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2.
J. Åberg B. Abrahamsson M. Grind G. Nyberg B. Olofsson 《European journal of clinical pharmacology》1997,52(6):471-477
Objective: The primary aim of this study was to investigate whether bioequivalence is achieved for a new fixed combination of extended-release
(ER) felodipine and controlled-release (CR/ZOK) metoprolol␣compared with the free combination of felodipine ER metoprolol
CR/ZOK. The second aim was to study whether there was an interaction in pharmacokinetics and pharmacodynamics between felodipine
and metoprolol when administered as ER formulation.
Methods: Two four-way cross-over studies were performed in 36 young subjects and 24 elderly subjects with frequent measurement of
drug plasma concentrations, blood pressures and heart rate. The pharmacokinetic analysis included enantioselective analysis
in six subjects.
Results: Bioequivalence between the fixed combination and the free combination was observed for the two drugs (mean difference 27%)
except for a minor deviation regarding Cmax of metoprolol in the elderly. No significant interaction was shown except for a small increase (6%) of metoprolol AUC in
the younger subjects. Mean plasma S-/R-enantiomer ratios were almost identical for the different treatments. Blood pressure and heart rate was significantly reduced
for the fixed combination compared with felodipine ER in the younger and the elderly subjects. No significant difference regarding
pharmacodynamics was detected between the fixed combination and the corresponding free combination.
Conclusion: The fixed combination consistently provides fairly constant and effective felodipine and metoprolol concentrations after
once-daily administration of one tablet. It is clinically interchangeable with the free combination of metoprolol CR/ZOK tablets
and felodipine ER tablets. Finally, felodipine and metoprolol do not interact on a pharmacokinetic level when administered
as the fixed combination.
Received: 29 October 1996 / Accepted in revised form: 21 March 1997 相似文献
3.
Danuta Wasserman Christer HellstrÖm Jerzy Wasserman Olof Beck Eva Andersson Marie Åsberg 《Archives of Suicide Research》1997,3(3):153-169
The aim of this study was to investigate markers of serotonin and immune function in suicidal patients. Cytotoxic activity of natural killer cells (NK) and CD16 lymphocytes were studied in 28 suicide attempters and 26 healthy controls, and related in patients to 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF). Patients with CSF 5-HIAA below the median had significantly lower NK cell activity than other patients. CD16 cell frequency was significantly lower in patients than in controls, and patients also tended to have lower NK cell cytotoxicity than healthy controls. There were no statistically significant correlations between 4-hydroxy-3methoxyphenyl glycol (HMPG), homovanillic acid (HVA), CSF cortisol and NK cell activity. The results support the hypothesis of compromised immune function in suicidal patients with evidence of disordered serotonin function. 相似文献
4.
Straight leg raising test versus radiologic size, shape, and position of lumbar disc hernias. 总被引:3,自引:0,他引:3
In 30 patients with a computed tomography-verified lumbar disc herniation, the relation between the straight leg raising test and the size, shape, and position of the hernia was evaluated before, 3, and 24 months after inception of nonoperative treatment. Hernia size was expressed as an index relating it to the size of the spinal canal. The limitation of the straight leg raising test was not related to size or position of the hernia. Before treatment, straight leg raising was equally restricted in patients with sharply pointed or blunt hernias, but after 3 months straight leg raising was less limited in patients with sharply pointed hernias, whereas after 24 months straight leg raising was regularly normalized. Size index was lower for sharply pointed hernias at all three computed tomography scans. A decrease in hernia size over time, irrespective of shape, was not correlated to a concomitant improvement in straight leg raising. It must be presumed that additional factors, such as inflammatory reactions affecting the nerve roots, are of importance for the magnitude of straight leg raising. 相似文献
5.
