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Biomedical subjects

P Turner

Publications and source records attributed to P Turner.

At least 55 records · Page 3Linked to original sources

A Canadian multicenter study of three fixed doses of controlled-release ipsapirone in outpatients with moderate to severe major depression.

Ipsapirone, an azapirone with 5-hydroxytryptamine (5-HT1A) partial agonist activity, has been shown in preliminary studies to be effective in the treatment of major depressive disorder. This 8-week, randomized, double-blind study compared the efficacy, safety, and tolerability of three fixed doses of controlled-release ipsapirone (10-, 30-, and 50-mg dose once daily) with placebo in 410 patients with moderate to severe major depression (Hamilton Rating Scale for Depression [HAM-D] score > or = 20). The 10-mg ipsapirone treatment arm was discontinued early in the study. A total of 390 patients were eligible for evaluation in the intent-to-treat sample. The primary efficacy variable was the change in HAM-D total score from baseline to visit 8. There was no significant difference in efficacy in the two treatment groups versus the placebo group. The overall treatment response, defined as a 50% decrease in the HAM-D total score from baseline, was 43% with ipsapirone 50 mg given once daily, 34% with ipsapirone 30 mg given once daily, and 35% with placebo. In subanalyses, ipsapirone 50 mg given once daily was superior to placebo according to the HAM-D Core Depression (mood, guilt, interest, psychomotor activity) subtotal (p = 0.0453) and Melancholic item (p = 0.0225). Ipsapirone 30 mg given once daily was superior to placebo only in patients with moderate depression (baseline HAM-D total score < or = 25; p = 0.0100). The most common adverse effect in all groups was headache. The only dose-dependent adverse effects were dizziness and nausea.

Adolescent↗

Clinical evaluation of keratometry and computerised videokeratography: intraobserver and interobserver variability on normal and astigmatic corneas.

AIMS: To evaluate intra- and interobserver variability in measurements on normal and astigmatic corneas with keratometry and computerized videokeratography. METHODS: Keratometric readings with the 10 SL/O Zeiss keratometer and topographic maps with the TMS-1 were obtained by two independent examiners on 32 normal and 33 postkeratoplasty corneas. Inter- and intraobserver coefficients of variability (COR) for measurements of steep and flat meridian power and location, in addition to the magnitude of astigmatism, were assessed. RESULTS: Compared with TMS-1, the 10 SL/O keratometer showed a superior repeatability in measuring normal corneas (intraobserver COR for keratometry and TMS-1 respectively: 0.22 and 0.30 D for steep meridian power; 0.18 and 0.44 D for flat meridian power; 0.26 and 0.40 D for astigmatism; 5 degrees and 26 degrees for steep meridian location; 5 degrees and 13 degrees for flat meridian location). Astigmatism intraobserver COR (0.20 D and 0.26 D for the two observers) and interobserver COR (0.28 D) of the keratometer for normal corneas was very good and not affected by observers' experience. Repeatability of the TMS-1 on normal corneas was found to be: (a) observer related, and (b) astigmatism related. A novice observer showed a much greater COR (1.62 D for astigmatism, 30 degrees for flat meridian location) compared with the experienced examiner (0.40 D for astigmatism, 13 degrees for flat meridian location). Higher deviation scores were observed for corneas with higher astigmatism. For the postkeratoplasty corneas, again the keratometer achieved superior reproducibility (astigmatism interobserver COR 1.12 D for keratometry, 4.06 D for TMS-1; steep meridian location interobserver COR 10 degrees for keratometry, 34 degrees for TMS-1). CONCLUSION: Keratometric readings are more reproducible than topographic data both for normal and postkeratoplasty corneas. The two instruments should not be used interchangeably especially on highly astigmatic corneas. For the TMS-1, users with the same level of experience should be employed in clinical or experimental studies.

Adult↗

[Application of immunochromatographic test for diagnosis and surveillance of bancroftian filariasis].

