Validierung eines klinischen Routine-Systems zur computerisierten Erstellung von MMPI-Befunden bei psychiatrischen Patienten

Zusammenfassung Das MMPI-Interpretationssystem von Lachar (1974), das gegenüber den bisher verfügbaren Systemen eine Reihe von Vorteilen aufweist, wurde in einer deutschen Version an 1190 stationären psychiatrischen Patienten auf seine Gültigkeit hin untersucht. Von den 153 Texten der Interpretationsbibliothek wurden diejenigen 114 Texte, die voneinander unabhängige Merkmale eines MMPI-Profils interpretieren, bei jedem Vorkommen im Einzelfall von dem behandelnden Psychiater hinsichtlich der interpretativen Treffsicherheit beurteilt. Im Durchschnitt wurden von jeweils 100 Texten 83 als zutreffend bezeichnet. Bei der Analyse der einzelnen Programmteile zeigte sich, daß die Treffsicherheit bei psychopathologisch auffälligen MMPI-Profilen wesentlich höher war als bei Profilen im Normbereich. Die in dieser Untersuchung gefundenen Trefferraten korrelierten hoch mit denen der amerikanischen Originaluntersuchung, was die spezifische und replizierbare Gültigkeit der einzelnen Texte bestätigt. Das vorliegende Interpretationssystem bietet damit auf der Grundlage des MMPI eine Persönlichkeitsbeschreibung, für die in verschiedenen psychiatrischen Einsatzbereichen und verschiedenen Sprachen eine gute interpretative Treffsicherheit im Einzelfall nachgewiesen ist.Eine frühere Fassung dieser Arbeit wurde auf dem 31. Kongreß der Deutschen Gesellschaft für Psychologie in Mannheim vorgetragen. Ich danke Frau Dipl. Psych. Kornelia Zangl und Frau Dr. Pola Engel-Sittenfeld für ihre Hilfe bei der Übersetzung der Interpretationstexte. Langjährige wertvolle Mitarbeit haben Frau Irmtraud Reinhold bei der Testdurchführung, Frau Gabi Kunze bei der Programmierung des Interpretationssystems und bei der Verarbeitung der Daten geleistet     

A single-blind study of combined pulse oximetry and capnography in children

This single-blind study examined four levels of monitoring in 402 pediatric cases. Patients were randomly assigned to one of four groups: 1) oximeter and capnograph; 2) only oximeter; 3) only capnograph; or 4) neither oximeter nor capnograph data available to the anesthesia team. An anesthesiologist, not involved in patient care, observed all cases and continuously recorded hemoglobin oxygen saturation (Spo2), ECG, expired CO2, and the oximeter plethysmographic output. Mean age, weight, ASA physical status, airway management (mask or endotracheal tube), and anesthetic technique were similar in each group. Two-hundred sixty problems were documented in 153 patients. Fifty-nine events in 43 patients resulted in "major" desaturation (Spo2 less than or equal to 85% for greater than or equal to 30 s). Fifteen "major" capnograph events (esophageal intubation, disconnection, accidental extubation, or obstructed endotracheal tube) were observed in 11 patients; 8 of these also developed varying degrees of desaturation. One-hundred thirty "minor" desaturation events (Spo2 less than or equal to 95% for greater than 60 s) and 79 "minor" desaturation events (hypercarbaria or hypocarbia) were observed. A number of problems fulfilled criteria in multiple categories. Infants less than or equal to 6 months of age had the highest incidence of major desaturation events (18 of 65 [27%]) compared to toddlers 7-24 months of age or children greater than 24 months of age (P less than 0.001). Blinding the oximeter data increased the number of patients (12 vs. 31) experiencing major desaturation events (P = 0.003); blinding the capnograph data altered neither the frequency of desaturation events nor the incidence of major capnograph events.(ABSTRACT TRUNCATED AT 250 WORDS)     

The relation between the current underlying pacemaker activity and beta-adrenoceptors in cardiac Purkinje fibres: A study using adrenaline,procaine, atenolol and penbutolol

