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Biomedical subjects

H Wynne

Publications and source records attributed to H Wynne.

At least 19 recordsLinked to original sources
PubMed2004

Dietary vitamin K influences intra-individual variability in anticoagulant response to warfarin.

The relationship between dietary intake of vitamin K, fat, plasma vitamin K concentrations and anticoagulation response to warfarin within individuals, as well as the contribution of dietary vitamin K to differences in warfarin dose requirements between individuals were investigated in 53 patients on warfarin therapy who had stably controlled anticoagulation. Each patient completed a dietary record of all foods consumed on a daily basis for 4 weeks. Each week a blood sample was taken for measurement of the international normalized ratio (INR), plasma vitamin K, triglycerides and warfarin enantiomer concentrations. The patients' genotype for CYP2C9 was also determined. Regression analysis of the data showed that, for each increase of 100 microg in the daily dietary intake of vitamin K averaged over 4 d, the INR was reduced by 0.2. There was no correlation between warfarin daily dose and average daily dietary vitamin K intake when calculated over 28 d. The regression model for warfarin dose showed that, while dietary vitamin K had no effect, CYP2C9 genotype (P = 2%) and age (P < 1%) significantly contributed to inter-patient variability in warfarin dose requirements. A consistent intake of vitamin K could reduce intrapatient variability in anticoagulation response and thus improve the safety of warfarin therapy.

Adult↗
PubMed1997

Behavioral and neuroendocrine effects of the partial NMDA agonist D-cycloserine in healthy subjects.

The effect of D-cycloserine, a partial agonist of the N-Methyl-D-Aspartate (NMDA) receptor, were assessed in a (neuroendocrine) challenge paradigm to to examine NMDA systems in male healthy volunteers, using a double-blind, placebo-controlled crossover design. Oral D-cycloserine (15, 50, and 150 mg) was readily absorbed and its plasma concentration increased dose-dependently. Behavioral and hormonal responses were measured for 240 minutes after administration of the drug. D-cycloserine was well tolerated and did not induce side-effects according to the Visual Analog Scales (VAS), the Brief Psychiatric Rating Scale (BPRS) and the Adverse Events Checklist (AEC) & codes. D-cycloserine failed to elicit a neuroendocrine response as evaluated by cortisol, prolactin, and luteinizing hormone (LH) plasma levels. The present result suggests that D-cycloserine can readily be administered to healthy volunteers but that, in the dosages used, neuroendocrine secretion fails to serve as a model for testing NMDA receptor function in humans.

Adult↗
PubMed1997

Paracetamol poisoning in the north east of England: presentation, early management and outcome.

1. Paracetamol is increasingly involved in self-poisoning in the United Kingdom and remains a common cause of fatal poisoning. 2. To document the epidemiology and early management of paracetamol poisoning data were collected on consecutive patients with suspected paracetamol poisoning presenting to 6 hospitals in the North East of England over 12 weeks in 1994. 3. There were 400 presentations (attendance rate 1.14/10(3) population/yr) involving 343 persons (45% male). Paracetamol concentrations at 4 h correlated weakly with reported paracetamol dose (R = 0.49, P < 0.0001) and were similar comparing those treated and not treated by gastric decontamination. 4. In 38 (9%) cases paracetamol concentrations were above the appropriate nomogram treatment line, including 3% and 20% of patients who reported ingesting less than and more than 12 g respectively. In 21 patients acetylcysteine treatment was deferred until admission to the ward, the mean delay involved was 2.8 h. 5. One patient died, from arrhythmias caused by co-ingested dothiepin. 6. Paracetamol poisoning is common. Most cases do not have potentially toxic plasma paracetamol concentrations, but those who do often present late and antidotal treatment may be delayed inappropriately.

Acetaminophen↗
PubMed1996

Presentation of poisoned patients to accident and emergency departments in the north of England.

