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Biomedical subjects

J A Critchley

Publications and source records attributed to J A Critchley.

At least 19 recordsLinked to original sources
PubMed1995

Effects of fluvastatin on lipid profile and apolipoproteins in Chinese patients with hypercholesterolemia.

The effects of fluvastatin treatment on lipid profile and apolipoproteins were assessed in a group of 31 Chinese patients with hypercholesterolemia, maintained on a constant low-fat diet. Some patients had the additional cardiovascular risk factors of hypertension and non-insulin-dependent diabetes mellitus, and 6 patients had familial hypercholesterolemia. Baseline lipid levels were measured after a 4-week placebo period, and these were repeated after 4 weeks of treatment with fluvastatin 20 mg daily, and after 4 weeks of treatment with fluvastatin 40 mg daily. Total cholesterol, low density lipoprotein cholesterol, and apolipoprotein (apo) B were each reduced to the same extent with the 2 doses of fluvastatin (-20%, -26%, and -20%, respectively). Triglycerides and very low density lipoprotein cholesterol were also reduced by about 12% with the 2 doses of fluvastatin. Apo A-I was increased by 7% and high density lipoprotein cholesterol (HDL-C) was increased by 10% with the 40 mg dose. The increase in HDL-C was due to increases in both HDL2-C (18%) and HDL3-C (7%). Lipoprotein(a) levels did not show any significant change with the 2 doses of fluvastatin in this short-term study. One patient developed reversible asymptomatic elevation of liver enzymes with the higher dose of fluvastatin; otherwise the drug was well tolerated and no patients had to be withdrawn from the study.

Adult↗
PubMed1995

Gastric emptying following brain injury: effects of choice of sedation and intracranial pressure.

OBJECTIVE: To compare the effects of opioid and non-opioid sedation on gastric emptying. DESIGN: Prospective, randomized trial. SETTING: University teaching hospital ICU. PATIENTS: 21 brain injured patients requiring sedation, mechanical ventilation and intracranial pressure (ICP) monitoring for > 24 h. INTERVENTIONS: Patients were randomized to receive infusions of either morphine plus midazolam (M), or propofol (P). Gastric emptying was assessed by the paracetamol absorption technique and by residual volumes following a 200 ml test feed. MEASUREMENTS AND RESULTS: Pre-sedation Glasgow Coma Score, mean ICP and the presence of bowel sounds were noted. Plasma concentrations of paracetamol were measured over 3 h following a 1 g gastric dose. There were no differences in median peak paracetamol concentration (M, 18.5 versus P, 20.8 mg/l), median time to peak concentration (M, 20 versus P, 25 min), median area under the concentration-time curve (AUC), or in the median residual volumes at 1 h (M, 14 versus P, 10.5 ml) and 2 h (M, 5 versus P, 3 ml). In patients with ICP > 20 mmHg, paracetamol concentrations were lower (p < 0.05), and AUC after 30 min was lower (165 mg.min/l versus 411 mg.min/l, p = 0.023). Mean ICP was correlated with AUC (Kendall rank p = 0.027). Gastric emptying did not correlate with initial Glasgow Coma Score or presence of bowel sounds. CONCLUSIONS: Gastric emptying is not improved in patients with brain injury by avoiding morphine (1-8 mg/h) in the sedative regimen. Intracranial hypertension is associated with reduced gastric emptying.

Acetaminophen↗
PubMed1995

The effect of transcutaneous electrical nerve stimulation (TENS) on autonomic cardiovascular reflexes.

Transcutaneous electrical nerve stimulation (TENS) has been shown to have an anti-ischaemic effect in patients with angina and peripheral vascular disease that appears to be additional to any analgesic action. The mechanism for this anti-ischaemic effect is not known but it is possible that TENS interferes with the autonomic responses to ischaemia. To determine if TENS has any direct action on autonomic reflexes we have assessed the effect of high frequency TENS on a variety of standard tests of autonomic cardiovascular reflexes in 10 normal subjects. Tests were done on four consecutive days at the same time and TENS therapy or placebo was randomly allocated on 2 days each. Results of the tests were assessed by one person 'blinded' to the randomization order. These showed that TENS was associated with a significant reduction in the rise of the diastolic blood pressure (21.8 +/- 2.3 v. 17.6 +/- 17 mmHg; p < 0.05) during isometric exercise, using sustained Handgrip. There was no significant effect discernible on the changes of heart rate and blood pressure during the Valsalva manoeuvre, cold face stimulus or head-up tilt. Transcutaneous electrical nerve stimulation appears, therefore, to have a mild inhibitory action on those reflexes mediated predominantly by the sympathetic nervous system and this is more apparent when the stimulation may be greater, as during isometric exercise.

