Search PubMed⌕ Search

Biomedical subjects

S Campbell

Publications and source records attributed to S Campbell.

At least 271 records · Page 15Linked to original sources
PubMed1996

National survey of hospital-based pharmacokinetic services.

The status of pharmacokinetic services in the nation's hospitals was studied. A questionnaire was mailed in February 1995 to all 252 respondents to ASHP's 1994 national survey of hospital-based pharmaceutical services who indicated the provision of pharmacokinetic services in their institution. Ninety-eight completed questionnaires were returned (40.2% response rate). The pharmacokinetic services provided required an average of 19.1 person-hours per week, tended to be provided by staff pharmacists, were managed by the pharmacy department, tended to be most focused on aminoglycosides and vancomycin, required an average of 60 notes in patient charts per month, and relied on both computers and calculators for deriving values. There was little contact with patients during the consultation process. Drug concentration measurements tended to be scheduled by service providers, but confidence in the accuracy of the timing of dose administration and blood sampling was limited. Respondents believed that the services tended to be supported by other hospital personnel and that they were successful. There was very little expectation that the workload for providing pharmacokinetic services would increase in the near future. A national survey of hospital-based pharmacokinetic services showed that it took 19 hours per week on average to provide the services, that the focus was on aminoglycosides and vancomycin, and that the services were perceived to be supported by other departments.

Drug Monitoring↗
PubMed1996

Peptides containing a consensus Ras binding sequence from Raf-1 and theGTPase activating protein NF1 inhibit Ras function.

A key event in Ras-mediated signal transduction and transformation involves Ras interaction with its downstream effector targets. Although substantial evidence has established that the Raf-1 serine/threonine kinase is a critical effector of Ras function, there is increasing evidence that Ras function is mediated through interaction with multiple effectors to trigger Raf-independent signaling pathways. In addition to the two Ras GTPase activating proteins (GAPs; p120- and NF1-GAP), other candidate effectors include activators of the Ras-related Ral proteins (RalGDS and RGL) and phosphatidylinositol 3-kinase. Interaction between Ras and its effectors requires an intact Ras effector domain and involves preferential recognition of active Ras-GTP. Surprisingly, these functionally diverse effectors lack significant sequence homology and no consensus Ras binding sequence has been described. We have now identified a consensus Ras binding sequence shared among a subset of Ras effectors. We have also shown that peptides containing this sequence from Raf-1 (RKTFLKLA) and NF1-GAP (RRFFLDIA) block NF1-GAP stimulation of Ras GTPase activity and Ras-mediated activation of mitogen-activated protein kinases. In summary, the identification of a consensus Ras-GTP binding sequence establishes a structural basis for the ability of diverse effector proteins to interact with Ras-GTP. Furthermore, our demonstration that peptides that contain Ras-GTP binding sequences can block Ras function provides a step toward the development of anti-Ras agents.

3T3 Cells↗
PubMed1996

Results of a multicenter study of nebulized inhalant bronchodilator solutions.

The efficacy, persistence of bronchodilator action, and safety of the quaternary ammonium anticholinergic agent, ipratropium bromide (500 microgram), and placebo were compared when each was added in solution form to the beta-adrenergic agonist solution, metaproterenol sulfate (15 mg), and administered three times daily for 12 weeks to a total of 213 patients with chronic obstructive pulmonary disease (COPD). Subjects had a mean forced expiratory volume in 1 second (FEV1) of approximately 1 liter (37% of predicted) and were permitted to use nonanticholinergic therapy for COPD throughout the trial. The study was a randomized, double-blind, 85-day, parallel-group, eight-center study. On a 3 test days, 1, 43, and 85, mean peak responses for FEV1 and forced vital capacity and mean area under the curve were significantly higher for the iprathropium bromide-metaproterenol combination than for metaproterenol only. Duration of action was also significantly longer for the combination therapy than for the beta-agonist alone on test days 1 and 43. Neither treatment regimen produced an demonstrable effect on daily morning peak expiratory flow rates, reported respiratory symptoms, or quality of life. Both treatment regimens were similarly well tolerated with a comparable frequency of adverse events. These results suggest that the combination of iprathropium bromide and metaproterenol inhalation solutions offers a potential therapeutic advantage to patients with symptomatic COPD over nebulized metaproterenol alone without the risk of increased side effects.

