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Biomedical subjects

C Connolly

Publications and source records attributed to C Connolly.

At least 19 recordsLinked to original sources

Identification of women at high STD risk among STD clinic attendees: implications for STD programmes.

We showed an association between current infection with a recognized sexually transmitted infection (STI) pathogen and HIV infection in women but not in men with non-ulcerative genital disease. While the accuracy of recognition of male urethritis and genital ulcer syndromes is high, this is significantly less for non-ulcerative STIs in women. The symptoms associated with the latter have a broad differential diagnosis including conditions of a non-STI nature. Local sexually transmitted disease (STD) clinic attendees often comprise patients with and without STIs. We hypothesized that this may be responsible for the association of current STI pathogens and HIV in women. To identify a group of women that would be representative of a true STD clinic population we looked at those with a past history of treated genital ulcers. When we analysed in this subset the association of current STI pathogen and HIV infection, a pattern emerged that was comparable with that in men.

Adolescent↗

Diagnosis of bacterial vaginosis on self-collected vaginal tampon specimens.

A vaginal tampon specimen was previously shown to be suitable for the molecular diagnosis of non-ulcerative sexually transmitted infections (STIs). Different tampon fluid preparations were evaluated for the diagnosis of bacterial vaginosis (BV). Women with pregnancy related problems were enrolled. Two observers evaluated the different tampon fluid preparations and vaginal smears collected during speculum examination using the Nugent score. Using the Amsel criteria, 21% of the 84 women enrolled were diagnosed with BV. Results of the tampon fluid preparations and vaginal smears showed excellent agreement for both observers (Spearman >0.80). The overall sensitivity and specificity was 91.7% (95% CI: 81.6-96.5) and 79.3% (95% CI: 67.2-87.8), respectively, using the Amsel criteria as reference standard. The tampon provides a specimen for the combined diagnosis of non-ulcerative STIs and BV. This non-invasively collected specimen may facilitate self-initiated testing and population-based studies as well as longitudinal studies that are necessary to gain insight in the epidemiology of BV related to STIs and HIV.

Adult↗

Effects of methylenedioxymethamphetamine on noradrenaline-evoked contractions of rat right ventricle and small mesenteric artery.

We have compared the effects of methylenedioxymethamphetamine (MDMA) and cocaine on contractions to noradrenaline in 1 Hz paced rat right ventricular strips, and in rat small mesenteric artery and aorta. Noradrenaline increased the force of contraction of 1 Hz paced ventricular strips with a pD(2) (-log EC(50)) of 5.64+/-0.07. Both cocaine (10 microM) and MDMA (10 microM) significantly increased the potency of noradrenaline to 6.31+/-0.11 and 6.42+/-0.13, respectively. However, in the presence of cocaine (10 microM) which increased the potency of noradrenaline to 6.78+/-0.15, MDMA (10 microM) no longer increased the potency of noradrenaline (pD(2) of 6.78+/-0.32). Likewise, following chemical sympathectomy, MDMA failed to increase the potency of noradrenaline. The potency of the agonist isoprenaline, which is not a substrate for the noradrenaline transporter, was not increased by either cocaine or MDMA. In rat small mesenteric artery, but not aorta, MDMA and cocaine significantly increased the potency of noradrenaline, but in the presence of cocaine, MDMA had no further effect. Hence, MDMA shares with cocaine an ability to potentiate the actions of noradrenaline, an action in the case of MDMA which may involve competitive blockade of the noradrenaline transporter, rather than simply displacement of noradrenaline. Since cocaine is linked to an increased incidence of myocardial infarction, these results may have implications in terms of cardiac morbidity of MDMA.

Animals↗

Muscarinic versus nicotinic modulation of a visual task. a pet study using drug probes.

Little is known about acetylcholine (ACh) modulation of central visual processing in humans. Receptor densities in visual brain regions are differentially distributed suggesting that receptor subtypes have different functions. Using PET, we have previously described the brain regions activated by a simple pattern-flash stimulus in healthy elderly subjects. To evaluate muscarinic and nicotinic contributions to ACh modulation of visual processing, we scanned elderly subjects watching the pattern-flash stimulus during no drug, during physostigmine augmentation, and during scopolamine antagonism of physostigmine's action. These manipulations of ACh significantly altered regional cerebral blood flow (rCBF) in brain regions activated by the task. The pattern of rCBF values across drug conditions suggested that muscarinic and nicotinic effects were dissociated. Muscarinic action predominated in striate cortex (Brodmann Area, BA 17) and lateral visual association areas (BA 18, 19), while nicotinic action predominated in the thalamus and inferior parietal regions (BA 39/40). Both muscarinic and nicotinic actions increased rCBF in some regions while decreasing it in others. A parsimonious reconciliation of these results with functional anatomy suggests that muscarinic action modulates visual attribute processing, while nicotinic action modulates arousal and selective attention to the visual task.

