in these strains are directly upstream of an apparent operon encoding a two-component regulatory system, designated csrR-csrS. Compared with MGAS166, these mucoid mutants are more hemolytic and cause significantly more tissue damage in a murine model of skin infection. To extend these observations, we constructed an in-frame deletion in the gene encoding the response regulator, csrR, and we evaluated the expression of other known S. pyogenes virulence factors. We discovered that csrR mutants have enhanced transcription of sagA, a gene associated with streptolysin S (SLS) and speB, the gene encoding pyrogenic exotoxin B (SpeB). The mutants also express substantially higher SLS activity and SpeB antigen in late-exponential-phase cultures. There is no change in expression of emm, scpA, sic, or cpa (genes encoding other S. pyogenes virulence factors). CsrR- strains but not the wild-type parental strain produce necrotizing lesions in a mouse model of subcutaneous infection. A double mutant with deletions in both csrR and the capsular synthesis genes caused fewer and smaller necrotic skin lesions than the csrR mutants. However, this nonmucoid csrR strain was more likely than the wild type to yield necrotic lesions, suggesting that mucoidy contributes to virulence in this model of infection but that there are other csrR-regulated factors involved in the production of necrotic lesions.

Animals↗

PubMed1999

Establishment of the first international standard for nucleic acid amplification technology (NAT) assays for HCV RNA. WHO Collaborative Study Group.

BACKGROUND AND OBJECTIVES: The aims of this study were the establishment of a WHO International standard for HCV RNA for nucleic acid amplification technology (NAT) assays and the determination of the HCV RNA content of the candidate standard. MATERIALS AND METHODS: Twenty-two laboratories evaluated three candidate materials (two lyophilised, AA and BB, which were derived from the same source and one a liquid preparation, CC). All samples were HCV genotype 1 with a concentration of approximately 10(5) genome equivalents/ml. The methods used included the Roche Amplicor assay (version 1), Chiron Quantiplex (bDNA) assay, Organon Teknika NASBA assay, Transcription Mediated assay and various in-house assays, using single or nested primers. RESULTS: There was reasonable agreement between the overall mean NAT detectable units/ml obtained by the different assays except for some of the in-house assays using single primers which gave substantially lower estimates. These titres were 5.0 log10 for samples AA and BB and 4.6 log10 for sample CC. CONCLUSIONS: Sample AA was accepted as the candidate standard and assigned a titre of 10(5) international units (IU)/ml. The International Standard consists of a batch of vials each containing 50,000 IU/vial. Preliminary studies indicated that the material is stable at +4 degrees C and +20 degrees C for up to 200 days.

Gene Amplification↗

PubMed1999

Comparing the biological and cultural inheritance of personality and social attitudes in the Virginia 30,000 study of twins and their relatives.

Measures of four dimensions of personality (Psychoticism, Extraversion, Neuroticism, and Lie scores) and six aspects of social attitudes (to sex, taxation, militarism, politics, religion and a general conservatism scale) were obtained by mailed questionnaire from 29,691 US subjects including adult twins (n = 14,761) their parents (n = 2360), their spouses (n = 4391), siblings (n = 3184) and adult children (n = 4800). After correction for the average effects of age, sex and source of sample, familial correlations were computed for 80 distinct biological and social relationships. The data allow for the estimation of the additive and non-additive effects of genes, assortative mating, vertical cultural inheritance and other non-parental effects of the shared environment on differences in personality and social attitudes. The interaction of genetic and environmental effects with sex may also be analyzed. Model-fitting analyses show that personality and social attitude measures differ markedly in major features of family resemblance. Additive and dominant genetic effects contribute to differences in both personality and attitudes, but the effects of the family environment, including vertical cultural transmission from parent to child, are much more marked for social attitudes than for personality. There is substantial assortative mating for social attitudes and almost none for personality. The causes of family resemblance depend significantly on sex for almost every variable studied. These findings clarify and extend the more tentative findings derived from previous twin, family and adoption studies.

Adult↗

PubMed1998

Ranitidine bismuth citrate plus clarithromycin: a dual therapy regimen for patients with duodenal ulcer.

