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C Connolly

Publications and source records attributed to C Connolly.

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

Effects of the selective cyclooxygenase-2 inhibitor nimesulide on vascular contractions in endothelium-denuded rat aorta.

We have examined the effects of the selective cyclooxygenase-2 inhibitor nimesulide and the non-selective cyclooxygenase inhibitor indomethacin on vascular responsiveness of endothelium-denuded rat aorta. Isometric contractions were obtained to the alpha-adrenoceptor agonists phenylephrine (full agonist) and clonidine (partial agonist relative to phenylephrine) and to endothelin-1 and KCl. Maximum contractile responses to the partial agonist clonidine were significantly reduced by nimesulide (10 microM) and by indomethacin (10 microM) to 60.8 +/- 8.5% (n = 8) and 69.0 +/- 9.6% (n = 12) of control, respectively, as compared with the effects of vehicle (99.0 +/- 5.8%; n = 17). The inhibitors had lesser effects against contractions to phenylephrine: nimesulide had no significant effect, whereas indomethacin caused a small but significant reduction in the maximum contraction to phenylephrine to 90.3 +/- 5.0% (n = 12) of control (vehicle: 108.0 +/- 5.2%, n = 15 nimesulide: 111.8 +/- 5.9%, n = 5). Neither nimesulide nor indomethacin had any effect on contractions to endothelin-1 or KCl. These actions differed from the effects of the Ca2+ entry blocker nifedipine, which significantly reduced contractions to clonidine and KCl to a similar extent. The maximum contraction to clonidine was also significantly reduced by the thromboxane receptor antagonist SQ 29548 (1 microM) to 83.4 +/- 6.4% of control (n = 7) (vehicle 115.5 +/- 7.5%, n = 7). It is concluded that the cyclooxygenase inhibitors nimesulide or indomethacin reduce vascular responsiveness to alpha-adrenoceptor agonists in endothelium-denuded rat aorta, presumably by preventing the formation of vasoconstrictor prostaglandins in aortic smooth muscle by cyclooxygenase-2. This reduced vascular responsiveness was most clearly seen with the partial agonist clonidine.

Animals↗
PubMed1998

The description of gay and lesbian families in second-parent adoption cases.

Lesbians and gay men are turning to the courts to recognize their family relationships. In this article every reported court decision where a lesbian or gay couple has successfully completed a second-parent adoption is reviewed to analyze the presentation and judicial analysis of the petitioning parties in conjunction with the current debates within family theory. Traditional family theorists argue that the contemporary family is in transition but will always be recognizable as the traditional family; postmodern theorists argue that the traditional "family" is a fiction. Results from this study indicate that judges in second-parent adoption cases rely on a traditional definition and vision of the family in evaluating the gay and lesbian petitioners before them.

Adoption↗
PubMed1998

Pharmacokinetics of methyl palmoxirate, an inhibitor of beta-oxidation, in rats and humans.

Recent studies from our laboratory have shown that methyl palmoxirate (MEP), an inhibitor of mitochondrial beta-oxidation of long chain fatty acids, can be used to increase incorporation of radiolabeled palmitic acid into brain lipids and reduce beta-oxidation of the fatty acid. Thus, MEP allows the use of carbon labeled palmitate for studying brain lipid metabolism in animals and humans by quantitative autoradiography or positron emission tomography (PET). As it is essential to pretreat human subjects with an acute dose of MEP prior to intravenous injection of [1-11C]palmitate for PET scanning, this study was undertaken to determine the plasma elimination half-life of MEP in rats and human subjects and to provide insight about the drug's absorption and metabolism. A gas chromatographic method was developed to measure MEP in body fluids. Following oral administration of MEP to rats (2.5 and 10 mg/kg) and to humans, the unmetabolized drug could not be detected in plasma or urine (sensitivity of detection was 1 ng). However, when MEP was injected intravenously (10 mg/kg) in rats, a peak initial concentration could be measured in plasma (7.7 microg/mL), the clearance of the drug from plasma was rapid (t1/2 = 0.6 min), which indicates that MEP readily enters tissue lipid pools or is metabolized like long-chain fatty acids. As no adverse experience occured in the 11 human subjects studied, oral administration of a single dose of MEP was safe under the conditions of this study and may be used to increase the incorporation of positron labeled palmitic acid for studying brain lipid metabolism in vivo by PET.

