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Biomedical subjects

S Oliver

Publications and source records attributed to S Oliver.

At least 19 recordsLinked to original sources
PubMed2001

Multiple-dose pharmacokinetics and tolerability of gemifloxacin administered orally to healthy volunteers.

Gemifloxacin mesylate (SB-265805-S, LB-20304a) is a potent, novel fluoroquinolone agent with a broad spectrum of antibacterial activity. The pharmacokinetics and tolerability of oral gemifloxacin were characterized in two parallel group studies in healthy male volunteers after doses of 160, 320, 480, and 640 mg once daily for 7 days. Multiple serum or plasma and urine samples were collected on days 1 and 7 and were analyzed for gemifloxacin by high-performance liquid chromatography (HPLC)-fluorescence (study 1) or HPLC-mass spectrometry (study 2). Safety assessments included vital signs, 12-lead electrocardiogram (ECG) readings, hematology, clinical chemistry, urinalysis, and adverse experience monitoring. Gemifloxacin was rapidly absorbed, with a time to maximum concentration of approximately 1 h after dosing followed by a biexponential decline in concentration. Generally, maximum concentration and area under the concentration-time curve (AUC) increased linearly with dose after either single or repeat doses. Mean +/- standard deviation values of AUC(0-tau) on day 7 were 4.92 +/- 1.08, 9.06 +/- 2.20, 12.2 +/- 3.69, and 20.1 +/- 3.67 microg x h/ml following 160-, 320-, 480-, and 640-mg doses, respectively. The terminal-phase half-life was approximately 7 to 8 h, independent of dose, and was similar following single and repeated administrations. There was minimal accumulation of gemifloxacin after multiple dosing. Approximately 20 to 30% of the administered dose was excreted unchanged in the urine. The renal clearance was 160 ml/min on average after single and multiple doses, which was slightly greater than the accepted glomerular filtration rate (approximately 120 ml/min). These data show that the pharmacokinetics of gemifloxacin are linear and independent of dose. Gemifloxacin was generally well tolerated, although one subject was withdrawn from the study after 6 days at 640 mg for mild, transient elevations of alanine aminotransferase and aspartate aminotransferase not associated with any clinical signs or symptoms. There were no other significant changes in clinical chemistry, hematology or urinalysis parameters, vital signs, or ECG readings. In conclusion, the results of these studies, combined with the antibacterial spectrum and potency, support the further investigation of once-daily administration of gemifloxacin for indications such as respiratory tract and urinary tract infections.

Adult↗
PubMed2000

Lactogenic immunity following vaccination of cattle with bovine coronavirus.

In order to investigate the ability of an oil adjuvanted vaccine containing bovine coronavirus antigen to enhance lactogenic immunity in the calf, pregnant cows and heifers were vaccinated and specific virus neutralising antibody levels determined in serum, colostrum and milk. Pre-existing antibody titres (as a result of natural infection) in the serum of these animals were found to be significantly increased as a result of a single shot vaccination carried out between 2 and 12 weeks before calving. This was reflected in a similar increase in the titre and duration of specific antibody in milk and colostrum that was passed on to the calves. The overall response observed was highly dependent on an adequate antigen payload being incorporated within the single dose vaccine. No abnormal local or systemic reactions were observed as a result of vaccination. It is hoped that this approach will lead to the production of a superior commercial vaccine for the protection of neonatal calves against enteric coronavirus infection.

Animals↗
PubMed2000

3D raman sideband cooling of cesium atoms at high density

We laser cool 5x10(7) Cs atoms to a spin-polarized phase space density of 1/30, the highest ever obtained by laser cooling. It is achieved by compression and polarization gradient cooling in a 3D far-off-resonant optical lattice, followed by 3D Raman sideband cooling optimized at a density of 1.5x10(12) atoms/cm(3), and adiabatic release. In the lattice, 23% of the sites are occupied, 95% of the atoms are in the lowest energy magnetic sublevel, and 37% are in the lowest 3D vibrational state.

Journal Article↗
PubMed2000

Interventions for promoting smoking cessation during pregnancy.

