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Biomedical subjects

C J Doré

Publications and source records attributed to C J Doré.

At least 19 recordsLinked to original sources

Accelerated postnatal head growth follows preterm birth.

BACKGROUND: Poor growth after preterm birth, particularly poor head growth, is associated with impaired neurodevelopmental outcome. OBJECTIVE: To evaluate weight gain and head growth between birth and term in a contemporary cohort of preterm infants, taking into account breast milk intake and illness severity. METHODS: Subjects were inborn infants or=37 weeks postmenstrual age. Weight and head circumference (HC) were expressed as standard deviation score (SDS), growth between birth and discharge as SDS gain (SDSG), and illness severity and breast milk exposure as the number of days of level 1 (full) intensive care (%L1IC) and the number of days on which breast milk was received (%BM) as a percentage of days from birth to discharge. RESULTS: Infants showed poor postnatal weight gain but accelerated head growth. There was a highly significant fall in mean (SD) weight SDS between birth and discharge (-0.31 (0.96) and -1.32 (1.02) respectively, p<0.001) and a highly significant increase in HC SDS (-0.52 (0.95) and -0.03 (1.25) respectively, p = 0.003). %L1IC had a highly significant negative impact on weight SDSG (p = 0.006), and %BM had a significant positive impact on HC SDSG (p = 0.043). CONCLUSIONS: Accelerated postnatal head growth suggests catch up after antenatal restraint. This raises the possibility that poor neurocognitive outcomes after extremely preterm birth may in part be consequent on poor intrauterine brain growth. As postnatal head growth may be facilitated by breast milk, there is an urgent need to evaluate the optimal use of breast milk in preterm neonates. Illness severity is a significant determinant of poor postnatal weight gain.

Breast Feeding↗

The impact of ethnicity on glucose regulation and the metabolic syndrome following gestational diabetes.

AIMS/HYPOTHESIS: We assessed the impact of ethnic origin on metabolism in women following gestational diabetes mellitus (GDM). MATERIALS AND METHODS: Glucose regulation and other features of the metabolic syndrome were studied at 20.0 (18.2-22.1) months (geometric mean [95% CI]) post-partum in women with previous GDM (185 European, 103 Asian-Indian, 80 African-Caribbean). They were compared with the same features in 482 normal control subjects who had normal glucose regulation during and following pregnancy. RESULTS: Impaired glucose regulation or diabetes by WHO criteria were present in 37% of women with previous GDM (diabetes in 17%), especially in those of African-Caribbean and Asian-Indian origin (50 and 44%, respectively vs 28% in European, p=0.009). BMI, waist circumference, diastolic blood pressure, fasting triglyceride and insulin levels, and insulin resistance by homeostatic model assessment (HOMA), were increased following GDM (p<0.001 for all, vs control subjects). Where glucose regulation was normal following GDM, basal insulin secretion (by HOMA) was high (p<0.001 vs control subjects). Irrespective of glucose regulation in pregnancy, Asian-Indian origin was associated with high triglyceride and low HDL cholesterol levels, and African-Caribbean with increased waist circumference, blood pressure, and insulin levels, together with insulin resistance and low triglyceride concentrations. Nonetheless, the GDM-associated features were consistent within each ethnic group. The metabolic syndrome by International Diabetes Federation criteria was present in 37% of women with previous GDM, especially in non-Europeans (Asian-Indian 49%, African-Caribbean 43%, European 28%, p=0.001), and in 10% of controls. CONCLUSIONS/INTERPRETATION: Following GDM, abnormal glucose regulation and the metabolic syndrome are common, especially in non-European women, indicating a need for diabetes and cardiovascular disease prevention strategies.

Algorithms↗

A meta-analysis of the efficacy and toxicity of combining disease-modifying anti-rheumatic drugs in rheumatoid arthritis based on patient withdrawal.

