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C R Kumana

Publications and source records attributed to C R Kumana.

At least 19 recordsLinked to original sources
PubMed2006

Meta-analysis of large outcome trials of angiotensin receptor blockers in hypertension.

Angiotensin receptor blockers (ARBs), also known as sartans, block the activation of angiotensin type 1 receptors and have a recognised role in the treatment of heart failure and nephropathy. Since 2002, there have been three major outcome trials of ARBs in hypertension. We performed a meta-analysis to evaluate the impact of ARB on major outcomes. Randomised controlled trials of ARBs in hypertensive subjects with an average follow-up of at least 2 years and at least 100 major cardiovascular events were included. For each trial, the ARB used, number and characteristics of subjects, baseline and change in blood pressure, cardiovascular and noncardiovascular outcomes were recorded. Three trials involving 29 375 subjects were included in the meta-analysis. In Losartan Intervention For Endpoint (LIFE) and Study on Cognition and Prognosis in the Elderly (SCOPE) but not in Valsartan Antihypertensive Long-term Use Evaluation trial (VALUE), an ARB reduced the occurrence of the primary end point and stroke compared to control. Compared to other antihypertensive drugs, ARB treatment was associated with no significant change in all-cause mortality (relative risk ratio (RRR) 0.96, 95% CI: 0.88-1.06, P = 0.45). There was an increase in myocardial infarction (RRR, 1.12, 95% CI: 1.01-1.26, P = 0.041), but a decrease in new-onset diabetes mellitus (RRR, 0.80, 95% CI: 0.74-0.86, P < 0.0000001). In conclusion, the reduction in new-onset diabetes partly offsets any increase in the risk of myocardial infarction. Most hypertensive patients require more than one class of drugs. Small differences in treatment outcome should not over-ride the importance of good blood pressure control.

Aged↗
PubMed2004

Chloramphenicol succinate, a competitive substrate and inhibitor of succinate dehydrogenase: possible reason for its toxicity.

From our previous study [Eur. J. Clin. Pharmacol. 56 (2000) 405] we hypothesized that chloramphenicol succinate (CAPS) may be a competitive substrate for succinate dehydrogenase (SDH). It may be oxidized by SDH to release chloramphenicol (CAP), which may inhibit SDH by feed back mechanism. The present ex-vivo/in vitro study was aimed to investigate this possibility by using human tissues (bone marrow and liver samples) and animal tissues (rat liver and kidney). The effect of different SDH activators and specific inhibitors was studied on CAPS metabolism by SDH. The metabolites and reduction products were detected by using HPLC. In marrow samples, CAPS was slowly oxidized to form CAP. The formation of CAP (oxidation product) was enhanced by FAD and low malonate and inhibited by high malonate and 3-NPA. Similar results were obtained with mitochondria from human and rat tissues. These studies suggest that CAPS could be a competitive oxidative substrate and the metabolite CAP could be an inhibitor at the reduction site. Therefore, SDH could be a target molecule responsible for CAPS induced toxicity.

Animals↗
PubMed2004

Long-term combination therapy with aspirin and clopidogrel.

The possible additive antiplatelet effects of aspirin and clopidogrel have been explored in the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) and Management of Atherothrombosis with Clopidogrel in High Risk Patients (MATCH) studies. To assess the overall absolute beneficial and/or harmful impact of aspirin and clopidogrel combination therapy compared with monotherapy with either drug, we analyzed the results from both trials in terms of number needed to treat per year. Treating between 35 and 204 at-risk patients for 1 year with combination therapy appeared to prevent 1 patient from experiencing an adverse primary cardiovascular outcome; whereas, about 1 in 63 such patients appeared liable to major bleeding during that period. We determined that the evidence to date indicates no overall advantage for combination therapy with anti-platelet drugs in preference to monotherapy.

Angina, Unstable↗
PubMed2004

Increased adrenomedullin expression in lungs in endotoxaemia.

