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Biomedical subjects

J Ward

Publications and source records attributed to J Ward.

At least 19 recordsLinked to original sources
PubMed1992

Expression and characterisation of the korB gene product from the Streptomyces lividans plasmid pIJ101 in Escherichia coli and determination of its binding site on the korB and kilB promoters.

A 0.5kb Spel-BclI fragment containing the pIJ101 korB ORF was cloned into pUC8 under the control of the lacZ promoter, creating pQR206. In vitro coupled transcription-translation of pQR206 identified a protein product of approximately 10kDa, which corresponds to the predicted molecular weight deduced from the korB sequence. pQR206 was used to express the 10kDa KorB protein in vivo in E. coli. Crude E. coli protein extracts containing KorB were shown to bind to a 0.8kb kilB fragment and a 0.5kb korB fragment in gel retardation assays. DNasel footprinting indicated that the DNA recognition sequence of the KorB protein lies within a 60bp protected region encompassing the kilB promoter and a 36bp region encompassing the korB promoter.

Bacterial Proteins↗
PubMed1992

Synthesis and antiulcer activity of novel 5-(2-ethenyl substituted)-3(2H)-furanones.

In order to investigate new antiulcer agents, spizofurone 1 (AG-629) was fragmented and reassembled to generate 5-phenyl-2,2-dimethyl-3(2H)-furanone (bullatenone, 2). Because of the antiulcer activity of 2,5-phenyl-substituted 2,2-dimethyl-3(2H)-furanones (3-6) were made and shown to have poor activity. Insertion of an ethenyl link between the furanone and phenyl rings gave 5-(2-phenylethenyl)-2,2-dimethyl-3(2H)- furanone (7). This compound had better activity than 2. Compounds 8-41 were synthesized to evaluate the SAR in 5-(2-ethenyl substituted)-3(2H)-furanones. Electron-withdrawing substituents on the aromatic ring (8, 10, 19, and 20) gave 2-3-fold higher activity. Further increases in the activity were found when the phenyl ring was replaced by heterocyclic nuclei. Compounds that contained a thiophene (29), pyridine (24-26), or quinoline ring (32) had the best activity. Replacement of the methyl group on the furanone ring with a phenyl (34) or p-fluorophenyl (40) substituent in the 2-pyridine series gave compounds with activity that ranked with the best obtained in this study. The best compounds from the above SAR studies were evaluated in the ethanol-necrosis model for duration of cytoprotection action. Compounds 19, 24, and 29, which had the best duration of action, were tested with AG-629 in the acidified aspirin and indomethacin-induced lesion models. Only compound 24 had equivalent activity with AG-629 in both models.

Animals↗
PubMed1992

Flecainide-related alterations in the signal-averaged electrocardiogram: similarity between patients with or without ventricular tachycardia.

The signal-averaged electrocardiogram (SAECG) identifies patients at risk of sustained ventricular tachycardia (VT), but the influence of anti-arrhythmic agents on the SAECG is not yet established. We have evaluated the effects of flecainide on the SAECG (XYZ leads, high-pass filters 25 Hz and 40 Hz, noise level 0.2 microV-0.4 microV, Model 1200 EPX, ART) in 25 patients: 15 (VT group) had documented sustained VT (nine post-MI, two dilated cardiomyopathy, four normal hearts) and 10 (control group) had supraventricular arrhythmias and structurally normal hearts. The SAECG was recorded in all patients prior to, and 5 min following a flecainide infusion (2 mg.kg-1 over 10 min). Before flecainide administration an abnormal SAECG was recorded in six patients from the VT group and in no control patient. Following flecainide, 13 patients from the VT group and eight control subjects demonstrated abnormal SAECG. Flecainide produced similar significant percentage changes in all SAECG indices in both the VT and control groups: total QRS duration was prolonged by 26.0 +/- 10.4% vs 26.7 +/- 15.7%, late potential duration under 40 microV was prolonged by 55.5 +/- 62.0% vs 106.1 +/- 61.4%, and the root mean square voltage of the last 40 ms of the QRS was reduced by 42.1 +/- 34.9% vs 55.3 +/- 24.4%, respectively. We conclude that flecainide significantly changes the SAECG parameters in patients with and without a history of VT, irrespective of the underlying disease.

Electrocardiography↗
PubMed1992

Methadone maintenance and the human immunodeficiency virus: current issues in treatment and research.

This paper examines the changes that have occurred in methadone maintenance programmes in response to the advent of HIV and the adoption of harm minimization policies, and the implications of these changes for research. A need for the use of more rigorous research methods is identified and recommendations are made that take into account both the ethical and practical difficulties of conducting research in this area. Both old, unanswered questions that have resurfaced with the recent massive growth in methadone programmes in some countries, and new questions that need to be answered in order to improve the effectiveness of methadone maintenance in the fight against HIV infection are identified as future areas in need of research.

HIV Infections↗
PubMed1992

Development and validation of a multi-dimensional instrument for assessing outcome of treatment among opiate users: the Opiate Treatment Index.

This article presents a new instrument with which to assess the effects of opiate treatment. The Opiate Treatment Index (OTI) is multi-dimensional in structure, with scales measuring six independently measured outcome domains: drug use; HIV risk-taking behaviour; social functioning; criminality; health; and psychological adjustment. Psychometric properties of the Index are excellent, suggesting that the OTI is a relatively quick, efficient means of obtaining reliable and valid data on opiate users undergoing treatment over a range of relevant outcome domains.

Adolescent↗
PubMed1992

Nasal patency, aerobic capacity, and athletic performance.

