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Biomedical subjects

P A Rogers

Publications and source records attributed to P A Rogers.

At least 19 recordsLinked to original sources
PubMed2003

Opportunistic screening for genital chlamydial infection. I: acceptability of urine testing in primary and secondary healthcare settings.

OBJECTIVES: To determine the acceptability of opportunistic screening for Chlamydia trachomatis in young people in a range of healthcare settings. DESIGN: An opportunistic screening programme (1 September 1999 to 31 August 2000) using urine samples tested by ligase chain reaction (LCR). Data on uptake and testing were collected and in-depth interviews were used for programme evaluation. SETTING: General practice, family planning, genitourinary medicine clinics, adolescent sexual health clinics, termination of pregnancy clinics, and women's services in hospitals (antenatal, colposcopy, gynaecology and infertility clinics) in two health authorities (Wirral and Portsmouth and South East Hampshire). Main participants: Sexually active women aged between 16 and 24 years attending healthcare settings for any reason. MAIN OUTCOME MEASURES: Uptake data: proportion of women accepting a test by area, healthcare setting, and age; overall population coverage achieved in 1 year. Evaluation data: participants' attitudes and views towards opportunistic screening and urine testing. RESULTS: Acceptance of testing by women (16-24 years) was 76% in Portsmouth and 84% in Wirral. Acceptance was lower in younger women (Portsmouth only) and varied by healthcare setting within each site. 50% of the target female population were screened in Portsmouth and 39% in Wirral. Both the opportunistic offer of screening and the method of screening were universally acceptable. Major factors influencing a decision to accept screening were the non-invasive nature of testing and treatment, desire to protect future fertility, and the experimental nature of the screening programme. CONCLUSIONS: An opportunistic model of urine screening for chlamydial infection is a practical, universally acceptable method of screening.

Adolescent↗
PubMed2003

Opportunistic screening for genital chlamydial infection. II: prevalence among healthcare attenders, outcome, and evaluation of positive cases.

OBJECTIVES: To determine the prevalence and treatment outcomes among young women screened opportunistically for genital Chlamydia trachomatis and to evaluate the impact of screening in those participating. DESIGN: An opportunistic screening programme (1 September 1999 to 31 August 2000) using urine samples, tested by ligase chain reaction (LCR). In-depth interviews were used for programme evaluation. SETTING: Screening was offered in two health authorities at general practice, family planning, genitourinary medicine (GUM), adolescent sexual health, termination of pregnancy clinics and women's services in hospitals (antenatal, colposcopy, gynaecology and infertility clinics). Main participants: Sexually active women (16-24 years) attending for any reason. MAIN OUTCOME MEASURES: Screening data: prevalence of infection by age and healthcare setting; proportion of positive patients attending for treatment. Evaluation data: participants' attitudes and views towards screening and follow up. RESULTS: In total, 16 930 women (16-24 years) were screened. Prevalence was higher in younger women (16-20) than those aged 21-24 years and was highly variable at different healthcare settings (range 3.4%-17.6%). Prevalence was approximately 9% in general practice. The role of the project health advisers in managing results and coordinating treatment of positive individuals was essential; the vast majority of all positives were known to be treated. Women felt that screening was beneficial. Improving awareness and education about sexually transmitted infections is required to alleviate negative reactions associated with testing positive for infection. CONCLUSIONS: Prevalence of infection outside GUM clinics is substantial and opportunistic screening using urine samples is an acceptable method of reaching individuals with infection who do not normally present at specialist clinics.

Adolescent↗
PubMed2001

L-cysteine-mediated destabilization of dinitrosyl iron complexes in proteins.