Administration, Oral↗
PubMed1998

HIV infection and asymptomatic sexually transmitted infections in a rural South African community.

The objective was to determine the prevalence of HIV and other sexually transmitted infections (STIs) in a rural community. A population-based survey of adults in 110 homesteads was conducted in 1995. A questionnaire on demographics, sexual practices and history of STDs was administered. Neisseria gonorrhoeae and Chlamydia trachomatis infections were detected using ligase chain reaction (LCR) assay of urine. The seroprevalence of syphilis rapid plasma reagin (RPR) and Treponema pallidum haemagglutination assay (TPHA) and HIV infection (ELISA) was determined. Among 259 subjects the prevalence of HIV was 10.5%, N. gonorrhoeae 4.5%, C. trachomatis 6.1% and active syphilis 8.8%. All infections were asymptomatic. Forty per cent of sexually active men had more than one concurrent sexual partner. Only 14% of subjects had ever used condoms. The STI epidemic is being promoted by high levels of asymptomatic infections, high partner concurrency and low condom use.

Adult↗
PubMed1998

Pregnant women as a reservoir of undetected sexually transmitted diseases in rural South Africa: implications for disease control.

OBJECTIVES: This study was undertaken to determine the prevalence of sexually transmitted diseases (STDs) in pregnant women in rural South Africa and to determine the value of using abnormal urogenital symptoms to identify infected women. METHODS: This was a cross-sectional study of 327 patients attending prenatal clinics. RESULTS: Of the 271 women with complete data, 141 (52%) had at least 1 STD and 49 (18%) had more than 1. Abnormal symptoms were common (n = 225; 83%), but associations were weak, and the positive predictive value of different symptoms for infection ranged from 2% to 54%. CONCLUSIONS: Most STDs in rural South African women remain undetected and untreated. As the scope for laboratory diagnosis in resource-poor settings is limited, presumptive treatment of pregnant women and their partners may be a cost-effective option to reduce transmission of STDs and HIV infection.

Adult↗
PubMed1998

Should we take a history of prior treatment, and check sputum status at 2-3 months when treating patients for tuberculosis?

SETTING: Pinetown, South Africa (1975-1983). OBJECTIVE: To determine the value of previous treatment history and sputum smear examination at 2-3 months in predicting treatment failure and relapse in tuberculosis patients treated with four drugs given twice weekly for six months under direct observation. DESIGN: Four cohort studies among 562 ambulant adults with culture positive pulmonary tuberculosis, designed to test the effectiveness of isoniazid 600-900 mg, rifampicin 600 mg, pyrazinamide 2-3 g, and streptomycin 1-2 g, given twice weekly. The same drug regimen was given to all patients irrespective of previous treatment history. Therapy was not changed if smears remained positive at 2-3 months. RESULTS: Positive predictive values of a history of previous treatment for a positive smear at 2-3 months (18.3%), treatment failure (5.2%), and relapse (9.4%) were poor. Although patients with positive smears at 2-3 months were more likely to fail therapy than patients with negative smears (relative risk=4.5, 95% Confidence Interval [CI]: 1.6-12.8), positive predictive value for treatment failure was only 12.5%. Although relapse was more frequent in patients with positive smears than those with negative smears (9.7% vs 6.2%; P=0.4), most patients who relapsed had been smear negative at 2-3 months (18/21). CONCLUSION: A four-drug rifampicin-containing regimen can safely be given twice weekly under direct observation to both new and retreatment cases, and the 2-3 month smear examination can safely be omitted.

Adult↗
PubMed1998

In vitro biological characterization and antiangiogenic effects of PD 166866, a selective inhibitor of the FGF-1 receptor tyrosine kinase.

