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Biomedical subjects

H Ward

Publications and source records attributed to H Ward.

At least 55 records · Page 3Linked to original sources
PubMed1998

A novel multi-domain mucin-like glycoprotein of Cryptosporidium parvum mediates invasion.

Cryptosporidium parvum is a protozoan parasite which produces self-limited disease in immunocompetent hosts and devastating, persistent diarrhea in immunocompromised individuals. There is no effective treatment for cryptosporidiosis and little is known about the basic biology of the organism. Cloning and sequence analysis of the gene encoding GP900, a previously identified > 900 kDa glycoprotein, predicts a mucin-like glycoprotein composed of distal cysteine-rich domains separated by polythreonine domains and a large membrane proximal N-glycosylated core region. A trinucleotide repeat composed predominantly of the triplet ACA encodes the threonine domains. GP900 is stored in micronemes prior to appearance on the surface of invasive forms. The concentration of native GP900 which inhibits 50% (IC50) of invasion in vitro is low picomolar; the IC50 for a recombinant cysteine rich-domain is low nanomolar. These observations indicate that GP900 is a parasite ligand for a host receptor involved in attachment/invasion and suggest that immunotherapy or chemotherapy directed against GP900 may be feasible.

Amino Acid Sequence↗
PubMed1998

Ion-exchange column chromatographic method for assaying purine metabolic pathway enzymes.

High energy phosphate levels fall rapidly during cardiac ischemia and recover slowly (more than one week) during reperfusion. The slow recovery of ATP may reflect a lack of purine metabolic precursors and/or increased activity of purine catabolic enzymes such as 5'-nucleotidase (5'-NT, EC 3.1.3.5) and adenosine deaminase (ADA, EC 3.5.4.4). The activity of enzymes involved in both the catabolism of ATP precursors (5-NT and ADA) and the restoration of ATP from slow synthetic pathways [adenosine kinase (AK, EC 2.7.1.20), adenine phosphoribosyl transferase (APRT, EC 2.4.2.7) and hypoxanthine phosphoribosyl transferase (HPRT, EC 2.4.2.8)] may directly affect the rate of ATP recovery. Strategies to enhance recovery will depend on the relative activity of these enzymes following ischemia. Their activity in different species and their response to ischemia are not well characterized. Hence, rapid assay methods for these enzymes would facilitate detailed time course studies of their activities in postischemic myocardium. We modified a single ion-exchange column chromatographic method using DEAE-Sephadex to determine the products of incubation of 5'-NT, AK, APRT and HPRT with their respective substrates. The uniformity of the final product measurement procedure for all assays permits the activities of the four enzymes to be rapidly determined in a single tissue sample and facilitates the study of a large number of samples. This technique should also be useful for enzymes of the pyrimidine metabolic pathway.

5'-Nucleotidase↗
PubMed1998

Safety study of nonoxynol-9 as a vaginal microbicide: evidence of adverse effects.

Nonoxynol-9 (N-9) is virucidal in vitro, and is therefore a candidate microbicide for preventing sexual transmission of HIV. However, the activity of N-9 is nonspecific, suggesting that virucidal levels may produce adverse effects including epithelial disruption, inflammation of the genital mucosa, or both. A randomized placebo controlled trial of daily use of 100 mg of N-9 took place for 1 week in 40 female volunteers. Outcome measures included symptoms, colposcopic and histologic changes in the genital tract, and impact on vaginal flora. Genital irritation was reported by 10 of the N-9 and 5 of the placebo group. Colposcopy showed erythema in 9 of the N-9 group and 2 of the placebo group. Histologic inflammation was found in 7 of the N-9 group and 2 of the placebo group. Inflammatory changes were characterized by patchy infiltration of the lamina propria predominantly with CD8+ lymphocytes and macrophages, in the absence of epithelial disruption. A transient reduction in numbers of lactobacilli was observed in 9 of the 15 women using N-9, and 6 of 18 women using placebo. N-9 used for 7 days in a standard spermicidal dose was associated with increased irritation, colposcopic and histologic evidence of inflammation and was more frequently associated with reduction in numbers of lactobacilli during gel use. The clinical significance of the recruitment of cells susceptible to HIV infection to the genital mucosa is unknown but raises concerns about the suitability of N-9 as a microbicide when given in this dose.

Administration, Intravaginal↗
PubMed1998

Cryptosporidium: molecular basis of host-parasite interaction.

