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Biomedical subjects

J Feely

Publications and source records attributed to J Feely.

At least 73 records · Page 4Linked to original sources
PubMed1991

EEG and event related potentials in hepatic encephalopathy.

In recent years, there have been considerable developments in the application of EEG and event related potential technology to the diagnosis and assessment of hepatic encephalopathy in cirrhotic patients. A review of the literature on this subject is reported. The visually interpreted EEG is only of benefit in the late stages of hepatic encephalopathy. EEG spectral analysis allows identification of all stages of the condition. Brainstem auditory evoked responses are normal in encephalopathy. Visual evoked responses show an increase in the latency and eventual loss of individual component waves as encephalopathy progresses. Somatosensory evoked responses show a progressive prolongation of peak and inter-peak latency which correlates with the severity of encephalopathy. The auditory P300 evoked response shows an increased latency with the development of hepatic encephalopathy. Event related potentials provide objective diagnostic markers of the development of hepatic encephalopathy. The increased use of this technology in the assessment of patients with this condition should be of clinical benefit in its management.

Electroencephalography↗
PubMed1991

Pharmacogenetics and drug metabolism: an Irish perspective.

Genetic factors, particularly in relation to control of liver drug metabolism, are a major cause of variability in the response to drugs. In 145 Irish subjects 48% were fast acetylators of sulphadimidine in contrast to 80% in Chinese subjects. Eleven (7.6%) of our Irish population showed an improved ability to oxidise delrisoquine. The therapeutic implications of these findings are discussed.

Acetylation↗
PubMed1991

Effect of zinc supplementation on oxidative drug metabolism in patients with hepatic cirrhosis.

The pharmacokinetics of antipyrine were studied in seven zinc deficient patients with hepatic cirrhosis, before and after zinc supplementation. Each patient received zinc sulphate 660 mg daily for 30 days, restoring zinc status to normal as assessed by leucocyte zinc concentration. Antipyrine clearance was significantly reduced (P less than 0.05) and antipyrine elimination half-life increased (P less than 0.05) following administration of zinc sulphate without significant alteration in the apparent volume of distribution. It is concluded that supplementation of the zinc deficiency associated with hepatic cirrhosis impaired the hepatic oxidative metabolism of antipyrine.

Adult↗
PubMed1991

A comparison of drug protein binding and alpha 1-acid glycoprotein concentration in Chinese and Caucasians.

alpha 1-acid glycoprotein (AAG) concentration and the binding of both lignocaine and warfarin were compared in 15 healthy Chinese and age and sex matched Irish (Caucasian) subjects. Both the extent of lignocaine binding and AAG concentrations were significantly (P less than 0.05) lower in Chinese subjects. No difference was shown in warfarin binding. These results suggest that the binding of basic drugs may be significantly less in Chinese than Caucasians, and lower concentrations of the binding protein AAG are a major determinant of this difference.

Adult↗
PubMed1991

Drug-drug interactions in hospital.

Drug prescription charts of 200 randomly selected general medical patients in two Dublin hospitals were examined for potential drug-drug interactions. Using the Stockly Interaction alert, 37% of these patients had potential interactions but in only three was there clinical evidence that an interaction occurred. In an analysis of 150 spontaneous (yellow card) adverse drug reactions reports interactions contributed to only 8%. These results suggest that the importance of interactions as a cause of drug toxicity is commonly over-estimated.

Aged↗
PubMed1990

Insulin.

Explore the source record for details and available documents.

Animals↗
PubMed1990

Hospital formularies: need for continuous intervention.

The effects of introducing a hospital formulary alone and with active intervention were compared prospectively with regard to drug costs and the quality of prescribing. Intervention comprised feedback on prescribing habits, peer comparison, and information on drugs. Aspects of prescribing that were not subjected to intervention did not alter. In the year in which intervention occurred generic prescribing rose by 50%; inappropriate prescribing and overall use of third generation cephalosporins fell; and compliance with the recommended list of drugs was good. Overall, drug costs remained static, compared with a projected increase of 0.25 m pounds; in a comparative control hospital drug costs rose by 18%. During the next year, when no form of intervention took place, previous gains were eroded and drug costs rose. Continuous intervention, review, and feedback are required if a formulary is to continue to achieve its objectives.