Through direct synthetic efforts, we discovered a small molecule that is a nanomolar inhibitor of the human fibroblast growth factor-1 receptor (FGFR) tyrosine kinase. PD 166866, a member of a new structural class of tyrosine kinase inhibitors, the 6-aryl-pyrido[2,3-d]pyrimidines, was identified by screening a compound library with assays that measure protein tyrosine kinase activity. PD 166866 inhibited human full-length FGFR-1 tyrosine kinase with an IC50 value of 52.4 +/- 0.1 nM and was further characterized as an ATP competitive inhibitor of the FGFR-1. In contrast, PD 166866 had no effect on c-Src, platelet-derived growth factor receptor-beta, epidermal growth factor receptor or insulin receptor tyrosine kinases or on mitogen-activated protein kinase, protein kinase C and CDK4 at concentrations as high as 50 microM. PD 166866 was a potent inhibitor of basic fibroblast growth factor (bFGF)-mediated receptor autophosphorylation in NIH 3T3 cells expressing endogenous FGFR-1 and in L6 cells overexpressing the human FGFR-1 tyrosine kinase, confirming a tyrosine kinase-mediated mechanism. PD 166866 also inhibited bFGF-induced tyrosine phosphorylation of the 44- and 42-kDa (ERK 1/2) mitogen-activated protein kinase isoforms in L6 cells, presumably via inhibition of bFGF-stimulated FGFR-1 tyrosine kinase activation. PD 166866 did not inhibit platelet-derived growth factor, epidermal growth factor or insulin-stimulated receptor autophosphorylation in vascular smooth muscle, A431 or NIHIR cells, respectively, further supporting its specificity for the FGFR-1. In addition, daily exposure of PD 166866 to L6 cells at concentrations from 1 to 100 nM resulted in a concentration-related inhibition of bFGF-stimulated cell growth for 8 consecutive days with an IC50 value of 24 nM. In contrast, PD 166866 had little effect on platelet-derived growth factor-BB-stimulated growth of L6 cells or serum-stimulated vascular smooth muscle cell proliferation. Finally, PD 166866 was found to be a potent inhibitor of microvessel outgrowth (angiogenesis) from cultured artery fragments of human placenta. These results highlight the discovery of PD 166866, a new nanomolar potent and selective small molecule inhibitor of the FGFR-1 tyrosine kinase with potential use as antiproliferative/antiangiogenic agent for such therapeutic targets as tumor growth and neovascularization of atherosclerotic plaques.

3T3 Cells↗
PubMed1998

Impact of the human immunodeficiency virus epidemic on mortality among adults with tuberculosis in rural South Africa, 1991-1995.

SETTING: In the Hlabisa district tuberculosis programme, South Africa, the prevalence of human immunodeficiency virus (HIV) infection among adults with tuberculosis increased from 36.0% in 1993 to 65.9% in 1997, and the annual tuberculosis caseload increased from 321 in 1991 to 1250 in 1996. OBJECTIVE: To examine the impact of the HIV epidemic on mortality among adults with tuberculosis from 1991 to 1995. METHODS: Data were extracted from the control programme database. As the programme started in July 1991, data for this year were combined with those for 1992. RESULTS: All-cause mortality among all those diagnosed with tuberculosis increased by 45.6%, from 9.2% (55/599) in 1991/92 to 13.4% (96/714) in 1995 (P = 0.02). Among smear-positive patients only, mortality increased by 134%, from 4.4% to 10.3% (P = 0.003). The case-fatality rate (CFR) increased in most age groups of both sexes, the largest increase (157.5%) being among women aged 15-34 years. CFR was highest among those with smear-negative disease (24.7% in 1995). In multifactorial analysis, independent risk factors for mortality were increasing age (P = 0.0001), HIV infection (odds ratio [OR] 3.5, 95 % confidence interval [CI] 2.3-5.4), smear-negative disease (OR 2.5, 95%CI 1.8-3.5), and diagnosis in 1995 vs 1991/92 (OR 1.8, 95%CI 1.2-2.7). Mortality among the HIV infected continued to accrue throughout treatment, whereas non-HIV-infected patients that died did so early in treatment. CONCLUSION: The HIV epidemic is increasing tuberculosis all-cause mortality. As well as having a direct effect on individuals, increased caseloads due to HIV may also contribute to increased mortality by reducing the health system's ability to provide adequate care.