INTRODUCTION: Combinations of disease-modifying anti-rheumatic drugs (DMARDs) are increasingly used to treat rheumatoid arthritis (RA). Early trials showed their toxicity while recent trials suggest superior efficacy. Trials of DMARD combinations have enrolled different types of patient (early or established RA), used different designs (step-up, parallel or step-down) and utilized a range of outcome measures. We undertook a systematic review of combination DMARD therapy for RA and carried out a meta-analysis to evaluate the evidence for efficacy and toxicity. METHOD: Medline, PubMed and EmBase were searched using MESH headlines 'arthritis, rheumatoid', 'drug therapy, combination' and 'randomized controlled trial' (RCT) for papers published from 1975 to April 2004. References from published articles were also searched. Three independent assessors evaluated abstracts and selected trials for detailed examination. Trials were excluded if their quality was poor, were not published in English or studied DMARDs not licensed to treat RA. Two independent assessors extracted data. Efficacy was assessed by the numbers of patients withdrawn due to lack of efficacy. Toxicity was assessed by the numbers of patients withdrawn due to adverse events. Risk ratios (RR) with 95% confidence intervals (CI) were calculated and meta-analysis was carried out based on a random effects model. Sensitivity analyses evaluated different treatment combinations, trial designs, study populations and outcome measures. RESULTS: Fifty-three potentially relevant RCTs were identified. Twelve were excluded due to: using unlicensed DMARDs (n = 3); reporting in journal supplements of RCTs already included (n = 2); follow-up of an earlier RCT, report of biological outcomes or pharmacokinetics (n = 5); and non-English language publications (n = 2). Forty-one RCTs were evaluated in detail and another five excluded (three open-labelled studies and two with high patient attrition); 36 studies were included in the meta-analysis. These comprised 13 step-up, 16 parallel and 7 step-down trials. Nine assessed early RA and 27 established RA. Seven added steroids to DMARD monotherapy and one study added steroids to DMARD combinations. Six assessed methotrexate (MTX) plus tumour necrosis factor (TNF) inhibitors. Overall, combination DMARD therapy was more effective than monotherapy (RR 0.35; 95% CI 0.28, 0.45) although the risk of toxicity was also slightly higher (RR 1.37; 95% CI 1.16, 1.62). Combinations of MTX with TNF inhibitors and MTX with sulphasalazine or anti-malarials showed good efficacy/toxicity ratios. CONCLUSIONS: DMARD combinations vary in their efficacy/toxicity ratio. MTX plus sulphasalazine and/or anti-malarials and MTX plus TNF inhibitors have particularly favourable benefit/risk ratios.

Antirheumatic Agents↗

Severity of asymptomatic carotid stenosis and risk of ipsilateral hemispheric ischaemic events: results from the ACSRS study.

OBJECTIVES: This study determines the risk of ipsilateral ischaemic neurological events in relation to the degree of asymptomatic carotid stenosis and other risk factors. METHODS: Patients (n=1115) with asymptomatic internal carotid artery (ICA) stenosis greater than 50% in relation to the bulb diameter were followed up for a period of 6-84 (mean 37.1) months. Stenosis was graded using duplex, and clinical and biochemical risk factors were recorded. RESULTS: The relationship between ICA stenosis and event rate is linear when stenosis is expressed by the ECST method, but S-shaped if expressed by the NASCET method. In addition to the ECST grade of stenosis (RR 1.6; 95% CI 1.21-2.15), history of contralateral TIAs (RR 3.0; 95% CI 1.90-4.73) and creatinine in excess of 85 micromol/L (RR 2.1; 95% CI 1.23-3.65) were independent risk predictors. The combination of these three risk factors can identify a high-risk group (7.3% annual event rate and 4.3% annual stroke rate) and a low risk group (2.3% annual event rate and 0.7% annual stroke rate). CONCLUSIONS: Linearity between ECST per cent stenosis and risk makes this method for grading stenosis more amenable to risk prediction without any transformation not only in clinical practice but also when multivariable analysis is to be used. Identification of additional risk factors provides a new approach to risk stratification and should help refine the indications for carotid endarterectomy.

Brain Ischemia↗

Hepatic triglyceride content and its relation to body adiposity: a magnetic resonance imaging and proton magnetic resonance spectroscopy study.