Costs and Cost Analysis↗
PubMed1990

The auditory P300 event-related potential: an objective marker of the encephalopathy of chronic liver disease.

Recently many variants of electroencephalogram-evoked responses have been studied as potential diagnostic aids in the detection and evaluation of hepatic encephalopathy. This study assesses the value of the auditory P300 event-related potential--a slow component of the auditory evoked response--as a tool in this field. Twenty-one nonencephalopathic and 12 encephalopathic (grade 1/2) cirrhotic patients and 26 controls were assessed clinically and psychometrically. Electroencephalogram spectral analysis and visual evoked response recordings were also conducted. An auditory P300 wave was elicited using the standard two-tone discrimination paradigm. The latency and amplitude of this wave were measured. The latency of the P300 was found to be significantly increased in the encephalopathic patients compared with both nonencephalopathic cirrhotic and control groups (p less than 0.05). Amplitude of the wave was decreased in both nonencephalopathic and encephalopathic patients, but this was not statistically significant. This study suggests that the latency of the P300 is a good marker of grades 1 and 2 clinical hepatic encephalopathy. The delays in the P300 latency may indicate that encephalopathic patients have a deterioration of their stimulus evaluation abilities.

Chronic Disease↗
PubMed1990

Influence of aminoglutethimide on plasma levels of medroxyprogesterone acetate.

To confirm that concomitant administration of aminoglutethimide (AG) reduces plasma levels of medroxyprogesterone acetate (MPA), MPA levels were assayed in six patients with advanced breast cancer receiving the two agents. Patients had disease resistant to AG and were studied during conversion to therapy with MPA. Hydrocortisone was discontinued at the commencement of study and MPA introduced and given at a constant dose of 800 mg daily while AG was reduced in dose from 250 mg b.d. to 125 mg b.d. and then discontinued. MPA levels were measured after two weeks at each dose of AG and after two weeks on MPA alone. Mean MPA levels showed a progressive and significant (P less than 0.01) rise as the AG dose was reduced--180 ng ml-1, 250 ng ml-1 and 740 ng ml-1 respectively. MPA levels were always in excess of the accepted therapeutic level of 100 ng ml-1 and plasma cortisol levels fell in parallel with the rise in MPA levels.

Adult↗
PubMed1990

Enzyme induction and inhibition.

The rate and extent of drug metabolism significantly influences drug effect. Enzyme induction by increasing the metabolism of drugs may result in important drug interactions. Other implications of enzyme induction include alterations in the metabolism of endogenous substrates, vitamins and activity of extrahepatic enzyme systems. Similarly a wide range of drugs may produce clinically significant drug interactions following enzyme inhibition. Assessment of enzyme induction and inhibition in man involves diverse methods including the use of model drugs.

Enzyme Induction↗
PubMed1990

Severity of cirrhosis and the relationship of alpha 1-acid glycoprotein concentration to plasma protein binding of lidocaine.

The concentration of alpha 1-acid glycoprotein, the major determinant of the plasma protein binding of basic drugs, and the extent of lidocaine protein binding was related to the severity of liver disease in 30 cirrhotic patients. In comparison with matched control subjects, alpha 1-acid glycoprotein concentration (77 +/- 7 versus 37 +/- 3 mg/dl; mean +/- SEM; p less than 0.01) and lidocaine binding (69% +/- 2% versus 35% +/- 2%; p less than 0.01) was markedly reduced. There was a significant negative correlation (r = 0.78; p less than 0.01) between free lidocaine and alpha 1-acid glycoprotein concentration. Furthermore, both were significantly related to the severity of liver disease, as assessed by use of the Child Turcotte classification.

Adult↗
PubMed1990

Tissue zinc status and drug elimination in patients with chronic liver disease.

1. The zinc status and drug-metabolizing ability of 15 patients with histologically diagnosed hepatic cirrhosis were studied. Zinc status was assessed using both serum and leucocyte zinc concentrations, and drug-metabolizing ability was assessed by antipyrine kinetics. 2. Patients with cirrhosis were found to have lower serum and leucocyte zinc concentrations when compared with a healthy control group. 3. Leucocyte zinc content and antipyrine clearance were correlated. Those patients with the lowest leucocyte zinc content had the greatest impairment of drug metabolism. Antipyrine elimination and serum zinc concentrations were not correlated. 4. Leucocyte zinc concentrations and antipyrine clearance were not influenced by the severity of liver dysfunction, as assessed by using the Child Turcotte classification. 5. These results suggest that tissue zinc depletion in some patients with hepatic cirrhosis may explain in part the impaired capacity to metabolize drugs.