Aged↗

Double-blind comparison of ropivacaine 7.5 mg ml(-1) with bupivacaine 5 mg ml(-1) for sciatic nerve block.

Two groups of 12 patients had a sciatic nerve block performed with 20 ml of either ropivacaine 7.5 mg ml(-1) or bupivacaine 5 mg ml(-1). There was no statistically significant difference in the mean time to onset of complete anaesthesia of the foot or to first request for post-operative analgesia. The quality of the block was the same in each group. Although there was no statistically significant difference in the mean time to peak plasma concentrations the mean peak concentration of ropivacaine was significantly higher than that of bupivacaine. There were no signs of systemic local anaesthetic toxicity in any patient in either group.

Adult↗

Spinal anaesthesia for Caesarean section with bupivacaine 5 mg ml(-1) in glucose 8 or 80 mg ml(-1).

The standard spinal preparation of bupivacaine contains a high concentration of glucose (80 mg ml(-1)). However, the addition of only a small amount of glucose (8 mg ml(-1)) to plain solutions of bupivacaine results in a solution which, although no more than marginally hyperbaric, produces a more predictable block when used for spinal anaesthesia in non-pregnant patients. However, bupivacaine 5 mg ml(-1) in glucose 8 mg ml(-1) has a density [1.00164 (SD 0.00008) at 37 degrees C] which is relatively greater than that of the cerebrospinal fluid (CSF) of the pregnant patient at term (1.0003 at 37 degrees C) because CSF density decreases during pregnancy. Therefore, a double-blind, randomized, controlled study was carried out to compare intrathecal bupivacaine (glucose 8 mg ml(-1)) with bupivacaine (glucose 80 mg ml(-1)) in 40 pregnant patients at term. Although there was no difference between groups in onset of sensory block, dose of ephedrine or patient satisfaction, patients receiving bupivacaine (5 mg ml(-1)) with glucose (8 mg ml(-1)) had persistently higher sensory blocks between 60 and 120 min after intrathecal injection, suggesting that the spread of spinal solutions in the pregnant patient at term is not dependent on density.

Adolescent↗

Severe, rapidly progressive human immunodeficiency virus type 1 disease in newborns with coinfections.

AIM: To describe a severe form of rapidly progressive HIV-1 infection manifesting in the neonatal period. METHOD: Prospective cohort study, King Edward VIII Hospital, Durban, South Africa. HIV-1-exposed neonates with hepatosplenomegaly, lymphadenopathy or persistent pneumonia within the first 28 days of life were investigated for perinatal infections. Confirmation of neonatal HIV-1 infection, HIV-1 subtype and clinical outcomes were studied. RESULTS: Twenty-three (72%) of 32 symptomatic HIV-1-exposed neonates recruited at a mean of 15.2 days were HIV-1-infected. HIV-1 infection was detected in 5 patients who were tested within 48 h of birth, confirming congenital infection. Congenital infection was not excluded in any case. Median neonatal viral load at recruitment was 471,932 copies/ml and median CD4 was 777 cells/mm3. The predominant clinical presentation was growth retardation and prematurity. Perinatal infections detected included: tuberculosis (8), syphilis (6) and cytomegalovirus (10). All of the neonates with perinatal tuberculosis were HIV-1-coinfected. Maternal and neonatal viral load and CD4 at recruitment were not statistically different between the groups with tuberculosis vs. other coinfections. Gag gene sequence analysis confirmed closely aligned HIV-1 subtype C in mothers and neonates. Nineteen (83%) died by 9 months, with a mean age at death of 3.5 months. CONCLUSIONS: A distinct group of HIV-1-infected babies may clinically manifest in the neonatal period with perinatal coinfections, subsequent rapidly progressive HIV-1 and early death.

AIDS-Related Opportunistic Infections↗

Clozapine-associated reduction in arrest rates of psychotic patients with criminal histories.

