Zur Eliminationskinetik des Digoxin vor und während Spironolactonbehandlung

Zusammenfassung Im Tierversuch konnte unter hohen Spironolactondosen eine Beschleunigung der Digoxinelimination nachgewiesen werden, die auf eine vermehrte Metabolisierung des Digoxins nach Induktion mikrosomaler Leberenzyme zurückgeführt wurde. Deshalb wurde bei 8 Patienten die Eliminationskinetik des Digoxins vor Spironolactonbehandlung untersucht, wobei morgens nüchtern 0,1 mg³H-Digoxin intravenös als einmalige Dosis verabreicht wurde. Zur Messung der Digoxinkonzentration wurden venöse Blutproben zu bestimmten Zitpunkten bis zu 120 h entnommen, der Urin fraktioniert 5 Tage lang gesammelt. Zusätzlich wurde während der gesamten Versuchsperiode die im Stuhl ausgeschiedene Digoxinmenge bestimmt. Während der Messung der Digoxinelimination wurden gleichzeitig nicht-invasive Parameter des mikrosomalen Leberenzymsystems wie Antipyrinhalbwertszeit, Antipyrinclearance, Gamma-Glutamyl-transpeptidase im Blut und d-Glucarsäureausscheidung im 24 h-Urin gemessen. Danach wurde jedem Patienten 15 Tage lang eine therapeutische Erhaltungsdosis von 150 mg Spironolacton täglich verabreicht. 10 Tage nach Beginn der Spironolactonbehandlung wurde die oben beschriebene Untersuchung der Digoxinelimination zusammen mit den Parametern des mikrosomalen Leberenzymsystems wiederholt.Aufgrund der errechneten pharmakokinetischen Parameter ließen sich unter Spironolactonbehandlung keine Änderungen der globalen Eliminationskonstante respektive der Halbwertszeit des Digoxins nachweisen. Ebenso blieb das Verteilungsvolumen, die renale und metabolische Clearance unbeeinflußt, die Digoxinausscheidung im Faeces war während beiden Versuchsperioden nicht signifikant verschieden und betrug für die gemessene Zeitperiode etwa 15% der verabreichten Dosis. Außerdem zeigten die Parameter des mikrosomalen Enzymsystems der Leber keinerlei Änderungen vor und unter Spironolactonbehandlung. Aufgrund dieser Ergebnisse konnte unter den klinisch üblichen Spironolactondosen keine Veränderung der Digoxinelimination nachgewiesen und eine Enzyminduktion sicher ausgeschlossen werden. Deshalb sind die in der Literatur berichteten Änderungen der Digoxinausscheidung auf eine zu hohe Dosierung im Tierversuch zurückzuführen und haben für den Menschen keine therapeutische Bedeutung.Herrn Prof. Dr. E. Bauereisen zum 65. Geburtstag in Dankbarkeit gewidmet     

Neutrophil responses to platelet-activating factor

1-O-Alkyl-2-O-acetyl-sn-glyceryl-3-phosphorylcholine (i.e., platelet-activating factor) was prepared and confirmed to possess potent platelet aggregating activity. It was also potent in aggregating and degranulating rabbit and human neutrophils. When injected into rabbits, the lipid induced profound neutropenia, thrombocytopenia, and anaphylactic symptoms. The lyso derivative of this lipid, 1-O-alkyl-sn-glyceryl-3-phosphorylcholine, was inactive or several orders of magnitude weaker in inducing these responses. The acetylated lipid appears to be a potent stimulator of both platelets and neutrophils. Its anaphylactic-like toxicity may be related, at least in part, to its ability to aggregate or otherwise stimulate these cells.This work was supported by NIH grants AI09169, AI10732, AI14929, HL16769, HL14164, and AMI1799.     

Relation of impaired lymphocyte proliferative function to other major human immunodeficiency virus type 1-induced immunological changes.

Human immunodeficiency virus (HIV) type 1 (HIV-1) induces impairment of immune function reflected in reduced lymphocyte proliferative responses. Many other immune changes are induced by HIV-1, but their relationship to lymphocyte functional defects is not known. The present study was designed to correlate functional defects with other HIV disease parameters. Cryopreserved samples from 118 HIV-1-positive subjects and 40 seronegative individuals were examined. The main findings were that impaired proliferative responses to mitogens correlated with (i) decreased cell surface expression of the interleukin-2 receptor (CD25), (ii) increased expression of HLA-DR antigens on CD4 cells, (iii) reduced CD4 and increased CD8 cell numbers, and (iv) increased levels of serum immune complex dissociated p24 antigen. However, impaired function was not associated with increased serum neopterin, beta2-microglobulin, or soluble interleukin-2 receptor or with CD38 antigen expression on lymphocytes. In summary, proliferative functional impairment correlated with some, but not all, immunological changes associated with HIV-1 infection. Most of the phenotypic markers that correlated with altered function are cell surface molecules with significant roles in lymphocyte proliferation and were associated primarily with CD4 cells, compatible with the view that dysregulation of CD4 cells is responsible for impaired function.     

M. Quadriceps femoris of Man,a muscle with an unusual enzyme activity pattern of energy supplying metabolism in mammals

1. The following enzyme activities were estimated in needle-biopsy samples of the lateral part of the human quadriceps femoris muscle: triosephosphate dehydrogenase (TPDH), lactate dehydrogenase (LDH), NAD : glycerol-3-phosphate dehydrogenase (GPDH), hexokinase (HK), NAD: malate dehydrogenase (MDH), citrate synthase (CS) and hydroxyacyl-CoA dehydrogenase. 2. Although the enzyme activities in muscles of women were lesser than in those of men, no difference was found in the calculated enzyme activity ratios. There is thus no sex-dependent metabolic type-differentiation in this muscle. 3. The human quadriceps femoris is a low-activity muscle, in comparison with muscles of homoiotherm laboratory animals. The enzyme activity ratio of TPDH to CS, characterizing the glycolytic pyruvate formation to aerobic oxidative capacities, shows this muscle to be of an intermediate type in this respect, similarly as the extensor digitorum longus of the rat. The relatively very high capacity of glucose phosphorylation (HK), the high aerobic regeneration of cytoplasmic dehydrogenated NAD (GPDH) and the very low anaerobic regeneration (LDH), show the unusually high proportion of carbohydrates (glucose) which can be broken down aerobically.     

