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Biomedical subjects

K Fitzpatrick

Publications and source records attributed to K Fitzpatrick.

At least 19 recordsLinked to original sources
PubMed2000

Effects of a serotonin 5-HT(4) receptor antagonist SB-207266 on gastrointestinal motor and sensory function in humans.

BACKGROUND: Serotonin 5-HT(4) receptors are located on enteric cholinergic neurones and may regulate peristalsis. 5-HT(4) receptors on primary afferent neurones have been postulated to modulate visceral sensation. While 5-HT(4) agonists are used as prokinetic agents, the physiological role of 5-HT(4) receptors in the human gut is unknown. AIMS: Our aim was to characterise the role of 5-HT(4) receptors in regulating gastrointestinal motor and sensory function in healthy subjects under baseline and stimulated conditions with a 5-HT(4) receptor antagonist. METHODS: Part A compared the effects of placebo to four doses of a 5-HT(4) receptor antagonist (SB-207266) on the cisapride mediated increase in plasma aldosterone (a 5-HT(4) mediated response) and orocaecal transit in 18 subjects. In part B, 52 healthy subjects received placebo, or 0.05, 0.5, or 5 mg of SB-207266 for 10-12 days; gastric, small bowel, and colonic transit were measured by scintigraphy on days 7-9, and fasting and postprandial colonic motor function, compliance, and sensation during distensions were assessed on day 12. RESULTS: Part A: 0.5, 5, and 20 mg doses of SB-207266 had significant and quantitatively similar effects, antagonising the cisapride mediated increase in plasma aldosterone and acceleration of orocaecal transit. Part B: SB-207266 tended to delay colonic transit (geometric centre of isotope at 24 (p=0.06) and 48 hours (p=0.08)), but did not have dose related effects on transit, fasting or postprandial colonic motor activity, compliance, or sensation. CONCLUSION: 5-HT(4) receptors are involved in the regulation of cisapride stimulated orocaecal transit; SB 207266 tends to modulate colonic transit but not sensory functions or compliance in healthy human subjects.

Adolescent↗
PubMed1999

Lack of pharmacokinetic interaction between ropinirole and theophylline in patients with Parkinson's disease.

OBJECTIVE: Ropinirole and theophylline have the potential to interact, because they use the same hepatic cytochrome P450 (CYP1A2) as their major metabolic pathway. The present study investigated the effect of steady-state oral theophylline on the pharmacokinetics of ropinirole at steady state and the effect of steady-state ropinirole on the pharmacokinetics of a single intravenous (i.v.) dose of theophylline, both in patients with idiopathic Parkinson's disease (PD). METHODS: Pharmacokinetic parameters (AUC and Cmax) for i.v. theophylline were compared before and after a 4-week period of oral treatment with ropinirole (2 mg t.i.d.) in 12 patients with PD. Patients were then maintained at this dose of ropinirole, and oral theophylline was co-administered at doses of up to 300 mg b.i.d. The parameters AUC, Cmax and tmax for ropinirole were compared before, during and after oral theophylline co-treatment. RESULTS: Co-administration of ropinirole did not significantly change the pharmacokinetics of i.v. theophylline (mean AUC with and without ropinirole: 68.6 micog x h(-1) x ml(-1) and 70.0 microg x h(-1) x ml(-1), respectively: mean Cmax with and without ropinirole: 11.07 microg x ml(-1) and 11.83 microg x ml(-1), respectively). Similarly, there were no significant changes in ropinirole pharmacokinetics when the drug was co-administered with oral theophylline (mean AUC for ropinirole with and without theophylline: 21.91 ng x h(-1) x ml(-1) and 22.09 ng x h(-1) x ml(-1), respectively; mean Cmax for ropinirole with and without theophylline: 5.65 ng x ml(-1) and 5.54 ng x ml(-1), respectively; median tmax for ropinirole with and without theophylline: 2.0 h and 1.5 h, respectively). CONCLUSION: These results suggest a lack of significant pharmacokinetic interaction between the two drugs at current therapeutic doses.

Administration, Oral↗
PubMed1999

The effect of steady-state ropinirole on plasma concentrations of digoxin in patients with Parkinson's disease.

