Pharmacokinetics--a relevant factor for the choice of a drug?

Pharmacokinetics may be utilized as a tool in the drug development process, either with respect to therapeutics or in allowing a drug's disposition characteristics to be defined. If two drugs of the same class have a similar dose-efficacy profile, then the favourable/unfavourable balance of the pharmacokinetic characteristics of the drugs may determine the drug of choice. Pantoprazole, a proton pump inhibitor, appears to meet the above criteria and has been found to exhibit reliable, predictable pharmacokinetic characteristics as opposed to other members of the class. The pharmacokinetics of pantoprazole over a range of intravenous and oral doses are described in healthy volunteers and are compared with values obtained for omeprazole. Studies in patients with severe cirrhosis, renal failure, and in the elderly are also described as well as potential interactions due to food and five other drugs.     

In vivo study of degradation of poly-(D,L-) lactide and poly-(L-lactide-co-glycolide) osteosynthesis material]

AIMS. Comparison of the degradation of poly(D,L)lactide (Resorb X) or poly(lactide-co-glycolide) (LactoSorb) in vivo. MATERIAL AND METHODS. LactoSorb and Resorb X osteosynthesis plates were fixed at the lateral aspect of the femora of 26 Chinchilla rabbits using the respective osteosynthesis screws. After intraperitoneal injection of fluorochromes the screw plate bone blocks were resected after 1, 6, 12, 14, 16, 21, 26 months and radiologic, histologic as well as fluorescence microscopic examinations were carried out. RESULTS. Newly formed bone was detectable above and beneath the polymers 1 month after the implantation. The implants were totally covered by newly formed bone after 6 months. While the LactoSorb screws were found to be as birefringent as after 1 month, in the Resorb X screws a continuous resorption by phagocytizing marrow cells starting from the periphery was detectable. Resorb X was totally resorbed in histologic slides 12 months after implantation, while total resorption of LactoSorb lasted 14 months; both polymers were replaced by marrow cells. Bone remodeling was not finished 26 months after implantation in both polymers. CONCLUSION. Resorption of Resorb X was finished earlier than the resorption of LactoSorb. Both materials were found by fluorescence microscope to be completely resorbed after 12 or 14 months, but bone remodeling of the screw holes was not yet finished 26 months after implantation.     

Ist Radio(chemo)therapie wirklich der zukünftige Standard für die Behandlung von Oropharynxkarzinomen?

Treatment of patients with oropharyngeal squamous cell carcinoma (OPSCC) requires interdisciplinary collaboration. Besides oncologic control, organ and function preservation are important priorities. One treatment option is primary concomitant chemoradiotherapy (CRT), particularly for locally advanced head and neck cancer. Another option is sequential CRT, where induction chemotherapy may be followed either by radiation alone or by CRT. An important aspect of these modalities is the development of functional sequelae with regards to swallowing as a direct consequence of radiogenic fibrosis, as well as tissue ctoxicity associated with cisplatin-based chemotherapy. Conventional open surgical approaches are being increasingly replaced by transoral surgical modalities with less treatment-related morbidity. As a further, equally important goal of appropriately indicated surgery, adjuvant (C)RT may be omitted or the dose significantly reduced. The advantages of primary surgery over primary CRT may be less obvious in cases still requiring adjuvant treatment, although not necessarily completely eliminated. For patients with human papillomavirus (HPV)-driven OPSCC, it is important to note that primary surgery may provide comparable or even increased survival benefit. To date, there is no evidence for a clear advantage of primary CRT over primary surgery in this group. In these cases, a de-escalated treatment package may be the preferred option. Here, the application of radioimmunotherapy as well as a reduced radiation dose may minimize long-term treatment-related morbidities.     

Physical fitness in people with a spinal cord injury: the association with complications and duration of rehabilitation

OBJECTIVE: To assess the association between physical fitness and its recovery over time on the one hand, and complications and duration of phases of rehabilitation on the other. DESIGN AND SETTING: Prospective cohort study at eight rehabilitation centres. SUBJECTS: People with a spinal cord injury were assessed four times: at the start of active rehabilitation (n = 110), three months later (n = 92), at discharge (n = 137) and a year after discharge from inpatient rehabilitation (n = 91). MAIN MEASURES: Physical fitness was defined as aerobic capacity, determined at each occasion by the peak oxygen uptake (peak Vo(2); L/min) and the peak power output (peak PO; W) during a maximal exercise test. On these occasions, spasticity, musculoskeletal and neurogenic pain were determined (1 = present; 0 = absent). During inpatient rehabilitation, complications (urinary tract infection, pulmonary infection or pressure sore) and bed rest were registered (1 = complication; 0 = no complications, and 1 = bed rest; 0 = no bed rest). Complications and bed rest occurring during the year after discharge were registered similarly. RESULTS: Multilevel random coefficient analyses revealed associations in multivariate models (P 相似文献   

Reduction of creatine kinase and creatine kinase-MB indexes of infarct size by intravenous verapamil

In a prospective, controlled study, 29 patients were randomly allocated to receive intravenous verapamil, 5 to 10 mg/hour, for 2 days starting at a mean of 8 hours after the onset of myocardial infarction. Twenty-five patients received no specific treatment and served as control subjects. Left ventricular (LV) filling pressure in all patients was initially less than 15 mm Hg. Age, infarct localization and hemodynamic values on admission (Swan-Ganz catheter) were comparable in both groups. Maximal creatine kinase (CK) and creatine kinase-MB (CK-MB) values were markedly lower in the verapamil group than in the control group (CK 547 vs 703 U/liter, p less than 0.05; CK-MB 51 vs 68 U/liter, p less than 0.025), as was infarct weight (48 vs 65 g-Eq, p less than 0.03; CK-MB 31 vs 49 g-Eq, p less than 0.005). Arterial blood pressure was 10% lower in the verapamil group than in the control group. Systemic vascular resistance and LV filling pressure remained unchanged. Verapamil reduced myocardial infarction size by about 30% in patients without LV failure and the arterial pressure was reduced.