Adolescent↗
PubMed1997

A descriptive study of BRCA1 testing and reactions to disclosure of test results.

BACKGROUND: The identification of the BRCA1 gene is a powerful tool for predicting a patient's lifetime risk for carcinoma of the breast and ovary when she has hereditary breast/ovarian carcinoma (HBOC) syndrome. The process of BRCA1 testing and genetic counseling and participants' reactions to test results, are described. METHODS: Education about the natural history of HBOC syndrome and the pros and cons of genetic testing was provided to 14 HBOC families comprised of 2549 bloodline relatives. Of these, 388 underwent DNA testing. After informed consent was given by participants, formal linkage analysis and gene mutation studies were performed on the families. Qualitative data on intentions and emotional reactions were collected by physicians/counselors during the genetic counseling sessions. RESULTS: Of those tested, 181 received their results after further genetic counseling. Seventy-eight of them were positive and 100 were negative for BRCA1 gene mutation. Three had ambiguous findings. The most common reasons given for seeking DNA testing were concern about risk to children and concern about surveillance and prevention. Prophylactic mastectomy was considered by 35% of women who tested positive, whereas prophylactic oophorectomy was considered an important option by 76%. Twenty-five percent of both BRCA1 positive and negative individuals were concerned about discrimination by insurance companies. Eighty percent of those who tested negative reported emotional relief, whereas over one-third of those who tested positive reported sadness, anger, or guilt. CONCLUSIONS: DNA testing of patients with HBOC syndrome must be performed in the context of genetic counseling. The authors' results demonstrate the many complex clinical and nonclinical issues that are important in this process.

Adult↗
PubMed1997

Comparison of the effects of nitric oxide synthase inhibition and guanylate cyclase inhibition on vascular contraction in vitro and in vivo in the rat.

We have investigated the differences between the nitric oxide synthase inhibitor (NOSI), L-NMMA, and the guanylate cyclase inhibitors (GCI), methylene blue and LY 83583, in their abilities to increase vasoconstrictor responses in vitro and in vivo. In rat small mesenteric arterial rings, 1 h exposure to the NOSI, L-NMMA (100 microM), and the GCI, methylene blue (10 microM), alone or in combination with L-NMMA, caused a significant reduction in the maximum relaxation to ACh in mesenteric arteries pre-contracted with the thromboxane mimetic U46619 (10 microM). Hence, both NOSI and GCI inhibit endothelium-dependent relaxations to ACh in rat small mesenteric artery. However, 1 h exposure to L-NMMA and L-NNA (both 100 microM), but not methylene blue (10 microM), significantly increased the contractile response to U-46619 (10 microM) in rat small mesenteric artery. It was decided to investigate further this difference between NOSI and methylene blue. In rat small mesenteric arterial rings, L-NMMA (10 microM) and LY 83583 (1-10 microM) significantly increased the contractile response to KCl (40 mM) or to noradrenaline (10 microM), when administered during the contraction. However, methylene blue (1-10 microM) increased the contractile response to KCl but not noradrenaline. In rat aortic rings, L-NMMA (100 microM), methylene blue (1-10 microM) and LY 83583 (1-10 microM) significantly increased the contractile response to KCl (40 mM) or to noradrenaline (1 microM). In the pithed rat preparation, L-NMMA (40.3 micromol kg(-1), i.v.) significantly increased the pressor response both to bolus injection of noradrenaline (3.13 nmol kg[-1]) and to spinal pressor nerve stimulation. However, methylene blue (3.13-15.6 micromol kg[-1]) or LY 83583 (4.0-40.0 micromol kg[-1]), failed to affect pressor responses to either NA or pressor nerve stimulation. Hence, there are differences between NOSI and GCI in their abilities to increase vasoconstrictor responses, especially when comparing responses in vitro and in vivo. This suggests that nitric oxide has actions in addition to activation of guanylate cyclase to modulate vasoconstrictor responses, presumably by membrane hyperpolarisation, and that this action may be more important in vivo.