BACKGROUND: Hepatic steatosis is associated with obesity and type II diabetes. Proton magnetic resonance spectroscopy (1H MRS) is a non-invasive method for measurement of tissue fat content, including intrahepatocellular lipids (IHCL) and intramyocellular lipids (IMCL). PATIENTS AND METHODS: We used 1H MRS and whole body magnetic resonance imaging (MRI) to assess the relationship between IHCL accumulation, total body adipose tissue (AT) content/distribution, and IMCL content in 11 subjects with biopsy proven hepatic steatosis and 23 normal volunteers. RESULTS: IHCL signals were detectable in all subjects but were significantly greater in hepatic steatosis (geometric mean (GM) 11.5 (interquartile range (IQR) 7.0-39.0)) than in normal volunteers (GM 2.7 (IQR 0.7-9.3); p=0.02). In the study group as a whole, IHCL levels were significantly greater in overweight compared with lean subjects (body mass index (BMI) >25 kg/m2 (n=23): GM 7.7 (IQR 4.0-28.6) v BMI <25 kg/m2 (n=11): GM 1.3 (IQR 0.3-3.6; p=0.004)). There was a significant association between IHCL content and indices of overall obesity (expressed as a percentage of body weight) for total body fat (p=0.001), total subcutaneous AT (p=0.007), and central obesity (subcutaneous abdominal AT (p=0.001) and intra-abdominal AT (p=0.001)), after allowing for sex and age. No correlation between IHCL content and IMCL was observed. A significant correlation was observed between serum alanine aminotransferase and liver fat content (r=0.57, p=0.006). CONCLUSIONS: Our results suggest that hepatic steatosis appears to be closely related to body adiposity, especially central obesity. MRS may be a useful method for monitoring IHCL in future interventional studies.

Abdomen↗

The effect of remifentanil on the middle latency auditory evoked response and haemodynamic measurements with and without the stimulus of orotracheal intubation.

BACKGROUND AND OBJECTIVE: Changes in the middle latency auditory evoked response following the administration of opioids have been shown. However, it remains unclear as to whether these changes are due to a direct depressant effect of opioids on the middle latency auditory evoked response itself, or an indirect effect on account of their action in attenuating central nervous system arousal associated with noxious stimuli. By comparing changes in the middle latency auditory evoked response in intubated and non-intubated patients, receiving saline or remifentanil in different doses, this study attempts to answer this question. METHODS: Fifty-four patients were anaesthetized with isoflurane and nitrous oxide (0.9 MAC) and randomized to 1-6 groups. Groups 1-3 received a bolus injection of either saline 0.9%, low-dose remifentanil (1 microg kg(-1)) or high-dose remifentanil (3 microg kg(-1)) prior to intubation of the trachea. Groups 4-6 were not intubated following the bolus injection. RESULTS: Pa and Nb amplitudes of the middle latency auditory evoked response increased by 82% and 79% with intubation in the saline group (P < 0.005) and these changes were not seen in the patients given remifentanil. There was a significant linear trend for the reduction in Pa and Nb amplitude with increasing remifentanil dose (P < 0.05). In the absence of endotracheal intubation remifentanil had no effect on either the amplitudes or latencies of the waves Pa and Nb and there was no effect of dose. For the haemodynamic measurements remifentanil attenuated the pressor response to intubation (P < 0.001) and had a significant dose-related effect (P < 0.001) in the absence of intubation. CONCLUSIONS: We demonstrated an effect of remifentanil on both the middle latency auditory evoked response and haemodynamic changes to endotracheal intubation. For the non-intubated patients there was only an effect of remifentanil on the haemodynamic measurements. This suggests that remifentanil has an effect on the middle latency auditory evoked response in attenuating the arousal associated with intubation of the trachea but has no effect in the absence of a stimulus.

Adult↗

Reliability, repeatability and sensitivity to change of externally and self-paced walking tests in COPD patients.

