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151.
Hovgaard Lars Brøndsted Helle Buur Anders Bundgaard Hans 《Pharmaceutical research》1995,12(3):387-392
A series of O-cyclopropane carboxylic acid ester prodrugs of various -blocking agents was synthesized. All prodrugs were hydrolyzed to give their parent compounds in aqueous phosphate buffer of pH 7.4 and in 80% human plasma. The half-lives in buffer solutions varied from 4 hours for the timolol prodrug to about 1 day for the prodrug of alprenolol. In human plasma the half-lives were shorter, ranging from 1 to 7 hours. The formation of the O-cyclopropane carboxylic acid ester derivatives significantly increased the lipophilicities of the -blockers as measured by the distribution coefficient between n-octanol and aqueous phosphate buffer of pH 7.4. To characterize the biomembrane permeability characteristics of the -blockers, transport properties across Caco-2 cell monolayers were investigated. An increase in lipophilicity resulted in a higher permeability of the prodrugs as compared to the parent compounds. Hence, acebutolol experienced an increment of a factor 17 on the apparent permeability coefficient, Papp, whereas Papp for the more lipophilic drug propranolol was increased by a factor of only 1.26. Some conversion of the prodrugs to their parent compounds was observed during the transport and appeared to be due to enzymatic intracellular metabolism.Deseaced. 相似文献
152.
Claude P. Tousignant David R. Bevan Andrew A. Eisen John C. Fenwick Martin G. Tweedale 《Journal canadien d'anesthésie》1995,42(3):224-227
An 18-yr-old male asthmatic was paralyzed with atracurium for a period of seven days to facilitate mechanical pulmonary ventilation. After withdrawal of the muscle relaxant, train-of-four neuromuscular monitoring demonstrated rapid recovery of normal function. Three days later he developed acute quadriparesis without respiratory compromise. Electrophysiological studies showed normal conduction velocities, low compound muscle action potential amplitudes and evidence of denervation. Most cases of post-ventilatory weakness in the ICU involve the use of vecuronium and pancuronium. It has been suggested that the steroid nucleus in these muscle relaxants may be responsible. Our patient developed generalised weakness after treatment with atracurium, a benzylisoquinolinium muscle relaxant. Thus, it appears that the steroid nucleus of vecuronium and pancuronium is not essential in causing post-ventilatory weakness. 相似文献
153.
Pharmacokinetics of thiopental after single and multiple intravenous doses in critical care patients
H. Russo J. Brès M. P. Duboin B. Roquefeuil 《European journal of clinical pharmacology》1995,49(1-2):127-137
Thiopental was administered to neurosurgical patients for cerebral protection and its pharmacokinetic parameters were determined after a single bolus of 540, 1000 or 1500 mg (3 subjects) or after multiple doses of 250 mg (5 subjects) and 500 mg (2 subjects) every two hours for up to 7 days. The data were analysed by a two- or three- compartment model and linear kinetics. After a single IV bolus, the mean initial volume of distribution (V1) was 0.4811·kg–1, and the steady-state volume of distribution (Vss) was 2.16 1·kg–1. The distribution (t1/2) and elimination (t1/2) half-lives were 0.590 and 5.89 h, respectively, and the mean residence time (MRT) was 7.44 h. The clearance was 5.41 ml·min–1·kg–1. With repeated injections, the pharmacokinetic parameters for each patient were estimated taking into account all administered doses and blood samples, which were taken whenever possible daily at steady state and after the last dose. The variability observed in the pharmacokinetic parameters of thiopental reflected by the coefficient of variation (CV%) was wide but was of similar magnitude within patients (CVintra) as it was between patients (CVinter). The steady-state trough plasma concentration (Cmin obs) ranged from 4.8 to 30 mg·1–1 (mean 16.0 mg·1–1 and median 14.3 mg·1–1). Peak concentrations (Cmax obs) ranged from 8.35 to 45 mg·1–1 (25.4 mg·1–1, and median 23.3 mg·1–1). The values of V1 and Vss were similar to those obtained after a single dose. For V1, the mean was 0.333 1·kg–1. The mean Vss was 2.68 1·kg–1, with a CVintra of 12.6 to 56% and a CVinter of 13.2%. A shorter distribution half-life t1/2 was noted on multiple dosing; the mean value was 0.122 h. The elimination half-life t1/2 and the mean residence time became longer due to a decrease in clearance. For t1/2 the mean value was 16.3 h. The mean MRT was 21.9 h, CVintra 9.19 to 48.5%, and the CVinter 35.3%. The mean clearance was 2.16 ml·min–1·kg–1, CVintra 7.28 to 25.5%, and the CVinter 20.4%. This value is 50% lower than after a single dose.Identification of the kinetic parameters of thiopental allows simulation of the effects of doses on subsequent plasma levels and will permit a priori prediction of day to day adjustment of drug dosage. 相似文献
154.