Acetylcholine↗
PubMed1997

Vascular actions of octreotide in the portal hypertensive rat.

1. We have investigated the actions of the somatostatin analogue octreotide in the portal hypertensive Wistar rat in vivo and in rat small mesenteric artery and aorta in vitro. 2. In small mesenteric artery, octreotide (0.1-0.3 microM) failed to produce any direct contraction, nor did it affect contractions to noradrenaline (NA, 10 microM) or endothelium-dependent relaxations to acetylcholine. 3. In rat aorta, octreotide (0.3 microM) and somatostatin (1 microM) failed to affect contractions to NA (1 microM), or concentration-contractile response curves to NA. 4. In rat vas deferens, octreotide and somatostatin significantly reduced contractile responses to electrical stimulation with pD2 values (-log IC50) of 8.19 +/- 0.10 (n = 4) and 8.16 +/- 0.26 (n = 4), respectively. Hence, the lack of effect of these agents in aorta or mesenteric artery was not due to lack of efficacy or inappropriate choice of concentration. 5. In the anaesthetized portal hypertensive rat, intravenous injection of octreotide (1-100 microg kg[-1]) did not significantly affect systemic blood pressure, nor did it affect mesenteric vascular conductance as measured by laser doppler flow probes. However, octreotide (100 microg kg[-1]) significantly reduced vascular conductance to 74.2 +/- 7.7% of control (n = 6) in porto-systemic shunt vessels as measured by laser doppler flow probes. 6. Phenylephrine (1 microg kg[-1]) significantly raised blood pressure and significantly decreased vascular conductance in both mesenteric (66.6 +/- 3.7% of control) and porto-systemic shunt vessels (58.7 +/- 10.0% of control). 7. It was concluded that octreotide has selective effects on porto-systemic shunt vessles in vivo in the portal hypertensive rat.

Animals↗
PubMed1997

Epidemiology of syphilis in pregnancy in rural South Africa: opportunities for control.

The paper describes the epidemiology, risk factors and impact on pregnancy outcome of syphilis in pregnant women in rural South Africa. Prevalence was determined from laboratory records. A case-control study of 200 women (50 cases with syphilis) was done to investigate possible risk factors. To determine the impact on pregnancy outcome, and to evaluate the effect of treatment, a retrospective cohort was constructed. Overall prevalence of syphilis was 6.5%; it was highest in the urban antenatal clinic (9%). The odds ratios for syphilis in women gravidity 3-5 compared to gravidity 6 was 3.2 and 2.3 compared to women with gravidity 2 or less. For women with a previous birth, those with a previous perinatal death were 3.2 times more likely to have syphilis after adjusting for other risk factors. Pregnancy outcome was available for 187 women. The adjusted odds ratio of an adverse pregnancy outcome in women with syphilis was 11.8. All still births occurred in women with syphilis. The prevalence of syphilis is high in this rural area and screening should be applied to all women. Although screening was comprehensive, less than half of the detected cases were fully treated and a poor perinatal outcome ensued. On-site testing for syphilis at the time of booking would allow treatment to start immediately.

Adolescent↗
PubMed1997

Tampon sampling for diagnosis of bacterial vaginosis: a potentially useful way to detect genital infections?

Genital tract infections are important causes of ill health in developing countries, but diagnosis is difficult. Bacterial vaginosis (BV) was correctly diagnosed by using a vaginal specimen obtained by tampon sampling in 22 of 24 women (91.6%) for whom BV was diagnosed by Gram staining. The yield for other vaginal infections was higher (28% for Trichomonas vaginalis and 32.7% for Candida albicans) than it was for cervical infections (0% for Neisseria gonorrhoeae and 30% for Chlamydia trachomatis). Tampon sampling was acceptable to patients and may facilitate diagnosis of genital infections in developing countries.