Nitric oxide is a signaling molecule in intercellular communication as well as a powerful weapon used by macrophages to kill tumor cells and pathogenic bacteria. Here, we show that when Escherichia coli cells are exposed to nitric oxide, its ferredoxin [2Fe-2S] cluster is nitrosylated, forming the dinitrosyl iron complex with a characteristic EPR signal at g(av) = 2.04. Such formed ferredoxin dinitrosyl iron complex is efficiently repaired in E. coli cells even in the absence of new protein synthesis. However, the repair activity is completely inactivated once E. coli cells are disrupted, indicating that repairing the ferredoxin dinitrosyl iron complex requires cellular reducing equivalents. In search of such cellular factors, we find that l-cysteine can effectively eliminate the EPR signal of the ferredoxin dinitrosyl iron complex and release the ferrous iron from the complex. In contrast, N-acetyl-l-cysteine and reduced glutathione are much less effective. l-Cysteine seems to have a general function, since it can also remove the otherwise stable dinitrosyl iron complexes from proteins in the cell extracts prepared from the E. coli cells treated with nitric oxide. We propose that l-cysteine is responsible for removing the dinitrosyl iron complexes from the nitric oxide-modified proteins into which a new iron-sulfur cluster will be reassembled.

Cysteine↗
PubMed2001

National surveillance of HIV-1 subtypes for England and Wales: design, methods, and initial findings.

The HIV-1 infections detected in an ongoing national unlinked anonymous HIV surveillance program were subtyped and analyzed according to demographic and risk characteristics. Of the 893 anti--HIV-1--positive specimens allocated to an exposure group, 70% could be subtyped. Almost 25% of infections subtyped were non-B, mostly subtypes A, C, and D. Non-B infections were rare in homosexual and bisexual men and in drug injectors. Forty percent of infections in heterosexual men attending genitourinary medicine clinics were non-B subtypes; of these, 25% were subtype A infections and 59% were subtype C infections. For female clinic attendees, 61% were non-B subtype infections, of which 48% were subtype A infections and 42% were subtype C infections. Of the clinic attendees born in the United Kingdom and Europe, 14% of the men and 35% of the women were infected with non-B subtypes. In contrast, 78% of infections in antenatal patients were non-B subtypes, of which 61% were subtype A and 29% were subtype C. Extrapolation to the estimated 29,700 prevalent adult infections in the United Kingdom indicates that approximately 8,100 (27%) such infections are non-B subtypes and that these are found almost entirely in heterosexuals. The findings suggest spread of infection of non-B subtypes to heterosexuals born in the United Kingdom from individuals infected in regions of high prevalence.

Acute Disease↗
PubMed2001

Localization of vascular endothelial growth factor-D in malignant melanoma suggests a role in tumour angiogenesis.

Expression of angiogenic and lymphangiogenic factors by tumours may influence the route of metastatic spread. Vascular endothelial growth factor (VEGF) is a regulator of tumour angiogenesis, but studies of the inhibition of solid tumour growth by neutralizing anti-VEGF antibodies indicated that other angiogenic factors may be involved. VEGF-D may be an alternative regulator because like VEGF it is angiogenic and it activates VEGF receptor-2 (VEGFR-2), an endothelial cell receptor which is a key signalling molecule in tumour angiogenesis. This study reports the generation of monoclonal antibodies to the receptor-binding domain of VEGF-D and the use of these antibodies to localize VEGF-D in malignant melanoma. VEGF-D was detected in tumour cells and in vessels adjacent to immunopositive tumour cells, but not in vessels distant from the tumours. These findings are consistent with a model in which VEGF-D, secreted by tumour cells, activates endothelial cell receptors and thereby contributes to the regulation of tumour angiogenesis and possibly lymphangiogenesis. In addition, VEGF-D was detected in the vascular smooth muscle, but not the endothelium, of vessels in adult colon. The endothelium of these vessels was negative for VEGFR-2 and VEGFR-3. As VEGF receptors can be up-regulated on endothelium in response to vessel damage and ischaemia, these findings of a specific localization of VEGF-D in smooth muscle of the blood vessels suggest that VEGF-D produced by vascular smooth muscle could play a role in vascular repair by stimulating the proliferation of endothelial cells.

Animals↗
PubMed2001

Expression of the chemokines, monocyte chemotactic protein (MCP)-1 and MCP-2 in endometrium of normal women and Norplant users, does not support a central role in macrophage infiltration into endometrium.