Adrenomedullin (AM) is a peptide involved in cardiovascular homeostasis and in inflammation. We examined its expression in a rat model of endotoxaemia. Male Sprague-Dawley rats received intraperitoneal injection of 5 or 10 mg/kg lipopolysaccharide (LPS), or saline as control. Rats were killed at 1, 3, 6, 12 and 24 h after injection. LPS at 5 mg/kg, but not saline, increased plasma AM significantly at 3 h. At 10 mg/kg, plasma AM was raised at 3, 6 and 12 h. Immunoreactive AM concentration in lung increased after 5 or 10 mg/kg LPS, but not saline. PreproAM mRNA level in lung was significantly increased at 3 and 6 h. In conclusion, endotoxin stimulates the expression of AM in the lungs and increases its circulatory concentration. AM may be involved in the systemic response to sepsis.

Adrenomedullin↗
PubMed2002

Systemic availability of arsenic from oral arsenic-trioxide used to treat patients with hematological malignancies.

AIMS: Arsenic trioxide (As2O3) is increasingly used to treat hematological malignancies. This involves daily intravenous (i.v.) administration for 4-8 weeks, with its attendant drawbacks: inconvenience, risks and expense of maintaining suitable vascular access and hospitalization. We therefore developed an oral formulation, administered it to patients and set out to assess the resulting systemic bioavailability of arsenic. METHODS: With ethics committee approval, nine patients with refractory/relapsed acute myeloid leukemia were recruited after giving informed consent. On day 1, each received 10 mg As2O3 by i.v. infusion over 1 h. Each patient swallowed 10 mg As2O3 in 10 ml oral solution 24 h later (day 2) and on subsequent days thereafter. Prior to and until 48 h post-i.v. dosing, timed venous blood samples were drawn and corresponding plasma and whole blood arsenic concentrations were determined by atomic absorption spectroscopy. Systemic bioavailability was inferred from the area under the arsenic level versus time curve (AUC) using the trapezoidal rule. Day-1 AUC after i.v. dosing was taken to be 100% and that attributed to oral dosing (day 2) was then calculated. The 48-h arsenic levels in blood cells were calculated using hematocrit values and corresponding plasma and whole blood arsenic concentrations. RESULTS: Respective day-2 mean plasma and blood AUCs attributed to oral dosing were 99% and 87% of corresponding day-1 values. On average, 48-h blood cell arsenic levels were 270% greater than in plasma ( P=0.013). No patient suffered unexpected complications, and five went into remission. CONCLUSIONS: Compared with i.v. dosing, our oral As2O3 formulation was more convenient and cost effective, and the ensuing systemic bioavailability of arsenic appeared similar. Arsenic seemed to be concentrated in the cellular fraction of blood 48 h after starting As2O3 treatment.

Acute Disease↗
PubMed2001

Curtailing unnecessary vancomycin usage in a hospital with high rates of methicillin resistant Staphylococcus aureus infections.

AIMS: To implement and monitor the effectiveness of a strategy to curb unnecessary use of vancomycin and teicoplanin for inpatients in a teaching hospital/tertiary referral centre where 33% of S. aureus isolates (72% from ICU patients) were methicillin resistant. METHODS: A sample of 182 vancomycin/teicoplanin inpatient prescriptions surveyed, revealed that only 31 (17%) conformed with Centre for Disease Control (CDC) guidelines. Following education (ward-rounds, bulletins) on appropriate CDC based guidelines for prescribing glycopeptides directed at relevant clinicians, 'Immediate Concurrent Feedback' (ICF) was gradually deployed throughout the hospital. This entailed review of respective inpatient records on the next working day. If the indication was deemed not to conform with our guidelines, the prescriber was issued a memo (copied to the supervising doctor). Each memo detailed the 'errant' incident, listed appropriate indications and explicitly advised desisting from such prescribing and suggested alternative therapy if necessary. Corresponding glycopeptide usage data for our hospital and others in Hong Kong were retrieved and analysed as were samples of records of our inpatients with staphylococcal septicaemia (pre and during ICF). RESULTS: Compared with baseline values, during 2 years of ICF, inpatient prescribing of vancomycin and teicoplanin deemed to conform increased to 71% (773/1086); difference 54% (P < 0.0001, 95% CIs 47-62%). Corresponding average monthly usage (DDDs/1000 admissions) decreased from 76 (pre-ICF) to 45; mean difference 31 (P < 0.0001, 95% CIs 24, 38). Mortality from staphylococcal bacteraemia remained unchanged. No comparable changes in glycopeptide usage ensued in comparator hospitals. CONCLUSIONS: ICF can be used safely to curb irrational overuse of vancomycin and teicoplanin in a hospital with high methicillin resistant S. aureus infection rates.