The patency of the nasal airway may directly affect pulmonary ventilation, with obstruction and increased nasal resistance resulting in increased pulmonary resistance, hypoxia, and hypercapnea. Nine aerobic athletes were evaluated to assess the role of the nasal airway on aerobic capacity and athletic performance. A step-ladder graded maximal aerobic capacity test was performed under three test conditions: obstructed, decongested with oxymetazoline hydrochloride, and saline control. No differences in maximum VO2, work load, oxygen saturation, maximal blood pressure, heart rate, or respiratory rate were noted between test conditions. Pre-exercise nasal resistance was lower in the decongested compared to control conditions, but no differences were found after exercise. Athletic performance was not influenced by nasal patency in this model.

Airway Resistance↗
PubMed1992

Institutionalism and schizophrenia 30 years on. Clinical poverty and the social environment in three British mental hospitals in 1960 compared with a fourth in 1990.

In their comparison of chronic schizophrenic patients in three British mental hospitals in 1960, Wing and Brown found a strong association between the poverty of the social environment and the severity of 'clinical poverty' (blunted affect, poverty of speech, and social withdrawal). Between 1960 and 1968 the social environments of all three hospitals improved and a weak causal relationship between social poverty and clinical poverty was reported in a proportion of patients. Using the same assessment instruments as Wing and Brown, the present study re-examined the relationship between social and clinical poverty in the long-stay schizophrenic population of a fourth British mental hospital in 1990. The association found between social and clinical poverty was much weaker than in 1960. Reluctance on the part of patients to be discharged from the institution was unrelated to length of stay. There was no significant difference in severity of illness between the patients in the present study and those in the earlier study. However, patients in the former group spent more time doing nothing than those in the hospital with the most understimulating environment three decades before, with four-fifths doing nothing for over five hours a day, despite a greatly increased ratio of nurses to patients.

Attitude to Health↗
PubMed1992

Health promotion for older people.

Health promotion for older people, or preventive geriatrics, has the potential to transform people's lives by providing greater satisfaction and by reducing both physical and psychological ill health. General practitioners are key personnel in any health promotion programme but should, ideally, co-ordinate their activities with other health professionals. The basic tool for general practitioners is a screening programme for all older people and for people at special risk.

Activities of Daily Living↗
PubMed1992

Pap smear tests in general practice. An update.

Reduction of deaths due to cervical cancer by two-yearly Papanicolaou smear screening of women at risk aged 18 to 70 years is now a national health goal. We report a study conducted with general practitioners that suggests improving levels of coverage of women at risk. Our research, however, has also identified unexpected challenges in documenting preventive care in general practice.

Adolescent↗
PubMed1992

When research involves your receptionist. A checklist for GPs and staff.

General practitioners have a key role in health care. Research must continue in general practice to maintain and improve this role. Whenever research involves receptionists directly in data collection, general practitioners should understand fully the nature of the research and the workload it is likely to impose. All members of the staff can be involved in deciding whether to participate. Once your assistance is enlisted, an explicit charter of rights and responsibilities ought to ensure a secure basis for a successful collaboration.

Female↗
PubMed1991

Rapid induction of early osteoarthritic-like lesions in the rabbit knee by continuous intra-articular infusion of mammalian collagenase or interleukin-1.

Aminophenyl mercuric acetate (APMA)-activated collagenase (C) (60 U/ml) obtained from in vitro cultures of human skin fibroblasts or recombinant interleukin-1 beta (IL-1 beta) (200 U/ml) was infused continuously for 7 days into the rabbit knee synovial space by means of an implanted Alzet osmotic pump. In stability studies in vitro, activated C or IL-1 incubated for 7 days at 37 degrees C, showed no significant loss of biological activity. Alterations in knee cartilage morphology and proteoglycan (PG) content were determined histologically, and the incidence of cartilage damage calculated. C or IL-1 vehicles infused for 7 days, caused no damage. Incidences of damage for C or IL-1 (n = 8-9), respectively, were as follows: loss PG: 88% and 100%; chondrocyte disorganization and loss, 50% and 78%, fissures and or fraying, 25% and 78%; and convergence of inflammatory cells, 25% and 66%. These results confirm the important role of C and IL-1 in cartilage damage.

Animals↗
PubMed1991

Prevention of invasive Haemophilus influenzae type b disease: lessons from vaccine efficacy trials.

To assess vaccines, multiple laboratory investigations and immunogenicity studies are conducted but the ultimate tests of the effectiveness of a vaccine are field trials that evaluate disease prevention. Immunogenicity studies are often used as a surrogate for protection, but it is often difficult to determine precisely the level of antibody needed for protection and it is not always clear what immunologic factors most determine protection. However, efficacy trials are difficult to conduct well and there are only a limited number of ways to perform such studies. Nonetheless, the results of efficacy studies are essential for the appropriate selection of the best Hib vaccines and to establish recommendations for optimal use. The first Hib vaccine, the PRP (polyribosylribitol phosphate) polysaccharide vaccine, was shown by several efficacy studies to have no protective efficacy in young infants, and to have only limited, if any, efficacy in older children. The first Hib polysaccharide conjugate vaccine, PRP-D, is more immunogenic and provides better protection than PRP in older children (greater than 18 months of age), but it has limitations in both immunogenicity and protective efficacy when given to children younger than 6 months of age. Newer, more promising, Hib conjugate vaccines are now available, and include HbOC, PRP-OMP, and PRP-T vaccines. Each is currently being evaluated in field trials to evaluate protective efficacy and the methods and results of these trials will be reviewed. The control of invasive Hib disease worldwide will depend upon the appropriate application of knowledge derived from these field trials.

Bacterial Vaccines↗