PubMed HealthSearch

Biomedical subjects

C R Kumana

Publications and source records attributed to C R Kumana.

At least 19 recordsLinked to original sources

Audit exposes flawed blood sampling for "digoxin levels".

Therapeutic "digoxin level" monitoring in selected wards was audited. Time elapsing between the last dose and blood sampling was considered appropriate if greater than or equal to 6 h. If such details were not entered on the requisition, the maximum time elapsing was estimated as "appropriate" or "inappropriate" from the time samples were logged into the laboratory and the time the last dose was entered in the patient's treatment sheet. In 22 requisitions detailing sampling time, nine were considered inappropriate. In an additional 150 instances, timing was estimated as inappropriate in 45. Among the 118 requests where timing (estimated or labelled) was appropriate, available plasma digoxin concentrations yielded a mean of 1.0 nM, compared to 1.6 nM in the corresponding 54 patients with premature sampling; this difference was both clinically and statistically significant (95% confidence limits 0.8-1.2 and 1.3-1.9 nM, respectively, p less than 0.001). Premature blood sampling for digoxin levels was common and associated with higher concentrations than when appropriate. Such inappropriate timing may not have serious consequences, but digoxin levels are a matter of record and are used for teaching; due attention to timing could provide more reliable information and avoid wasting valuable resources.

Aged

Pyrrolizidine alkaloid composition of three Chinese medicinal herbs, Eupatorium cannabinum, E. japonicum and Crotalaria assamica.

The pyrrolizidine alkaloid composition of three Chinese herbs, "pei lan", "cheng gan cao" and "zi xiao rong," identified respectively as Eupatorium cannabinum, Eupatorium japonicum (Compositae) and Crotalaria assamica (Leguminosae), were studied by fast atom bombardment mass spectrometry and gas chromatography-electron impact mass spectrometry. Viridiflorine, cynaustraline, amabiline, supinine, echinatine, rinderine and isomers of these alkaloids were found in the Eupatorium species. Monocrotaline was the only pyrrolizidine alkaloid detected in the Crotalaria species.

Drugs, Chinese Herbal

Treatment of acute cerebral hemorrhage with intravenous glycerol. A double-blind, placebo-controlled, randomized trial.

BACKGROUND AND PURPOSE: Hitherto, treatment of acute cerebral hemorrhage with intravenous glycerol has not been evaluated in rigorous clinical studies with sufficient patient numbers. METHODS: We undertook a double-blind, stratified and randomized, placebo-controlled clinical trial. Only patients with a first stroke admitted to the hospital within 24 hours after onset of symptoms were recruited, provided computed tomography confirmed hemorrhage and informed consent was obtained. After stratification into alert, semicoma, and coma subgroups using the Glasgow Coma Scale, 107 patients received active treatment (500 ml of 10% glycerol in saline by intravenous infusion over 4 hours on 6 consecutive days) and 109 were given corresponding saline treatment. Using a variety of objective scoring systems, patients were followed up for up to 6 months. RESULTS: At follow-up, all measures of outcome in the treated and control groups were very similar. At 6 months, respective mortality rates were 37 of 107 and 33 of 109. Corresponding mean +/- SD improvements in Scandinavian Stroke Study Group scores were 8.35 +/- 16.9 versus 11.55 +/- 15.6 (long-term) and 0.64 +/- 7.3 versus 2.40 +/- 6.9 (prognostic), and improvements in the Barthel Index ratings were 10.72 +/- 24.7 versus 13.95 +/- 23.3, respectively. Glasgow Coma Scale score improvements in the survivors were 0.81 +/- 1.5 and 1.16 +/- 1.7 in the treated and control groups, respectively. Hemolysis (generally subclinical) was the only adverse effect of glycerol noted. CONCLUSIONS: In the absence of any clinically or statistically significant difference in outcome between the treated and control groups, this trial provides no justification for glycerol therapy following acute cerebral hemorrhage.