Somatization among older primary care attenders

BACKGROUND: The importance of somatization among older primary care attenders is unclear. We aimed to establish the prevalence, persistence and associations of somatization among older primary care attenders, and the associations of frequent attendance. METHOD: One hundred and forty primary care attenders over 65 years were rated twice, 10 months apart, on measures of somatization, psychiatric status, physical health and attendance. RESULTS: The syndrome of GMS hypochondriacal neurosis had a prevalence of 5% but was transient. Somatized symptoms and attributions were persistent and associated with depression, physical illness and perceived poor social support. Frequent attenders (top third) had higher rates of depression, physical illness and somatic symptoms, and lower perceived support. CONCLUSION: Somatization is common among older primary care attenders and has similar correlates to younger primary care somatizers. Psychological distress among older primary care attenders is associated with frequent attendance. Improved recognition should result in benefits to patients and services.     

Aeration selects for mucoid phenotype of Pseudomonas aeruginosa.

A mucoid strain of Pseudomonas aeruginosa isolated from a patient with cystic fibrosis and its nonmucoid revertant were grown in a chemically defined alginate-promoting medium under batch and continuous culture conditions. Selection for the mucoid and nonmucoid phenotype was accomplished by varying the levels of air available to the culture. The addition of air at a rate of 0.5 liters/min to the nonmucoid revertant growing under batch or continuous culture conditions resulted in a greater than 50% decrease in viability over a 10-h incubation period. In contrast, aeration of the mucoid culture maintained a totally mucoid population and there was no decrease in viability over a 55-h incubation. Aeration of a mixed population of the mucoid and nonmucoid phenotype (1:1) resulted in selection for the mucoid phenotype within the first 20 h of cocultivation. The correlation between the mucoid phenotype and alginic acid was demonstrated by the production of 580 micrograms of uronic acid per mg (dry weight) of cells by the mucoid phenotype and less than 1 microgram of uronic acid per mg (dry weight) of cells by the nonmucoid revertant. These results suggest that nonmucoid revertants may have an unusual sensitivity to aeration, which may indicate a mechanism for natural selection of the mucoid phenotype in vivo.     

Urban adolescents' perceptions of their neighborhoods: An examination of spatial dependence

Spatial dependence exists when the variation between observations is dependent on spatial location. In the present study, geostatistical methods were used to examine spatial dependence in adolescents' perceptions of their neighborhoods: whether adolescents living in close proximity perceived their neighborhoods more similarly than adolescents living further apart. Participants included 343 adolescents (53% male; 91% African American) enrolled in sixth grade, residing in Baltimore City, with geocoded home addresses. These addresses were used in combination with a measure of perceived neighborhood disorder and disadvantage to compute variogram plots, a geostatistical technique used to evaluate spatial dependence. Results indicated that perceptions of youth residing in close geographic proximity were more similar than perceptions of youth residing further apart. Adjusting for census‐level characteristics, but not individual and family characteristics, resulted in decreased variation among participants but did not eliminate the spatial dependence. Findings highlight the utility of geostatistical methods for social science research. © 2004 Wiley Periodicals, Inc. J Comm Psychol 32: 277–293, 2004.     

Chest pain with normal coronary arteries: a comparative study of psychiatric and social morbidity

Ninety-nine patients with chest pain and a presumptive diagnosis of coronary heart disease were assessed blindly within 24 hours of angiography, using standardized psychiatric and social interviews and a personality inventory. Thirty-one patients had normal coronary arteries (NCA), 15 had slight disease and 53 had significant coronary obstruction. Twenty-eight (61%) of the 46 patients with insignificant disease and 12 (23%) of the 53 with significant obstruction had psychiatric morbidity. Associations between the overall severity of psychiatric morbidity and measures of social maladjustment were strongest in the patients with normal coronary arteries. The 26 men with insignificant coronary artery disease had higher scores of neuroticism and extraversion than the 41 with important coronary occlusions. No differences were observed when the same comparisons were made for the women. The findings indicate that approximately two thirds of patients with normal and near-normal coronary arteries have predominantly psychiatric rather than cardiac disorders: the symptoms in these patients are more likely to represent the somatic manifestations of anxiety and overbreathing than the consequences of underlying cardiac disease. Physicians should be aware of the ways in which neurotic illness may present with symptoms mimicking cardiac disease, especially when cardiovascular symptoms are accompanied by phobic symptoms and unexplained shortness of breath.     

An Analytic Model of Subminiature Auditory Sensation System for Sound Source Localization

It is reported that some types of insects have a remarkable ability to detect the direction of an incident sound even though its acoustic sensory organs are in very close proximity each other. Maybe the ears are jointed by a cuticular structure with which the separated motions can be coupled mechanically and thus be magnified. In this paper, a detailed model is setup to describe the principle of this type of localization using a mechanical coupled structure. The transfer functions and the responses of the model in terms of time and frequency are analyzed to describe the mechanism of its ability of directional hearing. This analytical model provides a method to design the experimental model for the predetermined incident sound pressure, and the analysis of this model shows that this structure have the ability to determine the direction of the incident stimulus.