BACKGROUND: The combination of ranitidine bismuth citrate (RBC) and clarithromycin (CLR) was compared with each treatment alone for the eradication of H. pylori and healing of duodenal ulcers in patients infected with H. pylori. METHODS: This two-phase, randomized, double-blind, placebo-controlled, multicenter study evaluated 203 patients with an active duodenal ulcer treated with either (1) RBC 400 mg BID for 4 weeks plus CLR 500 mg TID for the first 2 weeks; (2) RBC 400 mg BID for 4 weeks plus placebo TID for the first 2 weeks; (3) placebo BID for 4 weeks plus CLR 500 mg TID for the first 2 weeks; or (4) placebo BID for 4 weeks plus placebo TID for the first 2 weeks. Patients with healed ulcers after treatment entered a 24-week observation phase for the assessment of H. pylori and ulcer relapse. RESULTS: Four-week ulcer healing rates were higher with RBC + CLR (71%) and RBC alone (66%) compared with placebo (15%; p < 0.05) and CLR alone (49%). H. pylori eradication rates were significantly higher with RBC + CLR (86%) compared with RBC alone (0%, p < .001) or CLR alone (24%, p < .001). Ulcer recurrence rates after 6 months were lower in patients eradicated of H. pylori infection (17%) compared with patients who remained infected (43%). All treatments were well tolerated. CONCLUSIONS: Ranitidine bismuth citrate plus clarithromycin is a simple, convenient, and well-tolerated dual therapy regimen that is effective in eradicating H. pylori and healing duodenal ulcers in patients infected with H. pylori. The eradication of H. pylori in patients with healed ulcers significantly reduces the rate of ulcer relapse.

Adolescent↗

PubMed1997

Age changes in the causes of individual differences in conservatism.

Age-related changes are analyzed in the correlation of 3416 monozygotic and 3780 dizygotic U.S. twin pairs aged between 9 and 75+ years for conservatism scores derived from a 28-item social attitude inventory. The effects of the shared environment are overwhelming in twins aged 20 years or younger. In older twins, genetic effects appear to play a larger role. A more dynamic conception of the interaction between genes and environment in the development of complex human differences is needed.

Adolescent↗

PubMed1997

First clinical experiences with specific sheep Fab fragments in snake bite. Report of a multicentre study of Vipera berus envenoming.

OBJECTIVES: To evaluate the efficacy and safety of specific, ovine Fab fragments in the treatment of envenoming by the common adder, Vipera berus. DESIGN: Open study with historical controls. SETTING: Multicentre study involving patients (n = 30) with V. berus envenoming, treated in 18 Swedish hospitals during 1991-94. MAIN OUTCOME MEASURES: Initial symptoms, clinical course after treatment, duration of hospital stay and adverse effects of the antivenom were evaluated. Two earlier studied patient groups, given either equine F(ab)2 antivenom (n = 30) or no antivenom (n = 16), were used as controls. RESULTS: Specific ovine Fab fragments influenced favourably the acute symptomatology as well as the long term clinical course. Acute symptoms such as hypotension, shock, vomiting, diarrhoea and CNS-depression resolved quickly. The incidence of extensive swelling involving the trunk and the length of hospital stay were both reduced significantly compared to nontreated patients (23 vs. 88% and 3.5 vs. 6 days). Also the incidence of anaemia was reduced (23 vs. 44%). These results were consistent with those obtained with equine F(ab')2 antivenom, but with ovine Fab there were no immediate anaphylactic reactions or serum sickness. CONCLUSION: Specific Fab fragments produced from sheep immunized with V. berus venom were safe and effective in counteracting the effects of V. berus bite in humans. These results justify further studies of this new treatment for snake envenoming.

Adolescent↗

PubMed1997

A comparison of the Eating Disorder Examination and a general psychiatric schedule.

OBJECTIVE: The aim of this study is to investigate the adequacy of a general interview schedule for the purpose of assessing bulimia nervosa. METHOD: In two waves of data collection 18-24 months apart, 250 women were assessed for disordered eating. The first interview was typical of that included in many psychiatric interview schedules and was used to screen women for selection in a subsequent interview. This latter interview, using the Eating Disorder Examination, represents the 'gold standard' for the assessment of disordered eating. RESULTS: While the psychiatric interview satisfactorily assessed disturbed eating in general, it seemed less capable of accurately assessing cases of bulimia nervosa in particular, the major weakness being the overestimation of binge-eating. CONCLUSIONS: Structured psychiatric interviews are suitable for screening purposes to identify women with disordered eating, but identification of bulimia nervosa requires further assessment with a suitable instrument.

Bulimia↗

PubMed1997

International collaborative study to evaluate a recombinant L ferritin preparation as an International Standard.