BACKGROUND: Smoking remains one of the few potentially preventable factors associated with low birthweight, very preterm birth and perinatal death. OBJECTIVES: The objective of this review was to assess the effects of smoking cessation programs implemented during pregnancy on the health of the fetus and infant, on the mother and on the family. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register and the Cochrane Tobacco Addiction Group trials register. SELECTION CRITERIA: Randomised and quasi-randomised trials of smoking cessation programs implemented during pregnancy. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and data were extracted independently by two reviewers. MAIN RESULTS: Forty-four trials were identified: 37 trials including 16,916 women provided data on smoking cessation and/or perinatal outcomes, as did one cluster-randomised trial including 3000 women. Over 800 women were included in trials of smoking relapse prevention. There was substantial variation in the intensity of the intervention and the extent of reminders and reinforcement through pregnancy. Based on 34 trials there was a significant reduction in smoking in the intervention groups (odds ratio 0.53, 95% confidence interval 0. 47 to 0.60), an absolute difference of 6.4% women continuing to smoke. The eight trials with validated smoking cessation, a high intensity intervention and a high quality score had an odds ratio of 0.53, 95% confidence interval 0.44 to 0.63 and an absolute difference in continued smoking of 8.1%. The subset of trials with information on fetal outcome revealed a reduction in low birthweight (odds ratio 0.80, 95% confidence interval 0.67 to 0.95), a reduction in preterm birth (odds ratio 0.83, 95% confidence interval 0.69 to 0. 99) and an increase in mean birthweight of 28g (95% confidence interval 9 to 49). There were no differences in very low birthweight or perinatal mortality. Five trials of smoking relapse prevention showed no significant difference. The single large cluster-randomised trial showed no evidence of a decrease in continued smoking or adjusted mean birthweight. REVIEWER'S CONCLUSIONS: Smoking cessation programs in pregnancy appear to reduce smoking, low birthweight and preterm birth, but no effect was detected for very low birthweight or perinatal mortality.

Female↗
PubMed2000

Effects of sibutramine alone and with alcohol on cognitive function in healthy volunteers.

AIMS: To investigate the effects of sibutramine in combination with alcohol in a double-blind, randomised, placebo-controlled, four-way crossover study in 20 healthy volunteers. METHODS: On each study day each volunteer received either: sibutramine 20 mg+0.5 g kg-1 alcohol; sibutramine 20 mg+placebo alcohol; placebo capsules+0.5 g kg-1 alcohol; or placebo capsules+placebo alcohol. Alcohol was administered 2 h following ingestion of the study capsules. During each study day, assessments of cognitive performance were made prior to dosing, and at 3, 4.5, 6 and 10 h post dosing. Blood alcohol concentration was estimated using a breath alcometer immediately prior to each cognitive performance test session. Each study day was followed by a minimum 7 day washout period. RESULTS: Alcohol was found to produce statistically significant impairments in tests of attention (maximum impairment to speed of digit vigilance=49 ms) and episodic memory (maximum impairment to speed of word recognition=74 ms). Alcohol also increased body sway (maximum increase 17.4 units) and lowered self rated alertness (maximum decrease 13.6 mm). These effects were produced by an inferred blood alcohol level of 53.2 mg dl-1. Sibutramine was not found to potentiate any of the effects of alcohol. There was a small, yet statistically significant, interaction effect observed on the sensitivity index of the picture recognition task. In this test, the combined effects of sibutramine and alcohol were smaller than the impairments produced by alcohol alone. Sibutramine, when dosed alone, was associated with improved performance on several tasks. Sibutramine improved attention (mean speed of digit vigilance improved by 21 ms), picture recognition speed (improvement at 3=81) and motor control (tracking error at 3 h reduced by 1.58 mm). Also sibutramine improved postural stability (reducing body sway at 3 h by 14.2 units). Adverse events reported were unremarkable and consistent with the known pharmacology of sibutramine and alcohol. CONCLUSIONS: There was little evidence of a clinically relevant interaction of sibutramine with the impairment of cognitive function produced by alcohol in healthy volunteers. The single statistically significant interaction indicated a reduction, rather than a worsening, of alcohol-induced impairment when sibutramine is taken concomitantly. Sibutramine when administered alone is associated with improved performance on several tasks.