Patch testing was carried out in 851 atopic patients; 181 atopic dermatitis (AD) patients were additionally tested with 50% dilutions of the test substances. The occurrence of allergic and irritant reactions was frequent, being 57% and 33% for AD patients aged 28-41 years and 19-27 years, respectively. Among age-matched allergic rhinitis (AR)/allergic conjunctivitis (AC) or asthma (A) patients, the number of allergic reactions varied from 25 to 30%, and for irritant reactions was 24%. In all groups, nickel, fragrance-mix, balsam of Peru and neomycin were the commonest allergens. Contact allergy to ingredients of topical medicaments was common among AD patients and patients with severe and long-lasting dermatitis were most frequently sensitized. However, sensitivity to multiple substances was not common among those patients. The number of irritant reactions was considerable, but 50% dilution of the test substances did not solve the problem. 相似文献
6.
7.
Serial sections of formalin-fixed, paraffinembedded blocks from two asymptomatic, non-AIDS cases of progressive multifocal leukoencephalopathy (PML) were stained with a double-label immunocytochemical method for detection of glial fibrillary acidic protein and JC virus (JCV) capsid proteins and with luxol fast blue/hematoxylin-eosin. In case 1 small, rounded lesions of about 1-mm diameter were seen within a restricted area in the posterior part of the superior frontal gyrus of both cerebral hemispheres, suggesting an early manifestation of the disease. Fully developed demyelinated lesions of the classical type with JCV-infected oligodendrocytes appeared in the white matter and along its border with the cortex. Lesswell-developed lesions, believed to be precursors to the fully developed ones, were seen in the gray and white matter. Of special interest were areas which contained small collections of enlarged, glial fibrillary acidic protein (GFAP)-positive astrocytes without capsid antigen and which seemed to lack destruction of myelin as judged from the appearance of matching serial sections stained for myelin. Large lesions in the brain of case 2 showed the well-known features of advanced PML. The close relation between some astrocytes and oligodendrocytes with viral antigen raises the possibility of early intercellular passage of virus. Vacuolation, seen within or near lesions in both cases, has previously been noted in the CNS infected by HIV, but not in PML. It is suggested that PML, a disease of both oligodendrocytes and astrocytes, may actually begin in astroglial cells which, under the influence of a restricted JCV infection, become reactive, express GFAP and pass on virus to the more highly susceptible oligodendrocytes with which they are in contact.Supported in part by a grant N.S.07596 from the National Institute of Neurological Disorders and Stroke. The work was carried out in the Laboratory of Experimental Neurophathology, NINDS, and in the Department of Pathology II, Karolinska Institute, Stockholm 相似文献
8.
Håkan Eriksson Joakim Tedroff Karl-Åke Thuomas Sten-Magnus Aquilonius Per Hartvig Karl-Johan Fasth Peter Bjurling Bengt Långström Karl-Göran Hedström Edith Heilbronn 《Archives of toxicology》1992,66(6):403-407
A series of positron emission tomography scans was made on two monkeys during a 16-month period when they received manganese(IV)oxide by subcutaneous injection. The distribution of [11C]-nomifensine uptake, indicating dopamine terminals, was followed in both monkey brains. The brain distributions of [11C]-raclopride, demonstrating D2 dopamine receptors, and [11C]-l-dopa, as a marker of dopamine turnover, were followed in one monkey each. The monkeys developed signs of poisoning namely unsteady gait and hypoactivity. The [11C]-nomifensine uptake in the striatum was reduced with time and reached a 60% reduction after 16 months exposure. This supports the suggestion that dopaminergic nerve endings degenerate during manganese intoxication. The [11C]-l-dopa decarboxylation was not significantly altered indicating a sparing of [11C]-l-dopa decarboxylation during manganese poisoning. A transient decrease of [11C]-raclopride binding occurred but at the end of the study D2-receptor binding had returned to starting values. The magnetic resonance imaging (MRI) revealed that the manganese accumulated in the globus pallidus, putamen and caudate nucleus. There were also suggestions of gliosis/edema in the posterior limb of the internal capsule. MRI might be useful to follow manganese intoxication in humans as long as the scan is made within a few months of exposure to manganese, i. e. before a reversal of the manganese accumulation. 相似文献
9.
