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Biomedical subjects

D Vaughan

Publications and source records attributed to D Vaughan.

At least 19 recordsLinked to original sources
PubMed1999

Two-state mixed renewal processes for chronic disease.

We develop a model based on a two-state mixed renewal process and propose its use for modelling disease activity in studies of chronic conditions. We specify Weibull forms for the conditional transition intensities to allow for time trends, and bivariate frailties to accommodate subject-to-subject variability in the disease process. Extensions of this model are considered for stratified analyses in which strata are defined by the number of past exacerbations. Data from a motivating study of chronic bronchitis are analysed to illustrate the methodology.

Anti-Infective Agents↗
PubMed1998

Bioavailability of oral ciprofloxacin in early postsurgical patients.

OBJECTIVE: To evaluate the absorption of oral ciprofloxacin within 24 hours of laparotomy for major elective surgery or peritonitis. DESIGN: In this prospective trial, patients were given a 750-mg oral close the morning after major elective surgery (n=15) or surgery for peritonitis (n=7). Healthy volunteers served as controls (n=9). Serial urine and blood samples were drawn during the subsequent 12 hours, and pharmacokinetic measures were determined by standard high-performance liquid chromatography assay procedures. SETTING: Multicenter, university-affiliated hospitals. MAIN OUTCOME MEASURES: Drug absorption as determined by area under the concentration time curve, maximum concentration, and time to maximum concentration. RESULTS: Oral bioavailability was reduced in elective surgery and peritonitis patients compared with controls. Among the 15 elective surgery patients, 27% (4/15) showed no absorption. The remaining 73% (11/15) had an area under the curve comparable with that of controls (8.3+/-1.6 (mg/[L x h]). Among all patients, those who showed drug absorption vs those who showed no absorption did not differ with respect to malignant neoplasm, case type, age, or biochemistry. However, patients showing no absorption were significantly heavier than patients showing absorption (patients showing absorption, 15%+/-3% over ideal body weight vs patients showing no absorption, 29%+/-6% over ideal body weight; P<.05). When elective surgery patients were stratified by presence or absence of obesity (25% above ideal body weight), mean area under the curve in nonobese patients was 9.80+/-2.37 vs 0.91+/-0.56 (mg/(L x h) in obese patients (P<.05). CONCLUSIONS: Oral bioavailability was reduced for peritonitis surgery patients on the first day postoperatively, and for obese elective surgery patients. To achieve adequate serum levels requires continuation of intravenous antibiotics in patients with peritonitis, and adjustment of oral dosage in obese patients in the early period after elective surgery.

Administration, Oral↗
PubMed1998

Early closure of a randomized trial: surgery and postoperative radiotherapy versus radiotherapy in the management of intra-oral tumours.

Tumours of the oral cavity/oropharynx occur relatively infrequently in the UK. The management of such lesions, especially the squamous cell carcinomas, is still a little controversial. Some centres advocate radiotherapy while others adopt surgery and radiotherapy. In an attempt to resolve the question of which approach gives the better results, a multicentre randomized trial was established to compare surgery plus postoperative radiotherapy with radical radiotherapy alone. It was anticipated that 350 patients would be required to give a statistically significant result, but, after 35 patients had been entered, the trial was closed prematurely with a marked difference in overall survival in favour of the combination arm (P = 0.0006). At this analysis, carried out 23 months after trial closure, the survival difference between the two arms remains statistically significant for all causes of mortality (P = 0.001; relative death rate = 0.24; 95% CI 0.10-0.59).

Adult↗
PubMed1998

A 1-year community-based health economic study of ciprofloxacin vs usual antibiotic treatment in acute exacerbations of chronic bronchitis: the Canadian Ciprofloxacin Health Economic Study Group.