Adult↗
PubMed2000

Ziprasidone and the pharmacokinetics of a combined oral contraceptive.

AIMS: To determine whether multiple doses of ziprasidone alter the steady-state pharmacokinetics of the component steroids, ethinyloestradiol and levonorgestrel, of an oral contraceptive; to evaluate the tolerability of a co-administered combined oral contraceptive and ziprasidone; and to compare plasma concentrations of prolactin in subjects taking a combined oral contraceptive with placebo or ziprasidone. METHODS: Nineteen women taking a combined oral contraceptive (ethinyloestradiol 30 microg day(-1) and levonorgestrel 150 microg day(-1)) were enrolled into a double-blind, placebo-controlled, two-way crossover study. They received ziprasidone 40 mg day- 1 in two divided daily doses or placebo for 8 days (days 8-15) in one of two 21 day treatment periods separated by a 7 day washout period. Venous blood samples were collected immediately before and up to 24 h after the morning dose of oral contraceptive and ziprasidone or placebo on day 15 of each 21 day treatment period. These were assayed for ethinyloestradiol and levonorgestrel and the resulting data used to derive pharmacokinetic data for these steroids. Additional samples were collected immediately before and 4 h after the morning dose of oral contraceptive and ziprasidone or placebo on day 15 of each 21 day treatment period for prolactin assay. All observed and volunteered adverse events were recorded throughout the study. RESULTS: The mean AUC(0,24 h), Cmax and tmax for ethinyloestradiol and the mean AUC(0, 24 h) and Cmax for levonorgestrel during ziprasidone co-administration were not statistically significantly different from corresponding values occurring during placebo co-administration. The tmax for levonorgestrel was approximately 0.5 h longer. Concomitant therapy with a combined oral contraceptive and ziprasidone did not result in adverse events not previously seen with either preparation alone. CONCLUSIONS: The findings of this study suggest that, based on pharmacokinetic and tolerability data, ziprasidone may be co-administered with ethinyloestradiol and levonorgestrel without loss of contraceptive efficacy or increased risk of adverse events.

Adolescent↗
PubMed2000

Do we do what they say we do? coding errors in urology.

OBJECTIVE: To determine the accuracy of routine data coding in a large multispeciality urological unit. Materials and methods From the clinical records, the diagnosis and procedure codes were ascribed to 106 finished consultant episodes (FCEs) in urology, by two urological trainees. The codes were compared with those ascribed by professional hospital coders (and of which the trainees were unaware) from information written on the audit form by junior medical staff. Where there were discrepancies in codes an error was recorded and the stage in the coding process in which it occurred was determined. RESULTS: Forty-eight coding errors were found in 38 of the 106 (36%) FCEs; 34 (71%) were caused by inaccurate coding and 14 (29%) were the result of the incorrect completion of audit forms. CONCLUSION: The clinical codes generated from the authors' department do not accurately reflect the clinical practice. If coding errors of this magnitude are typical of urology units in general, the concept of hospital performance tables (which will be generated using routine clinical data) is untenable unless data recording is given higher priority.

Forms and Records Control↗
PubMed2000

Pharmacokinetics and tolerability of gemifloxacin (SB-265805) after administration of single oral doses to healthy volunteers.