Administration, Inhalation↗
PubMed1996

Maternal serum testing for alpha-fetoprotein and human chorionic gonadotropin in high-risk pregnancies.

To evaluate the variations and potential clinical use of serial maternal alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) in pregnancies at risk of pregnancy-induced hypertension (PIH) and/or intrauterine growth retardation (IUGR), we investigated the relationship between placental sonographic findings, uterine artery Doppler measurements, and maternal serum AFP, hCG, and uric acid levels between 20 and 34 weeks of pregnancy. Maternal serum samples were collected from 41 singleton pregnancies with bilateral uterine notches and/or an increased uterine artery pulsatility index at 20-24 weeks. Maternal serum AFP, intact hCG and free alpha and beta subunits, and uric acid circulating levels were measured in all cases at 20-24 weeks and 25-28 weeks. Placental sonographic investigations comprised measurements of thickness and morphology. Twenty pregnancies had a normal outcome and 21 had an adverse outcome, including eight complicated by severe PIH with fetal IUGR, eight by isolated IUGR, three by mild PIH with normal fetal growth, and two by placental abruption. At the time of the first scan, the placental thickness and maternal serum levels of AFP, hCG, and uric acid were significantly increased in pregnancies with adverse outcomes, compared with those with a normal outcome. In subsequent maternal serum examinations, the incidence of elevated hormonal levels fell for AFP, intact hCG, and beta-hCG, whereas it increased for the uric acid level. No difference was found at any stage for the alpha-hCG level. Seven out of 11 pregnancies complicated by PIH presented with elevated MSAFP and MShCG and a large heterogeneous placenta at the first visit, whereas no pregnancy with a normal outcome presented with similar features. This study has shown a significant association between abnormal development of the utero-placental circulation, elevated MSAFP and MShCG at mid-gestation, and subsequent adverse pregnancy outcome. Serial measurements of MSAFP and MShCG do not provide extra information for the follow-up of these pregnancies.

Chorionic Gonadotropin↗
PubMed1996

Accuracy of laparoscopic ultrasonography in the staging of upper gastrointestinal malignancy.

Laparoscopic ultrasonographic staging was compared prospectively with conventional computed tomography (CT) and ultrasonographic staging of 24 lower-third oesophageal tumors and 20 gastric malignancies. Following laparoscopic ultrasonography, seven patients regarded as being resectable after conventional imaging were excluded from surgical exploration because of ascites with peritoneal deposits (four patients), liver metastases (one), advanced local disease (one) and poor tolerance of general anaesthesia (one). Preoperative T and N stages were compared with the pathological staging following resection in 34 patients. Laparoscopic ultrasonography was significantly more accurate than conventional CT and ultrasonography in assessment of the primary tumour (91 versus 64 per cent, P < 0.01) and nodal status (91 versus 62 per cent, P < 0.05). The addition of laparoscopic ultrasonography to conventional procedures for staging upper gastrointestinal malignancy improved the overall accuracy of staging. Although this may have future implications for the selection of patients for multimodality treatment, management decisions are currently based on laparoscopic findings, which in this study resulted in a resection rate of 97 per cent.

Gastrointestinal Neoplasms↗
PubMed1996

Preterm labour and delivery.

Preterm birth is a major cause of perinatal morbidity and mortality. It accounts for 5-10% of all births, and any treatment to prevent it could have a profound effect on neonatal outcome in both human and economic terms. The pathogenesis of both term and preterm birth remain poorly understood. Our ability to predict those at risk of preterm labour is also inaccurate, despite the creation of scoring systems, uterine activity monitoring, cervical ultrasound and several biochemical markers. Current drug therapies for preterm labour have not been shown in randomised controlled trials to significantly affect perinatal morbidity and mortality. Furthermore, most are associated with significant maternal or fetal side effects. Nitric oxide (NO) is a potent smooth muscle relaxant, produced when NO synthase acts on the amino acid L-arginine. Its presence has been demonstrated in human myometrium. We have conducted an observational study which has suggested that glyceryl trinitrate (GTN), and NO donor, may be effective in prolonging gestation. A randomised trial comparing GTN to intravenous ritodrine is currently recruiting patients; results will be available in the Spring of 1997. Few side effects have so far been encountered. Evidence suggests that GTN, an NO donor, should be a safe and effective tocolytic and early observations are encouraging; randomised trials currently underway should determine the significance of this breakthrough in the management of preterm labour.