OBJECTIVE: To evaluate the costs, consequences, effectiveness, and safety of ciprofloxacin vs standard antibiotic care in patients with an initial acute exacerbation of chronic bronchitis (AECB) as well as recurrent AECBs over a 1-year period. DESIGN: Randomized, multicenter, parallel-group, open-label study. SETTING: Outpatient general practice. PATIENTS: A total of 240 patients, 18 years or older with chronic bronchitis, with a history of frequent exacerbations (three or more in the past year) presenting with a type 1 or 2 AECB (two or more of increased dyspnea, increased sputum volume, or sputum purulence). MAIN OUTCOME MEASURES: The assessment included AECB symptoms, antibiotics prescribed, concomitant medications, adverse events, hospitalizations, emergency department visits, outpatient resources such as diagnostic tests, procedures, and patient and caregiver out-of-pocket expenses. Patients completed the Nottingham Health Profile, St. George's Respiratory Questionnaire, and the Health Utilities Index. The parameters were recorded with each AECB and at regular quarterly intervals for 1 year. These variables were compared between the ciprofloxacin-treated group and the usual-care-treated group. RESULTS: Patients receiving ciprofloxacin experienced a median of two AECBs per patient compared to a median of three AECBs per patient receiving usual care. The mean annualized total number of AECB-symptom days was 42.9+/-2.8 in the ciprofloxacin arm compared to 45.6+/-3.0 days in the usual-care arm (p=0.50). The overall duration of the average AECB was 15.2+/-0.6 days for the ciprofloxacin arm compared to 16.3+/-0.6 days for the usual-care arm. Treatment with ciprofloxacin tended to accelerate the resolution of all AECBs compared to usual care (relative risk=1.20; 95% confidence interval [CI], 0.91 to 1.58; p=0.19). Treatment assignment did not affect the interexacerbation period but a history of severe bronchitis, prolonged chronic bronchitis, and an increased number of AECBs in the past year were associated with shorter exacerbations-free periods. There was a slight, but not statistically significant, improvement in all quality of life measures with ciprofloxacin over usual care. The only factors predictive of hospitalization were duration of chronic bronchitis (odds ratio=4.6; 95% CI, 1.6, 13.0) and severity of chronic bronchitis (odds ratio=4.3; 95% CI, 0.8, 24.6). The incremental cost difference of $578 Canadian in favor of usual care was not significant (95% CI, -$778, $1,932). The cost for the ciprofloxacin arm over the usual care arm was $18,588 Canadian per quality-adjusted life year gained. When the simple base case analysis was expanded to examine the effect of risk stratification, the presence of moderate or severe bronchitis and at least four AECBs in the previous year changed the economic and clinical analysis to one favorable to ciprofloxacin with the ciprofloxacin-treated group having a better clinical outcome at lower cost ("win-win" scenario). CONCLUSIONS: Treatment with ciprofloxacin tended to accelerate the resolution of all AECBs compared to usual care; however, the difference was not statistically significant. Further, usual care was found to be more reflective of best available care rather than usual first-line agents such as amoxicillin, tetracycline, or trimethoprim-sulfamethoxazole as originally expected. Despite the similar antimicrobial activities and broad-spectrum coverage of both ciprofloxacin and usual care, the trends in clinical outcomes and all quality of life measurements favor ciprofloxacin. In patients suffering from an AECB with a history of moderate to severe chronic bronchitis and at least four AECBs in the previous year, ciprofloxacin treatment offered substantial clinical and economic benefits. In these patients, ciprofloxacin may be the preferred first antimicrobial choice.

Adolescent↗
PubMed1998

Update on plasminogen activator inhibitor-1.

Plasminogen activator inhibitor-1 (PAI-1) is produced by the endothelium and determines the rate and extent of fibrinolysis. Recent data on PAI-1 gene polymorphism and the potential role of glucose in regulating PAI-1 expression in vascular disease are reviewed.

Blood Glucose↗
PubMed1997

Use of protein-C concentrate, heparin, and haemodiafiltration in meningococcus-induced purpura fulminans.