Adult↗
PubMed1995

Comparison of the pharmacokinetics and pharmacodynamics of oral doses of perindopril in normotensive Chinese and Caucasian volunteers.

1. The pharmacokinetics of perindopril and perindoprilat and the hormonal and haemodynamic responses following a single oral dose were studied in 12 Chinese and 10 Caucasian healthy, normotensive volunteers on two occasions. Perindopril was given on the first occasion as a 4 mg dose and then after at least 10 days as a weight-adjusted dose of 4 mg/70 kg. Plasma was sampled for assay of perindopril, perindoprilat, plasma renin activity (PRA), aldosterone, angiotensin I (AI) and ACE activity. Urine was collected for perindopril and perindoprilat assay. A radioimmunoassay technique was used to measure the prodrug and its active metabolite. 2. The time to maximum concentration (tmax) for perindopril was shorter for the Chinese group after the 4 mg dose (median 0.5, range 0.5-1.5 h vs median 1.0, 0.5-1.5 h P < 0.05) and also tended to be shorter after the weight-adjusted dose (median 0.5, range 0.5-1.0 h vs median 1.0, range 0.5-3.0 h). Cmax and AUC tended to be higher after the 4 mg dose in the Chinese group who had a lower body weight than the Caucasians. 3. The tmax of perindoprilat tended to be shorter for both doses and there was a tendency towards a higher Cmax after the 4 mg dose in the Chinese group but there was no statistically significant difference between the two groups. 4. There were no differences in the levels of PRA, plasma AI, plasma aldosterone or the degree of ACE-inhibition for either dose in the two ethnic groups. 5. Blood pressure was measured at intervals up to 24 h post-dose in both the supine and standing positions. Perindopril reduced blood pressure acutely with respect to the pre-dose level with good tolerability in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1995

Unrestricted availability of a plasma paracetamol assay service resulting in an increased number of inappropriate requests.

Previously, prior approval from the on-call chemical pathologist was required in our hospital for plasma paracetamol measurements. However, since May 1992, there have been no restrictions on ordering this assay. We have assessed the consequences of this policy change by comparing the number and appropriateness of requests for plasma paracetamol measurements in Chinese patients admitted to our hospital with acute poisoning over two six-month periods (July-December) in 1991 and 1993. Requests were considered appropriate if paracetamol ingestion was suspected or unknown drugs were ingested. The number of patients having plasma paracetamol concentrations assayed increased from 51 in 1991 to 141 in 1993 (176%). The corresponding increase in the number of Chinese patients admitted to two of our eight general wards with poisoning was estimated to be 93%. The proportion of 'appropriate' plasma paracetamol measurements dropped from 55% in 1991 to 21% in 1993. Eight patients had plasma paracetamol concentrations above the recommended treatment line; they were all from the group in whom the requests were appropriate. Three of the 135 patients in the group with 'inappropriate' requests were found to have slightly elevated but far from toxic plasma paracetamol concentrations. Unrestricted availability of plasma paracetamol measurements resulted in an increase in the number of inappropriate requests.

Acetaminophen↗
PubMed1995

Poisoning due to Chinese proprietary medicines.

1. To determine the toxic potentials of those Chinese proprietary medicines (CPM) which are commonly used for self-poisoning by adults in Hong Kong, all patients admitted to four of the eight general medical wards at the Prince of Wales Hospital between January 1988 and December 1993 were retrospectively studied. 2. There were 54 women and 17 men with their age ranging from 15 to 86 years. Twenty-three subjects (32%) also took alcohol, chemicals or drugs. Of the 51 subjects (72%) who had taken topical medicaments, 22 had no symptoms while 28 had minor features of gastrointestinal irritation (n = 26), mild (n = 2) or severe (n = 1) salicylate poisoning. Of the 17 subjects (24%) who had taken CPM tablets/capsules, nine had mild symptoms including nausea/vomiting and drowsiness. The three remaining patients (4%) who had ingested liquid CPM preparations were asymptomatic. Elevated plasma salicylate or paracetamol concentrations (> 0.1 mmol l-1) were found in some patients who had taken topical medicaments and CPM tablets/capsules, respectively. All the 71 patients completely recovered. 3. Most of the CPM used for self-poisoning in Hong Kong were of low to moderate toxicity except for those containing wintergreen oil (methyl salicylate).