1. A 12 week prospective survey of all patients of any age with confirmed or suspected poisoning presenting to six accident and emergency departments in the North East of England was performed to establish the local incidence and patterns of presentation of poisoning. 2. 945 episodes of poisoning involving 852 patients were recorded representing approximately 1.2% of all A&E presentations and suggesting an annual attendance rate of 2.7 per 1000 persons per year. 3. Attendance rates varied threefold between hospitals and were similar in males and females overall; between the ages of five and 14 attendances were more common in females (1.9 vs 0.6/10(3)/y) while between 0 and 4 y (3.1 vs 2.4) and 25 and 34 y (3.9 vs 2.9/10(3)/y) they were more common in males. 4. The median interval between poisoning and presentation was 2 h (mean 4.1 h) and only 19% of cases presented within 1 h. Presentation was most common between Friday evening and Tuesday morning and in the late afternoon and evening. 5. 6% of the patients presented more than once with poisoning during the study period and 37% had a past history of deliberate self-harm. The most common poisons involved were paracetamol (43%), opioids (15%) and benzodiazepines (15%). 6. The study illustrates the frequency of presentations of poisoning to A&E departments. The high rate of poisoning in young men and the increasing use of paracetamol are particular causes for concern.

Acetaminophen↗
PubMed1996

Factors affecting hospital admission and length of stay of poisoned patients in the north east of England.

1. Poisoning is a common reason for presentation to hospital and hospital admission but there is no agreed policy for managing these patients. This study examined the management of patients presenting with poisoning and the factors affecting the probability of hospital admission and prolonged stay. 2. Data on all cases of poisoning presenting to six Accident and Emergency departments in the North East of England over 12 weeks in 1994 was collected prospectively from A&E notes. Length of stay and outcome were recorded from hospital computer records. 3. Overall, 73% of patients were admitted to a medical ward. Probability of admission was not independently affected by age or gender but was increased in those with intentional poisoning (Odds Ratio (OR) 3.3 [95% CI 1.8, 6.1]), a history of self harm (OR 1.7, [1.0, 2.9]) or potentially hazardous poisoning (OR 3.7 [2.1, 6.6]). There were significant variations between hospitals (50-80%) which could not be attributed to case mix. 4. Prolonged stay (> 2 nights) was more common in patients over 65 years (OR 6.8 [2.9, 16.1]), those with intentional poisoning (OR 2.7 [1.1, 6.6]) and those with potentially hazardous poisoning (OR 2.6 [1.4, 4.9]). Mean hospital stay was 1.5 days and varied significantly between hospitals from 0.8 to 2.1 days and this was independent of case mix. 5. There are appreciable variations in the management of poisoning between hospitals which are not explained by patient characteristics. Savings would occur if rates of admission and duration of stay were reduced by those hospitals where admission is more frequent or hospital stay is longer. However, the impact of this on long term morbidity is unknown.

Adolescent↗
PubMed1995

The influence of age, liver size and enantiomer concentrations on warfarin requirements.

1. We have tested the hypothesis that the fall in hepatic mass with age influences the age related increase in sensitivity to warfarin. In 39 otherwise healthy outpatients, aged 50-87 years, stabilised on warfarin for prophylaxis of thromboembolism, age, mean International Normalised Ratio (INR), and mean warfarin dosage were recorded. Liver volume was measured by ultrasound, and plasma was assayed for trough concentrations of (R)- and (S)-warfarin. 2. There was a negative correlation between age and liver volume (r = -0.41; P = 0.01) and age and dose (r = -0.53; P = < 0.001) and a positive correlation between liver volume and dose (r = 0.49; P = 0.002). There was no significant correlation between dosage and (R)- and (S)-warfarin concentrations, nor between dosage and INR. 3. The regression model including both age and liver volume data showed a better fit for estimation of warfarin dosage requirement than regression models based on age and liver volume data alone. Ninety-five per cent prediction intervals for warfarin dose requirements were wide, whether age alone, or age and liver volume were used in calculations. 4. Due to inter-individual variation in warfarin dosage requirements related to other influences, both explained and unexplained, routine measurement of age and liver volume would not contribute further clinically useful information to that obtained by the INR test currently used for predicting warfarin dosage requirements.

Age Distribution↗
PubMed1994

Pattern of inhibition of parasympathetic activity in response to incremental bolus doses of atropine in carotid sinus hypersensitivity.