AIM: To evaluate the usefulness of immunochromatographic test (ICT) for rapid diagnosis and surveillance of Wuchereria bancrofti infection. METHODS: The monoclonal antibody based-ICT assay was used to detect filarial antigens in the sera from bancroftian filariasis patients. RESULTS: 111 out of 116 bancroftian microfilaria cases showed positive ICT reaction, giving a positive rate of 95.7%. Serum samples from 12 malayian microfilaremia cases, 33 ascariasis cases, 20 schistosomiasis japonica cases and 6 trichinellosis cases were all found negative in ICT, demonstrating a specificity of 100%. In 73 chronic filariasis cases with elephantiasis, hydrocoele, and chyluria cases, 18 showed ICT positive, among whom 16 revealed microfilaremia, suggesting that the ICT positive cases were with active infections. Of the 30 microfilaremia cases before single dose ivermectin treatment, 29 were ICT positive (96.7%). A negative conversion of microfilaremia was observed in all cases 8-14 days post-treatment. Upon following up to 6 and 12 months, microfilaremia reappeared in 5 and 7 cases, respectively. 5 out of 13 ICT positive cases were found microfilaremic at 6 month post-treatment, while among the rest of 8, 5 were found microfilaremic at 12 month post-treatment. Parallel use of ICT with routine blood film examination in Houda village, Zhecheng County, Henan Province for a post-control surveillance survey in 132 local individuals revealed 9 microfilaremia cases were also ICT positive. Of the 123 persons with negative blood examination, only 1 was ICT positive. CONCLUSION: ICT is a rapid and simple method with high sensitivity and specificity, and might be used for the diagnosis, efficacy evaluation as well as a tool for post-control surveillance of bancroftian filarasis.

Animals↗

Needle stick injuries in country general practice.

AIMS: The aims of this study were to determine the frequency of needle stick injury (NSI) in general practice, to determine what measures were being taken to protect against needle stick injury, and to gather other information regarding work practices, risk perception, and knowledge of transmission. METHODS: A postal survey was undertaken of all general practitioners and one practice nurse per practice address in selected areas of New Zealand. RESULTS: The response rate was 82%. An incidence rate of 22 needle stick injuries in 100 health care workers per 6 month period was found. For general practitioners alone the incidence rate was 25 in 100 per 6 month period and for practice nurses it was 17 in 100 per 6 month period. Recommended precautionary measures were not being followed by most individuals. CONCLUSIONS: Needle stick injury is a substantial problem in general practice and exposes general practitioners and practice nurses to a serious risk of infection from bloodborne transmissible agents. All patients should be considered to pose a potentially high risk of infection and recommended precautionary measures should be followed at all times.

Accidents, Occupational↗

Physiotherapists' use of evidence based practice: a cross-national study.

This study investigated clinical physiotherapists' reasons for their use of treatment techniques, with a particular focus on their utilisation of journal review and research literature. A questionnaire was completed by 180 physiotherapists in England and 141 physiotherapists in Australia. Despite the greater prevalence of pre-registration degree respondents in Australia, there were no differences between the two national groups in their reasons given for choice of treatment techniques. The basis of over 90% of each groups choice of techniques reflected what was taught during their initial training. Experience of treatment effects on prior patients, and information gained in practice-related courses, were also primary reasons. Research literature ranked least in importance as a basis for choosing techniques, and review articles fared little better. The results indicated that these physiotherapists relied mainly on information gained from formal pre- and post-registration courses. By implication, the most obvious means of influencing physiotherapists' attitudes to research utilisation lies with those responsible for physiotherapy education.

Attitude of Health Personnel↗

Care of the patient requiring mechanical ventilation.

Today patients that are otherwise stable may require mechanical ventilation for prolonged periods of time. The medical-surgical nurse may be expected to care for these patients in a setting outside the intensive care unit. Basic knowledge of the modes of ventilation, assessment, and troubleshooting of ventilators and assessment and care of the patient requiring mechanical ventilation are reviewed in this article.

Critical Care↗

Inadequacy of iridium implant as sole radiation treatment for operable breast cancer.

In order to avoid a prolonged course of external irradiation as part of breast conservation therapy, 27 patients received an iridium implant to the primary tumour bed as sole radiation treatment. Surgery was standardised comprising tumourectomy and axillary clearance. Using a rigid implant afterloading with iridium192 wires, 55 Gy was delivered on a continuous basis over 5 days. After 6 years median follow-up, relapse of cancer within the treated breast has occurred in 10 of the 27 patients (37%). Compared with historical controls treated by similar surgery and iridium192 implant (20 Gy) with external radiotherapy (46 Gy), there was a significantly increased breast relapse rate in those treated by iridium implant alone. However, the incidence of distant metastases and overall survival was similar. Thus, a continuous iridium192 implant delivering 55 Gy in 5 days is not an effective means of achieving local control in patients with operable breast cancer.

Brachytherapy↗

Aspartame pharmacokinetics - the effect of ageing.