Gemifloxacin (known as SB-265805 or LB-20304) is a potent, novel fluoroquinolone compound with a broad spectrum of antibacterial activity. The pharmacokinetics and tolerability of oral gemifloxacin were characterized in healthy male volunteers after a single dose of 20, 40, 80, 160, 320, 600, or 800 mg. Multiple serum and urine samples were collected and analyzed for gemifloxacin using high-performance liquid chromatography with fluorescence detection. Safety assessments included vital signs, 12-lead electrocardiogram readings, hematology, clinical chemistry, urinalysis, and adverse-experience monitoring. Gemifloxacin was rapidly absorbed after all doses. Maximum concentrations of gemifloxacin in serum (C(max)) were achieved approximately 1 h after dosing, after which concentrations in serum declined in a biexponential manner. Values of C(max) and the area under the concentration-time curve in serum from 0 h to infinity (serum AUC(0-infinity)) increased linearly with dose. Serum AUC(0-infinity) values (mean +/- standard deviation) were 0.65+/-0.01, 1.28+/-0.22, 2.54+/-0.31, 5.48+/-1.24, 9.82+/-2.70, 24.4+/-7.1, and 31.4+/-7.6 microg. h/ml following 20-, 40-, 80-, 160-, 320-, 600-, and 800-mg doses, respectively. The terminal phase elimination half-life was independent of dose, with an overall mean of 7.4+/-2.0 h. The profiles indicated that the pharmacokinetic profile is suitable for a once-daily dosing regimen. Approximately 25 to 40% of the administered dose was excreted unchanged in the urine, and renal clearance (ca. 150 ml/min) was independent of dose. There were no significant changes in clinical chemistry, hematology, or urinalysis parameters, vital signs, or 12-lead electrocardiogram readings in subjects, irrespective of dose. The results of these studies support the further investigation of once-daily administration of gemifloxacin.

Administration, Oral↗
PubMed2000

Studies of the latency of pelvic floor contraction during peripheral nerve evaluation show that the muscle response is reflexly mediated.

PURPOSE: Whether neuromodulation using an implanted sacral nerve stimulator acts by its effects on pelvic afferent or efferent nerves remains to be determined. However, it has been observed that eliciting an "anal wink" is helpful in the optimal siting of the foraminal stimulating electrode. This observation has been interpreted as indicating that a direct effect on efferent pelvic innervation is an important functional component of the technique. We studied the latency of this motor response to determine whether it is consistent with neuromodulation working via a direct efferent mechanism. MATERIALS AND METHODS: We studied 9 women with urinary retention undergoing the first stage of a stimulator implant (peripheral nerve evaluation). Stimulation was applied to an electrode placed in the S3 foramen and the latency of the response of the striated anal sphincter, a contraction which gives rise to the "anal wink," was measured using a concentric needle electrode placed in the striated part of the anal sphincter. RESULTS: Mean latency of response was 98 milliseconds (range 52 to 140), which is approximately 10 times longer than would be expected from that resulting from direct motor nerve stimulation. CONCLUSIONS: Our results indicate that anal sphincter contraction observed during peripheral nerve evaluation is the result of an afferent mediated response.

Adult↗
PubMed1999

A systematic review of the effectiveness of health promotion interventions in the workplace.

The aim of this study was to identify and critically review evaluations of the effectiveness of health promotion programmes in the workplace. In line with guidelines for 'good practice' within the literature on workplace health promotion, this study aimed to assess the extent to which evaluated interventions considered employees' expressed needs or involved employee-employer partnerships. Overall, 110 outcome evaluations were located. Only a quarter of these reported that interventions were implemented in response to the explicit needs and/or views of the employees and very few involved partnerships. Most of the programmes targeted individual behaviour and supportive organizational change was limited. The majority of the outcome evaluations were not sufficiently rigorous to make a strong case for the effectiveness of workplace health promotion. However, some pointers to success were identified. It was concluded that there seems to be a wide disparity between what counts as 'good practice' within workplace health promotion and what is reported in the evaluation of effectiveness literature. This is not to say that 'good practice' does not exist, but that either such programmes are not rigorously evaluated for their effectiveness and/or that many of the evaluation findings remain outside the public domain.

Health Promotion↗
PubMed1998

Interaction of phosphatidic acid and phosphatidylserine with the Ca2+-ATPase of sarcoplasmic reticulum and the mechanism of inhibition.