Bacterial Infections↗
PubMed1997

Family planning services in developing countries: an opportunity to treat asymptomatic and unrecognised genital tract infections?

OBJECTIVE: To determine the prevalence of asymptomatic and unrecognised genital tract infections among women attending a family planning clinic in rural South Africa. METHODS: 189 consecutive women had genital samples taken to diagnose infection with Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, Candida albicans, Treponema pallidum, and HIV, and to diagnose bacterial vaginosis. RESULTS: Mean age was 25 years; 155 (82%) were unmarried, 156 (83%) were currently using contraception, and 41 (22%) reported having an STD treated in the preceding 12 months. Although none volunteered abnormal urogenital symptoms, 74 (39%) had at least one elicited by direct questioning. 119 women (63%) had at least one genital infection: N gonorrhoeae (eight; 4%), C trachomatis (14; 8%), T vaginalis (26; 14%), C albicans (56; 30%), active syphilis (15; 8%), HIV (44; 24%), and bacterial vaginosis (29; 15%). 49 women (26%) had multiple infections. Most infections (71; 60%) were asymptomatic. Symptomatic women failed to recognise and report their symptoms, and routine services failed to detect the infections. CONCLUSION: Prevalence of genital tract infection is high among these women, most infections are asymptomatic, and symptomatic infections are frequently not recognised. Women attending family planning clinics in such settings should be screened for syphilis and offered testing for HIV infection. Strategies to detect and treat other genital infections need to be developed.

Adult↗
PubMed1996

Liver function in early Lyme disease.

To evaluate the frequency, pattern, and severity of liver function test abnormalities in patients with Lyme disease associated with erythema migrans (EM), 115 individuals with no other identifiable cause for liver function test abnormalities who presented with EM between July 1990 and September 1993 were prospectively evaluated. For individuals with abnormal liver function tests, common causes of hepatitis, including hepatitis A, B, and C, were excluded. A local control group was used for comparison. Forty-six (40%) patients had at least one liver test abnormality, and 31 (27%) had more than 1 abnormality compared with 19 (19%) and 4 (4%) of controls, respectively (P < .01 for each comparison). gamma-Glutamyl transpeptidase (28%) and alanine transaminase (ALT) (27%) were the most frequently elevated liver function tests among Lyme disease patients. Anorexia, nausea, or vomiting was reported by 30% of patients, but did not occur more frequently in patients with elevated liver function tests compared with those with normal values. Patients with early disseminated Lyme disease were more likely to have elevated liver function studies (66%) compared with patients with localized disease (34%) (P = .002). After antibiotic treatment, elevated liver function tests improved or resolved in most patients. Liver function test abnormalities are common in patients with EM but were mild, most often not associated with symptoms, and improved or resolved by 3 weeks after the onset of antibiotic therapy in most patients.

Adult↗
PubMed1996

Directly observed therapy for tuberculosis in rural South Africa, 1991 through 1994.

OBJECTIVES: This paper describes an audit of a community-based tuberculosis treatment program involving directly observed therapy in South Africa. METHODS: A program audit of 2473 consecutive tuberculosis patients in Hlabisa Health District, KwaZulu/Natal, South Africa, was conducted between 1991 and 1994. RESULTS: Monthly admissions increased from 34 per month in 1991 to 66 in 1994. Of 2186 patients managed in Hlabisa, 1903 (87%) received directly observed therapy. Of those receiving directly observed therapy, 1034 (55%) were supervised by volunteers; 743 (72%) of these were supervised by storekeepers. Among those patients managed locally, 1679 (85%) of 1967 surviving patients completed treatment. Completion rates for patients supervised by health workers and non-health workers were the same. Completion fell from a high of 90% in 1992 to 78% in 1994. Mortality increased from 5% in 1991 to 10% in 1994. CONCLUSIONS: Community-based directly observed therapy that uses an intermittent drug regime and volunteers as supervisors can achieve high treatment completion rates for tuberculosis, even in resource-poor settings.

Adult↗