Aspartame is an intense sweetener which is increasingly used in the UK. It is registered at an acceptable daily intake (ADI) of 40 mg/kg, although there are no previous data relating to the metabolism of aspartame in older people. Twelve young and 12 elderly volunteers each received a single dose of approximately 40 mg/kg of aspartame. Baseline concentrations of phenylalanine (the main metabolite of aspartame) rose after ingestion with a significantly higher maximum concentration (Cmax) (81.3 vs. 63.3 micromol/1, p<0.01) and area under the plasma concentration-time curve extrapolated to infinity AUC 9(0-infinity)(518.7 vs. 353.5 micromol . h/l, p<0.01) in the elderly group. The higher concentrations reflected a significant fall in volume of distribution (V) from 2.03 to 1.59 1/kg (p <0.05) and clearance (CL) from 7.3 to 4.9 ml/min/kg (p <0.005) in the elderly group. The greater effect on CL than on V resulted in a small but non-significant rise in elimination half life (3.5 to 3.9 hours). The sizes of the differences were modest implying that there is no need on pharmacokinetic grounds for a change in the ADI for older people.

Adult↗

Effects of heat shock on gram negative bacteria: use of lysis by sodium dodecyl sulphate as a probe for the integrity of DNA.

Rheograms of Alcaligenes eutrophus (NCIMB 40529) and Escherichia coli (C90 NCIMB 10616) cells lysed by sodium dodecyl sulphate were compared before and after a variety of heat shock regimes. It was found that unheated cells produced a very characteristic shear thickening rheogram which could be destroyed by DNase treatment. Cells which had been subjected to heat shock produced rheograms very similar to DNase digested material. We thus suggest that the rheogram is largely due to the presence of intact DNA molecules. The extent and nature of the heat shock affected the shape of the rheogram of the SDS lysed material. Heat shock of cells after SDS lysis did not appear to significantly damage the DNA. Storage of the cells at 10 degrees C before heat shock considerably reduced the shear thinning effect of subsequent heat shock at 90 degrees C. We attribute the shear thinning effect of the heat shock to the action of nucleases which are activated and then depolymerise the DNA molecules.

Alcaligenes↗

Simultaneous resistance to metronidazole, co-amoxiclav, and imipenem in clinical isolate of Bacteroides fragilis.

A blood-culture isolate of Bacteroides fragilis, taken from a woman after elective laparotomy, was resistant to metronidazole and had reduced susceptibility to imipenem and co-amoxiclav. After treatment with imipenem, pus drained from the pleural cavity yielded an identical isolate that had become highly resistant to imipenem and co-amoxiclav. Emergence of full resistance to the beta-lactam antibiotics was accompanied by a tenfold rise in the specific activity of a metallo-beta-lactamase. Clinicians need to be alert to simultaneous resistance to metronidazole, co-amoxiclav, and imipenem and development of high-level resistance to imipenem in B fragilis during treatment with this agent.

Adult↗

Effect of ageing and propranolol administration on myocardial beta-adrenoceptor receptor function in mature rats.

Ageing is accompanied by diminishing myocardial tissue beta-adrenoceptor responses. The relative contribution of maturation and senescence to reported age-related changes in cell-surface beta-adrenoceptor dysfunction has not been established, since previous investigation has incorporated young rats lacking full maturity. We have examined myocardial ventricle membrane beta-adrenoceptor function in mature young (6 month) and old (26 month) male Wistar rats and the effect of propranolol infusion for seven days on beta-adrenoceptor function in these groups. beta 1-adrenoceptors comprised 63-72% of total beta-adrenoceptor density in both groups. beta 1-adrenoceptor densities were similar in young and old rats (young, 20.4 +/- 2.3; old, 24.7 +/- 1.4 fmol/mg protein +/- S.E.). beta 2-adrenoceptor densities were higher in older rats (young, 8.2 +/- 0.5, n = 9; old, 13.6 +/- 1.8, n = 9 fmol/mg protein +/- S.E., P < 0.025). Subcutaneous infusion of propranolol for seven days with miniosmotic pumps was accompanied by an increase in beta 1- and beta 2-adrenoceptor densities in young rats only (beta 1-, 38%, P < 0.05; beta 2- 52%, P < 0.025). beta 1-adrenoceptor agonist affinity and adenylate cyclase response to isoprenaline, GTP, Gpp(NH)p, Mn2+ and forskolin were not affected by age or propranolol infusion in either age-group. These findings demonstrate that male Wistar rats do not exhibit changes in myocardial ventricle beta-adrenoceptor-G-protein coupling capacity or adenylate cyclade activation with ageing beyond maturity.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Henderson-Hasselbalch equation is inadequate for the measurement of transmembrane diffusion of drugs and buccal drug absorption is a useful alternative.