Adrenergic beta-Agonists↗
PubMed1996

Success of intrauterine insemination using cryopreserved donor sperm is related to the age of the woman and the number of preovulatory follicles.

OBJECTIVE: Our objective was to assess parameters associated with a successful outcome of intrauterine insemination (IUI) using cryopreserved donor sperm. DESIGN: We analyzed 750 consecutive donor IUI cycles undertaken by 363 women in an assisted conception clinic. The main outcome measure was clinical pregnancy. RESULTS: IUI was performed in 94.7% of the 750 IUI treatment cycles commenced and 180 clinical pregnancies occurred. The clinical pregnancy rate per cycle was 26.4%. The rate was significantly related to the patient's age (30.5% for age < or = 35 years and 18.1% for age > 35 years; P < 0.006) and whether there was one or more than one preovulatory follicles [20.9, 34.4, and 31.5% for one, two, and three or four follicles with a mean diameter of 14 or more mm at the time of human chorionic gonadotropin (hCG) administration; P = 0.006]. Two to four preovulatory follicles were present in 12.6% of the natural cycles, 43.6% of clomiphene citrate or tamoxifen, and 59.9% of gonadotropin stimulated cycles. The difference in the number of preovulatory follicles between stimulated and unstimulated cycles was highly significant (P < 0.0001). Pregnancy rates were 29.9% in gonadotropin-stimulated cycles, 23.6% in clomiphene citrate- or tamoxifen-stimulated cycles, 23.6% in clomiphene and 20.1% in unstimulated cycles. The difference in pregnancy rates between gonadotropin-stimulated and natural cycles was significant (P = 0.038). Cycle fecundity rates were not significantly affected by the number of previous treatment cycles, duration of infertility, gravidity and parity of the patient, presence of a spontaneous luteinizing hormone (LH) surge before the administration of hCG, or number of motile sperm in the insemination specimen. CONCLUSIONS: Success of IUI using cryopreserved donor sperm is related to the age of the women and whether there is one or more than one preovulatory follicles.

Cryopreservation↗
PubMed1996

The effects of S-nitrosoglutathione on platelet activation, hypertension, and uterine and fetal Doppler in severe preeclampsia.

OBJECTIVE: To determine the effects of the platelet-specific nitric oxide donor S-nitrosoglutathione on women with severe preeclampsia. METHODS: Ten women with severe preeclampsia or preeclampsia with severe fetal compromise at 21-33 weeks' gestation each received a 60-90-minute intravenous infusion of 50-250 micrograms/minute of S-nitrosoglutathione. Each was hypertensive, despite conventional oral antihypertensive therapy in eight. Maternal blood pressure, heart rate, platelet activation, uterine artery, and fetal Doppler indices were measured during the infusion. RESULTS: A dose-dependent reduction in mean arterial pressure from 125 mmHg (95% confidence interval [CI] 117-133) to 103.5 (95% CI 97-111) (P < .005) and an increase in pulse rate from 73.7 beats per minute (95% CI 64.3-84.5) to 89.1 (95% CI 81.2-97.8) (P < .02) was observed during the infusion. Mean uterine artery resistance index fell from 0.76 (95% CI 0.73-0.81) to 0.70 (95% CI 0.65-0.75) (P < .009). Platelet activation measured by P-selectin expression was reduced from 3.02% (95% CI 2.09-4.36) to 1.22% (95% CI 0.94-1.58) (P < .01). Fetal Doppler indices (umbilical artery, middle cerebral artery, and thoracic aorta) showed no significant changes during the infusion. CONCLUSION: S-nitrosoglutathione infusion reduced material mean arterial pressure, platelet activation, and uterine artery resistance without further compromising fetal Doppler indices. This study suggests that platelet-specific nitric oxide donors may prove beneficial in the management of severe preeclampsia.