The endometrium contains many leukocytes, including macrophages, the numbers varying with the time of the menstrual cycle and being maximal peri-menstrually. The long-acting progestogenic contraceptive Norplant, has a high rate of discontinuation due to uterine bleeding; this is associated with large numbers of endometrial macrophages. Monocyte chemotactic proteins (MCP) act to recruit and activate monocytes into sites of inflammation. This study compared the cellular localization of endometrial MCP-1 and MCP-2 across the normal menstrual cycle and in users of Norplant. Both MCP-1 and MCP-2 were present in normal endometrium, but with very different patterns of cellular location and considerable variability between individuals. MCP-1 of epithelial origin was present in 77% of tissues, while stromal staining was present in 52% and vascular staining in 34% of samples. MCP-1 was also released from both epithelial and stromal cells in culture. MCP-2 staining was predominantly epithelial and was found in 52% of tissues while stromal staining was present in only 3/56 samples. Vascular staining of MCP-2 was found in 2/56 samples. The epithelial staining was mostly punctate and sometimes within uterine secretions. No correlation of staining for MCP-1 or -2 with the phase of the cycle was found in any cellular compartment. Very little immunoreactive MCP-1 or MCP-2 was detected in endometrium from Norplant users regardless of morphological subtype. These distributions do not support a role for either MCP-1 or MCP-2 in the migration of macrophages into the endometrium and suggest that these cytokines may have other functions in this tissue.

Cells, Cultured↗
PubMed2001

Focal vascular endothelial growth factor correlates with angiogenesis in human endometrium. Role of intravascular neutrophils.

Vascular endothelial growth factor (VEGF) is expressed in human endometrium, but the cellular source of VEGF for endometrial angiogenesis has not been determined. In the present study the relationship between focal VEGF associated with microvessels and endothelial cell proliferation was examined in three layers of human endometrium at various stages of the menstrual cycle (menstrual, proliferative and secretory). Immunohistochemical analysis of full thickness endometrium from 18 hysterectomy samples without endometrial pathology were examined. The percentage of proliferating vessels was higher in proliferative compared to secretory endometrium, but this was only statistically significant in the basalis layer. A significantly greater percentage of VEGF-expressing microvessels was observed in proliferative than secretory endometrium (P < 0.05). The most VEGF-expressing microvessels were observed in the subepithelial capillary plexus, followed by the functionalis and least were present in the basalis. There was a significant correlation between focal VEGF-expressing microvessels and proliferating vessels for the subepithelial capillary plexus (R(s) = 0.70, P = 0.008), the functionalis (R(s) = 0.70, P = 0.001) and the basalis (R(s) = 0.76, P < 0.001). Focal VEGF associated with microvessels was found in marginating and adherent neutrophils. These data suggest that neutrophils in intimate contact with endometrial endothelium may be a source of intravascular VEGF for vessels undergoing angiogenesis by elongation or intussusception, particularly during the proliferative phase of rapid endometrial growth.

Adult↗
PubMed2001

Characteristics of those who repeatedly acquire sexually transmitted infections: a retrospective cohort study of attendees at three urban sexually transmitted disease clinics in England.

BACKGROUND: Individuals who repeatedly acquire sexually transmitted infections (STIs) may facilitate the persistence of disease at endemic levels. Identifying those most likely to become reinfected with an STI would help in the development of targeted interventions. GOAL: To investigate the demographic and behavior characteristics of sexually transmitted disease (STD) clinic patients most likely to reattend with an STI. STUDY DESIGN: The proportion of patients attending three STD clinics in England between 1994 and 1998 who reattended for treatment of acute STI within 1 year was estimated from Kaplan-Meier failure curves. A Cox proportional hazard model was used to investigate the relation between rate of reattendance with an acute STI and patient characteristics. RESULTS: Of the 17,466 patients presenting at an STD clinic with an acute STI, 14% reattended for treatment of an STI within 1 year. Important determinants of reinfection were age, sexual orientation, and ethnicity: 20% of 12- to 15-year-old females (adjusted hazard ratio [HR], 1.90; CI, 1.13-3.18, compared with 20- to 24-year-old females), 22% of homosexual men (adjusted HR, 1.30; CI, 1.07-1.58, compared with heterosexual men), and 25% of black Caribbean attendees (adjusted HR, 1.87; CI, 1.63-2.13, compared with whites) reattended for treatment of acute STI within 1 year. In addition, 21% of those with a history of STI (adjusted HR, 1.42; CI, 1.28-1.59, compared with those with no history of STI) and 17% of individuals reporting three or more partners in the recent past (adjusted HR, 1.53; CI, 1.34-1.73, compared with those with one partner) reattended for treatment of an acute STI within 1 year. CONCLUSIONS: In this STD clinic population, teenage females, homosexual men, black Caribbean attendees, individuals with a history of STI, and those reporting high rates of sexual partner change repeatedly re-presented with acute STIs. Directing enhanced STD clinic-based interventions at these groups may be an effective strategy for STI control.