Acute Disease

Lack of association between slow acetylator status and spontaneous lupus erythematosus.

The Chinese in Southeast Asia are recognized as a population group that has a relatively high prevalence of rapid "acetylators" and a relatively high incidence of systemic lupus erythematosus. This study was designed to evaluate the possibility that there were environmental lupus erythematosus provocative substances eliminated by acetylation that resulted in a preponderance of slow acetylators among patients with the disease. We compared acetylator status in 36 Chinese women with mild, stable, and confirmed lupus erythematosus and 36 healthy control subjects matched for age, sex, and ethnic origin. Acetylator status was determined by use of HPLC to assay 5-acetylamino-6-formylamino-3-methyluracil/methylxanthine (AFMU/MX) and AFMU/(AFMU + MX) ratios in urine 1 to 4 hours after drinking a strong cup of coffee (caffeine). By use of parametric and nonparametric methods of analysis, the frequency distribution of AFMU/MX and AFMU/(AFMU + MX) ratios in both the patients and control subjects were determined to be very similar. Thus there was no association between slow acetylator status and lupus erythematosus in the study subjects.

Acetylation

Investigation of intravascular haemolysis during treatment of acute stroke with intravenous glycerol.

1. In patients with acute strokes entering a large ongoing randomised double-blind controlled trial of intravenous glycerol therapy, the extent and pathogenesis of any ensuing haemolysis were evaluated using standard clinical investigations and in vitro techniques. 2. Twenty patients received 10% glycerol in saline (500 ml over 4 h on 6 consecutive days) and 15 received corresponding control treatment with saline. 3. Intravascular haemolysis was evident after the first infusion; compared with the controls the glycerol group had i) a greater mean reduction in serum haptoglobin concentration (P less than .05), and ii) a greater proportion exhibiting haemoglobinaemia (P = 0.03). 4. After 6 days of glycerol treatment, the mean reduction in haemoglobin concentration was only 0.8 g more than in controls; this difference being neither clinically nor statistically significant. 5. Glycerol therapy was not associated with haemoglobinuria, renal insufficiency or disseminated intravascular coagulation. 6. Exposure of red blood cells to 1-10% glycerol in vitro did not induce haemolysis per se; on re-exposure to lower concentrations lysis ensued provided a minimum osmotic gradient was present. 7. Whilst taking standard dosage regimes of glycerol, the stroke patients we studied manifested a degree of intravascular haemolysis but its consequences were not clinically significant; lysis probably ensued after venous blood acquiring high glycerol concentrations mixed with blood containing little or no glycerol.

Acute Disease

Pattern of anti-asthmatic drug utilization in Hong Kong compared to other parts of the world.

Inhaled drugs are now considered first line agents for the treatment of asthma, whereas oral beta-agonists, theophylline and its derivatives have been relegated to a secondary role. To determine whether current prescribing in Hong Kong conforms to these recommendations, we have evaluated anti-asthmatic drug utilization in the territory as reflected by 1984-86 drug sales (courtesy Medical and Health Department, Hong Kong). Sales/prescription statistics were also obtained from corresponding agencies of other governments and from published literature. If appropriate, data for comparison was expressed as defined daily doses (DDDs) per 1000 inhabitants per day. In contrast to the pattern of utilization in several developed nations, in Hong Kong (a) oral anti-asthmatic agents (particularly beta agonists) were more commonly utilized than inhaled drugs, and (b) inhaled therapy mainly consisted of non-selective beta-agonists, steroids being very rare. Further education is required to improve anti-asthmatic drug utilization patterns in the community.

Asthma

Cephalosporin and aminoglycoside utilization in different parts of the world.