Summary The pacemaker current — i _K2 — in cardiac Purkinje fibres was analysed using the voltage clamp technique described by Deck et al. (1964). (–)-Adrenaline (5.5 · 10^–6 M) causes the wellknown shift of the Hodkin-Huxley kinetics in the depolarizing direction. Procaine (7.3·10^–4 M) does not cause any further shift of s in the presence of adrenaline. Atenolol (3.8·10^–5 M) causes a backshift of the kinetics in the negative direction in the presence of adrenaline and procaine. The instantaneous current-voltage relationship ( ) is altered neither with adrenaline, nor with procaine or atenolol. The results exclude the possibility that the local anaesthetic side effect of many beta-adrenoceptor blocking agents may be involved in the backshift of the s-kinetics. The voltage dependence of the reciprocals of the time constants is shifted in a similar way as s by the sympathomimetic or blocking drugs. Following the application of (–)-adrenaline (5.5·10^–6 M) the (–)-isomere of penbutolol (1.7 and 3.5·10^–6 M) is about equally effective in shifting the kinetics back as the (+)-isomere (3.5·10^–5 M). In the presence of (–)-adrenaline, the (+)- and (–)-forms of penubutolol cause virtually no change of the instantaneous current-voltage relationship, . Thus, (–)-adrenaline and (+)- and (–)-penbutolol are aiming for the s-kinetics whose voltage dependence is controlled by the electric field near the i _K2-channel of the membrane and do not influence the number of the i _K2-channels. These findings suggest that the sympathomimetic or blocking agents influence the s-kinetics of the pacemaker current i _K2 by altering the electric field; the fully activated current-voltage relationship which is proportional to the number of the open i _K2-channels is not subject to any appreciable modification. The results conclusively show that the kinetics of the pacemaker current can be controlled by beta-adrenoceptors.     

First experience with gamma probe guided sentinel lymph node surgery in penile cancer

Because of the curative approach, the detection of lymph node metastases in squamous cell carcinoma (SCC) of the penis is of significant clinical relevance. Sentinel lymph node (SLN) identification by means of lymphangiography has been proven to be insufficiently safe. However, the high morbidity of inguinal lymphadenectomy and the considerable individual variability regarding the location of lymph node metastases justify the necessity of a technique that enables the identification of SLNs. Since 1998, SLNs have been intraoperatively identified and selectively dissected, after peritumoral injection of technetium-99m nanocolloid and using lymphoscintigraphy, in three patients (one with malignant melanoma and two with SCC). At least one SLN could be detected in each patient. The maximum surgical time was 30 min. There were no severe complications. Lymph node metastases did not occur in any patient. Upon a mean follow-up of 10 months, all patients are currently free of tumor. Owing to the long-term results of sentinel lymphadenectomy in malignant melanoma of other locations and our preliminary results with respect to penile carcinoma, we consider the current method appropriate as the only primary operation for lymph node staging in early stages and, in combination with modified inguinal lymphadenectomy, in locally advanced stages. Received: 24 November 1999 / Accepted: 21 April 2000     

Ethylcellulose: a new type of emulsion stabilizer.

Cellulose ethers, in particular hypromellose, represent an interesting alternative when emulsions have to be stabilized avoiding conventional low molecular weight surfactants. So far this option has been only described for the formulation of oil-in-water (o/w) emulsions. Since surfactant-free water-in-oil (w/o) emulsions seem to be also attractive as drug carriers, ethyl cellulose, an oil-soluble cellulose derivative, was studied for its ability to stabilize w/o emulsions. Measurements of the interfacial tension confirmed that ethylcellulose was positively adsorbed at the water/oil interface with diverse lipids. Appearance of model emulsions was dependent on the processing temperature. At low temperatures (15 degrees C) cream-like o/w emulsions were obtained. Processing at 30 degrees C yielded fluid w/o-lotions. Investigation of the microstructure showed that the surface of the emulsion droplets was covered with particles which formed a mechanical barrier. These colloidal particles were shown to be a precipitate of ethylcellulose which forms when the polymer which was dissolved in the lipid phase comes into contact with water. Thus, ethylcellulose was demonstrated to represent a new type of particulate polymeric emulsifier.     

ECL Cell Histamine Mobilization Studied byGastric Submucosal Microdialysis in Awake Rats:Methodological Considerations