In COPD, several walking tests have been proposed to measure exercise tolerance but their relative merits are uncertain. We studied 57 moderate-to-severe, stable COPD patients (mean FEV1 35 +/- 12% predicted). Within a 2-month period, we compared reliability (inter-subject variability) and repeatability (intra-subject variability) of the most widely used 6-min walks (6MWD), with self-paced 2-min walks (2MWD) and externally paced, incremental shuttles (Shuttle). On 9 separate days either of the three 6MWD, 2MWD or Shuttles were performed (nine walks of each type). Then, each walk was performed before and after bronchodilators (BD) to assess sensitivity to change (mean change/standard deviation of change (sensitivity index--SI)). For all exercise tests, reliability was >90% (2MWD 95%, 6MWD 92% and Shuttle 91%). Repeatability was excellent (overall <10% intra-subject variation; for 2MWD 5%, 6MWD 8% and Shuttle 9%). On average, the first walking distance was significantly shorter, but there were no significant differences between second and third walks. Dyspnoea scores were much less reproducible. BD produced highly significant improvements in Shuttle (pre-BD 27 SD=11 --> post-BD 30 SD=11), 6MWD (424 m SD=115 --> 462 m SD=106) and 2MWD (153 m SD=35 --> 162 m SD=34), (P < 0.0001). SI was similar for all walks (6MWD 0.84, 2MWD 0.75 and Shuttle 0.76). In moderate-to-severe COPD, 2MWDs are as informative as 6MWDs without their disadvantages. Self-paced walks are as useful as externally paced Shuttles.

Aged↗

A quantitative study of the neural changes underlying pyloric stenosis in dogs.

This study aimed to quantify the neural changes in congenital pyloric stenosis in dogs and to study the comparative anatomy between this condition in dogs and that in infantile hypertrophic pyloric stenosis. Eight specimens from the pylorus of dogs with pyloric stenosis and six control specimens were examined using conventional histology and immunohistochemistry for a range of neural antigens. The changes in the proportion of nerves immunoreactive for each antigen were quantified and analysed statistically. The morphology of the nerves in the diseased dogs was similar to that in controls. Only vasoactive intestinal peptide was reduced in expression in dogs (median proportion in control dogs 0.57, in diseased dogs 0.17; P = 0.065). This study demonstrates both morphological similarities and significant differences between closely related conditions in dogs, humans and other species.

Animals↗

The early bactericidal activity of streptomycin.

SETTING: Patients with sputum smear-positive, newly diagnosed pulmonary tuberculosis studied at Tygerburg Hospital, Cape Town, for their early response to streptomycin (SM). OBJECTIVE: To determine the standard early bactericidal activity (EBA), namely the fall in viable counts of tubercle bacilli in 16-hour sputum collections during the first 2 days of treatment with SM. DESIGN: Patients were randomised to logarithmically spaced daily doses of 7.5, 15 or 30 mg/kg SM. A comparison by standard biological assay methods was then made with previous estimations of the EBA of paromomycin in doses of 7.5 and 15 mg/kg. RESULTS: An EBA of 0.133 obtained with 30 mg/kg SM differed significantly from zero (P = 0.0009), while the EBAs of 0.043 with 15 mg/kg and -0.025 with 7.5 mg/kg did not so differ. A linear regression equation of EBA = -0.2587 + 0.2627 log10 dose was obtained with significant slope (P = 0.007). Paromomycin was estimated to be 1.745 more potent than SM with wide 95% confidence limits (0.6-28.6), indicating that it cannot be considered more potent than SM. CONCLUSIONS: The low EBAs show that SM has low, dose-related, bactericidal activity in cavities, consistent with results from clinical trials. If streptomycin-resistant bacilli are present, paromomycin is probably the aminoglycoside of choice.

Adult↗

Epidural analgesia and backache: a randomized controlled comparison with intramuscular meperidine for analgesia during labour.

BACKGROUND: Concern has been expressed that epidural analgesia for labour may be associated with a higher incidence of backache. METHODS: A prospective randomized trial investigating the effect of epidural analgesia on the outcome of labour in nulliparae, mothers were randomized to receive either epidural analgesia or meperidine. A questionnaire on postnatal symptoms was sent to them 6 months after delivery. RESULTS: In all, 611 mothers were studied; 310 were randomly allocated to receive i.m. meperidine up to 300 mg and 301 to receive epidural bupivacaine. The response rate to our questionnaire was 83%. Intention-to-treat analysis showed similar prevalence rates of postpartum backache in the epidural (48%) and meperidine groups (50%), with an observed difference (epidural-meperidine) of -2% (95% CI, -11 to +6%). After excluding mothers with backache before delivery, there were also similar incidence rates of postpartum backache in the epidural (29%) and meperidine groups (28%), observed difference 1% (95% CI, -8 to +10%). CONCLUSIONS: Epidural analgesia in labour was not associated with an increase in the prevalence or incidence of backache.