Patients with established reproducible cardioinhibitory carotid sinus hypersensitivity were studied to define the dose of atropine required to abolish the heart rate slowing in response to carotid sinus massage, the heart rate response to the Valsalva manoeuvre and salivary gland flow. Bolus doses of intravenous atropine were given to a cumulative dose of 700 mcg. Cardioinhibition was abolished in all patients with a total dose of 700 mcg. The heart rate ratio during the Valsalva manoeuvre did not vary significantly. The decline in salivary gland flow was evident earliest, at a dose of 75 mcg. In clinical studies, 700 mcg of atropine will abolish the diagnostic cardioinhibitory response to carotid sinus message in patients with the syndrome. This may not prevent syncope, as could occur in the key frequent vasodepressor form of carotid sinus hypersensitivity syndrome.

Aged↗
PubMed1994

The influence of ciprofloxacin on the pharmacokinetics and pharmacodynamics of a single dose of temazepam in the young and elderly.

The effect of pretreatment with a 4-day course of ciprofloxacin (500 mg twice daily) on the pharmacokinetics and pharmacodynamics of a single oral dose of temazepam (10 mg) was investigated in 12 healthy young and nine elderly patient volunteers in a crossover design study. Temazepam clearance was lower in the elderly than in the young, but this difference was not statistically significant. Ciprofloxacin had no significant effect on temazepam pharmacokinetics or pharmacodynamics in either age group.

Administration, Oral↗
PubMed1993

The effect of age and frailty upon blood esterase activities and their response to dietary supplementation.

1. The aims of this study were two-fold. First, to define ranges of blood esterase activities in three groups, namely young subjects, fit community dwelling elderly and frail, chronically hospitalised elderly subjects, and second, to determine whether low blood esterase activities in the frail patients could be altered by increasing their nutritional intake. 2. Plasma cholinesterase, aspirin esterase, paraoxonase and phenylacetate esterase activities were all significantly lower in the frail elderly compared with the young and fit elderly volunteers. The activity of red blood cell esterase was not different in the frail elderly. 3. Fourteen frail elderly patients were randomly assigned to receive either hospital meal provision plus supplemental feeding with Build-up (Nestle) and Maxijul (SHS Ltd) or hospital provision alone for 8 weeks. Dietary intake was measured for all patients at the start of the study and at week 8. Measurements of blood esterase (cholinesterase, phenylacetate esterase, paraoxonase, aspirin esterase and red blood cell esterase), albumin and anthropometric indices (weight, triceps skinfold thickness and mid arm circumference) were made before the study and repeated at week 4 and 8. 4. There was a significant increase in plasma cholinesterase at week 4 (P < 0.05) but this was not statistically significant at week 8. There were no significant changes in any of the other esterase activities or anthropometric measurements. 5. We conclude that the lower esterase activities of the frail chronically hospitalised elderly do not respond to dietary supplementation for a period of 8 weeks with routinely available products. The hypothesis that lower esterase activities are the direct result of undernutrition which would be corrected by dietary supplementation has not been supported by this study.

Aged↗
PubMed1993

Non-starch polysaccharide/dietary fibre supplementation using small meals in long-stay frail elderly patients.

Small meals of high non-starch polysaccharide (NSP)/dietary fibre cakes were offered to clinically stable continuing-care elderly patients, replacing the standard provision of low NSP/dietary fibre commercial cakes in an attempt to improve their well being. The study design was comprised of a 4 week control period, a 4 week intervention period, when modified cakes were offered, and finally a second 4 week control period. During intervention, an additional 33% NSP or 23% dietary fibre was offered, but only 7.7% and between 3.5% and 5.6% were consumed, respectively. Anthropometric measurements and bowel frequency did not change throughout the study but a decrease in aperient use was noted. From this study it was concluded that more comprehensive changes in food provision are required to achieve the current recommended consumption of NSP/dietary fibre in continuing-care elderly patients.

Aged↗
PubMed1991

The association of age with aspirin esterase activity in human liver.

The activity of the phase 1 enzyme aspirin esterase was studied in liver tissue from 16 patients, aged 45-88 years. No correlation between age and enzyme activity was found in post-mitochondrial, cytosolic and microsomal fractions. These results provide further evidence that age is not a major determinant of the activity of hepatic drug-metabolizing enzymes in man.

Aged↗