Anti-Bacterial Agents↗
PubMed2001

Increasing use of inhaled steroids associated with declining asthma mortality.

Increasing worldwide asthma prevalence and mortality has led to greater advocacy of inhaled agents, especially steroids. To determine whether corresponding drug usage trends had ensued locally, wholesale data (expressed as defined daily doses (DDDs)/1000 inhabitants/day) were compared for inclusive periods 1984-1986 and 1992-1994. Whereas absolute usage of anti-asthmatics increased by 79%, proportional inhaled usage increased markedly, especially of steroids (571%) and in hospitals. An odds ratio trend analysis revealed asthma mortality from 1992 onward had declined, particularly in males (p < 0.001). In Hong Kong, despite increasing asthma prevalence, more intensive use of anti-asthmatic drugs (especially inhaled steroids) was associated with declining asthma mortality.

Administration, Inhalation↗
PubMed2001

Cost-effectiveness analysis of applying the Cholesterol and Recurrent Events (CARE) study protocol in Hong Kong.

OBJECTIVE: To determine the cost-effectiveness of secondary prevention with pravastatin in Hong Kong patients with coronary heart disease and average cholesterol levels. DESIGN: Cost-effectiveness analysis based on published results of the CARE study. PATIENTS: Men and women post-myocardial infarction with average cholesterol levels. MAIN OUTCOME MEASURES: Cost-effectiveness analysis: cost per life saved, cost per fatal or non-fatal coronary event prevented, cost per procedure prevented, and cost per fatal or non-fatal stroke prevented. Cost-utility analysis: gross cost and net cost per quality-adjusted life year gained calculated using two alternative models. RESULTS: Cost per life saved or death prevented was HK$4,442,350 (non-discounted); cost per fatal or non-fatal cardiac event prevented HK$1,146,413; cost per procedure prevented HK$732,759; and cost per fatal or non-fatal stroke prevented HK$2,961,566. Net cost per quality adjusted life year gained was HK$73,218 and HK$65,280 non-discounted, respectively using the two alternative models. CONCLUSIONS: The results of this study can assist in prioritising the use of health care resources in Hong Kong but should be considered alongside the benefits and costs of alternative interventions for coronary heart disease.

Adult↗
PubMed2000

Metabolism of chloramphenicol succinate in human bone marrow.

OBJECTIVE/METHODS: The metabolism of chloramphenicol succinate (CAPS) by human bone marrow was studied in vitro using 75 marrow samples. Whole marrow samples were incubated with CAPS with or without reduced nicotinamide adenine dinucleotide phosphate for 1, 2 and 3 h at 37 degrees C. Ficoll-paque-separated marrow mononuclear cells and erythrocytes were similarly incubated. After precipitation and centrifugation, clear supernatant was analysed for the presence of metabolites using high-performance liquid chromatography. RESULTS: Only one metabolite was detected when CAPS was incubated for 3 h with whole marrow from 72 donors. Its retention time (RT 10.9 min) corresponded to chloramphenicol (CAP). When CAPS was incubated with samples of whole marrow, marrow mononuclear cells, marrow erythrocytes, marrow plasma and peripheral blood from one donor who had taken Traditional Chinese Medicine (TCM), three metabolite peaks were detected within 15 min to 1 h. The RT of two of these peaks corresponded to CAP and nitroso-CAP (RT 14.9 min), but one peak remained unidentified. These peaks were not detected in the control samples incubated without CAPS. Blood samples collected after 3 months and 6 months to reconfirm metabolic activity yielded no such metabolite peaks when incubated with CAPS for 1-3 h. Therefore induction of enzyme activity by TCM was suspected. Three metabolite peaks with the same RTs were also detected when CAPS was incubated for 3 h with whole marrow from two other donors. CONCLUSION: These studies demonstrated that CAPS may be metabolised to CAP and occasionally other metabolites in human bone marrow. This novel observation is particularly important because the bone marrow is known to be a target organ for chloramphenicol toxicity.

Bone Marrow↗