Acetaminophen↗
PubMed1995

Abnormal albuminuria as a predictor of mortality and renal impairment in Chinese patients with NIDDM.

OBJECTIVE: Microalbuminuria predicts mortality in non-insulin-dependent diabetes mellitus (NIDDM), but its association with deterioration of renal function remains more controversial than in insulin-dependent diabetes mellitus (IDDM). Using albumin-to-creatinine ratios (ACRs) in random spot urine samples is a convenient method for evaluating albuminuria. We studied prospectively the predictive values of albuminuria in NIDDM when assessed by this urine measurement. RESEARCH DESIGN AND METHODS: Between 1991 and 1992, we restudied the clinical and biochemical status of 403 Chinese NIDDM patients recruited in 1989 after a follow-up period of 26.6 +/- 3.2 months (mean +/- SD). Spot urine ACR was measured on two occasions and microalbuminuria was defined as a mean ACR between 5.6 and 38 mg/mmol. RESULTS: From the original cohort, 29 patients had died mostly because of cardiovascular events with or without renal failure. The overall relative risk of death in patients with abnormal albuminuria was 7.1 (P < 0.001) (microalbuminuria: 3.7, P = 0.04; macroalbuminuria: 11, P < 0.001). On multivariate analysis, the independent predictive factors for mortality were plasma creatinine (wald = 12.1, P < 0.001) and glucose concentrations (wald = 10.4, P < 0.001) in the normo- and microalbuminuric patients (n = 11) and age (wald = 4.4, P = 0.03) and plasma creatinine (wald = 8.2, P < 0.01) in the macroalbuminuric group (n = 18). In the survivors (n = 374), baseline spot urine ACR was independently associated with 2-year spot urine ACR in the normo- (P < 0.001), micro- (P < 0.01), and macroalbuminuric groups (P = 0.01). In addition, baseline spot urine ACR was independently related to 2-year plasma creatinine (P = 0.01) in the macroalbuminuric group. The rates of change of the reciprocal of plasma creatinine ( delta [Cr]-1) were -27.3 +/- 62.5, -43.4 +/- 68.6, and -108.8 +/- 98.81.mumol01.month-1 in the normo-, micro-, and macroalbuminuric groups, respectively (P < 0.001). The delta [Cr]-1 was independently and inversely related to the baseline spot urine ACR (P < 0.001) and 2-year systolic blood pressure (P < 0.001). CONCLUSIONS: Abnormal albuminuria as indicated by a random spot urine ACR > 5.6 mg/mmol predicts increased mortality and is associated with the progression of albuminuria and deterioration of renal function in Chinese NIDDM patients.

Aged↗
PubMed1995

Renal failure is uncommon in Chinese patients with paracetamol (acetaminophen) poisoning.

The reported incidence of renal failure in unselected patients with paracetamol poisoning is about 1-2%. Since the introduction of antidotal therapy for paracetamol poisoning in 1973, renal failure is now mainly seen in those admitted too late for effective therapy and is usually associated with liver damage. To determine the incidence of renal failure in Chinese patients with paracetamol poisoning, a retrospective survey was conducted of 224 patients admitted to the Prince of Wales Hospital, Hong Kong, with paracetamol poisoning from January 1988 to January 1994. Of the 28 patients at risk (plasma paracetamol concentrations above the recommended treatment line), 13 developed liver damage which was severe in 5. One patient with severe liver damage developed a transient increase in plasma creatinine concentration from 90 to 116 umol/L. All 28 patients completely recovered. Renal failure was uncommon in Chinese subjects (0.4%), and this was probably related to a lower incidence of liver damage which may be due to less chronic alcoholism as well as ethnic differences in paracetamol metabolism resulting in an inherent reduced susceptibility to its liver and renal toxicity.

Acetaminophen↗
PubMed1994

The estimation of paracetamol and its major metabolites in both plasma and urine by a single high-performance liquid chromatography assay.