AIMS: The aim of this single-blind study was to assess the effect of ropinirole, a novel treatment for Parkinson's disease, on the steady-state pharmacokinetics and safety of digoxin in 10 patients with Parkinson's disease. METHODS: There were three parts to the study: digoxin once daily plus placebo three times daily for 1 week; digoxin once daily plus ropinirole three times daily for 6 weeks; and digoxin once daily plus placebo three times daily for 1 week. Serial blood samples were collected over 24 h at the end of each part of the study for pharmacokinetic assessment. Pre-dose blood samples were collected on specific days throughout the study to assess the attainment of steady-state plasma levels of digoxin. The primary endpoints were AUC(0, tau) and Cmax for digoxin. RESULTS: There was a mean decrease of 10% in digoxin AUC (0, tau) (90% CI: 0.79, 1.01) and a 25% decrease in digoxin Cmax (90% CI: 0.58, 0.97) when ropinirole was co-administered, compared with digoxin alone Cmin plasma values for digoxin, however, were fairly constant throughout the study (point estimates 0.99, 95% CI: 0.85, 1.15). Changes in trough levels of digoxin are believed to be the most reliable way of assessing steady-state concentrations of digoxin, and therefore the clinical significance of an interaction. Changes in Cmax are too readily influenced by other factors. CONCLUSIONS: These results therefore indicate that on pharmacokinetic grounds no dose adjustment is necessary for digoxin co-administered with ropinirole.

Aged↗
PubMed1998

Effect of food on the pharmacokinetics of ropinirole in parkinsonian patients.

AIMS: Ropinirole is a specific non-ergoline dopamine D2-receptor agonist with antiparkinsonian properties. The pharmacokinetic parameters of ropinirole taken in the fasted condition were compared with those when it was co-administered with food. METHODS: This was an open, randomized, two sessions cross over study in 12 patients with Parkinson's disease, comparing the steady-state pharmacokinetic profiles of ropinirole on two different study days: 'fasted' and 'fed'. RESULTS: The mean Cmax was lower in the 'fed' regimen than in the 'fasted' one (-25%, P=0.002). The median tmax was observed 2.6 h later in the 'fed' regimen than in the 'fasted' regimen (P<0.05). There was a slight but significant decrease in AUC(0,8 h) in the 'fed' regimen (P=0.03). CONCLUSIONS: Food decreases the rate of absorption of ropinirole, but has little effect on the extent of absorption.

Aged↗
PubMed1994

Computer-enhanced medical decision making.

Many clinicians balk at their first encounter with this intriguing technology, often fearful that information systems might usurp their autonomous role as a health care provider. Methods of implementation and application of this concept, and how it is beginning to find greater acceptance are discussed in this article.

Decision Support Techniques↗
PubMed1993

Physician experience with viewing digital radiographs in an intensive care unit environment.

After several years of continuous operation, the utility of digital viewing stations as assessed by bedside clinicians has been investigated through the distribution of questionnaires to past and present users. The results of the questionnaire have indicated that the bedside physicians prefer using the workstations over handling film. For evaluation of line placements, chest tubes, and pleural effusions, the physicians prefer softcopy display over hardcopy. However, for analysis of air space disease and diagnosis of pneumothorax, images displayed on the workstation were not believed to be as useful as standard hardcopy.

Attitude of Health Personnel↗
PubMed1993

Time comparison of intensive care units with and without digital viewing systems.

As hospital radiology departments and intensive care units (ICUs) make plans to use or expand the usage of digital data outside of the radiology department, the need to assess the requirements of the potential recipients in the ICUs has become more important. The present operations in an ICU that uses digital viewing instead of film has been compared with a unit that does not. The difference in time between x-ray exposure and final image viewing was determined in both settings and compared. In this preliminary study, significant differences were found between the two units. The odds of having examination results actually accessed by the ordering physician in an hour or less were 9.5 times greater for the unit with digital viewing capability than for the one without it.

Coronary Care Units↗
PubMed1993

Computer applications in health care.

Computers are playing an ever-increasing role in health care. Computer-based medical records can improve data access, retrieval, output, decision support, and quality assurance. The author discusses computer innovation in medical record-keeping, laboratory data reporting, and drug delivery.

Clinical Laboratory Information Systems↗
PubMed1992

Automated acuity scoring within a computer based medical record.

This paper describes the initial development of a completely automated acuity scoring system that resides within the TMR bedside computing system at the Duke University Medical Center, Surgical Intensive Unit. The scoring system is based upon the APACHE II acuity scoring system and provides for the recalculation of acuity scoring at 12 hour intervals through the patient's ICU course. When comparing hand calculated versus computer generated acuity scores for 19 patients, discrepancies fell into three broad categories: 1) data available to the application differed from that available to the human scorer. 2) apparent transcription errors 3) data items lost or absent from the paper record. It remains to be determined if computer generated acuity scoring provides for a more accurate representation of the patient's acuity.