Impairment of bone turnover in elderly women with hip fracture 总被引:4,自引:0,他引:4
Kristina Åkesson Philippe Vergnaud Evelyne Gineyts Pierre D. Delmas Karl J. Obrant 《Calcified tissue international》1993,53(3):162-169
Summary Hip fracture is one of the most severe consequences of osteoporosis affecting aged women. However, abnormalities of bone turnover responsible for bone loss in this condition have not been clearly defined. To further evaluate the bone metabolic status of women sustaining hip fracture, we have prospectively measured serum osteocalcin as a marker of bone formation and urinary excretion of pyridinoline (Pyr) and deoxypyridinoline (D-pyr) cross-links as markers of bone collagen degradation in 174 independently living women (80 ± 8 years) within a few hours after a hip fracture. Comparison was made with 77 age-matched controls (80 ± 5 years) and 17 premenopausal women (39 ± 3 years). In addition 15 of the patients were followed with daily measurements during the first postoperative week. At the time of admission osteocalcin was 20% lower in the fractured women compared to the elderly controls (7.6 ± 3.8 vs. 9.5 ± 4.5 nglml,P = 0.001). Pyr and D-pyr were 36% and 40% higher, respectively (P = 0.0001), than in elderly controls and 85% and 76% higher than in premenopausal controls (P = 0.0001). Serum osteocalcin did not correlate with the cortisol level measured at the same time (r = 0.03, ns), nor with serum albumin and creatinine. Serum osteocalcin remained unchanged within 18 hours after fracture, whereafter it progressively decreased until the third postoperative day. No correlation was noted between the excretion of pyridinoline cross-links and the time elapsed from fracture.These data suggest that the abnormal levels of osteocalcin and pyridinolines are unrelated to traumatically induced acute changes, but reflect abnormalities of bone turnover existing prior to the fracture. Thus, hip-fracture patients have biochemical evidence of decreased bone formation and increased bone resorption when compared to age-matched controls. We suggest that these abnormalities may play a role in the decrease of the bone mass and the consequently increased bone fragility that characterize the osteoporotic hip fracture in the elderly. 相似文献
10.
Sverker Ljunghall M.D. Lars Benson M.D. Leif Wide M.D. Göran Åkerström M.D. Jonas Rastad M.D. 《World journal of surgery》1988,12(4):496-501
In vitro experiments have indicated that in primary hyperparathyroidism (HPT) the hyperfunctioning glands have a set point error, i.e., they are not autonomous but regulate serum calcium around a hypercalcémie value. In contrast, parathyroid function is suppressed in patients with hypercalcemia of causes other than HPT (e.g., malignancy or sarcoidosis). The basal measurements of serum parathyroid hormone (PTH) levels, however, cannot, alone, separate with precision HPT from other causes of hypercalcemia.Lowering of calcium, in order to stimulate secretion of PTH, was, therefore, achieved by either infusion of Na2 EDTA (24 mg/kg per hr) for 1 hour, or intramuscular injection of 100 IU salmon calcitonin.
All 35 patients with primary HPT displayed a significant increase of serum PTH concentrations, evaluated by a midregion/intact hormone assay, during the EDTA infusion, which lowered plasma ionized calcium by an average of 0.16 mmol/l. The injection with calcitonin reduced the calcium concentrations by 0.10 mmol/l after 8 hours and caused a rise in PTH in 80% of HPT patients. With both tests, the secretory response by PTH to the reduction of plasma calcium was generally evident while the patients were still hypercalcemic.
In 32 patients with other causes for hypercalcemia, primarily malignancy and sarcoidosis, similar reductions of plasma ionized calcium were obtained. In contrast to the HPT patients, none of them raised their serum PTH values during the test. Thus, stimulation of PTH secretion by a moderate reduction of serum calcium considerably improves the differential diagnosis of hypercalcemia since a significant secretory response appears to be exclusive for HPT.
Presented at the International Association of Endocrine Surgeons in Sydney, Australia, September, 1987.