Adult↗
PubMed1996

Relationship of ovarian stromal blood flow at the baseline ultrasound scan to subsequent follicular response in an in vitro fertilization program.

OBJECTIVE: To assess whether Doppler indices of intraovarian blood flow are related to the subsequent follicular response in an in vitro fertilization (IVF) program. METHODS: One hundred five women underwent ultrasonographic assessment of ovarian morphology, transvaginal color Doppler measurement of intraovarian blood flow and immunoassay of serum FSH during the early follicular phase of an IVF cycle. The subsequent follicular response was related to the Doppler data. RESULTS: Mean ovarian stromal peak systolic blood flow velocity was significantly correlated with the follicular response (P = .001), even after adjusting for the age of patient, type of ovary (polycystic or normal), total number of human menopausal gonadotropin ampules used, and serum FSH. Mean ovarian stromal pulsatility index was not related to the follicular response. Mean ovarian stromal peak systolic blood flow velocity was significantly lower (P = .007) in the poor-response group. The adjusted odds of a poor response increased significantly by an estimated 22% per cm/second decrease in velocity (P = .02). CONCLUSION: Ovarian stromal blood flow at the baseline ultrasound scan is correlated with subsequent follicular response and may be a new indicator for predicting ovarian responsiveness in an IVF program.

Adult↗
PubMed1996

The acute effects of intravenous frusemide on the renal kallikrein kinin system in man: relationship to dose.

Frusemide (f) is a potent natriuretic and diuretic that acts mainly on the luminal side of the ascending loop of Henle (Schlatter et al. (1983) Pflug. Arch. 396: 210-217). F increases the urinary excretion of prostaglandin (PG) E (Mackay et al. (1984) Contr. Nephrol. 41: 160-162) and its diuretic and natriuretic effects are blunted by indomethacin, suggesting that PGs are involved in the cellular action of this drug (Chennavasin et al. (1980) J. Pharmacol. Exp. Ther. 215: 77-81; Waller et al. (1987) Arch. Pharmacodyn. Ther. 290: 145-150). Several investigators have shown a rapid but short-lived rise in urinary kallikrein (UK) excretion after F administration in man, which could represent a 'wash-out' phenomenon rather than indicating a direct involvement of the kallikrein-kinin system (KKS) in mediating the action of F (Zschiedrich et al. (1979) Clin. Sci. 57: 247-250; Waller et al. (1987); Waller et al. (1990) Clin. Sci. 79: 117-121). However, using a mouse model, 5 days treatment with F has been shown to stimulate renal cortical tubular messenger RNA for tissue kallikrein (Penchow and Coghlan (1994) J. Hypertension 12 (Suppl. 3): 887). Urinary excretion of the components of the KKS is believed to reflect the intra-renal activity of the system (Bhoola et al. (1992) Am. Soc. Pharmacol. Exp. Ther. 44: 1-80). Therefore, if the KKS is directly involved in the natriuretic action of F, a dose-related release of the active components of the system would be expected. This study was designed to examine the effect of three intravenous (i.v.) doses of F on the urinary excretion of components of the renal KKS and the relationships of these components with the excretion of water, electrolytes and F.

Adult↗
PubMed1996

A comparison of intratumoural indices of blood flow velocity and impedance for the diagnosis of ovarian cancer.

The aim was to assess the value of blood flow velocity indices in an ultrasound-based test to discriminate between malignant and benign adnexal tumours. Fifty-one women (35 premenopausal and 16 postmenopausal) with persistent adnexal masses were scanned prior to surgery using transvaginal sonography with colour Doppler imaging. Intratumoural flow velocity waveforms obtained by pulsed Doppler sonography were used to determine the time averaged maximum velocity (TAMXV), peak systolic velocity (PSV), pulsatility index (PI) and resistance index (RI). The tumours were classified by histologic criteria (42 benign, 1 borderline and 8 malignant tumours). Two of the malignant and the single borderline tumour were stage I, five were stage III and one was stage IV. Detectable blood flow signals were found in all malignant and borderline tumours and in 33 of 42 (78.6%) of the benign tumours. TAMXV was the best parameter for discrimination of benign and malignant adnexal pathology and at a cut-off value of TAMXV > or = 12 cm/s to indicate malignancy, the sensitivity and specificity were 88.9% and 81.0%, respectively. At the same sensitivity level, this gave a better specificity than the PI < or = 0.90 (specificity 61.9%, P = 0.036), RI < or = 0.60 (specificity 54.8%, P = 0.010) and PSV > or = 16 cm/s (specificity 71.4%, P = 0.121). Discrimination between benign and malignant tumours was improved further by using two criteria rather than one. When the two criteria of a TAMXV of > or = 12 cm/s and a PI < or = 1.0 were applied simultaneously, the tumours could be characterised with a sensitivity of 88.9% and a specificity of 88.1%. Therefore, intratumoural PSV and TAMXV could be used to discriminate between benign and malignant adnexal tumours better than values for PI and RI. The best discrimination was achieved by using a combination of cut-off values for velocity and impedance parameters as two criteria to define malignancy.