BACKGROUND: Inflammatory and coagulation processes are both affected in meningococcaemia. Severe acquired protein-C deficiency in meningococcaemia is usually associated with substantial mortality: in survivors, skin grafts, amputation, and end-organ failure are not uncommon. Protein C is a natural anticoagulant and also has important anti-inflammatory activity. We assessed the effects of early replacement therapy with protein-C concentrate together with continuous veno-venous haemodiafiltration and conventional treatment in meningococcaemia. METHODS: 12 patients aged between 3 months and 27 years with meningococcaemia and severe acquired protein-C deficiency (mean 0.20 IU/mL) were studied. All patients had septic shock, widespread purpura, skin necrosis, and disseminated intravascular coagulopathy. After a test dose of protein-C concentrate, patients received a continuous infusion with the dose adjusted daily to keep the plasma concentration between 0.8 and 1.2 IU/mL. 11 patients were given unfractionated intravenous heparin (10-15 IU kg-1 h-1). Nine patients had haemodiafiltration and one had peritoneal dialysis. The Glasgow meningococcal septicaemia prognostic score and the paediatric risk of mortality score predicted a minimum mortality of 80% and 57%, respectively. FINDINGS: No patient died. No adverse reactions to the treatment were seen. Two patients had lower-limb amputations, one of whom had a thrombotic cerebrovascular accident; both patients had received the protein-C concentrate and heparin later than the rest of the group (60 h [16.97] vs 12 h [3.13]). One patient developed chronic renal failure despite receiving protein-C infusion 15 h after admission. INTERPRETATION: The acquired severe deficiency of protein C in meningococcaemia contributes to the pathogenesis of the thrombotic necrotic lesions in the skin and other organs and probably has an important role in the inflammatory response. Protein-C therapy is merely one approach to improve the host response in this syndrome. We suggest that a double-blind, randomised, controlled multicentre trial is needed to confirm our results.

Adolescent↗
PubMed1997

The orofacial cancer patient's support from the general practitioner, hospital teams, family, and friends.

BACKGROUND: After the diagnosis of cancer, about a third of patients have adjustment disorders. Of recently diagnosed patients, 5 to 15% experience serious psychological disturbances, but their distress is often undetected and untreated. Little attention has been directed to the patients' sources of support and their adequacy. METHODS: This study assessed a defined group (n = 49) of cancer patients' ratings of the support they received from general practitioners, hospital teams, family, and friends. Additional information was collected on the patients' interest in receiving further hospital services and their psychological morbidity (i.e., anxiety and depression). RESULTS: The results show wide variation in patients' perceptions of the helpfulness of the primary and secondary care teams, raising concern about the levels of help and support available to some cancer patients. CONCLUSIONS: Although this sample rated the help received from the hospital very highly, those patients who requested more information from the hospital sector showed little evidence of having had their general anxiety "buffered" by involvement of family members.

Adjustment Disorders↗
PubMed1997

Rice genetic resources: history, conservation, investigative characterization and use in Japan.

Rice has been grown in Japan for about 3000 years. Although both japonica and indica varieties have been grown in Japan, now japonica rices are grown. Japanese rice breeding has used an ecological breeding approach. While emphasis in rice breeding in the 1940's and 1950's focussed on yield in recent decades quality has been of major importance. Consumer preference and name recognition of high quality varieties, such as Koshihikari, has resulted in slow acceptance of new varieties. Rice germplasm was systematically collected throughout Japan between 1962 and 1963. Subsequent acquisition and collecting, in Japan and other countries, has resulted in 28,000 accessions being conserved in the National Genebank, based at the National institute of Agrobiological Resources (NIAR). Research on genetic diversity of rice using a range of techniques, for example esterase isozymes, has revealed clinal variation in rice radiating from the center of diversity of rice in and around southwest China. Newly found genes in traditional rice germplasm, such as genes for non-elongating mesocotyl, are now routinely identified on the rice genome. Pioneering studies on eco-genetic differentiation of species in the genus Oryza in Japan has revealed much about the complex genepool for which rice evolved. Pest and disease resistance sources, particularly to blast, bacterial blight and brown plant hopper, from many countries have been incorporated into Japanese varieties. Cold tolerance at the booting stage was found in the Indonesian variety Silewah. In the future in characterisation of rice germplasm and interaction between rice germplasm specialists and rice molecular scientists, both in Japan and internationally, will be corner stones to securing rice genetic diversity and rice improvement in the next century.