A recombinant L ferritin preparation, lyophilized in ampoules and designated 94/572, was evaluated by 18 laboratories in 9 countries for its suitability as an International Standard (IS). The preparation was assayed in a wide range of in-house and commercial immunoassays against the 2nd IS for ferritin (of spleen origin; 80/578). The immunological reactivity of the recombinant material was similar to that of the 2nd IS for ferritin in the majority of assays and demonstrated adequate stability in accelerated degradation studies. On the basis of the results presented here, the WHO Expert Committee on Biological Standardization established 94/572 as the 3rd IS for ferritin, recombinant.

Automation↗

PubMed1996

Social contact, social attitudes, and twin similarity.

The nature of the relationship between social contact and attitude similarly between twins was investigated using longitudinal data from a sample of Australian twins. Earlier research has suggested that social attitudes are not explained solely by shared environment; rather there are both genetic and environmental components that explain variance in social attitudes. Using three types of analyses we investigated the magnitude of the relationship and the direction of causation between attitude similarity and social contact. Longitudinal analysis of within-pair variance by level of contact suggests that attitude similarity leads to contact among the females and that similarity is both genetically and environmentally based. Analyses using a crosslag regression model suggest that similarity causes contact among MZ females. Biometrical analyses indicate differences in direction of causation for males and females. Among females, both genetic and shared environmental parameter estimates could be equated across contact groups, suggesting little relationship between contact and similarity. Among males, findings of smaller estimated heritability in the high-contact group suggest that similarity causes contact. However, an increased estimate of the contribution of shared environmental variance in the high-contact males could additionally suggest that contact leads to similarity.

Adolescent↗

PubMed1996

Effects of ranitidine bismuth citrate on gastric acid secretion and gastrin release in subjects with and without Helicobacter pylori infection.

BACKGROUND: Ranitidine bismuth citrate is a novel antiulcerant that provides the antisecretory activity of ranitidine and the gastric mucosal protection and antibacterial properties of bismuth. METHODS: This randomized, double-blind, placebo-controlled study evaluated the effects of single doses of ranitidine bismuth citrate 200 mg, 400 mg and 800 mg and ranitidine hydrochloride 150 mg on gastrin release and suppression of gastric acid secretion, and compared acid secretory profiles and gastrin release between Helicobacter pylori-negative and -positive patients. Plasma gastrin concentrations were determined by radioimmunoassay under basal conditions and in response to peptone meal stimulation. Acid secretion was measured under basal conditions and in response to peptone meal stimulation. Presence of H. pylori was determined by both 14C-urea breath test and ELISA serology. RESULTS: Inhibition of gastric acid output by ranitidine bismuth citrate was both time- and dose-dependent over the 9-h post-dose study period. Doses of ranitidine bismuth citrate 400 mg and ranitidine hydrochloride 150 mg, which are equimolar, produced similar suppression of acid output regardless of H. pylori status. Ranitidine bismuth citrate had no effect on plasma gastrin concentrations regardless of H. pylori status. All doses of ranitidine bismuth citrate were well tolerated. CONCLUSIONS: Ranitidine bismuth citrate caused time- and dose-dependent reductions in meal-stimulated and between-meal gastric acid output regardless of H. pylori status. The magnitude of decreased acid secretion was similar with ranitidine bismuth citrate 400 mg and ranitidine hydrochloride 150 mg. Ranitidine bismuth citrate had no effect on plasma gastrin concentrations.

Administration, Oral↗

PubMed1996

Collaborative study on assays of activated FIX (FIXa). On behalf of the factor VIII and factor IX subcommittee of the ISTH. International Society on Thrombosis and Haemostasis.

A collaborative study has been organised by NIBSC to examine the performance of FIXa assays between laboratories, and to investigate the need for a standard. Ampoules of 3 materials, one monocomponent concentrate (coded C) and 2 different preparations of purified human FIXa (one proposed reference preparation, coded A and a test material coded B), have been assayed in 11 laboratories for FIXa using either the NIBSC method or a local method, with local standards (if available, coded D) to determine their potencies. The data showed high between assay variability; with the exception of one laboratory, most of the between assay variation expressed as %geometric coefficients of variation (gcv) were over 15%. The interlaboratory gcv when preparation B was assayed against the local standard was over 1700%, suggesting that most of the local standards are poorly calibrated. The %gcv was improved to 80% when reference A was used as the standard. These data clearly show that an international reference standard for FIXa would help to standardise FIXa preparations and would also improve in house assays for FIXa. However, an accelerated degradation study has shown that reference A is not suitable as a long term standard and another material with suitable stabilizers has to be established as an international standard for FIXa.

Factor IX↗