Cephalosporin and aminoglycoside utilization in Hong Kong during 1984, 1985 and 1986, were evaluated from wholesale data and compared with corresponding Swedish statistics and with UK data from a survey of non-hospital prescriptions. Details regarding each drug and category were collated, adjusted for population and if appropriate expressed as defined daily doses (DDDs)/1000 inhabitants/day. With respect to cephalosporins: (a) overall sales (especially those of the newer and more expensive parenteral drugs) were increasing; (b) parenteral sales were much larger in Hong Kong hospitals than in the community (up to about 106 versus 16 kg/million inhabitants/year respectively), but in Sweden they were comparable (up to about 38 and 41 kg/million inhabitants/year respectively); (c) non-hospital oral utilization appeared greater in the UK than in Sweden and Hong Kong (up to about 0.7, 0.4 and 0.4 DDDs/1000 inhabitants/day respectively); (d) oral sales to hospitals were greater in Hong Kong than Sweden (up to 0.3 compared to 0.1 DDDs/1000 inhabitants/day respectively) and (e) oral paediatric formulations (liquids) were most popular in Hong Kong, a higher proportion of children in Hong Kong being one possible reason. Non-hospital sales of gentamicin and kanamycin in Hong Kong were much greater than in Sweden (up to about 0.20 and 0.06 vs. 0.01 and 0.00 DDDs/1000 inhabitants/day respectively), whereas UK utilization appeared almost non-existent. Topical neomycin sales in Hong Kong were much more popular than in Sweden (up to about 60 vs. 9 g/million inhabitants/day). These regional differences in antibiotic utilization may be related to respective health care systems (and thus the affordability and availability of drugs) and prescribing preferences (cultural and/or promoted by drug companies), quite apart from possible differences in drug efficacy, drug tolerance and the prevalence and severity of various infections.

Aminoglycosides

Fulminant hyperpyrexia induced by bleomycin.

Mild and self-limiting fever following bleomycin use is common, and a fatal hyperpyrexial response occurs rarely. In previously reported cases, such hyperpyrexia occurred either after the initial administration of the drug or during subsequent therapy following an initial pyrexial response. We describe a fatal hyperpyrexial reaction after bleomycin in a patient with T-cell lymphoma who had had no febrile response when she received her initial injection 3 weeks earlier. Since the occurrence of this hyperpyrexial response is unpredictable, health care workers as well as patients and relatives should always be alert to this potentially lethal complication and prompt measures should be taken in any patient who develops fever after bleomycin use.

Adult

Differences in diazepam pharmacokinetics in Chinese and white Caucasians--relation to body lipid stores.

We have compared diazepam pharmacokinetics in 16 Chinese and 18 white Caucasian healthy male volunteers, resident in Hong Kong and have correlated them with physical attributes. Serum concentrations of diazepam and desmethyldiazepam were measured in venous blood by an enzyme-linked immunoassay (0-3 h samples) and HPLC (3-72 h samples). Pharmacokinetic parameters were derived assuming a two compartment model, distribution phase less than 6 h, and 100% oral systemic availability. Compared with the Chinese the white Caucasians were older, heavier, taller, and fatter, as judged by skin fold thickness (SFT) and total body weight to 'Ideal' body weight (TBW/IBW) ratio; respective mean differences being 16%, 27%, 4%, 26%, and 15% (p less than 0.05). Mean diazepam apparent volume of distribution (V) and V/IBW were larger in the white Caucasians (52% & 39% respectively, p = 0.002). SFT and TBW/IBW ratio yielded the best correlations with V, V/TBW and V/IBW (0.50-0.75, p less than 0.05). Obesity indices contributed most to the overall regressions (R2 up to 0.52), and for V there was a further small effect (2%, partial F test) due to ethnic group, possibly reflecting stature. Mean peak diazepam concentration (Cmax) was similar in both ethnic groups. Time to Cmax (tmax) was more often prolonged in the Chinese (chi 2 test, p = 0.01). Body fat and stature may thus account for these inter-ethnic differences in the apparent volume of distribution of diazepam, a highly lipid-soluble drug.

Adult

Chemoprophylaxis with oral amoxycillin against bacterial endocarditis: when should second doses be administered after dentistry?