Conservation of Natural Resources↗
PubMed1995

Reduced requirement for antibiotic therapy targeting gram-negative organisms in febrile, neutropenic patients with cancer who are receiving antibacterial chemoprophylaxis with oral quinolones.

An open, nonrandomized, phase 2 study of 53 adult patients who had 60 neutropenic episodes was conducted to determine if quinolone antibacterial prophylaxis could reduce the need during febrile episodes for parenteral therapy directed at gram-negative organisms. Suspected infections among recipients of quinolones were treated empirically with vancomycin and ceftazidime; therapy with the latter was discontinued after 24-48 hours in the absence of infection due to gram-negative organisms. In five neutropenic episodes, patients had no fever or infection. An aerobic gram-negative bacillus was isolated during only 1 (1.8%) of 55 febrile episodes. Febrile episodes occurred at a median of day 15 of cytotoxic therapy. Vancomycin monotherapy was successful in 22 (50%) of 44 evaluable cases. Modification of the vancomycin regimen by the addition of metronidazole or rifampin increased the response rate to 40 (91%) of 44. Response occurred after a median of 4.5 days. Parenteral empirical therapy with amphotericin B was required in only 3 (7%) of 44 cases. The study strategy safely permitted a reduction in the amount and duration of antibiotic therapy directed against gram-negative organisms in febrile neutropenic patients.

Administration, Oral↗
PubMed1995

Proscar: five-year experience.

We assessed the long-term safety and efficacy of finasteride, an orally active 5 alpha-reductase inhibitor, in 2 previously reported groups of patients with symptomatic benign prostatic hyperplasia (BPH). Prostate volume was measured by magnetic resonance imaging, and the maximum urinary flow rate was assessed noninvasively. Symptoms were scored utilizing a patient self-administered symptom score questionnaire. Total symptom scores ranged from 0 (or asymptomatic) to 35 (severely symptomatic). After an initial double-blind period, the patients in study 1 were treated with 10 mg finasteride for 1 year and then switched to 5 mg finasteride for an additional 4 years, whereas patients in study 2 were treated with 5 mg finasteride for the entire 5 years. A total of 190 patients were randomized in the double-blind studies, 156 entered year 1 of the open extension and 70 patients completed 5 years of finasteride therapy. In both studies prostate volume was reduced from baseline by 30%, dihydrotestosterone was reduced by 72%, and the maximum urinary flow rate improved by approximately 1.5 ml/s. Prostate-specific antigen was decreased by approximately 50%. Finasteride was well tolerated; approximately 10% of patients reported sexual adverse experiences during the 5-year study period, which were considered drug related by the investigators. The incidence in reporting sexual adverse experiences did not increase with the increased duration of treatment: findings consistent with previous reports. In summary treatment of BPH with finasteride for 5 years inhibits the progression of the disease with an excellent safety profile and represents a low-risk medical option for the treatment of symptomatic BPH.

Aged↗
PubMed1994

Calcium-dependent block of ryanodine receptor channel of swine skeletal muscle by direct binding of calmodulin.