Host-parasite interactions occur at a number of stages during the process of infection with Cryptosporidium. Until recently, very little was known about the molecular basis of these interactions or of specific parasite and host molecules involved in them. Within the past decade significant advances have been made in our understanding of Cryptosporidium host-parasite interactions and in identifying molecules involved in them. However, with most interactions the story is far from complete and a number of gaps remain to be filled. This chapter reviews the existing knowledge of the molecular basis of various host-parasite interactions and of specific molecules that may be involved in them, and identifies areas in which further investigation is necessary. Identification of these molecules and elucidation of molecular mechanisms underlying the host-parasite interaction are of vital importance in developing strategies to combat cryptosporidiosis by targeted chemo- and immunotherapy.

Animals↗
PubMed1998

Sexual networks: the integration of social and genetic data.

New methods for studying sexual networks are presented, drawing upon routine procedures followed in genitourinary medicine clinics in the UK for tracing partners and identifying strains of infection. The routine social procedures were developed to incorporate a structured interview. The routine microbiological diagnosis of gonorrhoea was augmented by phenotyping and the development of new genetic techniques for the fine discrimination of gonococcal strains (opa-typing). Selected results from a study in Sheffield, UK show that each method has limitations, when conducted separately, but these are minimised when the methods are combined. Moreover, the use of simple and routine methods of data collection resolve issues of scale and sample that have beset other network studies, as they provide a means of covering a larger and defined population. Popular concepts about these methods are discussed in the conclusion. The integrated approach employed in our research raises questions both about social methods, 'of people who lie, particularly when they talk about sex', and about microbiological methods, 'of genes that tell the truth' and bypass what people say and think altogether. We argue that these stereotypes are misleading insofar as they suggest that genetic techniques can substitute for the social, and we suggest that even the finest discrimination of organisms at the genetic level will never obviate the need for their interpretation in the light of social data.

Adult↗
PubMed1998

Sexual networks and the transmission of HIV in London.

This paper discusses ways in which empirical research investigating sexual networks can further understanding of the transmission of HIV in London, using information from a 24-month period of participant observation and 53 open-ended, in-depth interviews with eighteen men and one woman who have direct and indirect sexual links with each other. These interviews enabled the identification of a wider sexual network between 154 participants and contacts during the year August 1994-July 1995. The linked network data help to identify pathways of transmission between individuals who are HIV+ and those who are HIV-, as well as sexual links between 'older' and 'younger' men, and with male prostitutes. There appears to be considerable on-going transmission of HIV in London. The majority of participants reported having had unprotected anal and/or vaginal sex within a variety of relationships. The implications of these findings for policies designed to prevent the transmission of HIV are discussed.

Adult↗
PubMed1998

Effect on normal vaginal flora of three intravaginal microbicidal agents potentially active against human immunodeficiency virus type 1.

The effect on normal vaginal flora of three intravaginal microbicides potentially active against human immunodeficiency virus type 1 was examined. Volunteers received dextrin sulfate (D2S), nonoxynol-9 (N-9), or docusate sodium in separate placebo-controlled studies. High vaginal swabs were obtained for bacterial culture before and after microbicide application. D2S did not affect the vaginal flora. However, lactobacilli decreased by > or = 10(2) cfu/mL in 9 (56%) of 16 women given N-9 and in 5 (63%) of 8 women given docusate sodium. Women using N-9 were also significantly more likely to become colonized abnormally (usually with aerobic gram-negative rods) than were those using placebo, as were women using docusate sodium. Women with reduced lactobacilli were less likely to regain normal flora than were those whose lactobacilli were unaffected. However, coliform colonization occurred whether lactobacilli produced H2O2 or not. Continuous use of N-9 could induce susceptibility to urinary and gynecological infection. It is essential that potential microbicides are examined for activity against normal vaginal flora.

Adult↗
PubMed1998

Partner notification for gonorrhoea: a comparative study with a provincial and a metropolitan UK clinic.