Many analytical methods exist for the assay of paracetamol in biological fluids, including colorimetry with chemical derivatization, direct spectrophotometry, chromatographic methods and immunoassays. Their development has been largely driven by the needs of clinical toxicology requiring the rapid, reliable and highly specific estimation of paracetamol in plasma samples to determine the need for antidote therapy. However, for in vivo metabolism studies, a specific assay method which can provide measurements of paracetamol and its metabolites in both plasma and urine is desired. A reversed-phase HPLC method with UV detection at 254 nm was developed to fulfil these requirements. The assay involves minimum sample preparation with a relatively short run time. The solvent system involves a simple isocratic elution with a composition of 0.1 M potassium dihydrogen orthophosphate-acetic acid-propan-2-ol, (100:0.1:0.75, v/v/v). The reproducibility of the assay was high with an inter-assay RSD of 0.2-1.7% for urinary paracetamol concentrations of 5-500 micrograms ml-1 and 0.1-3.3% for plasma concentrations between 5 and 25 micrograms ml-1. A similarly high degree of precision was found for the glucuronide, sulphate, cysteine and mercapturate metabolites of paracetamol. The same assay can be used to analyse both plasma and urine samples and thus was employed for studies on the metabolism of paracetamol in healthy subjects and in patients with various diseases.

Acetaminophen↗
PubMed1994

Pharmacists' attitudes toward adverse drug reaction reporting in Hong Kong.

OBJECTIVE: To study the attitudes and knowledge of pharmacists in Hong Kong toward the reporting of adverse drug reactions (ADRs). METHODS: In December 1993, all pharmacists who were working in retail shops (n = 230), hospitals (n = 44), or outpatient clinics (n = 12) in Hong Kong were sent a questionnaire as well as a letter explaining the purpose of the survey. RESULTS: One hundred and twenty-nine pharmacists (retail pharmacies 40.4 percent, hospitals 68.2 percent, outpatient clinics 50 percent) responded. Although 93 percent of the pharmacists in this survey agreed that it is necessary to report ADRs, a much smaller proportion (14.7 percent) had actually done so in the previous 12 months. Most pharmacists (87.4 percent) were not aware of any ADR reporting system in Hong Kong. There did not appear to be a relationship between ADR reporting and the length or place of practice, workload, or patient contact time. Severe or unusual ADRs and ADRs to new products were perceived to be significant enough to report. CONCLUSIONS: The great majority of pharmacists in Hong Kong agreed on the necessity of reporting ADRs. The lack of knowledge of an ADR reporting program might have led to nonreporting in the past. It is important that there be continuing efforts to promote ADR reporting programs.

Adverse Drug Reaction Reporting Systems↗
PubMed1992

Atrial natriuretic peptide and urinary dopamine output in non-insulin-dependent diabetes mellitus.

1. Disturbances of sodium and water homoeostasis may contribute to the close association between diabetes, hypertension and proteinuria. We therefore studied the patterns of two natriuretic hormones, plasma atrial natriuretic peptide and urinary dopamine, in 165 Chinese patients with non-insulin-dependent diabetes mellitus controlled by diet or oral hypoglycaemic agents on two occasions over a 6-week period. Patients were divided into three groups based on the mean value of two 24h urinary albumin excretion measurements. In group 1, 88 patients had normoalbuminuria (urinary albumin excretion < or = 30 mg/day), in group 2, 48 patients had microalbuminuria (urinary albumin excretion between 30 and 300 mg/day), and in group 3, 29 patients had macroalbuminuria (urinary albumin excretion > or = 300 mg/day). 2. The supine systolic blood pressure (mean +/- SD) was higher in patients with abnormal albuminuria (group 1: 140.9 +/- 27.4 mmHg; group 2: 158.1 +/- 26.4 mmHg; group 3: 166.7 +/- 23.9 mmHg; F = 13.1, P < 0.001, analysis of variance). Urinary sodium output was similar in these three groups of patients. The geometric means (anti-logarithm of 95% confidence interval logarithm) of plasma atrial natriuretic peptide concentrations increased with increasing proteinuria [group 1: 33.3 (29.9-37.1) pg/ml; group 2: 39.1 (34.2-44.6) pg/ml; group 3: 50 (38.6-54.7) pg/ml; F = 4.24, P < 0.01; analysis of variance], whereas those of urinary dopamine output were related inversely to proteinuria [group 1: 1291.7 (1167.2-1437.0) nmol/day; group 2: 1142.3 (975.9-1337.2) nmol/day; group 3: 982.7 (775.7-1245) nmol/day; F = 3.10, P < 0.05, analysis of variance].(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial Natriuretic Factor↗
PubMed1992

Isradipine treatment for hypertension in general practice in Hong Kong.

