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Biomedical subjects

S Bower

Publications and source records attributed to S Bower.

At least 37 records · Page 2Linked to original sources

Cloning and characterization of the Bacillus subtilis birA gene encoding a repressor of the biotin operon.

The Bacillus subtilis birA gene, which regulates biotin biosynthesis, has been cloned and characterized. The birA gene maps at 202 degrees on the B. subtilis chromosome and encodes a 36,200-Da protein that is 27% identical to Escherichia coli BirA protein. Three independent mutations in birA that lead to deregulation of biotin synthesis alter single amino acids in the amino-terminal end of the protein. The amino-terminal region that is affected by these three birA mutations shows sequence similarity to the helix-turn-helix DNA binding motif previously identified in E. coli BirA protein. B. subtilis BirA protein also possesses biotin-protein ligase activity, as judged by its ability to complement a conditional lethal birA mutant of E. coli.

Amino Acid Sequence

Follicular fluid levels of midazolam, fentanyl, and alfentanil during transvaginal oocyte retrieval.

OBJECTIVE: To investigate the time course of changes in follicular fluid (FF) concentrations of midazolam (Roche Products Ltd., Welwyn Garden City, United Kingdom), fentanyl (Janssen Pharmaceuticals Ltd., Wantage, United Kingdom), and alfentanil (Janssen Pharmaceuticals Ltd.) during ultrasound-guided transvaginal oocyte collection. STUDY DESIGN: Forty-five patients with tubal infertility were randomized to receive a bolus IV dose of midazolam, fentanyl, or alfentanil for sedation during ultrasound-guided transvaginal oocyte collection. Paracervical block with lignocaine was given for analgesia. Simultaneous blood and FF samples were drawn at 5-minute intervals after the bolus dose for analysis of drug levels. RESULTS: Data were obtained on 15 women receiving midazolam and fentanyl and on 13 women receiving alfentanil. Plasma levels of all agents rose to a peak and then fell in an exponential fashion as was expected. The FF levels of the agents continued to rise significantly to 25 minutes after the bolus dose, although the absolute level was low when compared with the blood level. There were no significant differences in fertilization or pregnancy rates in the three groups, but patient numbers were small. CONCLUSION: We conclude that midazolam, fentanyl, and alfentanil are found in FF after a single IV dose, but further investigation needs to be undertaken to investigate any potential influence on fertilization and implantation rates.

Adult

Human maternal uniparental disomy for chromosome 16 and fetal development.

Two severely growth-retarded fetuses found to have maternal uniparental disomy (UPD) for chromosome 16 and trisomy 16 placental mosaicism both had an unfavourable outcome. Antenatally, the first case was complicated by an unexplained raised maternal serum alpha-fetoprotein concentration, preterm premature rupture of the membranes, and growth retardation detectable at 21 weeks' gestation, whilst the other had an unexplained raised maternal serum human chorionic gonadotrophin level, a two-vessel cord on ultrasound, and cessation of growth at 25 weeks. At post-mortem, both babies had an imperforate anus. Fetal maternal UPD may explain the poor outcome that occurs in some cases of confined placental mosaicism for chromosome 16 and is also associated with specific fetal abnormalities.

Adult

Discordant iliac and femoral artery flow velocity waveforms in fetuses with single umbilical artery.

OBJECTIVE: The aim of this study was to investigate pelvic and femoral arterial flow velocity waveforms in fetuses with a single umbilical artery. STUDY DESIGN: Seven fetuses with single umbilical artery and no other ultrasonographically detected anomalies were studied with color Doppler ultrasonography at a median gestational age of 24 weeks (range 18 to 34 weeks). Flow velocity waveforms from the relevant vessels were obtained as follows: (1) umbilical artery from a free loop of cord, (2) common iliac artery from both sides just below the aortic bifurcation, (3) internal iliac artery and intraabdominal portion of the umbilical artery from the vessel visualized alongside the fetal bladder, and (4) femoral artery on both sides from the upper third of the fetal thigh. The pulsatility index was measured, and comparisons were made with the paired t test. A p value < 0.05 was considered significant. RESULTS: The pulsatility index in the umbilical artery was normal in all cases. There were highly significant differences between the common iliac arteries in each side (difference in pulsatility index 2.7, 95% confidence interval 2.0 to 3.5, p < 0.001). Significant differences between both femoral arteries were also noted (difference in pulsatility index 1.0, 95% confidence interval 0.3 to 1.7, p < 0.001). In both vessels the pulsatility index was always higher in the side that did not participate in the placental circuit. CONCLUSION: This study demonstrates that fetuses with single umbilical artery have asymmetric arterial blood flow patterns in the pelvic and lower extremities.