OBJECTIVE: The authors examined the relationship between treatment with clozapine and rates of arrest of psychotic outpatients with criminal histories. METHOD: Patients who had been given a DSM-IV psychotic diagnosis were selected from an urban outpatient clinic database. Background checks performed on 360 patients identified 165 (45.8%) with positive criminal histories in Massachusetts. The authors reviewed the charts of these patients to determine several variables, including whether and when they had received clozapine. A Poisson regression model was used to regress arrest rates against the variables of age, sex, onset of illness, birth cohort, and clozapine treatment. Risk ratios (i.e., percent change in arrest rates) were then calculated by computing the exponential of the Poisson regression coefficients. RESULTS: The 165 patients included in the analysis had a total of 1,126 arrests. The mean number of arrests was 6.8. Differences were found between the 65 patients who received clozapine and the 100 patients who did not in number of arrests, sex, and onset of illness. The regression revealed significantly higher arrest rate estimates associated with more recent birth cohort (4.8%) and with onset of illness (64.6%) and lower arrest rate estimates associated with higher levels of education (11.6%), receiving clozapine (32.6%), and receiving clozapine during specific periods of time (68.9%). CONCLUSIONS: Clozapine's effect on arrest rates in this group of patients is large enough to warrant further investigation. The data indicate that clozapine may reduce recidivism in subjects with criminal histories who are in need of antipsychotic medication.

Adult↗

Equipment. Out of order.

The NHS has underinvested in equipment for more than 20 years. Most hospitals have inadequate equipment inventories. More than half the anaesthetic machines in use are more than five years old and should be replaced. Almost a fifth of the equipment used in cancer treatment is obsolete. Current accounting systems act as a disincentive to replacing old equipment.

Capital Financing↗

Pathology services. Test match.

The UK's spending on pathology services is one of the lowest among developed countries. Increased expenditure on pathology would allow better targeting of treatment. Testing in general practice needs to be expanded.

Anti-Bacterial Agents↗

Factors influencing phenytoin-induced gingival enlargement.

AIM: To ascertain the prevalence and severity of phenytoin-induced gingival enlargement (PIGE) as well as the relationship between PIGE and risk factors. METHOD: An outpatient population of patients on phenytoin treatment and attending the epilepsy clinic at Prince Mshiyeni Memorial Hospital (PMMH) in Durban, South Africa, was requested to participate. A structured questionnaire was used to collect data on patients' demographics, social habits (e.g., drinking and smoking), dental and oral hygiene practices and medication history. Gingival enlargement, dental plaque and gingival bleeding was also measured to assess gingival health. Venous blood was collected for serum folate and phenytoin serum levels measurements. A regression analyses was then undertaken to ascertain the association between PIGE and the risk factors. Factors tested for correlation were serum phenytoin and folate levels, age, bacterial plaque, gingival inflammation, toothbrushing, smoking and alcohol consumption. The association between PIGE and the risk factors was assessed either individually, i.e., as a single entity or in combination--multifactorially. RESULTS: Of the 134 patients studied, 62% had PIGE scores > or = 1, while 8% had a PIGE score of zero. With the exception of plaque, which showed a moderate association with PIGE (r=0.4), no other factor on its own was statistically significantly related to PIGE. In the multiple linear regression analysis, factors which on their own did not have a strong influence became more important. Bacterial plaque (p=0.0001), younger age (p=0.01) and higher free serum phenytoin levels (p= 0.03), were associated with PIGE. Although known to be associated with periodontal diseases, smoking and alcohol, (p=0.03 and p=0.04 respectively), appeared to give some protection against PIGE. CONCLUSION: Risk factors associated with PIGE may have a synergistic effect. Bacterial plaque, however, appears the most important determinant of PIGE severity. This latter finding emphasises the importance of instituting a preventive plaque-control programme, particularly in young patients on phenytoin therapy.

Adolescent↗

Risk factors predicting complications in blood culture-proven typhoid fever in adults.

To create a prognostic model for complications of blood culture-proven typhoid fever in adults (> or = 15 y old), a retrospective cohort was assembled though review of the medical records of the hospitalized patients treated for typhoid fever over a 3-y period ending January 1995. Of the 59 patients included, 21 (35.6%) developed various complications of typhoid fever. No patient included died. Four baseline variables (abdominal pain, systolic blood pressure < 100 mmHg, hypoalbuminaemia < 32 g/l and laboratory evidence of disseminated intravascular coagulation) were independently associated with complications and were used to create a prognostic model. The prediction accuracy of the model was determined using the concordance index (c-index). The results (c-index, 0.915 [95%, CI, 89.0-93.0]) showed that the model predicted complications significantly better than chance. The model stratified patients into 3 prognostic stages: low risk for complications (0%; stage I), intermediate risk (42.9%; stage II) and high risk (92.3%; stage III) (p = 0.001). If validated in other settings, it will help clinicians in predicting complications in patients with blood culture-proven typhoid fever on admission.