Acute Disease↗
PubMed2001

Is bacterial vaginosis a sexually transmitted infection?

OBJECTIVES: To determine whether the risk factors associated with bacterial vaginosis (BV) are consistent with it being a sexually transmitted infection (STI) by comparing the characteristics of women with BV with those of women with infections recognised as being sexually and non-sexually transmitted. METHODS: A prospective cross sectional study was conducted among female patients presenting for diagnosis at a genitourinary medicine clinic in Sheffield between January 1996 and September 1998. Demographic and behavioural characteristics were reported from patient records and a standardised questionnaire was administered. Risk factor models for BV, two STIs, and two non-STIs were compiled using a multivariable logistic regression analysis. RESULTS: Among the 8989 females under 45 years eligible for analysis, the prevalence of BV was 12.9%. Risk factors associated with BV included some in common with gonorrhoea and Chlamydia trachomatis and some that were not associated with these two STIs. Risk factors common to BV and the STIs included having had more than one sexual partner in the past 3 months, having a history of a bacterial STI, being of black Caribbean ethnicity, and living in a deprived area. However, BV had a contrasting age profile, being most prevalent among those over the age of 30. BV was also more common in those who were divorced. CONCLUSIONS: BV is associated with some factors related to the acquisition of gonorrhoea and Chlamydia trachomatis. However, infection is not only determined by those factors and therefore factors other than sexual activity may be important in the development of the condition.

Adolescent↗
PubMed2001

Human endometrial angiogenesis.

Angiogenesis is the development of new microvessels from existing vessels, a process that involves microvascular endothelial cells. Physiological angiogenesis rarely occurs in adults except in the ovary and endometrium during the reproductive life of females. Angiogenesis occurs by sprouting and non-sprouting mechanisms. Since endothelial sprouts are not observed in human endometrium, we hypothesized that non-sprouting mechanisms such as intussusception and elongation are involved in endometrial angiogenesis. The demand for angiogenesis differs spatially and temporally in the endometrium: angiogenesis occurs in the basalis layer during menstruation and in the functionalis and subepithelial capillary plexus during the proliferative and early secretory stages. Most studies have failed to demonstrate a link between expression of endometrial angiogenic factors and new vessel growth. However, we demonstrated recently a strong relationship between vascular endothelial growth factor (VEGF) immunolocalized in in-travascular neutrophils and endothelial cell proliferation in each of the subepithelial capillary plexus, functionalis and basalis regions of the human endometrium. Our data also indicate that focal neutrophil VEGF has a role in the development of the subepithelial capillary plexus and functionalis microvessels during the proliferative phase of the menstrual cycle. We propose that neutrophils are an intravascular source of VEGF for vessels that undergo angiogenesis by intussusception and elongation.

Endometrium↗
PubMed2001

Role of vascular endothelial growth factor in endometrial vascular events before implantation in rats.