Blood Flow Velocity

Filtration of fentanyl is not the cause of the elevation of arterial blood pressure associated with post-bypass ultrafiltration in children.

Modified ultrafiltration after cardiopulmonary bypass in children has been shown to be associated with an increase in arterial blood pressure. As part of a series of studies to investigate the possible causes of this blood pressure elevation, the hypothesis that if filtration was removing a significant amount of fentanyl, then the increase in blood pressure might be due to pain was proposed. Ten children, aged between 0.5 and 9.3 years (median 3.8 years), weighing 5.9 to 25.5 kg (median 15.7 kg), underwent corrective cardiac surgery (incorporating modified ultrafiltration). A standard anesthetic protocol was followed, with up to 78 micrograms/kg of fentanyl given prebypass for analgesia. After completion of cardiopulmonary bypass, modified ultrafiltration was commenced at 100 mL/min until a hematocrit of 35% was reached. Samples were taken of arterial blood (prefiltration, 3, 10, and 20 minutes postfiltration), the venous reservoir blood (prefiltration) and the filtrate (5 and 10 minutes into filtration). Hemodynamic data were recorded both prefiltration and postfiltration. The hemodynamic data showed the expected rise in both systemic arterial pressure and cardiac index after ultrafiltration. The plasma fentanyl concentrations did not significantly change after ultrafiltration: 1.59 to 12.39 ng/mL (median 6.27 ng/mL) prefiltration and 2.05 to 15.59 ng/mL (6.29 ng/mL) at 3 minutes, 2.22 to 12.64 ng/mL (6.87 ng/mL) at 10 minutes, and 1.83 to 11.52 ng/mL (5.85 ng/mL) at 20 minutes postfiltration.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesia

Fetal hyperechogenic bowel following intra-amniotic bleeding.

OBJECTIVE: To test the hypothesis that increased echogenicity of the fetal bowel at second-trimester scans results from intra-amniotic bleeding. METHODS: We studied 726 patients undergoing second-trimester amniocentesis for advanced maternal age. Three groups were identified according to the color of the amniotic fluid (AF) obtained: clear fluid, blood-stained fluid, and dark brown fluid. Two to 4 weeks after the amniocentesis, all patients had a targeted ultrasound examination for the detection of fetal structural anomalies and markers of chromosomal abnormalities, which included a survey of the fetal bowel. The incidence of hyperechogenic bowel in each group was compared by Fisher exact test. P < .05 was considered significant. RESULTS: In 694 cases, the AF was clear (95%), in 20 blood-stained (3%), and in 12 dark brown (2%). Hyperechogenic bowel was detected in 14 fetuses with clear fluid (2%), in two with blood-stained fluid (10%), and in three with dark brown fluid (25%). Fetuses with proven intra-amniotic bleeding (ie, dark brown or blood-stained AF at amniocentesis) had a significantly higher incidence of hyperechogenic bowel compared to those with clear AF (five of 32 [15.6%] and 14 of 694 [2.0%], respectively; P < .001, 95% confidence interval for the difference in proportions 6.3-17.6%). CONCLUSIONS: Our study demonstrates that intra-amniotic bleeding is associated with an increased incidence of fetal hyperechogenic bowel at second-trimester ultrasound scans. This sonographic phenomenon may be due to the presence of blood in the fetal bowel caused by fetal swallowing of bloody AF.