Creatinine↗
PubMed1991

Studies of the pharmacokinetics and metabolism of 4-amino-propiophenone (PAPP) in rats, dogs and cynomolgus monkeys.

The pharmacokinetics and metabolism of 4-aminopropiophenone (PAPP), a cyanide antidote, have been studied in rats, dogs and cynomolgus monkeys using 14C-PAPP. Radiolabelled material was rapidly excreted in all three species, mainly in urine. In rats, PAPP was metabolized by N-acetylation, while in dogs, ring and aliphatic hydroxylation occurred. In monkeys, both N-acetylation and oxidation took place. In the latter pathway, PAPP was oxidized to p-aminobenzoic acid which underwent amino acid-conjugation to p-aminohippuric acid. In rat blood in vitro, the PAPP metabolites, p-aminobenzoic, p-aminohippuric and N-acetyl-p-aminobenzoic acid were only weak methaemoglobin producers.

Animals↗
PubMed1991

Bedside computerization of the ICU, design issues: benefits of computerization versus ease of paper & pen.

This paper describes the design considerations for the implementation of a bedside computer system in an intensive care environment. Specific issues discussed include application design, implementation problems, design revisions, and design solutions. Specific examples of the above issues include passive data acquisition from bedside devices and computer systems, automated nursing assessments, respiratory therapy assessments and integrated reports.

Consumer Behavior↗
PubMed1990

Trimetrexate in prostatic cancer: preliminary observations on the use of prostate-specific antigen and acid phosphatase as a marker in measurable hormone-refractory disease.

Thirty-one patients with bidimensionally measurable hormone-refractory prostatic cancer received trimetrexate (TMTX). Serial values of prostate-specific antigen (PSA) and acid phosphatase (SAP) were correlated with response. Five patients (17%; 95% confidence interval, 3% to 30%) achieved a partial remission for a median of 3 months (range, 3 to 7.5 months). Marker levels showed large variations with no discernible patterns. Serial PSA and SAP in 19 patients with abnormal baseline values showed a correlation with measurable disease response in only 68% (13 of 19) and 47% (nine of 19) of patients, respectively. Values were then smoothed using an exploratory data analysis technique of running medians and averages. Trends in marker changes were much more apparent. Several "decision rules" were evaluated for use of markers as indices of disease progression. A 50% increase from the patient's minimum value in either PSA or SAP on two successive determinations correlated with progression in 90% of cases in this trial. TMTX has modest activity in prostatic cancer, and further trials are not warranted. Biochemical markers do not uniformly reflect disease activity in hormone-refractory disease, and changes in biochemical markers must be interpreted cautiously when used as the sole end point to assess efficacy in clinical trials.

Acid Phosphatase↗
PubMed1988

Rapid detection of herpes simplex virus (HSV) antigen in human ocular infections.

The new HERPCHEK (Dupont, No. Billerica, MA) enzyme immunosorbent assay (EIA) was used in a double-blind clinical study for rapid and specific detection of ocular herpes simplex virus (HSV) infection. This 4-hour assay can be used to demonstrate conclusively the presence of HSV antigen without culture and thereby rapidly differentiate between HSV and other clinically similar ocular infectious diseases. Ocular samples were collected from 180 individuals including 30 patients with acute HSV, 90 with latent HSV (ie, currently asymptomatic but with a positive history), 11 with acute or latent varicella zoster virus, 30 with nonherpetic infections (due to adenovirus, Acanthamoeba or bacteria), and 19 normal controls. A clinical diagnosis was made by one of us (DPL) and duplicate tear-film samples obtained by swabbing the conjunctival cul-de-sac and cornea. Coded samples were tested by routine viral culture on Vero cell monolayers and also were run independently in the HERPCHEK test. During active HSV infection, the HERPCHEK correlated 100% with clinical diagnosis, and virus culture correlated 90% with clinical diagnosis. In all latent HSV ocular infections, other nonherpetic ocular infections and normal samples, both the HERPCHEK and culture assays were negative.

Antigens, Viral↗
PubMed1987

Midazolam sedation following open heart surgery.

Midazolam given as hourly intermittent injections was compared with the same dose given by infusion for postoperative sedation in patients after cardiopulmonary bypass. A stable concentration was rapidly attained with the infusion whereas 6-8 h was required to attain stable plasma (trough) concentrations in the intermittent injection group. Plasma concentrations decreased rapidly to low values within 6 h of discontinuation of therapy. High plasma concentrations and a long (16 h) half-life were noted in one patient who may be a slow metabolizer of the drug.

Adult↗