Abdominal Pain↗

Oral health in Hlabisa, KwaZulu/Natal--a rural school and community based survey.

AIMS: To investigate rates of dental caries and periodontal disease, available dental services and resources and perceived needs in a rural South African community. DESIGN: A cross-sectional field study including situational analysis and focus group discussions. SETTING: KwaZulu/Natal, South Africa. PARTICIPANTS: A total of 520 children, adolescents and adults. METHODS: WHO caries scores and periodontal CPI score were determined through clinical examinations in five age groups, 5-6 years, 12 y, 15 y, 35-54 y, 55 y+. Focus groups included ten 15-year-old children and ten adults. RESULTS: Caries prevalences and (mean scores) were 5-6 y 64% (dmft 3.0), 12 y 24% (DMFT 0.4), 15 y 27% (DMFT 0.8), 35-54 69% (DFT 2.6) and 55 y+ 80% (DFT 2.7). Most caries was untreated and where present, treatment had been extraction. Dental caries rates were low and except for 5-6 y were within WHO targets for the year 2000. Periodontal disease prevalence was high but would respond to improved oral hygiene. Knowledge of oral health was rudimentary. CONCLUSIONS: A district-wide oral health promotion programme is required preceded by research to define effective health education messages. Access to simple but effective preventive and curative services would seem reasonable. In view of the lack of resources ART is suggested as caries treatment.

Adolescent↗

Classification of osteoporosis and osteopenia in men is dependent on site-specific analysis.

To examine the diagnosis of osteoporosis and osteopenia in men based on bone density measurements at single or multiple sites using central and peripheral measurements, we studied 206 ambulatory, community-dwelling men over age 50. Bone mineral density of the hip, PA spine, forearm, and finger were assessed by dual-energy X-ray absorptiometry. The diagnosis of osteoporosis based on a single measurement ranged from 1% using the trochanter to 39% using Ward's triangle. Twenty-one percent of men had osteoporosis if the diagnosis was based on at least one osteoporotic value at three central sites (PA spine, total hip, femoral neck). Among these men using T-scores provided by the manufacturers, 51% of osteoporotic patients would be misclassified as normal using the accuDEXA((R)) (finger), and 37% of osteoporotic men would be misclassified as normal using the PA spine. We conclude depending on the number and selection of sites there is considerable variability in the classification and misclassification of osteoporosis and osteopenia in men.

Absorptiometry, Photon↗

Relapse and mortality among HIV-infected and uninfected patients with tuberculosis successfully treated with twice weekly directly observed therapy in rural South Africa.

OBJECTIVE: To determine post-treatment relapse and mortality rates among HIV-infected and uninfected patients with tuberculosis treated with a twice-weekly drug regimen under direct observation (DOT). SETTING: Hlabisa, South Africa. PATIENTS: A group of 403 patients with tuberculosis (53% HIV infected) cured following treatment with isoniazid (H), rifampicin (R), pyrazinamide (Z) and ethambutol (E) given in hospital (median 17 days), followed by HRZE twice weekly to 2 months and HR twice weekly to 6 months in the community under DOT. METHODS: Relapses were identified through hospital readmission and 6-monthly home visits. Relapse (culture for Mycobacterium tuberculosis) and mortality given as rates per 100 person-years observation (PYO) stratified by HIV status and history of previous tuberculosis treatment. RESULTS: Mean (SD) post-treatment follow-up was 1.2 (0.4) years (total PYO = 499); 78 patients (19%) left the area, 58 (14%) died, 248 (62%) remained well and 19 (5%) relapsed. Relapse rates in HIV-infected and uninfected patients were 3.9 [95% confidence interval (CI) 1.5-6.3] and 3.6 (95% CI 1.1-6.1) per 100 PYO (P = 0.7). Probability of relapse at 18 months was estimated as 5% in each group. Mortality was four-fold higher among HIV-infected patients (17.8 and 4.4 deaths per 100 PYO for HIV-infected and uninfected patients, respectively; P<0.0001). Probability of survival at 24 months was estimated as 59% and 81%, respectively. We observed no increase in relapse or mortality among previously treated patients compared with new patients. A positive smear at 2 months did not predict relapse or mortality. CONCLUSION: Relapse rates are acceptably low following successful DOT with a twice weekly rifampicin-containing regimen, irrespective of HIV status and previous treatment history. Mortality is substantially increased among HIV-infected patients even following successful DOT and this requires further attention.

AIDS-Related Opportunistic Infections↗