[Development and validation of the Subclinical Stress Symptom Questionnaire SSQ-25]. / Entwicklung und Validierung des Subklinischen Stresssymptom-Questionnaire SSQ-25.

BACKGROUND: Stress symptoms are widespread in the general population and often occur in the early course of mental disorders. However, no validated instrument was available for the study of subclinical stress symptoms and their relevance in the study of psychopathological trajectories. In order to advance and systematize the study of the etiology and pathogenesis of diseases in subclinical populations, the Subclinical Stress Symptom Questionnaire (SSQ-25) was developed in the present study. METHODS: In the course of three online studies, a total of 1174 subjects were recruited. The first study included item selection and the development of the questionnaire based on the analysis of item parameters, reliability, and exploratory factor analysis. To validate the factor structure, confirmatory factor analysis was used. Validation analyses were applied to distinguish the SSQ-25 from three clinical measures: Beck's Anxiety and Depression Inventory (BAI and BDI), and the Posttraumatic Stress Diagnostic Scale (PDS). In the third study the subclinical property of the instrument was investigated. RESULTS: Exploratory and confirmatory factor analyses revealed and confirmed a two-factor model (psychological and physiological stress symptoms). Cronbach's alpha was 0.95. The subclinical property of the SSQ-25 was confirmed by means of item information functions, scatter plots, residuals, and Koenker-Bassett tests as opposed to established clinical measures. DISCUSSION: The SSQ-25 is a comprehensive, reliable, and valid instrument that allows a valid assessment and differentiation of subclinical stress symptoms.

[War trauma and PTSD among German war survivors. A comparison of former soldiers and women of World War II]. / Kriegstraumata und PTBS bei deutschen Kriegsüberlebenden. Ein Vergleich ehemaliger Soldaten und Frauen des Zweiten Weltkriegs.

Stressful war experiences can cause posttraumatic stress disorder (PTSD) in survivors. To what extent were the soldiers and young women of World War II affected by PTSD symptoms over the course of their lives? Do these men and women differ in the traumatic experiences and PTSD symptom severity? To investigate these questions 52 male and 20 female Germans aged 81-95 years were recruited through newspaper advertisements and notices and interviewed regarding war experiences and PTSD symptoms. Of the men 2% and 7% met the criteria for current and lifetime PTSD diagnoses, respectively, as compared to 10% and 30% of the women, respectively. Using multiple linear regression a dose-response relationship between the number of trauma types experienced and PTSD symptom severity could be demonstrated. The slope of the regression curve was steeper for women than for men. When controlling for the number of different traumatic experiences women reported a significantly higher severity of PTSD symptoms than men. It is presumed that this difference in severity of symptoms can be attributed to qualitative differences in the type of traumatic stress factors during the war. The present study provides evidence that even today people continue to be affected by PTSD symptoms due to events which occurred during World War II; therefore, during patient contact with this age group the war experiences specific to each individual need to be considered as potential moderators of symptoms.

The dissolution and bioavailability of etodolac from capsules exposed to conditions of high relative humidity and temperatures.

The dissolution and bioavailability of etodolac from capsules exposed to high relative humidity and temperature were compared to those from capsules stored at room temperature (RT). Dissolution of stressed and control capsules was evaluated using a USP basket apparatus at 100 rpm with 900 mL pH 7.5 phosphate buffer (0.05 M) at 37 degrees C. The dissolution of etodolac from capsules exposed to stressed conditions was also evaluated with enzymes (pancreatin, 1%, w/v) added to the dissolution medium. The bioavailability of etodolac from capsules exposed to stressed conditions was compared in both dogs and humans to capsules stored at RT conditions. Capsules, 200 and 300 mg, exposed to stressed conditions failed the dissolution (without enzymes) specification [not less than 85% released (80% Q) in 30 min]. However, upon enzyme addition, all capsules met the specification. The rate and extent of absorption from these 200 and 300 mg etodolac capsules in dogs were equivalent to those from capsules stored at RT conditions that passed the dissolution specification. Similarly, the bioavailability of etodolac from 300 mg capsules that failed the dissolution specification upon exposure to stressed conditions was equivalent to that of control capsules in 24 adult male volunteers. Thus, an in vitro dissolution test with enzymes provides a better indication of stressed capsule performance in vivo.

Pharmacokinetics and bioavailability of medroxyprogesterone acetate in the dog and the rat.

Medroxyprogesterone acetate (MPA) has been administered to rats and dogs. Dogs received single oral doses of 2.5, 5, and 10 mg MPA and a single intravenous dose of 1 mg MPA. Rats received single oral doses of 0.2, 1, 5, and 20 mg kg-1 MPA and multiple oral doses (14 daily doses) of 0.2, 5, and 20 mg kg-1 MPA. Dog plasma MPA levels from the intravenous dose were characterized by a triexponential decay with disposition half-lives of 0.3, 1.8, and 21.6 h. A Loo-Riegelman analysis of the dog plasma MPA levels from oral doses indicated absorption was not a simple first-order process. The Weibull Function was used to characterize the absorption kinetics of MPA. The oral absorption of MPA in dogs appears to be dose-linear over the dosage range studied, and the absolute bioavailability was estimated at 27 per cent. Rat plasma MPA levels from single and multiple oral doses were analyzed by a non-compartmental approach. AUC and Cmax values were not dose-linear over the dosage range studied; indicative of the self-induced metabolism of MPA. Exposure of similar dosages of MPA to both the rat and the dog resulted in similar plasma profiles and pharmacokinetics.

A pharmacokinetic model for isosorbidedinitrate, isosorbide-2-mononitrate, and isosorbide-5-mononitrate.

A pharmacokinetic model is proposed to describe the plasma levels of isosorbidedinitrate (ISDN) and its two pharmacologically active metabolites, isosorbide-2-mononitrate (IS-2MN) and isosorbide-5-mononitrate (IS-5MN), following the oral administration of several 20-mg sustained release formulations of ISDN. Absorption of ISDN from the gastrointestinal tract appears first-order. A three compartment model is used to describe ISDN systemic plasma levels with t1/2 alpha = 7 min, t1/2 beta = 48 min and t1/2 gamma = 7.5 hr. The long t1/2 gamma is due to the slow release of ISDN from a peripheral compartment. ISDN undergoes extensive first-pass hepatic metabolism to IS-2MN and IS-5MN. The metabolic pathways appear to be close to saturation at an ISDN dose of 20 mg. Both IS-2MN and IS-5MN systemic plasma levels can be described by one compartment models with first-order elimination (respective elimination half-lives are 1.9 and 5.1 hr). The central compartment volumes of distribution for ISDN, IS-2MN and IS-5MN (116, 57, and 38 liters, respectively) are in agreement with reported literature values. This model is of particular usefulness as a formulation tool in designing sustained release ISDN formulations of the type investigated here since the observed first-order absorption rate constant correlates well with the in vitro first-order dissolution rate constant. Therefore, for these formulations, plasma levels can be simulated using data generated from in vitro dissolution studies, thus obviating the need for multiple human bioavailability studies.