The interaction of the Ca2+ binding protein calmodulin (CaM) with the ryanodine receptor of the sarcoplasmic reticulum (SR) of pig skeletal muscle was investigated by [3H]-ryanodine binding, planar bilayer recordings, and rapid filtration of 45Ca(2+)-loaded SR. Inhibition of [3H]-ryanodine binding by CAM was phosphorylation-independent, had an IC50 of approximately 0.1 microM and was optimal at 10 microM Ca(2+). CaM also inhibited [3H]-ryanodine binding to CHAPS-solubilized and purified ryanodine receptors, suggesting a direct CaM-ryanodine receptor interaction. In single channel recordings, CaM blocked Ca2+ release channels in a Ca(2+)-dependent manner by decreasing the number of open events per unit time without affecting the mean open time or unitary channel conductance. Rapid filtration of 45Ca2+ passively loaded into SR vesicles showed that CaM blocked Ca2+ release within milliseconds of exposure of SR to a Ca2+ release medium containing 10 microM CaM. In controls, an increase in extravesicular Ca2+ from 7 nM to 10 microM resulted in a release of 47 +/- 10% of the 45Ca2+ in 20 ms. CaM reduced the release to 23 +/- 12% in the same period. These results are compatible with a direct mechanism of Ca2+ release channel blockade by CaM and suggest that CaM could play a significant role in the inactivation of SR Ca2+ release during excitation-contraction coupling.

Animals↗
PubMed1994

Long-term stability of individual WISC-R IQS of learning disabled children.

Stability of IQ for race and gender was examined by analyzing the results of two administrations over 3 years of the WISC-R for 402 learning disabled children. About 50% of the variance in Test 2 was accounted for by scores on Test 1. Frequency of positive or negative difference for each IQ from Test 1 to Test 2 was presented. Direction of change in IQ was negative for the Verbal Scale and positive for changes on the Performance Scale.

Adolescent↗
PubMed1993

The association of Chiari type I malformation and neurofibromatosis type 1.

The association of neurofibromatosis type 1 (NF1) with Chiari malformations of the cerebellum and brain stem has been reported on only two previous occasions. The pathogenesis of both conditions has remained unclear, although the Chiari type I malformation is most likely due to hypoplasia of the posterior fossa with subsequent extension of the cerebellum through the foramen magnum. NF1 is also associated with a variety of cerebral dysplasias. We present a patient with both of these dysplastic lesions whose Chiari malformation was asymptomatic.

Adolescent↗
PubMed1992

Fast release of 45Ca2+ induced by inositol 1,4,5-trisphosphate and Ca2+ in the sarcoplasmic reticulum of rabbit skeletal muscle: evidence for two types of Ca2+ release channels.

The kinetics of Ca2+ release induced by the second messenger D-myoinositol 1,4,5 trisphosphate (IP3), by the hydrolysis-resistant analogue D-myoinositol 1,4,5 trisphosphorothioate (IPS3), and by micromolar Ca2+ were resolved on a millisecond time scale in the junctional sarcoplasmic reticulum (SR) of rabbit skeletal muscle. The total Ca2+ mobilized by IP3 and IPS3 varied with concentration and with time of exposure. Approximately 5% of the 45Ca2+ passively loaded into the SR was released by 2 microM IPS3 in 150 ms, 10% was released by 10 microM IPS3 in 100 ms, and 20% was released by 50 microM IPS3 in 20 ms. Released 45Ca2+ reached a limiting value of approximately 30% of the original load at a concentration of 10 microM IP3 or 25-50 microM IPS3. Ca(2+)-induced Ca2+ release (CICR) was studied by elevating the extravesicular Ca2+ while maintaining a constant 5-mM intravesicular 45Ca2+. An increase in extravesicular Ca2+ from 7 nM to 10 microM resulted in a release of 55 +/- 7% of the passively loaded 45Ca2+ in 150 ms. CICR was blocked by 5 mM Mg2+ or by 10 microM ruthenium red, but was not blocked by heparin at concentrations as high as 2.5 mg/ml. In contrast, the release produced by IPS3 was not affected by Mg2+ or ruthenium red but was totally inhibited by heparin at concentrations of 2.5 mg/ml or lower. The release produced by 10 microM Ca2+ plus 25 microM IPS3 was similar to that produced by 10 microM Ca2+ alone and suggested that IP3-sensitive channels were present in SR vesicles also containing ruthenium red-sensitive Ca2+ release channels. The junctional SR of rabbit skeletal muscle may thus have two types of intracellular Ca2+ releasing channels displaying fast activation kinetics, namely, IP3-sensitive and Ca(2+)-sensitive channels.

Animals↗