Brain activation during dichotic presentations of consonant-vowel and musical instrument stimuli: a 15O-PET study 总被引:1,自引:0,他引:1
Dichotic listening means that two different stimuli are presented at the same time, one in each ear. This technique is frequently used in experimental and clinical studies as a measure of hemispheric specialization. The primary aim of the present study was to record regional changes in the distribution of cerebral blood flow (CBF) with the 15O-PET technique to dichotically presented consonant-vowel (CV) and musical instrument stimuli, in order to test the basic assumption of differential hemispheric involvement when stimuli presented to one ear dominate over stimuli presented in the other ear. All stimuli were 380 ms in duration with a 1000 ms interstimulus interval, and were presented in blocks of either CV-syllable or musical instrument pairs. Twelve normal healthy subjects had to press a button whenever they detected a CV-syllable or a musical instrument target in a stream of CV- and musical instrument distractor stimuli. The targets appeared equally often in the right and left ear channel. The CV-syllable and musical instrument targets activated bilateral areas in the superior temporal gyri. However, there were significant interactions with regard to asymmetry of the magnitude of peak activation in the significant activation clusters. The CV-syllables resulted in greater neural activation in the left temporal lobe while the musical instruments resulted in greater neural activation in the right temporal lobe. Within-subjects correlations between magnitude of dichotic listening and CBF asymmetry were, however, non-significant. The changes in neural activation were closely mimicked by the performance data which showed a right ear superiority in response accuracy for the CV-syllables, and a left ear superiority for the musical instruments. In addition to the temporal lobe activations, there were activation tendencies in the left inferior frontal lobe, right dorsolateral prefrontal cortex, left occipital lobe, and cerebellum. 相似文献
155.
This study aimed at developing a dual setup of the photothrombotic ring stroke model with or without late spontaneous reperfusion in the region at risk and to explore the morphological consequences. The exposed crania of adult male Wistar rats were subjected to a ring-shaped laser-irradiation beam (o.d. 5.0 mm, 0.35 mm thick) for 2 min simultaneously with intravenous erythrosin B (17 mg/kg) infusion. Transcardial carbon-black perfusion revealed that a laser intensity of 0.90 W/cm(2) resulted in late, that is, starting at 72 h, spontaneous reperfusion, whereas the lowest laser intensity that produced lack of reperfusion at 7 days post-irradiation was 1.84 W/cm(2). Laser-Doppler flowmetry showed prompt cortical cerebral blood flow (cCBF) reduction both in the ring lesion and region at risk (12% and 25% of control values) after high-intensity irradiation; these reduced flow values were more rapid and pronounced than in the low-intensity irradiation setup as previously shown. The high- compared with low-intensity irradiation setup produced more frequent occurrence of thrombi in the ring-lesion region and a larger ischemic cortical lesion with a more rapid pace of ischemic cellular changes in the ring-lesion region and the region at risk. The region at risk transformed into pannecrosis in the high-intensity, but recovered morphologically in the low-intensity irradiation setup. This dual photothrombotic setup with or without spontaneous reperfusion enables the study of events related to ischemic cell survival or death in an anatomically predefined region at risk. 相似文献
156.
Prediction of hospitalizations by schizophrenia patients' assessment of treatment: an expanded study
This study examines whether schizophrenia patients' global assessment of treatment predicts outcome in community care. Eighty-five patients rated the extent to which their treatment was right for them. The outcome measure was assessed by means of a hospitalization index reflecting the duration of full and partial hospitalization within a follow-up period of 24 months. Patients who dropped out (n = 21) assessed their treatment more negatively than those who remained in the care system during follow-up. Patients with no hospitalization (n = 25) expressed a more negative assessment than patients who were hospitalized in the follow-up period at least once (n = 39). In this latter subgroup, however, patients with a more negative assessment had a longer duration of hospitalization during follow-up, and patients' assessment of treatment was the best single predictor of outcome (r = -0.50, P < 0.01). In a multiple regression analysis, patients' assessment of treatment, the number of previous hospitalizations and the hospitalization index in the two years prior to the interview, together, explained approximately half of the variance of outcome (adjusted R2 = 0.46). The findings underline the relevance of asking patients whether treatment is right for them, although the relationship between patients' assessment of treatment and long-term outcome seems more complex than previous studies suggested. 相似文献
157.