Two endometrial vascular events, increased permeability and endothelial cell proliferation, characterize the early stages of embryo implantation in rats. Vascular endothelial growth factor (VEGF), a heparin-binding homodimeric glycoprotein, is expressed in the uterus at the time of implantation. The aim of this study was to investigate the effects of systemic administration of blocking antibody to VEGF on endometrial vascular permeability and endothelial cell proliferation around the time of embryo implantation in rats. Rats were injected i.p. with 1.0, 0.8 or 0.6 ml of anti-VEGF antibody or control serum on day 3 of pregnancy and Evans blue dye was administered i.v. on day 5 of pregnancy. The number of implantation sites (blue bands along the uterus) was counted and endothelial cell proliferation was identified using double staining immunohistochemistry. The number of blue bands was significantly lower (P < 0.05) after injection of 1.0 ml blocking antibody (1.8 +/- 1.56) compared with that in control rats (11.6 +/- 1.97). The number of blue bands was significantly different among rats injected with 1.0 (1.8 +/- 1.56), 0.8 (6.0 +/- 3.67) or 0.6 (10.7 +/- 0.33) ml anti-VEGF antibody, indicating a concentration effect of anti-VEGF antibody. No significant differences in endothelial cell proliferation at embryo implantation sites were observed after injection with anti-VEGF antibody or control serum. At intersites (uterine zones between the blue bands), injection of 0.6 ml anti-VEGF antibody caused a significant reduction (P < 0.05) in the percentage of vessels with proliferating endothelial cells (7.25 +/- 2.39%), with a non-significant reduction using 1.0 or 0.8 ml anti-VEGF antibody. No significant differences in microvascular density at either embryo implantation sites or intersites were observed between rats injected with anti-VEGF antibody or control serum. In conclusion, VEGF is the main factor responsible for increased endometrial vascular permeability at implantation. It may regulate endometrial endothelial cell proliferation before implantation and at intersites, thus indicating that factors or mechanisms other than VEGF may regulate endothelial cell proliferation at the site of implantation.

Animals↗
PubMed2000

What a test for recent infection might reveal about HIV incidence in England and Wales.

BACKGROUND: A laboratory method has been developed that detects recent HIV infection and allows incidence to be estimated by testing single stored antibody-positive specimens. A theoretical exploration of the method's surveillance utility was carried out. METHODS: Using various data sources, HIV incidence rates were postulated. The confidence intervals (CI) for these postulated incidences were calculated using the expected number of recent infections for each postulated incidence, the actual number tested for HIV, and the known number of HIV-1 positives. A test for trend was used to determine when an important change in incidence could be recognized. RESULTS: If the incidence was 5% per annum (p.a.) in homosexual/bisexual men attending sexually transmitted diseases (STD) clinics in London, 64 recent infections would be expected in the 392 HIV-seropositive specimens and, if observed, would result in a 95% CI of 3.1-7.9% p.a. for the incidence rate. An incidence of 1% p.a. in pregnant women would be most unlikely as this would require detection of 193 recent infections, 26 more than the total 167 HIV-seropositive specimens found in 1997. In African women attending STD clinics in London, 30% of prevalent infections would be classified as recent if the incidence was 5% p.a. Further, if the incidence in homosexual/bisexual men were to fall by 50% over 3 years, a decrease of this magnitude would be recognized as significant within 2 years. CONCLUSIONS: The detuned assay will increase the information from HIV serosurveys even where prevalence and incidence are relatively low. Existing surveillance systems should be redesigned to take full advantage of the method.

Confidentiality↗
PubMed2000

Endometrial angiogenesis.

The endometrium is one of the few tissues in the adult where physiological angiogenesis occurs. Studies of endometrial angiogenesis are complicated by the continual changes in tissue growth and regression during the menstrual cycle, and differences between the two different zones of the endometrium--the functionalis and basalis. The mechanisms of angiogenesis in the endometrium may be different to those in solid tumours, requiring a re-evaluation of the relative importance of various angiogenesis promoters and inhibitors. None of the angiogenesis promoters or inhibitors have yet been demonstrated beyond doubt to have a biological role in endometrial angiogenesis in vivo. Thus, the mechanisms, timing and control of angiogenesis in the endometrium are far from being fully understood.

Angiogenesis Inhibitors↗
PubMed2000

Social and behavioural factors associated with HIV seroconversion in homosexual men attending a central London STD clinic: a feasibility study.