OBJECTIVE: To compare partner notification practice and outcomes at a provincial and a metropolitan clinic. DESIGN: Prospective study, following standardisation of partner notification policy. SETTINGS: Sheffield Department of Genitourinary Medicine, Royal Hallamshire Hospital and Jefferiss Wing Centre for Sexual Health, St Mary's Hospital, London. SUBJECTS: Consecutive patients with culture positive gonorrhoea between October 1994 and March 1996 who were interviewed by a health adviser. RESULTS: In Sheffield, 235 cases reported 659 outstanding contacts, of whom 129 (20%) were subsequently screened, and 65 (50%) had gonorrhoea. At St Mary's 510 cases reported 2176 outstanding contacts, of whom 98 (5%) were known to have been screened, and 53 (54%) had gonorrhoea. Patient or provider referral agreements appeared more productive in Sheffield, where 60% resulted in contact attendance, compared with 13% at St Mary's. Provider referral was used more frequently in Sheffield, for 44% of referrals, compared with 1% at St Mary's. Multivariate analysis showed that partner notification was less effective for casual and short term (< 7 days) partnerships in both centres, and for homosexual men at St Mary's. CONCLUSION: Partner notification outcomes were better in the provincial setting where contact attendance could be recorded more reliably and provider referral was used more extensively. The high proportion of contacts who remained untraced in both settings indicates the need for complementary screening and prevention initiatives.

Adult↗
PubMed1998

Sexual histories, partnerships and networks associated with the transmission of gonorrhoea.

We aimed to describe and compare sexual links among people with gonorrhoea, by studying patients in 2 UK departments of genitourinary medicine. Interviews were completed for 510 and 235 cases in London and Sheffield respectively. There was a greater proportion of cases in men, homosexual men, non-white and non-British people and fewer female sex workers in London. Total networks of 1738 people in London and 570 people in Sheffield were described. Large linked heterosexual networks identified in Sheffield were associated with local contact, including men with higher numbers of sexual partners. Condom use for vaginal sex was reported for 11% of heterosexual partnerships in Sheffield, and 27% in London, with little difference between regular and casual partners. It was more difficult to define networks in London due to a high proportion of relatively anonymous contacts. These difficulties suggest that research and interventions may profitably focus upon venues for meeting partners as well as partner notification.

Adolescent↗
PubMed1997

Epidemics of syphilis in the Russian Federation: trends, origins, and priorities for control.

After continuous decline throughout the 1980s, surveillance-defined estimates of the incidence of syphilis in Russia have shown a rapid and substantial increase during the 1990s. The reasons for this epidemic are unclear, but must be sought among changes both in sexual behaviour and in the patterns of provision, use, and effectiveness of diagnostic, treatment, and contact tracing services. High incidence of sexually transmitted disease causes correspondingly high levels of morbidity and suffering as well as significant health-care and other economic costs. Our current understanding suggests that the transmissibility of HIV is increased by infection with sexually transmitted disease. The syphilis epidemic together with changes in sexual behaviour, increased travel and migration, and rapid increases in injecting drug use may create the conditions for an epidemic of sexually acquired HIV infection in Russia that substantially outstrips those encountered in most Western European countries.

Adolescent↗
PubMed1997

Health seeking behaviour and the control of sexually transmitted disease.

What people do when they have symptoms or suspicion of a sexually transmitted disease (STD) has major implications for transmission and, consequently, for disease control. Delays in seeking and obtaining diagnosis and treatment can allow for continued transmission and the greater probability of adverse sequelae. An understanding of health seeking behaviour is therefore important if STD control programmes are to be effective. However, taboos and stigma related to sex and STD in most cultures mean that gaining a true picture is difficult and requires considerable cultural sensitivity. At the moment relatively little is known about who people turn to for advice, or about how symptoms are perceived, recognized or related to decisions to seek help. It is argued that such knowledge would assist programme planners in the development of more accessible and effective services, that studies of health seeking behaviour need to include a combination of qualitative and quantitative methods, and that studies should include data collection about people who do not present to health care facilities as well as those who do. A pilot protocol for studying STD-related health seeking behaviour in developing countries is briefly presented.

Clinical Protocols↗
PubMed1997

A descriptive study of the self-perceived needs of carers for dependants with a range of long-term problems.

BACKGROUND: This study aimed to identify qualitatively the need for health and social care of carers looking after dependants from different patient groups in a geographically defined area--Fife, Scotland. It was the first stage of a systematic process designed to assess and meet carers' needs. METHOD: Subjects for the study were unpaid (or 'informal') carers looking after dependants who were known to statutory or voluntary services. A series of 14 focus group discussions with carers of dependants from seven different patient groups took place. The main outcome measure was the qualitative descriptions of carers' self-reported health and social needs. RESULTS: Needs 'common' to carers across all care groups were identified. These related to the need for: information (diagnostic, prognostic and where to obtain help), improved communication with professionals, relief from stress, respite care, training and practical support. Within each area of 'common' need, carers had specific needs, which related to the particular needs of their dependant. There were also needs that were identified by carers from one or more patient groups. Carers did not necessarily recognize themselves as carers at an early stage in their caring career. Therefore, their dependants' early medical contact with their general practitioner or hospital specialist was seen by carers as a crucial point at which their own needs for information and help could be recognized. Other opportunities for health professionals to help carers related to involving carers in case management, the provision of counselling and training carers to provide care themselves. CONCLUSION: Many of the needs described by carers were of a social nature. However, carers also described needs relating to the health services--health professionals need to be proactive in recognizing carers' health and information needs and are required to recognize carers' contribution to the welfare of their dependant. In Fife, a multi-faceted approach was used to meet these needs. The challenge for the health service is to find a way to do this at a national level.