We wished to confirm and extend a previous correlational study of our group, suggesting that positive symptoms in schizophrenia were linked to an increase in certain types of memory errors, and negative symptoms to a decrease in other types of errors. A post-hoc analysis was conducted in 33 schizophrenic patients and 40 normal control subjects on memory errors collected in a free recall task and two types of recognition tasks. The memory errors were intrusions and list errors in free recall, and decision bias towards false alarms in recognition, all assumed to reflect a source-monitoring failure. In a first analysis, the patient sample was split along the median for positive symptoms as rated by the Scale for the Assessment of Positive Symptoms (SAPS). In a second analysis, it was split along the median for negative symptoms as rated by the Scale for the Assessment of Negative Symptoms (SANS). Patients with high ratings of positive symptoms made more memory errors (intrusions, list errors, false alarms) than those with low ratings, supporting the hypothesis of a link between positive symptomatology and source-monitoring failure. On the other hand, patients with high ratings of negative symptoms made fewer of these errors than the other patients. Fewer errors were specifically associated with more affective flattening, alogia and anhedonia, whereas avolition was entirely unrelated to them. 相似文献
158.
Lung cancer risk in male workers occupationally exposed to diesel motor emissions in Germany. 总被引:4,自引:0,他引:4
I Brüske-Hohlfeld M M?hner W Ahrens H Pohlabeln J Heinrich M Kreuzer K H J?ckel H E Wichmann 《American journal of industrial medicine》1999,36(4):405-414
BACKGROUND: Although in several epidemiological studies exposure to diesel motor emissions (DME) shows an elevated lung cancer risk, it is still controversial whether DME is a human carcinogen. METHODS: In a pooled analysis of two case-control studies on lung cancer in Germany a total of 3498 male cases with histologically or cytologically ascertained lung cancer and 3541 male population controls were included. Information about lifelong occupational and smoking history was obtained by questionnaire. Drivers of lorries, buses, taxies, diesel locomotives and forklift trucks, bulldozers, graders, excavators, and tractors, were considered as exposed to DME and their cumulative exposure was estimated. All odds ratios were adjusted for smoking and asbestos exposure. RESULTS: The evaluation of lung cancer risk for all jobs with DME-exposure combined showed an odds ratio of OR=1.43 (95%-CI: 1.23-1.67). Most pronounced was the increase in lung cancer risk in heavy equipment operators (OR=2. 31 95%-CI: 1.44-3.70). The risk of tractor drivers increased with length of employment and reached statistical significance for exposures longer than 30 years (OR=6.81, 95%-CI: 1.17-39.51). The group of professional drivers (e.g., trucks, buses, and taxies), showed an increased risk only in West Germany (OR=1.44, 95%-CI: 1. 18-1.76), but not in East Germany (OR=0.83, 95%-CI: 0.60-1.14). DME-exposure in other traffic related jobs (e.g., diesel engine locomotive drivers, switchmen, forklift operators) was associated with an odds ratio of OR=1.53 (95%-CI: 1.04-2.24). CONCLUSIONS: The study provides further evidence that occupational exposure to diesel motor emissions is associated with an increased lung cancer risk. 相似文献
159.
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
160.
Alexander Bischoff Claude Tonnerre Louis Loutan Hans Stalder 《Sozial- und Pr?ventivmedizin》1999,20(11):283-287
This small-scale study attempts to examine the languages spoken in medical consultations during a one-month period in an outpatient clinic in Geneva and the ways health professionals use to communicate with their allophone patients, in particular by using interpreters. Patients of foreign origin accounted for 58% of all the consultations during the survey. Of these, 37% were Non-French-speakers (NFS). The four major language groups of NFS were Albanian, Somali, Tamil and Serbo-croat. Qualified interpreters were used in 24% of the consultations, relatives acting as interpreters in 17%, and in the other consultations without anyone interpreting (59%), a common language had to be negotiated: French, English, Italian, Spanish or German. In only 14% of the consultations without interpreters, both patient's and doctors ability to speak a common language was rated as good. Our data suggest that there has been an increasing awareness of the possible language barriers in the medical outpatient clinic. Even if proxy solutions (informal interpreters or the use of a common language) still play an important role, access to an interpreter service has been widely used. This calls for systematic and regular interpreter use, planning the interpreting needs in a timely manner. In the future, training in working with interpreters should become an integral part to the introductory sessions for the junior physicians assigned to the outpatient clinic. 相似文献