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1.
Quinidine kinetics after a single oral dose in relation to the sparteine oxidation polymorphism in man. 总被引:6,自引:5,他引:1 下载免费PDF全文
The kinetics at a single oral dose (400 mg) of quinidine were studied in four extensive metabolizers (EM) and four poor metabolizers (PM) of sparteine. The clearance of quinidine by 3-hydroxylation was significantly lower in PM than in EM, but the difference was small (25-30%). This finding suggests that 3-hydroxylation, in part, is catalyzed by the same isoenzyme of cytochrome P450, P450db1 which oxidizes sparteine. Otherwise, no significant phenotypic differences in total or metabolic clearance were found and it is concluded that the metabolism of quinidine is largely carried out by P450 isoenzymes different from P450db1. A biexponential decline in the log plasma quinidine concentration vs time curves was observed in all subjects, and the mean elimination half-life was 11-12 h. This is about twice as long as generally reported in the literature. 相似文献
2.
M Kirchhoff M Davidsen H Br?nnum-Hansen B Hansen H Schnack L S Eriksen M Madsen M Schroll 《International journal of epidemiology》1999,28(2):211-218
BACKGROUND: Cardiovascular mortality has been declining in Denmark over the past 20 years. Trends in incidence of myocardial infarction (MI) over the period 1982-1991 are described within the framework of the World Health Organization MONICA Project. METHODS: The DAN-MONICA heart register included all cases of MI in 25-74-year-old men and women living in 11 municipalities around Glostrup County Hospital evolving over a period of 10 years. They were identified retrospectively based mainly on relevant ICD diagnoses in death certificates and hospital discharge reports. Cases meeting WHO-MONICA criteria for definite or possible MI, recurrent as well as first-ever MI, were registered. Subsequent tracing of cases through national registers on deaths and hospitalizations by means of the patient's civil registration number ensured the completeness of the registration. RESULTS: A total of 6025 cases of MI occurred in the period, 4532 among men and 1493 among women. A total of 2923 men and 1047 women had a first-ever MI in the period. The age-standardized rates show a definite decline over the registration period for men and a less distinct decline for women. CONCLUSIONS: The DAN-MONICA heart register meets the requirements for completeness and uniformity throughout the registration period. Causes and magnitude of bias are well described. Even when possible sources of bias are taken into account, the incidence of MI decreased significantly over the 10-year-period 1982-1991 by an average of 5.0% per year for men and 3.5% per year for women. 相似文献
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Summary The chest radiographs of 309 patients with rheumatoid arthritis (RA) were compared with those of 309 controls matched for sex and age. Cardiac enlargement was more frequent in RA females than in controls (P<0.05) and the frequency of aortic shadow enlargement was higher in RA patients aged 60 years than in controls (P<0.05). Both cardiac and aortic enlargement was significantly related to several parameters of the severity and the activity of RA, corticosteroid therapy, and elevated blood pressure. A high mortality was present in patients with aortic enlargement and in patients with ECG signs of myocardial ischaemia. 相似文献
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Anne-Sofie Caroline Jensen Christoffer Polcwiartek Peter Søgaard Rikke Nørmark Mortensen Line Davidsen Mette Aldahl Matilde Alida Eriksen Kristian Kragholm Christian Torp-Pedersen Steen Møller Hansen 《The American journal of medicine》2019,132(2):200-208.e1
Background
Patients with chronic heart failure have vulnerable myocardial function and are susceptible to electrolyte disturbances. In these patients, diuretic treatment is frequently prescribed, though it is known to cause electrolyte disturbances. Therefore, we investigated the association between altered calcium homeostasis and the risk of all-cause mortality in chronic heart failure patients.Methods
From Danish national registries, we identified patients with chronic heart failure with a serum calcium measurement within a minimum 90 days after initiated treatment with both loop diuretics and angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers. Patients were divided into 3 groups according to serum calcium levels, and Cox regression was used to assess the mortality risk of <1.18 mmol/L (hypocalcemia) and >1.32 mmol/L (hypercalcemia) compared with 1.18 mmol/L–1.32 mmol/L (normocalcemia) as reference. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated.Results
Of 2729 patients meeting the inclusion criteria, 32.6% had hypocalcemia, 63.1% normocalcemia, and 4.3% hypercalcemia. The highest mortality risk was present in early deaths (≤30 days), with a HR of 2.22 (95% CI; 1.74-2.82) in hypocalcemic patients and 1.67 (95% CI; 0.96-2.90) in hypercalcemic patients compared with normocalcemic patients. As for late deaths (>30 days), a HR of 1.52 (95% CI; 1.12-2.05) was found for hypocalcemic patients and a HR of 1.87 (95% CI; 1.03-3.41) for hypercalcemic patients compared with normocalcemic patients. In adjusted analyses, hypocalcemia and hypercalcemia remained associated with an increased mortality risk in both the short term (≤30 days) and longer term (>30 days).Conclusion
Altered calcium homeostasis was associated with an increased short-term mortality risk. Almost one-third of all the heart failure patients suffered from hypocalcemia, having a poor prognosis. 相似文献7.
Anders Bork Davidsen Marie Mardal Sys Stybe Johansen Petur Weihe Dalsgaard Kristian Linnet 《Drug testing and analysis》2020,12(7):987-993
The new psychoactive substance (NPS) 3‐HO‐PCP, a phencyclidine (PCP) analog, was detected in a law enforcement seizure and in forensic samples in Denmark. Compared with PCP, 3‐HO‐PCP is known to be a more potent dissociative NPS, but no toxicokinetic investigations of 3‐HO‐PCP are yet available. Therefore, 3‐HO‐PCP was quantified in in vivo samples, and the following were investigated: plasma protein binding, in vitro and in vivo metabolites, and metabolic targets. All samples were separated by liquid chromatography and analyzed by mass spectrometry. The unbound fraction in plasma was determined as 0.72 ± 0.09. After in vitro incubation with pooled human hepatocytes, four metabolites were identified: a piperidine‐hydroxyl‐and piperidine ring opened N‐dealkyl‐COOH metabolite, and O‐glucuronidated‐ and O‐sulfate‐conjugated metabolites. In vivo, depending on the sample and sample preparation, fewer metabolites were detected, as the O‐sulfate‐conjugated metabolite was not detected. The N‐dealkylated‐COOH metabolite was the main metabolite in the deconjugated urine sample. in vivo analytical targets in blood and brain samples were 3‐HO‐PCP and the O‐glucuronidated metabolite, with 3‐HO‐PCP having the highest relative signal intensity. The drug levels of 3‐HO‐PCP quantified in blood were 0.013 and 0.095 mg/kg in a living and a deceased subject, respectively. The 3‐HO‐PCP concentrations in deconjugated urine in a sample from a living subject and in post‐mortem brain were 7.8 and 0.16 mg/kg, respectively. The post mortem results showed a 1.5‐fold higher concentration of 3‐HO‐PCP in the brain tissue than in the post mortem blood sample. 相似文献
8.
Jasinghe VJ Xie Z Zhou J Khng J Poon LF Senthilnathan P Glaser KB Albert DH Davidsen SK Chen CS 《Journal of hepatology》2008,49(6):985-997
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