Adolescent↗
PubMed1997

Sex workers and the control of sexually transmitted disease.

OBJECTIVES: To describe and assess measures to control sexually transmitted diseases (STDs) among sex workers and their partners. METHODS: A review of medical, historical and social literature, focusing on selected cases. RESULTS: Measures to control disease in sex workers today are often prompted by concerns about HIV transmission. However, the literature shows that prostitution varies from one place and time to another, together with the risk of sexually transmitted disease. A broad social definition of prostitution rather than a narrow reference to levels of sexual activity is important for effective disease control, as an understanding of the relation between social disadvantage and sexual activity enables the provision of occupational services that sex workers actually want and use. Social prejudice and legal sanctions cause some sex workers and their partners to avoid even the most appropriate and accessible specialist services. Therefore targeted programmes can only complement, and not replace, general measures to control STDs, which are developed for other social groups or the local population as a whole. CONCLUSIONS: Sex workers and sex work differ from one place to another and so a single model for STD control is inappropriate. None the less, occupational health risks suggest a general need for specialist services. Where these do not compound the disadvantages that sex workers already suffer, medical services are likely to offer significant benefits in prevention, early diagnosis, and treatment of STDs. As the stigma of prostitution leads many people to remain invisible to services, a general health infrastructure and anti-discriminatory measures will be equally important to effective disease control.

Delivery of Health Care↗
PubMed1997

Improved survival of en bloc renal allografts from pediatric donors.

PURPOSE: We developed a technical and immunological protocol to increase survival of renal transplants from pediatric donors. MATERIALS AND METHODS: En bloc kidneys (22) were procured from donors weighing 2 to 14 kg. (1 to 60 months old) and transplanted into adult recipients. In group 1 (12 patients) sequential therapy was used for kidneys with more than 35 hours of cold storage and immediate triple therapy (cyclosporine, azathioprine and prednisone) was used for those with less than 35 hours of cold storage. In group 2 (10 patients) OKT3 induction therapy was used. Mean followup was 4.7 years. RESULTS: Mean blood pressure at 1 and 4 years was not significantly different between the groups. Mean serum creatinine was not significantly different between the groups at 1 year but it was significantly less in group 2 at 4 years (1.9 +/- 1.0 versus 1.2 +/- 0.24 mg./dl., p <0.05). At 1 year of followup the complication rate was 75% in 9 of 12 patients in group 1, including 4 infections or leaks (2 lost), 6 rejections (3 lost) and 3 cases of thrombosis or hemorrhage, and 20% (p <0.01) in group 2 (1 patient had the hemolytic uremic syndrome leading to graft loss). Graft survival was significantly greater in group 2 at all 4 years of followup (p = 0.05). CONCLUSIONS: The success of pediatric en bloc renal transplantation can be enhanced by induction therapy in healthy recipients.

Child, Preschool↗
PubMed1997

Fluvoxamine in the treatment of obsessive-compulsive disorder and related conditions.

The mainstay of the pharmacologic treatment of obsessive-compulsive disorder (OCD) is a 10- to 12-week trial of a potent serotonin reuptake inhibitor (SRI) at an adequate dose. Double-blind, placebo-controlled trials have established the anti-obsessive-compulsive (OC) efficacy of five different SRIs. One of the most thoroughly studied of these SRIs is fluvoxamine, the focus of this article. Fluvoxamine's pharmacologic and pharmacokinetic properties, its efficacy, and guidelines for its clinical use in OCD and related disorders are briefly reviewed. Potential drug-drug interactions are discussed and placed in clinical perspective. The management of common SRI-induced side effects is also addressed. Recent comparative studies suggest that fluvoxamine may be equivalent in efficacy to clomipramine, yet better tolerated. Fluvoxamine shows promise in the treatment of several so-called OC-spectrum disorders, but additional controlled trials are needed.

Adolescent↗