A 6-week open study of the introduction of isradipine treatment was conducted in general practice in Hong Kong. 303 Chinese patients with mild to moderate hypertension entered the study. Side effects were reported in 21% of patients and caused withdrawal from the study in 3 patients. The main side-effects were headache, dizziness, palpitation and flushing and these were not more frequent than reported in other studies with isradipine or with placebo. Supine blood pressure was reduced (P less than 0.01) from 170 +/- 20/102 +/- 6 mmHg to 153 +/- 19/92 +/- 8, 147 +/- 18/88 +/- 7 and 144 +/- 14/87 +/- 6 mmHg at 2, 4 and 6 weeks respectively in evaluable patients. Similar reductions occurred in standing blood pressure and there was no evidence of postural hypotension. Normalization and responder rates at 6 weeks were 86% and 69% respectively. Dosage was increased from 2.5 mg b.d. to 5 mg b.d. at 4 weeks in patients with diastolic blood pressure greater than 90 mmHg and their further response was greater than those remaining on 2.5 mg b.d.

Antihypertensive Agents↗
PubMed1992

Hospital admissions due to adverse reactions to Chinese herbal medicines.

Chinese herbal medicines (CHM) are commonly used in Hong Kong. To determine the importance of adverse reactions to CHM as a cause of medical admissions in Hong Kong, all 1701 patients admitted to two general medical wards at the Prince of Wales Hospital over an eight-month period were prospectively studied. In only three patients (0.2%) was the admission attributed to the adverse effects of CHM. These were life-threatening in two cases ('dazao'-induced angio-neurotic oedema and liquorice-induced hypokalaemic periodic paralysis). Despite this low incidence of adverse reactions, in communities where CHM are commonly used, it is important that there is a continuing effort to collect new information on the safety of these compounds.

Adolescent↗
PubMed1991

Increased oxidative metabolism of paracetamol in patients with hepatocellular carcinoma.

Oxidative metabolism (OM) of paracetamol was studied in 19 patients with hepatocellular carcinoma (HCC), 39 with chronic hepatitis B virus infection (CHBV) and 26 healthy controls. Paracetamol (1.5 g) was given and the subsequent 24 h urine collection assayed for paracetamol and its metabolites by HPLC. HCC patients showed greatly increased OM, as reflected by the combined fractional recoveries of mercapturic acid and cysteine conjugates (22%), in comparison with controls (7%) and CHBV patients (10%). As the cytochrome P-450 dependent OM of xenobiotics has been implicated in carcinogenesis, it is interesting that two CHBV patients also had increased OM.

Acetaminophen↗
PubMed1991

Gastric emptying in the postpartum period.

We measured gastric emptying, using the technique of paracetamol absorption, in eight women on their first and third postpartum day. Gastric emptying was rapid and there was no difference between the first and third day in the time to peak plasma concentration of paracetamol. Six women returned after six weeks for a further study. Gastric emptying was still rapid but the metabolism of paracetamol appeared to be slower than that found during the immediate postpartum period. These findings suggest that fluid fasting guidelines in patients more than one day postpartum need not be different from those in non-pregnant patients.

Absorption↗
PubMed1990

Effects of nalmefene on feeding in humans. Dissociation of hunger and palatability.

Effects of nalmefene on eating were investigated in two groups of ten male volunteers, in a double-blind placebo-controlled study. The nalmefene treated group ate 22% less, both in terms of absolute weight and caloric intake, of a standardised buffet-meal than did the placebo group. No differences in subjective ratings of hunger or satiety were found between the groups, suggesting that the reduced feeding was not a consequence of any change in motivation to eat. When analysed by nutrient content, nalmefene was found to reduce fat and protein, but not carbohydrate, intakes. Analyses of intakes of individual foods showed a differential effect of nalmefene on foods rated as highly palatable. Thus the apparent nutrient specificity of nalmefene appeared to be an indirect consequence of its effect on palatability. Nalmefene also caused slight increases in self-rated alertness, and decreases in ratings of tiredness and elation, although it was thought unlikely that these accounted for observed changes in eating behaviour. No other side-effects were detected, and performance on a choice reaction time task was unaffected. These results add weight to suggestions that endogenous opioids are involved in reward-related aspects of feeding associated with food palatability.

Adolescent↗