Analgesia, Epidural↗

Investigation of relationship between reduced, oxidized, and protein-bound homocysteine and vascular endothelial function in healthy human subjects.

Previous studies investigating homocysteine and vascular disease have relied on total plasma homocysteine as the sole index of homocysteine status. We examined the dynamic relationship between vascular endothelial function and concentrations of total, protein-bound oxidized, free oxidized, and reduced homocysteine to identify the homocysteine form associated with endothelial dysfunction in humans. We investigated 14 healthy volunteers (10 men, 4 women). Brachial artery flow-mediated dilatation was measured at baseline and at 30, 60, 120, 240, and 360 minutes after oral (1) L-methionine (50 mg/kg), (2) L-homocysteine (5 mg/kg), and (3) placebo. Plasma concentrations of total, protein-bound oxidized, free oxidized, and reduced homocysteine were measured at each time point, and nitroglycerin-induced dilatation at was assessed at 0, 120, and 360 minutes. Flow-mediated dilatation fell, and concentrations of total, protein-bound oxidized, free oxidized, and reduced homocysteine increased after oral homocysteine and oral methionine (all P<0.05 for difference in time course compared with placebo). Flow-mediated dilatation showed a reciprocal relationship with reduced homocysteine during both homocysteine and methionine loading. In both loading studies, peak reduction in flow-mediated dilatation coincided with maximal reduced homocysteine concentrations. In contrast, there was no consistent relationship between flow-mediated dilatation and free oxidized homocysteine, protein-bound oxidized homocysteine, or related species. Nitroglycerin-induced dilatation was unchanged by oral homocysteine and oral methionine (P>0.10 compared with placebo). Reduced homocysteine is closely associated with endothelial dysfunction during oral methionine and oral homocysteine loading. Our observations support the hypothesis that reduced homocysteine is the deleterious form of homocysteine for vascular function in vivo and suggest a less important role for other homocysteine species.

Administration, Oral↗

The effects of repeated antenatal glucocorticoid therapy on the developing brain.

Antenatal glucocorticoid (GC) therapy improves infant outcome following preterm birth. As approximately 50% of women given a first course of antenatal GCs remain undelivered 7-14 d later, many clinicians administer further courses. GCs are known to be neurotoxic and there is concern that exposure during early development may have adverse effects on the immature brain. The aim of this investigation was to compare magnetic resonance (MR) indices of brain maturation in infants exposed to repeated antenatal GC therapy and born at or close to term, with non-GC exposed control infants. MR images were obtained during quiet sleep without sedation. T1 weighted volume images were obtained in the sagittal plane and T1, T2 weighted spin echo and inversion recovery images in the transverse plane. Brain volume and surface area were calculated from segmented image slices, and a measure of the complexity of cortical folding, the whole cortex convolution index (WCCI), from computerized analysis of a vector coded contour following algorithm. Analysis of covariance was used to compare the two groups after allowing for the effect of postmenstrual age. There were 10 infants in the GC group (range of antenatal GC exposure, 3-11 courses) and 6 controls. Each GC course comprised two 12-mg IM doses of betamethasone 24 h apart. GC exposed infants had a significantly lower WCCI (p = 0.001) and smaller surface area (p = 0.02), after allowing for postmenstrual age. There was no significant difference in brain volume (p = 0.5). Repeated antenatal GC exposure results in measurable differences in brain maturation when compared with gestational age matched non-GC exposed controls. The clinical relevance of these observations is not known.

Betamethasone↗

Validation of endobronchial biopsy specimens for nerve quantitation by computer-assisted image analysis.

The aim of this study was to assess the validity of endoscopic bronchial biopsy specimens for the quantitation of nerves. To this end, endobronchial biopsy was simulated ex vivo on surgically resected lung specimens and nerve densities were compared in airway smooth muscle of biopsy and surrounding tissue. Specimens were stained immunohistochemically for the general neural marker protein gene product 9.5 (PGP 9.5) and for vasoactive intestinal peptide (VIP), and nerve densities were quantitated using computer-assisted image analysis. Nerve density for total (PGP 9.5-immunoreactive) nerves was slightly higher in biopsies than in corresponding lung tissue, but this difference did not reach statistical significance (p=0.08). There was also no significant difference in the density of VIP-immunoreactive nerves (p=0.60). These findings support the use of endobronchial biopsy specimens to quantitate nerves in asthma and other airway diseases.