Amniocentesis

Long-term prognosis of transient lone bilateral blindness in adolescents and young adults.

We describe a group of 14 patients aged 8-38 years at presentation who had one or more sudden transient attacks of bilateral blindness. Eight patients described bilateral blindness as their only symptom whereas six others experienced some mild associated symptoms. Visual loss always developed within seconds and attacks were often precipitated by exercise, stress, or postural change. Of 13 patients available for review, none suffered a major vascular event during a mean follow up of 10 years. When adolescents and young adults present with transient bilateral blindness, investigations are unlikely to reveal a cause and the long-term prognosis appears benign.

Adolescent

Doppler ultrasound screening as part of routine antenatal scanning: prediction of pre-eclampsia and intrauterine growth retardation.

OBJECTIVE: To assess the value of incorporating continuous wave Doppler ultrasound of the uterine arteries into the routine scan as a screening test in an unselected population. DESIGN: A cross sectional study by multiple operators using continuous wave Doppler ultrasound to obtain flow velocity waveforms (FVW) from both uterine arteries of all women attending for routine anomaly scan at 18 to 22 weeks over a period of 12 months. An abnormal FVW in either uterine artery was used to predict intrauterine death, antepartum haemorrhage and three different degrees of severity of pre-eclampsia and growth retardation, singly and in combination. SETTING: King's College Hospital, London. SUBJECTS: Two thousand, four hundred and thirty women attending for routine anomaly ultrasound scan. RESULTS: A total of 2430 women were scanned with a 90% follow up rate. The results demonstrate higher sensitivities than previous studies, but with a high proportion of false positive tests. By including an early diastolic notch in the definition of an abnormal FVW the prediction of pre-eclampsia is markedly improved; the relative risk to a woman with an abnormal waveform of developing moderate or severe pre-eclampsia is increased 24-fold. Although the positive predictive value for babies less than the 5th centile for gestation is only 15%, those at risk of neonatal complications may be identified. CONCLUSION: This simple test can be performed at a routine visit and a group of women can be identified for further assessment and possible therapeutic intervention.

Blood Flow Velocity

Antiplatelet and anticoagulant therapy.

Antiplatelet therapy is clearly indicated for long-term secondary prevention after transient ischemic attack and ischemic stroke. In stroke-free patients with atrial fibrillation, oral anticoagulants reduce the risk of stroke, and antiplatelet agents may be a lower risk alternative. For the early treatment of the acute phase of ischemic stroke, the role of antiplatelet and anticoagulant therapy is unclear, but is being evaluated in large clinical trials.

Aspirin

Improved prediction of preeclampsia by two-stage screening of uterine arteries using the early diastolic notch and color Doppler imaging.

OBJECTIVE: To assess the value of the early diastolic notch and color Doppler imaging of the uterine arteries at 24 weeks' gestation in a two-stage Doppler screening test for preeclampsia. METHODS: Two thousand fifty-eight unselected women had an initial screening study with continuous-wave Doppler at 18-22 weeks' gestation. Color Doppler imaging was used at 24 weeks' gestation to examine both uterine arteries in 273 women with initial abnormal results (high resistance index or diastolic notch). RESULTS: Three hundred twenty-nine women (16%) had abnormal flow velocity waveforms at the first stage and 104 (5.1%) at the second stage of Doppler screening. The presence of an early diastolic notch in the flow velocity waveform was significantly better than a high resistance index at predicting preeclampsia at both 20 and 24 weeks; the relative risk of developing significant preeclampsia for a woman with a persistent notch at 24 weeks was increased 68-fold. All women delivered before 34 weeks because of severe preeclampsia had abnormal waveforms at both stages of screening. CONCLUSION: An early diastolic notch in the flow velocity waveform is a better predictor of preeclampsia than are conventional impedance indices. Preeclampsia can be predicted effectively by two-stage Doppler screening.

Adult

Effects of different hepatic pathologies on disposition of alfentanil in anaesthetized patients.