Adult↗
PubMed1996

Assessment of uterine artery blood flow on the day of human chorionic gonadotropin administration by transvaginal color Doppler ultrasound in an in vitro fertilization program.

OBJECTIVE: To assess whether measurement of uterine artery blood flow impedance (the pulsatility index) as determined by transvaginal color Doppler ultrasound on the day of hCG administration in patients undergoing IVF can predict pregnancy and implantation rates. DESIGN: Prospective observational study of women undergoing IVF. SETTING: A tertiary referral center for assisted reproduction. PATIENTS: One hundred thirty-five patients undergoing 139 IVF cycles. INTERVENTION: Transvaginal color Doppler assessment of uterine artery pulsatility index on the day of administration of hCG. MAIN OUTCOME MEASURES: Mean pulsatility index of the left and right uterine arteries, pregnancy rate, and embryo implantation rate. RESULTS: The patients were grouped into pregnant and nonpregnant groups and according to whether the pulsatility index was low (1.00 to 1.99), medium (2.00 to 2.99), or high (> or = 3.00). The pregnancy rates were 13.8%, 34.7%, and 14.3% for the low, medium, and high pulsatility index groups, respectively, and were not significantly different. The implantation rates for the same groups were 10.7%, 16.3%, and 5.4%, respectively. The implantation rate for all the patients with pulsatility index < 3.00 (and especially 2.00 to 2.99) was significantly higher than the high pulsatility index group. CONCLUSIONS: The study suggests that the measurement of uterine artery pulsatility index on the day of hCG predicts subsequent implantation rates. It may allow the administration of hCG to be deferred until uterine artery pulsatility index falls to < 3.00, which may result in improved implantation rates.

Adult↗
PubMed1996

Prediction of oocyte recovery rate by transvaginal ultrasonography and color Doppler imaging before human chorionic gonadotropin administration in in vitro fertilization cycles.

OBJECTIVE: To detect and quantify follicular vascularity before hCG administration in women undergoing IVF-ET. To correlate follicular vascularity with the oocyte recovery rate after direct follicle aspiration. DESIGN: A prospective, longitudinal study of consecutive women undergoing IVF-ET at the assisted conception unit of King's College Hospital, London and having at least 20 follicles between the two ovaries on the day of hCG administration. INTERVENTIONS: An Acuson 128XP1O computed sonography system (Acuson Ltd., Uxbridge, United Kingdom) was used to measure follicular diameters, indices of blood flow impedance (pulsatility index), peak systolic velocities (Vmax), and the proportion of follicles demonstrating pulsatile vascularity, i.e., follicular vascularity index. For the purpose of analysis, each woman was classified into one of four groups (I to IV) based on their oocyte recovery rate. RESULTS: The mean age, duration of infertility, Dmax, pulsatility index, and Vmax were similar in the four groups, but the follicular vascularity index was higher in the groups with the highest oocyte recovery rates. Furthermore, there was a positive correlation between the follicular vascularity index and the oocyte recovery rate. CONCLUSION: The follicular vascularity index correlates positively with oocyte recovery rates. Detection and quantification of follicular vascularity with color Doppler imaging can therefore be used to predict oocyte recovery rate and hence may be useful in determining the most appropriate time to administer hCG to optimize oocyte recovery rates.

Adult↗