Supported by the Swedish Medical Research Council. 相似文献
Resumen Experimentos in vitro han señalado que en el hiperparatiroidismo primario (HPT) las glándulas hiperfuncionantes tienen un error en su set point, o sea que no son autónomas sino que regulan el calcio sérico alrededor de un valor hipercalcémico. Por el contrario, la función paratiroidea es suprimida en pacientes con hipercalcemia de causa diferente de HPT (e.g., neoplasias malignas o sarcoidosis). Las mediciones basales de los nivelés séricos de hormona paratiroidea (PTH) de por sí no son capaces de diferenciar con precision entre el HPT y la hipercalcemia de otras causas.La disminución del nivel de calcio sérico, con el objeto de estimular secreciones de PTH, fue lograda con la infusión de Na2 EDTA (24 mg/Kg por hora) por 1 hora o la inyección i.m. de 100 UI de calcitonina de salmón.Todos los 35 pacientes con HPT primario exhibieron un aumento significativo de las concentraciones séricas de PTH, determinadas mediante la medición de la fraction media/intacta de PTH en el curso de la infusion de EDTA, la cual redujo el nivel plasmático de calcio ionizado en un promedio de 0.16 mmol/l. La inyección de calcitonina redujo las concentraciones de sérico en 0.10 mmol/l a las 8 horas y resultó en un aumento de la PTH en 80% de los pacientes con HPT. Con ambas pruebas la respuesta secretoria de PTH a la reducción del calcio plasmático generalmente apareció evidente aún mientras los pacientes se hallaban hipercalcémicos.En 32 pacientes con hipercalcemia de causa diferente, se lograron reducciones similares de la concentration plasmática del calcio ionizado. Por el contrario de lo observado en los patientes con HPT, ninguno demostró elevatión de sus niveles séricos de PTH en el curso de la prueba. Por consiguiente, el estímulo de la secretión de PTH mediante la reductión moderada de calcio sérico incrementa considerablemente la (ie501-01)acidad de establecer el diagnóstico diferencial de la hipercalcemia, puesto que una significativa respuesta secretoria parece ser caracteristíca exclusiva del HPT.
Résumé L'expérimentation in vitro a démontré que dans l'hyperparathyroïdisme (HPT), les glandes hyperactives ont un point mort erroné, c'est-à-dire qu'elles ne sont pas autonomes mais règlent la calcémie autour d'une valeur de référence déjà hypercalcémique. En revanche, la fonction parathyroîde est déprimée chez le patient dont l'hypercalcémie est due à une cause autre que l'HPT (cancer ou sarcoïdose par exemple). La mesure des niveaux de base de la parathormone (PTH), cependant, ne permet pas de distinguer l'hypercalcémie de l'HPT des autres causes d'hypercalcémie avec précision.Dans le but de stimuler la sécrétion de PTH, la calcémie était abaissée soit en perfusant les patients avec une solution de Na2 EDTA (24 mg/Kg) pendant une heure, soit par une injection intramusculaire de 100 U de calcitonine de saumon.Trente-cinq patients ayant un HPT primitif présentaient une augmentation significative des concentrations en PTH sérique, évaluée par l'étude immunologique de la portion moyenne intacte, pendant la perfusion d'EDTA. La portion de calcium plasmatique ionisée a été abaissée en moyenne de 0.16 mmol/l. L'injection de calcitonine a réduit la concentration en calcium par 0.10 mmol/l après huit heures et a provoqué une augmentation en PTH chez 80% des patients à HPT. Quel que soit le test, la réponse de PTH à la réduction de calcium plasmatique était généralement évidente alors que le patient était toujours hypercalcémique.Chez 32 autres patients ayant pour cause d'hypercalcémie cancer ou sarcoïdose, des réductions similaires en calcium plasmatique ionisé ont été obtenues. Aucun malade, contrairement aux patients HPT, n'a vu son niveau de PTH monter pendant le test. Ainsi, la stimulation de sécrétion de PTH par une réduction modérée de calcium sérique améliore considérablement le diagnostic différentiel des hypercalcémies puisque la réponse sécrétoire significative paraît être le fait exclusif des HPT.
Presented at the International Association of Endocrine Surgeons in Sydney, Australia, September, 1987.
Supported by the Swedish Medical Research Council. 相似文献