The sarcoplasmic reticulum of skeletal muscle contains anionic phospholipids as well as the zwitterionic phosphatidylcholine and phosphatidylethanolamine. Here we study the effects of anionic phospholipids on the activity of the Ca2+-ATPase purified from the membrane. Reconstitution of the Ca2+-ATPase into dioleoylphosphatidylserine [di(C18:1)PS] or dioleoylphosphatidic acid [di(C18:1)PA] leads to a decrease in ATPase activity. Measurements of the quenching of the tryptophan fluorescence of the ATPase by brominated phospholipids give a relative binding constant for the anionic lipids compared with dioleoylphosphatidylcholine close to 1 and suggest that phosphatidic acid only binds to the ATPase at the bulk lipid sites around the ATPase. Addition of di(C18:1)PS or di(C18:1)PA to the ATPase in the short-chain dimyristoleoylphosphatidylcholine [di(C14:1)PC] reverse the effects of the short-chain lipid on ATPase activity and on Ca2+ binding, as revealed by the response of tryptophan fluorescence intensity to Ca2+ binding. It is concluded that the lipid headgroup and lipid fatty acyl chains have separate effects on the function of the ATPase. The anionic phospholipids have no significant effect on Ca2+ binding to the ATPase; the level of Ca2+ binding to the ATPase, the affinity of binding and the rate of dissociation of Ca2+ are unchanged by reconstitution into di(C18:1)PA. The major effect of the anionic lipids is a reduction in the maximal level of binding of MgATP. This is attributed to the formation of oligomers of the Ca2+-ATPase, in which only one molecule of the ATPase can bind MgATP dimers in di(C18:1)PS and trimers or tetramers in di(C18:1)PA. The rates of phosphorylation and dephosphorylation for the proportion of the ATPase still able to bind ATP are unaffected by reconstitution. Larger changes were observed in the level of phosphorylation of the ATPase by Pi, which became very low in the anionic phospholipids. The fluorescence response to Mg2+ for the ATPase labelled with 4-(bromomethyl)-6,7-dimethoxycoumarin was also changed in di(C18:1)PS and di(C18:1)PA, so that effects of Mg2+ became comparable with those seen on phosphorylation for the unreconstituted ATPase. The anionic phospholipids could induce a conformational change in the ATPase on binding Mg2+ equivalent to that normally induced by phosphorylation or by binding inhibitors such as thapsigargin.

Adenosine Triphosphate↗
PubMed1998

The antibacterial activity of acetic acid and Burow's solution as topical otological preparations.

At present there are no topical otological preparations on the World Health Organisation's essential drug list, largely due to the ototoxic potential of preparations containing aminoglycoside antibiotics. Acetic acid and Burow's solution have long been used in the treatment of the discharging ear. The aim of this study was to ascertain the antibacterial activity of these two preparations against the most commonly occurring bacteria isolated from discharging ears in our department. Twenty fresh isolates of each of the following organisms--Pseudomonas aeruginosa, Staphylococcus aureus, Proteus mirabilis and Streptococcus pyogenes--were plated onto blood agar and tested against one per cent, two per cent and three per cent acetic acid and Burow's solution (13 per cent aluminium acetate). The activity of each agent was ascertained by the size of the zone of inhibition of bacterial growth. Burow's solution showed significantly larger average zones of inhibition than acetic acid (p < 0.001). The two per cent and three per cent acetic acid as well as the Burow's solution were active against all the organisms tested.

Acetates↗
PubMed1998

Antibiotic choice in acute and complicated sinusitis.

The microbiology of 87 patients admitted to hospital, over a five-year period, with acute sinusitis was retrospectively analysed. Sixty-three patients had one or more of an orbital, intracranial, soft tissue or bony complication. Eighty-four patients had maxillary sinus washouts, while 48 required a surgical procedure to their sinuses, and 33, drainage of an empyema. Streptococcus milleri and Haemophilus influenzae were the commonest organisms isolated from sinus aspirates (44 per cent), with a noticeable absence of Streptococcus pneumoniae (10 per cent). Organisms cultured from intracranial, soft tissue or orbitral empyemas were predominantly Streptococcus milleri (50 per cent) and Staphylococcus aureus (25 per cent) with an absence of Haemophilus influenzae (four per cent) and Streptococcus pneumoniae (four per cent). Ampicillin is an appropriate first line antimicrobial agent in patients with acute complicated sinusitis with the addition of cloxacillin in cases with an empyema. Chloramphenicol or ceftriaxone is used in cases with an intracranial complication.

Acute Disease↗