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Biomedical subjects

N Harding

Publications and source records attributed to N Harding.

16 recordsLinked to original sources
PubMed2001

Multiple-dose pharmacokinetics and safety of two regimens of quinupristin/dalfopristin (Synercid) in healthy volunteers.

Quinupristin/dalfopristin (Q/D) is a novel streptogramin antibiotic for the treatment of severe gram-positive infections. The purpose of this open, nonrandomized, parallel-group, phase I trial was to evaluate Q/D pharmacokinetics after single and repeated doses under the two different dosing regimens corresponding to the effective doses and to evaluate tolerability. Two groups of 10 healthy volunteers received multiple 1-hour intravenous infusions of 7.5 mg/kg Q/D either every 8 or 12 hours for 4 or 5 days, respectively. Plasma concentrations of Q, D, and metabolites were determined using high-performance liquid chromatography and selective microbiological assays. The two regimens q8h and q12h lead to the same disposition profile after single and repeated administration. Single-dose data confirmed the high plasma clearances of Q and D (about 0.90 l/h/kg) obtained previously. Unchanged drugs were the main components in plasma, with each of the three metabolites representing about 20% (in terms of the AUC ratio) of the parent drugs. Comparable steady-state concentrations were reached from day 2 of both regimens. A similar moderate increase in Cmax and AUC (about 20%) of parent drugs was observed between the first and last day of treatment. This phenomenon, which was also observed for the metabolites, was not expected considering the short terminal disposition half-lives of the parent drugs and trough plasma concentrations of all components mostly below the limits of quantitation at steady state, whatever the dosing regimen. The clearances of parent drugs at steady state were about 20% lower as compared with that observed following the first drug administration (statistically significant difference). No trend suggesting a treatment effect on any laboratory parameter, vital signs, or electrocardiographic parameters was identified. However, 80% of subjects reported venous adverse events probably related to treatment.

Adolescent↗
PubMed2000

Pharmacokinetics of quinupristin/ dalfopristin in patients with severe chronic renal insufficiency.

OBJECTIVE: To compare the pharmacokinetic profile of a single intravenous injection of quinupristin/dalfopristin, a new injectable streptogramin, in healthy young individuals and patients with severe chronic renal insufficiency. A secondary objective was to assess the relative tolerability of this dose in these patients compared with healthy individuals. PATIENTS AND PARTICIPANTS: 13 patients with severe chronic renal insufficiency (creatinine clearance 6 to 28 ml/min/1.73m2) were individually matched for gender, bodyweight and age to a healthy volunteer. METHODS: Participants received a single dose of quinupristin/dalfopristin 7.5 mg/kg bodyweight as a continuous 1-hour intravenous infusion, followed by serial blood sampling. RESULTS: The disposition profile of unchanged quinupristin was similar in the 2 groups. However, the elimination of quinupristin derivatives in patients with renal impairment tended to be decreased: mean peak plasma drug concentration (Cmax) and area under the concentration-time curve from zero to infinity (AUCinfinity) of quinupristin plus its active derivatives were about 1.4 times higher in the patients with renal impairment compared with healthy volunteers. The mean Cmax and AUCinfinity of both unchanged dalfopristin and dalfopristin plus its active derivatives were about 1.3 times higher in renally impaired patients than in healthy volunteers. Adverse events were generally mild and transient. No severe or serious adverse events were reported and no participants prematurely discontinued the study. Venous tolerability tended to be better in healthy volunteers than in the patients with renal impairment. CONCLUSION: These results suggest that no formal reduction in the dosage of quinupristin/dalfopristin is necessary in patients with severe chronic renal impairment.

Adult↗
PubMed2000

Pharmacokinetics, pharmacodynamics, and safety of inhaled cyclosporin A (ADI628) after single and repeated administration in healthy male and female subjects and asthmatic patients.

Severe asthmatics treated with oral/inhaled corticosteroids are at risk of side effects (adrenal suppression). Oral cyclosporin A has been effective in asthma treatment, and nebulized cyclosporin A has been administered for approximately 6 months with no nephrotoxicity or hepatotoxicity, suggesting a wider therapeutic margin for an inhaled cyclosporin A for treatment of asthma. Single- and repeated-dose studies in healthy and asthmatic male and female subjects were conducted to determine the pharmacokinetics, pharmacodynamics, and safety of a new formulation of inhaled cyclosporin A (ADI628) metered-dose inhaler (MDI). ADI628 had roughly dose-linear increases in blood concentrations with moderate variability after single and multiple administration in healthy subjects. Steady-state ADI628 concentrations reflected an effective half-life of 7.0 to 12.5 hours. No overt gender-related differences were observed after single inhaled 10 mg ADI628 dose. However, asthmatics and females (20 mg dose group) had lower ADI628 concentrations as compared to healthy males, probably due to lower inspiratory flow rates and probably not due to disease- or gender-related differences in metabolism/elimination of ADI628. Renal excretion was a minor route of elimination for ADI628 with no dose- or gender-related differences. The blood ADI628 exposure in humans was 1/3- to 1/6-fold lower than the no-effect dose in dogs. Also, the blood ADI628 exposure after the highest inhaled dose was much lower than after the administration of the efficacious oral cyclosporin A dose (3 mg/kg) for treating asthma. The highest steady-state dose (10 mg bid) resulted in ADI628 concentrations that are not typically associated with systemic nephrotoxicity or immunosuppression. Furthermore, repeated inhaled doses of ADI628 were safe and generally well tolerated with no apparent systemic immunosuppressive activity in healthy and asthmatic subjects.