We have studied the influence of different hepatic pathologies on the disposition of alfentanil in 23 unpremedicated patients (six healthy control subjects, six patients with liver dysfunction of alcoholic aetiology and 11 patients with non-alcohol related liver disease). All patients received a bolus of alfentanil 500 micrograms i.v. as supplement to 67% nitrous oxide and isoflurane in oxygen anaesthesia. Plasma drug concentrations were measured in venous blood samples at intervals up to 24 h by radio-immunoassay and protein binding was determined by equilibrium dialysis. Kinetic estimates were determined using non-compartmental analysis. Patients with non-alcoholic liver disease had lesser plasma clearance (114.8 (range 66.8-213.5) ml min-1) than the alcoholic group (158.8 (100.0-220.7) ml min-1) or controls (187.4 (125.2-269.5) ml min-1). In all three groups, there was considerable intersubject variability, with a bimodal distribution in the non-alcoholic group. This group also had a smaller apparent volume of distribution at steady state. Mean residence time was prolonged in the alcoholic group compared with controls (284.9 (217.8-362.2) min vs 226.8 (201.2-250) min). Protein binding was decreased in the alcoholic group compared with controls (84.9 (SD 4.2)% vs 89.3 (2.1)%); this was attributable to a lesser plasma alpha 1-acid glycoprotein concentration (0.55 (0.18) g litre-1 vs 0.89 (0.21) g litre-1). Free drug clearance was reduced in both liver dysfunction groups compared with controls.

Adult

Plasma concentrations of bupivacaine following combined sciatic and femoral 3 in 1 nerve blocks in open knee surgery.

We administered combined femoral 3 in 1 and sciatic nerve blocks to provide postoperative pain relief in 22 consecutive patients undergoing elective knee replacement surgery under spinal anaesthesia. The patients were allocated randomly to two groups. In group A (n = 11) the blocks were performed with 0.5% bupivacaine (with adrenaline) 3 mg/kg body weight and in group B (n = 11) 0.5% plain bupivacaine in the same dose was used. Serial plasma concentrations of bupivacaine were measured for up to 2 h and the duration of postoperative analgesia was measured in both groups. No significant differences were found between the two groups. There were no clinical signs or symptoms of bupivacaine toxicity in each group. This study demonstrated that, after combined sciatic and 3 in 1 femoral block, concentrations of bupivacaine associated with toxicity were not reached, even though the dose of bupivacaine administered exceeded the manufacturer's recommended dose by 50%.

Anesthesia, Spinal

Doppler velocimetry studies of the uterine artery in the early prediction of pre-eclampsia and intra-uterine growth retardation.

Pre-eclampsia/proteinuric pregnancy-induced hypertension (PPIH) and intra-uterine growth retardation (IUGR) are associated with incomplete trophoblastic invasion of the uterus in the first half of pregnancy. The uteroplacental circulation can be observed using Doppler ultrasound. We have performed two mid pregnancy screening studies of our antenatal population in the last three years, to assess the use of Doppler velocimetry studies at that time in predicting the subsequent development of PPIH and IUGR. In the first study continuous wave Doppler ultrasound was used to study the uterine circulation. The Resistance Index (RI) was measured once in both uterine arteries in 925 patients between 16 and 24 weeks gestation. There was a significant association between an abnormal RI (greater than 95th centile) and the subsequent development of PPIH, IUGR and severe complications of pregnancy. However, even though the specificity (95%) was high the sensitivity was low (25%). There was no significant association with nonproteinuric hypertension. In an attempt to improve the sensitivity for the second study, colour flow imaging and the use of a diastolic notch as well as an elevated RI were introduced. 2437 patients had continuous-wave Doppler studies of the uterine circulation performed at 20 weeks gestation. 16% had abnormal waveforms, persisting in 5.4% at 24 weeks and 4.6% at 26 weeks when measured with colour/pulsed Doppler. The high sensitivity (76%) of this innovation at 20 weeks is retained at 24 and 26 weeks, while the specificity (from 86% to 97%) and positive predictive value (13% to 44%) improve progressively with gestation.(ABSTRACT TRUNCATED AT 250 WORDS)

Arteries