Biomarkers↗

Randomized, placebo-controlled, crossover trial of low-dose oral methotrexate in children with extended oligoarticular or systemic arthritis.

OBJECTIVE: Juvenile idiopathic arthritis (JIA) can persist through adolescence and adulthood, resulting in significant disability. The use of low-dose oral methotrexate (MTX) for persistent polyarthritis has been shown to be effective by the USA/USSR collaborative study group. However, 2 of the most disabling subgroups of JIA, systemic and extended oligoarthritis, were underrepresented in that study. The present study was therefore conducted to investigate the efficacy of MTX in these 2 subgroups. METHODS: Patients under the age of 16 years who fulfilled the International League of Associations for Rheumatology criteria for systemic or extended oligoarticular arthritis were eligible for this multicenter, double-blind, placebo-controlled crossover trial. Forty-five patients with systemic and 43 with extended oligoarticular arthritis were enrolled. The dosage of MTX or placebo was 15 mg/m2, which could be increased to 20 mg/m2 after 2 months. Core outcome variables were considered as primary measures, giving a final score of "improved" or "not improved." Secondary measures included scores of systemic features and biochemical laboratory measures. Assessment of function was not included since there were no validated functional measures at the start of this trial in 1991. RESULTS: In the extended oligoarticular arthritis group, MTX treatment produced significant improvement in 3 of 5 core variables (erythrocyte sedimentation rate, physician's global assessment of disease activity, and parent's global assessment of disease activity). By the primary improvement criteria, there was significant overall improvement during MTX treatment. In the systemic arthritis group, only 2 of 5 core variables were significantly improved (physician's and parent's global assessment of disease activity). Systemic features were not part of the core variables, but the systemic feature score was not significantly different between MTX and placebo treatment. There was no significant overall improvement in this group during MTX treatment. However, no significant interaction between disease subgroup and treatment effect was demonstrated. When the data from both disease subgroups were combined, there was significant clinical improvement during MTX treatment (P = 0.006). CONCLUSION: MTX 15-20 mg/m2 given orally once a week was found to be an effective treatment for both extended oligoarticular and systemic JIA in this shortterm trial. Long-term efficacy needs to be addressed in future studies.

Adolescent↗

Microsatellite instability and allelic imbalance in primary and secondary colorectal cancer.

BACKGROUND: Several studies of colorectal cancer have shown an association between the number and type of genomic defects and the stage of disease. A subset of colorectal tumours are due to inactivation of DNA mismatch repair genes and these tumours exhibit microsatellite instability. The aim of the present study was to compare and contrast the genomic defects present in both the primary and metastatic stages of the disease using microsatellite probes. METHODS: Modifications of the allelic profiles of 25 microsatellite regions were studied in a total of 85 colorectal tumours using fluorescent polymerase chain reaction (PCR) technology and subsequent direct analysis on an automatic sequencer. This approach was used because it allows the study of microsatellite instability and allelic imbalance. Stepwise logistic regression analysis was used to develop a model to predict whether the tumour was primary or secondary from the percentage of allelic imbalance. Subsequently, a group of 17 patients with primary colorectal tumours was analysed prospectively to test the proposed model. RESULTS: Six of 39 primary tumours showed microsatellite instability compared to 0 of 29 liver metastases (P = 0.03). Primary tumours showed significantly less allelic imbalance than liver metastases (P < 0.001). Three probes (d18s53, d9s158 and d10s191) were selected for use in a model to classify a tumour as primary or secondary on the basis of the degree of allelic imbalance. When tested prospectively this model had a specificity of 82%. CONCLUSIONS: The present study demonstrates the potential importance of using microsatellite probes both as a diagnostic tool and as a research technique to investigate the mechanisms of tumour progression. An important clinical finding is that none of the colorectal liver metastases showed microsatellite instability (0 of 29). This analysis also confirmed other work that has shown a direct relationship between the degree of allelic imbalance and the stage of disease.

Alleles↗

Randomized controlled comparison of epidural bupivacaine versus pethidine for analgesia in labour.