Administration, Inhalation↗
PubMed1999

Staff confidence in dealing with aggressive patients: a benchmarking exercise.

Interacting with potentially aggressive patients is a common occurrence for nurses working in psychiatric intensive care units. Although the literature highlights the need to educate staff in the prevention and management of aggression, often little, or no, training is provided by employers. This article describes a benchmarking exercise conducted in psychiatric intensive care units at two Western Australian hospitals to assess staff confidence in coping with patient aggression. Results demonstrated that staff in the hospital where regular training was undertaken were significantly more confident in dealing with aggression. Following the completion of a safe physical restraint module at the other hospital staff reported a significant increase in their level of confidence that either matched or bettered the results of their benchmark colleagues.

Adaptation, Psychological↗
PubMed1997

Trainees' interactional skills when performing Pap smears. A needs assessment.

OBJECTIVE: Specific interactional behaviours are known to reduce the anxieties and discomforts associated with Papanicolaou (Pap) smears. Few studies have documented doctors use of such strategies or the needs of young doctors to learn them. This descriptive study was conducted to identify trainees learning needs as part of a larger study in the Royal Australian College of General Practitioners (RACCP) Training Program in New South Wales. METHOD: Audioptaped consultations with women seeing a trainee for a Pap smear during the first 3 weeks of the CP term were analysed using a 29 item interactional skills rating scale. Intra-rater reliability (i.e. consistency of rating of the researcher) was checked on a random sample of audiotapes. RESULTS: Rates of specific interactional skills in the 23 audiotaped consultations were low. Trainees explained the procedure in seven consultations (30%). No trainees explained a stop signal. Ten women (43%) were told how to find out the result of their Pap smears. No trainees offered written information Smoking status was ascertained in only two consultations (9%). CONCLUSIONS: This study adds to increasing evidence that undergraduate medical education in Australia fails to equip graduates with practical skills in preventive care. Our findings have implications for GP supervisor and the RACGP Training Program. Specifically, trainees clinical behaviour when taking Pap smears should be observed improved and assessed during supervised training before entry into independent practice.

Clinical Competence↗
PubMed1996

Regional variations in the utilization rate of vaginal and abdominal hysterectomies in the United Kingdom.

BACKGROUND: Large geographic variations in hysterectomy rates are well known; however, very little is known about geographic variations in the route of the procedure, i.e. whether it is performed abdominally or vaginally. We compared utilization rates for abdominal and vaginal hysterectomies for the 14 Regional Health Authorities of England, and Northern Ireland over a three-year period. METHODS: Data were collected in the form of hospital episode statistics and small area analysis techniques were used to document regional variations. RESULTS: Large regional differences in the utilization of vaginal hysterectomies were recorded. Three areas in particular (Northern Ireland, Yorkshire and NW Thames) displayed high vaginal to abdominal ratios. Northern Ireland recorded the highest ratio (0.366), Mersey Regional Health Authority the lowest (0.139). The use of the vaginal route was found to increase with age, and was the most common route for the > 65 years age group. CONCLUSION: Despite an increasing volume of evidence advocating the use of the vaginal route, there appears to be a resistance to its use, except in older women. The role of physician practice style, and in particular group clinical judgement, is highlighted as being significantly involved in explaining the observed geographic variations.

Adult↗
PubMed1993

OPADE: development of an European computerized drug prescription system.

Many computerized drug prescription systems have been developed but they are rarely used in clinical practice because of their lack of integration with the functioning of medical institutions and the difficulty of building and maintaining a complete knowledge base on drugs. We present in this paper a system, called OPADE, which answers these shortcomings and we argue that a system actually used by practitioners may introduce a positive feed back loop in the prescribing process.

Clinical Pharmacy Information Systems↗
PubMed1991

Striking a bargain.

Explore the source record for details and available documents.

Collective Bargaining↗
PubMed1983

Paradoxical response of malignant melanoma to methotrexate in vivo and in vitro.

Methotrexate (MTX) shows consistent cytotoxicity for melanoma cells in vitro but it is ineffective in clinical use at equivalent concentrations in vivo. This apparent paradox has been investigated by cell culture techniques and results quantified by cell number. In an in vitro model of high dose MTX therapy followed by leucovorin rescue (HD-MTX-LCR) there was survival of both melanoma and choriocarcinoma cell lines but not of an acute lymphocytic leukaemia cell line. The 70H metabolite of MTX was identified by HPLC in plasma samples of melanoma patients treated by HD-MTX-LCR, in which MTX concentrations approximately 10(-5) M were maintained for 24 h. However, metabolism per se is unlikely to account for the lack of response to MTX clinically. In vitro 70H MTX (10(-7) - 10(-6) M) was two orders of magnitude less cytotoxic for melanoma than MTX (10(-9) - 10(-8) M). The cellular accumulation of [3H]-MTX, using a rapid gradient centrifuge technique for separation of melanoma cells from medium, was reduced in the presence of 70H-MTX. The results suggest that reduced cellular uptake of MTX combined with biochemical rescue of tumour cells may partially explain the paradoxical lack of clinical response of melanoma to the drug.

Animals↗