Abstract: The ECL cells are endocrine/paracrine cells in the acid‐producing part of the stomach. They secrete histamine in response to circulating gastrin. Gastric submucosal microdialysis has been used to study ECL‐cell histamine mobilization in awake rats. In the present study we assess the usefulness and limitations of the technique. Microdialysis probes were implanted in the gastric submucosa. Histological analysis of the stomach wall around the probe revealed a moderate, local inflammatory reaction 1–2 days after implantation; the inflammation persisted for at least 10 days. Experiments were conducted 3 days after the implantation. The “true” submucosal histamine concentration was determined by perfusing at different rates (the zero flow method) or with different concentrations of histamine at a constant rate (the no‐net‐flux method): in fasted rats it was calculated to be 87±5 (means±S.E.M.) nmol/l and 76±9 nmol/l, respectively. The corresponding histamine concentrations in fed rats were 93±5 and 102±8 nmol/l, respectively. With a perfusion rate of 74 μl/hr the recovery of submucosal histamine was 49%, at 34 μl/hr the recovery increased to 83%. At a perfusion rate below 20 μl/hr the microdialysate histamine concentration was close to the actual concentration in the submucosa. The ECL‐cell histamine mobilization was independent of the concentrations of Ca²⁺ in the perfusion medium (0–3.4 mmol/l Ca²⁺). In one experiment, histamine mobilization in response to gastrin (10 nmol/kg/hr subcutaneously) was monitored in rats pretreated with prednisolone (60 mg/kg) or indomethacin (15 mg/kg). The two antiinflammatory agents failed to affect the concentration of histamine in the microdialysate either before or during the gastrin challenge, which was in accord with the observation that the inflammatory reaction was modest and that inflammatory cells were relatively few around the probe and in the wall of the probe. In another experiment, rats were given aminoguanidine (10 mg/kg) or metoprine (10 mg/kg) 4 hr before the start of gastrin infusion (5 nmol/kg/hr intravenously). Metoprine (inhibitor of histamine N‐methyl transferase) did not affect the microdialysate histamine concentration, while aminoguanidine (inhibitor of diamine oxidase) raised both basal and gastrin‐stimulated histamine concentrations. We conclude that microdialysis can be used to monitor changes in the concentration of histamine in the submucosa of the stomach, and that the inflammatory reaction to the probe is moderate and does not affect the submucosal histamine mobilization.     

Pharmacodynamic differences between species exemplified by the novel anticancer agent CHS 828

When a candidate drug enters clinical trials, decisions regarding dosing are mainly based on animal data. Occasionally, toxicity problems are faced in the clinic because of unexpected species differences in pharmacokinetics or pharmacodynamics between humans and preclinical species. Fludarabine and topotecan are examples of such drugs. In the first clinical trials of the new agent CHS 828, the maximum tolerated dose was reached earlier than expected from animal data. This paper discusses the issue of species differences in the development of anticancer drugs, and preclinical models for detection and quantification of such differences. Pharmacokinetic and hematological toxicity data of CHS 828 from studies in rats and humans are presented. In vitro sensitivity to CHS 828 and some established cytotoxic agents was measured in lymphocytes from humans and rats and in a panel of human and rodent cell‐lines. 10–100 times higher CHS 828 exposure was tolerated by rats than by patients. In both in vitro cell systems, CHS 828 showed higher potency in human cells compared to rodent cells. A species difference was evident also for fludarabine, but not for doxorubicin and cisplatin. CHS 828 pharmacokinetics were similar across species. In conclusion, the lower tolerance of CHS 828 in humans than in rats could be detected in vitro in cultures of peripheral lymphocytes. Preclinical studies of species differences could help the interpretation of in vivo effect studies as well as the choice of starting dose for clinical trials. We suggest peripheral lymphocytes from different species as a potential model system for such studies. Drug Dev. Res. 61:218–226, 2004. © 2004 Wiley‐Liss, Inc.     

Vaccination of patients with advanced ovarian carcinoma with the anti-idiotype ACA125: immunological response and survival (phase Ib/II).

PURPOSE: A Phase I/IIb multicenter study was conducted to evaluate the safety and immunogenicity of the anti-idiotypic antibody vaccine ACA125 that functionally imitates the tumor antigen CA125 in 119 patients with advanced ovarian carcinoma. A preliminary report on the initial 42 patients demonstrated safety and immunogenicity. EXPERIMENTAL DESIGN: Using the complete intention-to-treat population (n = 119) who received a mean of 9.7 ACA125 applications, survival was analyzed with respect to immunological responses. RESULTS: In 81 patients (68.1%), a specific anti-anti-idiotypic antibody (Ab3) response could be induced. Additionally, the development of CA125-specific antibodies (Ab1') and antibody-dependent cell-mediated cytotoxicity of CA125-positive tumor cells was observed in 50.4% and 26.9% of patients, respectively. The median survival of all patients was 19.4 months (range, 0.5-56.1 months). Ab3-positive patients showed a significantly longer survival (median, 23.4 months; P < 0.0001) as compared with Ab3-negative patients (median, 4.9 months). A positive Ab3 response remained associated with longer survival when controlling for other prognostic factors including FIGO (International Federation of Gynecologists and Obstetricians) stage, response to and type of first-line chemotherapy, number of previous treatments, or concomitant antitumor therapy. With regard to safety, repeated vaccination was well tolerated. No serious adverse events related to the application of ACA125 occurred. CONCLUSIONS: Although the uncontrolled design of this study prevents definitive conclusions with respect to subgroups, the data support a relationship between Ab3 response and survival time. Thus, the need for further randomized, controlled clinical trials to establish efficacy of the vaccine ACA125 seems to be indicated.