1. The transmembrane diffusion of weakly acidic or basic drugs is being commonly assessed from their degree of ionization or ratio unionized/ionized forms (ratio U/I) as calculated from Henderson-Hasselbalch equation (HHEq). 2. Buccal drug absorption (BA) at pH 5-9 has been proposed as an in vivo model for passage of drugs across lipid membranes. 3. Area under the curve (AUC) of BA against pH 5-9 of 18 basic drugs has been reported to be significantly related to their pH dependent renal excretion. 4. We have calculated, using HHEq, ratios U/I of 10 weak bases at pH 5-9 and 10 weak acids at pH 4-8, whose percentage BA at these pH levels was available in the literature. 5. These ratios were not related to their %BA at corresponding pH levels. 6. Therefore it is proposed that HHEq is inadequate in the anticipation of transmembrane diffusion of drugs and AUC of %BA of drugs at pH 4-9 is a useful alternative.

Absorption↗

Role of NF-kappa B in the regulation of inducible nitric oxide synthase in an MTAL cell line.

The effects of cytokines, lipopolysaccharide (LPS), 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP), and pyrrolidine dithiocarbamate (PDTC), an inhibitor of nuclear factor kappa B (NF-kappa B) activation, on inducible nitric oxide synthase (iNOS) expression were studied in the medullary thick ascending limb of Henle's loop cell line ST-1. LPS + interferon-gamma (IF-gamma) promoted a time-dependent increase in nitrite (a NO metabolite) and iNOS mRNA and the appearance of NF-kappa B p50 and p65 in nuclear protein extracts. Actinomycin D but not cycloheximide prevented the LPS + IF-gamma induction of iNOS mRNA and NO synthesis, indicating that iNOS transcriptional activation by LPS + IF-gamma does not require newly synthesized proteins. PDTC inhibited the LPS + IF-gamma induction of NO, iNOS mRNA, and the appearance of NF-kappa B in nuclear protein extracts, suggesting that NF-kappa B mobilization and trans-activation of the iNOS gene mediates this induction. In contrast to other cell types, cycloheximide did not alter iNOS mRNA stability, and 8-BrcAMP did not alter basal or LPS+IF-gamma induced NO production in ST-1 cells.

8-Bromo Cyclic Adenosine Monophosphate↗

Identification of constitutive and inducible forms of nitric oxide synthase in human platelets.

A number of cell types possess an L-arginine-nitric oxide (NO) pathway. We studied the presence of constitutive and inducible forms of NO synthase in human platelets. N omega-nitro-L-arginine, an inhibitor of NO synthase, potentiated thrombin-induced aggregation of washed human platelets, whereas L-arginine inhibited it. The direct evidence for the presence of constitutive form of NO synthase came from the observation of conversion of tritium-labeled L-arginine to tritium-labeled L-citrulline by washed platelets suspended in Ca(++)-rich but not in Ca(++)-free buffer. Incubation of washed platelets in Ca(++)-free buffer with cytokines (tumor necrosis factor-alpha and interferon-gamma) or cytokines plus lipopolysaccharide caused a marked increase in the conversion of [3H]L-arginine to [3H]L-citrulline, suggesting the presence of inducible form of NO synthase. Gel electrophoresis identified an approximately 130 kd protein band with NO synthase in the platelet cytosol, which on isolation converted [3H]L-arginine to [3H]L-citrulline. This 130 kd protein required the presence of Ca++, reduced nicotinamide adenine dinucleotide phosphate tetrahydro-L-biopterin, and flavin adenine dinucleotide for expression of NO synthase activity. Platelet sonicates demonstrated presence of nitrite, and its concentrations were lowered by preincubation of platelets with NG-nitro-L-arginine methyl ester and enhanced in cytokine-treated platelets. Reverse-transcription polymerase chain reaction demonstrated messenger RNA expression of the constitutive endothelial (but not brain) and inducible isoforms of NO synthase in platelets. These observations indicate that human platelet cytosol possesses both constitutive and inducible forms of NO synthase.

Amino Acid Oxidoreductases↗