The adequacy of serum bactericidal activity after oral amoxycillin given as prophylaxis against infective endocarditis was studied using a double blind randomised protocol in healthy volunteers having dentistry. One hour before their procedure 38 patients received 3 g amoxycillin syrup and 12 received matching placebo. Venous blood samples were drawn before and one and nine hours after dosing and serum amoxycillin concentrations determined using a standard bioassay. Samples containing amoxycillin had inhibitory titres measured against two reference isolates of viridans streptococci known to have caused infective endocarditis. The susceptibility to amoxycillin of one strain was high and the other low, respective minimal bactericidal and inhibitory concentrations being 0.08 and 0.04 mumol/l (0.03 and 0.015 microgram/ml) and 2.74 and 1.37 mumol/l (1 and 0.5 microgram/ml). Amoxycillin was detected in only post-treatment samples of patients given the active drug. There were no significant correlations between one or nine hour drug concentrations and age or physical characteristics, nor was there any relation to preceding food consumption. Correlations between drug concentrations at one and nine hours were weak (r = 0.34; p less than 0.05), but between corresponding drug concentrations and serum inhibitory titres there were consistent correlations (r = 0.46-0.48; p less than 0.005). Against the low susceptibility reference isolate bactericidal amoxycillin concentrations were encountered in only 20 of the 38 nine hour samples (95% confidence limits 34% and 66%). When repeat doses of amoxycillin are indicated after dentistry they should be given about four hours later, not eight hours later as commonly practised.

Administration, Oral

A class experiment in clinical pharmacology using beta-adrenoceptor antagonist drugs.

Cardiac beta-adrenoceptor blocking activity was evaluated in a between-subject study carried out as a class experiment with pre-clinical medical students participating in a practical pharmacology course. From each of 10 groups of students, three healthy male volunteers, took oral propranolol 80 mg, pindolol 10 mg or placebo, according to a double-blind randomised protocol. Pre-treatment, and 45-60 min (1 h) and 105-120 min (2 h) post-treatment heart rate (HR) was determined electrocardiographically in the last 15 s during periods of rest (sitting for 5 min), isometric exercise (applying a standardized hand grip to a rolled sphygmomanometer cuff to elevate pressure from 50 to 150 mm Hg; 2 min) and dynamic exercise (bicycle ergometry with a load of 150 W for 3 min). Reductions from pre-treatment HR yielded statistically significant differences during exercise (isometric and dynamic) between all corresponding changes on placebo and active drugs (P less than 0.05-0.01), except with the 1 h post-propranolol hand grip HR. At rest, only the difference between 2 h HR changes on placebo and propranolol achieved statistical significance (P = 0.05); presumably, the partial agonist activity of pindolol overcame any minimal HR slowing liable to occur at rest. Cardiac beta-adrenoceptor blocking activity as judged by reductions in HR from pretreatment values, was more evident during cycling than during hand grip; and during hand grip than at rest.

Adrenergic beta-Antagonists

Selectivity of beta adrenoreceptor antagonist drugs assessed by histamine bronchial provocation.

In a double-blind, within-patient, randomized study, 12 mild asthmatics were given single oral doses of propranolol (80 mg), metoprolol (100 mg), timolol (10 mg), or placebo. Resting heart rate and forced expiratory volume in one sec (FEV1) were measured before and 90 min after treatment. Nonspecific bronchial reactivity was measured by inhaled histamine at 90 min. Following each active drug, resting heart rate changed to a similar extent and to a greater degree than after placebo (p less than 0.01). Changes in FEV1 were small and not different from those after placebo. In contrast, after each active drug, bronchial reactivity increased more than after placebo. The degree of reactivity with each active drug was similar but the differences from corresponding placebo values were significant (p less than 0.05). We conclude that, in mild asthmatics, nonspecific bronchial reactivity is a more sensitive index of airway effects than resting FEV1. Moreover, in the context of this study, since the beta-blockers were given in doses likely to induce equivalent cardiac beta-blockade, there is no evidence to suggest that any one of them is more "cardioselective" than the others.

Adolescent