An unmatched retrospective case control study was conducted to test the feasibility of investigating social and behavioural factors which may have contributed to recent HIV seroconversion in a group of homosexual men. Participants, recruited from a London sexually transmitted disease (STD) clinic, were sexually active and had had a negative HIV test with a subsequent test (positive (cases) or negative (controls)) within three to 15 months. Twenty cases and 22 controls were recruited between February and October 1995. There was no difference between cases and controls in: the number of regular or casual sexual partners, the proportion who were unaware of their regular partners' serostatus (cases 60%, controls 59%), or the proportion who had known HIV-positive regular partners (cases 20%, controls 23%). A significant difference in sexual behaviour was found only when the HIV status of partners, if known, was taken into account: cases were more likely than controls to have had unprotected receptive anal intercourse with a partner not known to be HIV-negative (OR = 5.5, CI = 1.15-29.50). Fifty per cent of the cases and 27% of the controls acquired acute STDs between the two HIV tests. All participants achieved high self-efficacy scores, but the controls believed their peers placed a greater value on safer sex. Cases cited emotional issues and the use of drugs and alcohol as contributing to their seroconversion, whereas controls cited a commitment to safer sex and the avoidance of high-risk situations as contributing to their remaining HIV-negative. The results illustrate the importance of acknowledging the concept of 'negotiated safety' in studies of sexual behaviour; seroconversion was only associated with unprotected sex with a partner not known to be HIV-negative. Despite high self-efficacy scores, indicating the skills to negotiate safer sex, high levels of unsafe anal intercourse were reported. Differences between cases and controls included the importance of safer sex, periods of emotional vulnerability, influence of peers and the appropriate use of condoms. There is a need for these results to be confirmed in a larger and more powerful study.

Adult↗
PubMed2000

Matrix metalloproteinase-1 and -3 and mast cells are present in the endometrium of women using progestin-only contraceptives.

Progestin-only contraceptives are associated with menstrual bleeding disturbances; a major reason why these agents are discontinued. The pathogenesis of such abnormal uterine bleeding associated with progestin-only contraceptives remains ill-defined. Matrix metalloproteinases (MMP)s and mast cells (MC)s are postulated to be involved in endometrial breakdown observed in normal menstruation. In this study comparisons were made of the immunolocalization of MMP-1 and -3 and MC in endometrium from women using Norplant or depot medroxyprogesterone acetate (DMPA) with normal controls. Positive MMP immunostaining was observed focally in stromal cells and adjacent extracellular matrix. Quantitative assessment revealed significantly higher MMP-1 immunostaining associated with the use of Norplant compared with DMPA or menstrual phase controls. Endometrial MMP-1 immunostaining in DMPA users was similar to that in menstrual controls. Positive MMP-3 immunolocalization was observed in a minority of endometrial samples. Activated MC, shown by the presence of extracellular MC tryptase, predominated in the endometrium of Norplant and DMPA users as also observed in menstrual phase controls. There was no correlation between MMP immunostaining, number of MC and number of bleeding days reported. These results indicate that in women using progestin-only contraceptives, endometrial MMP-1, -3 and MC demonstrate similarities to menstrual phase controls but also variation with different progestins.

Adult↗
PubMed2000

Isolation, characterization and long-term culture of human myometrial microvascular endothelial cells.

Angiogenesis, defined as the growth of new vessels from pre-existing vessels, involves microvascular rather than large vessel endothelial cells. Accordingly, microvascular endothelial cell (MEC) proliferation assays are an appropriate in-vitro model of angiogenesis. We have developed a method for the isolation and long-term culture of large numbers of MEC from the human myometrium, tissue readily available from hysterectomy specimens. Human myometrial MEC were positively selected from tissue dissociated sequentially with collagenase and trypsin using Ulex europeaus antigen-1 (UEA)-coated dynabeads. Cultured myometrial MEC displayed characteristic endothelial phenotype and function for up to 14 passages: cobblestone morphology, formed capillary-like tubes on Matrigel, expressed CD31, Factor VIII-related antigen, bound UEA lectin, incorporated 1,1'-dioctadecyl-1,3,3,3', 3'-tetramethylindocarbocyanine perchlorate-labelled acetylated low density lipoprotein, migrated and proliferated in response to basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), but not epidermal growth factor. Optimal growth of human myometrial MEC occurred in a simple medium comprising M199, 5 ng/ml bFGF, 15% human serum, 5% fetal calf serum (FCS) and heparin. Human serum was essential for growth, although there was a synergistic effect when FCS was included. Almost identical dose-response curves were obtained for bFGF- and VEGF-induced myometrial MEC proliferation in early and late passage cells. Therefore myometrial MEC are a good model for in-vitro studies of uterine angiogenesis, since they have a stable phenotype and proliferative responsiveness to VEGF and bFGF for up to 14 passages.

Adult↗