Antipyrine↗
PubMed1990

Allopurinol influences aminophenazone elimination.

The authors observed an interaction between allopurinol and both theophylline and warfarin in 2 patients. To determine the possible effect of allopurinol on hepatic oxidative metabolism a [14C]-aminophenazone (aminopyrine) breath test was performed before and during treatment with allopurinol 100mg daily in 5 patients with hyperuricaemia. Allopurinol prolonged the [14CO2]-aminophenazone half-life from 72 +/- 13 to 104 +/- 16 minutes (mean +/- SEM, p less than 0.05). It is possible that allopurinol may produce clinically significant drug interactions through an inhibitory effect not only on xanthine oxidase metabolism but also on oxidative metabolism.

Allopurinol↗
PubMed1990

Effects of drugs on glucose tolerance in non-insulin-dependent diabetics (Part I).

Non-insulin-dependent diabetes mellitus (NIDDM) is being increasingly diagnosed as its importance as a risk factor for the development of cardiovascular disease continues to be recognised. Good metabolic control remains a major goal of drug therapy as it decreases the severity and incidence of diabetic complications. Many drugs have been known to interfere with glucose control, either in a beneficial or, more commonly, in a deleterious fashion. Unfortunately in many instances drug-induced effects have not been looked at specifically in NIDDM. Thiazide diuretics have been shown to cause a deterioration in glucose control not only in the general population but especially in patients who have impaired glucose tolerance. While the effect appears less with potassium supplementation and the lower dosage employed nowadays, thiazide diuretics are best avoided in diabetic patients. Loop diuretics have been reported to reduce glucose control to a lesser extent than thiazides. Although indapamide would appear not to interfere with blood sugar control in NIDDM, higher doses that cause potassium loss may cause a deterioration. beta-Adrenoceptor antagonists have been reported to cause a rise in blood sugar and glycosylated haemoglobin in NIDDM. The effect may be more marked in patients on oral hypoglycaemic agents as opposed to diet alone and in those on concomitant thiazide diuretics. The greatest effect was seen with propranolol, and the least with cardioselective and the less lipophilic beta-blockers. It is of interest that alpha-blockade with prazosin seems to antagonise beta-adrenoceptor blocker-induced deterioration in glucose control. The calcium antagonists have differing effects which may be structure related. In some, but not all, studies use of the dihydropyridines such as nifedipine has been associated with a deterioration in glucose control in NIDDM. Long term studies are needed to assess definitively their effect on glucose control. Verapamil, on the other hand, has in 1 small study been found to have a beneficial effect on glucose control in NIDDM. Centrally acting alpha-agonists such as the antihypertensive drug clonidine have not been shown to result in a deterioration in glucose control when used in NIDDM, although there are isolated case reports. Long term therapy with the more specific agonist guanfacine was reported in 1 uncontrolled study to have a beneficial effect on glucose tolerance in NIDDM. Uncontrolled studies suggest that phenothiazines may aggravate diabetic control. The significance of a number of recent observations is not fully clear.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Flash visual evoked responses in the early encephalopathy of chronic liver disease.

In recent years many variants of EEG sensory evoked responses have been studied as potential diagnostic aids in the detection and quantification of hepatic encephalopathy (HE). This study assesses the value of the flash visual evoked response (VER). Twenty-six controls and 21 non-encephalopathic and 12 encephalopathic (grade 1/2), biopsy-proven, cirrhotic patients were assessed clinically, psychometrically, and electrophysiologically. Flash VER from three different leads were obtained from each patient. Data from the fronto-occipital leads gave the best differentiation between the subjects. The P2 and N3 peak latencies were significantly increased in the two liver groups and correlated with the mental state and psychometric results. The N3 latency had a 92% specificity and a 50% sensitivity in the detection of grade 1/2 HE. This study suggests that the N3 latency changes may be a good marker of early clinical HE and useful in the longitudinal assessment of individual patients.

Adult↗