We compared the incidence of Caesarean delivery in nulliparous women randomized to receive epidural analgesia with those randomized to intramuscular (i.m.) pethidine. On admission to the delivery suite in established labour, 802 nulliparae had already agreed to be randomized with respect to their first analgesia. One hundred and eighty-eight women required either no analgesia or 50% nitrous oxide in oxygen (Entonox) only. Of the remaining 614 women, 310 were randomly allocated to receive i.m. pethidine up to 300 mg and 304 to receive epidural bupivacaine. Labour management was standardized according to the criteria for active management of labour. The intention-to-treat analysis showed similar Caesarean section rates in those randomized to epidural (12%) or pethidine analgesia (13%). The difference in Caesarean rate was -1.1% with 95% confidence intervals from -6.3% to +4.1%. The normal vaginal delivery rates were similar (epidural, 59%; pethidine, 61%).

Adolescent↗

Effect of intravaginal clindamycin cream on pregnancy outcome and on abnormal vaginal microbial flora of pregnant women.

OBJECTIVES: To determine whether intravaginal clindamycin cream reduces the incidence of abnormal pregnancy outcome in women with abnormal vaginal microbial flora graded as intermediate or BV and to investigate the effect of the antibiotic on vaginal microbial flora. METHODS: A prospective cohort study of pregnant women in an antenatal clinic of a district general hospital. The subjects were 268 women who had abnormal vaginal microbial flora at first clinic visit by examination of a Gram-stained vaginal smear and 34 women with a normal vaginal flora. Two hundred and thirty-seven women were evaluable. Women with abnormal Gram-stained smears (graded as II or III) on clinic recall were randomised to receive treatment (intravaginal clindamycin cream) or placebo and followed to assess outcome of pregnancy, vaginal flora, and detection of Mycoplasma hominis and Ureaplasma urealyticum after treatment. RESULTS: Abnormal outcomes of pregnancy were not significantly different in treated and placebo groups by Chi square (P = 0.2). However, women with grade III flora responded better to clindamycin than women with grade II flora by numbers of abnormal outcomes (P = 0.03) and return to normal vaginal flora (P = 0.01) (logistic regression analysis model). This may be due to differences in vaginal bacterial species in these grades. Women whose abnormal vaginal flora had spontaneously returned to normal on follow-up and were therefore not treated (revertants) had as many abnormal outcomes as placebos suggesting that damage by abnormal bacterial species occurred early in pregnancy. CONCLUSIONS: Gram-stain screening distinguishing grade II from grade III flora may be helpful in prescribing treatment other than clindamycin for women with grade II flora. Earlier diagnosis and treatment may be more effective in preventing an abnormal outcome, possibly as soon as pregnancy is diagnosed or even offered as a pre-conception screen.

Adult↗

Glycaemic index as a determinant of serum HDL-cholesterol concentration.

BACKGROUND: Diet influences the prevalence of coronary heart disease (CHD). Insulin sensitivity and concentrations of HDL cholesterol, two metabolic predictors of CHD, are also influenced by diet. Dietary carbohydrates with a high glycaemic index cause a high postprandial glucose and insulin response, and are associated with decreased insulin sensitivity and an increased risk of CHD. This study examined whether the glycaemic index of dietary carbohydrates is a determinant of serum HDL-cholesterol concentrations. METHOD: Dietary, anthropometric, and biochemical data from the 1986-87 Survey of British Adults (n=2200) were reanalysed by a multiple regression model, which examined the relation between serum total cholesterol, HDL-cholesterol, and calculated LDL-cholesterol concentrations and various dietary characteristics, including the type of carbohydrate, the glycaemic index, and fat intake. FINDINGS: Among the 1420 participants with complete data, there was a significant negative relation between serum HDL-cholesterol concentration and the glycaemic index of the diet for both men (regression coefficient -0.00724 [95% CI -0.0101 to -0.00434], p=0.02) and women (-0.01326 [-0.0162 to -0.0102], p<0.0001). No other significant relation was found with total cholesterol or LDL-cholesterol concentration or with any other dietary carbohydrate or fat constituent. INTERPRETATION: In a cross-sectional study of middle-aged adults, the glycaemic index of the diet was the only dietary variable significantly related to serum HDL-cholesterol concentration. Thus, the glycaemic index of the diet is a stronger predictor than dietary fat intake of serum HDL-cholesterol concentration.

Adult↗