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An attempt to define "psychic structure" leads to the conclusion, that "structure" provides adaptive behavioral strategies for the interaction of the person with a physical and social world by representing experiences of earlier interactions in memory processes. Compatibility of different definitions of "structure" in psychopathology and psychoanalysis is being discussed. Developmental aspects of a "theory of mind" in children and of different modes of representation have to be addressed. A "multiple code theory" of W. Bucci is introduced. Conclusions for diagnosis and therapy in psychodynamic approaches will be drawn. It has to be faced, that children represent optimal structures in each level of psychic development, noting the importance of age-relevant normative measures.

Quality management for screening programmes of preschool children is a valuable tool to manage the process of investigation, data computing and evaluation of data and its systemic biases. As an example the quality of structure and processing of the system was evaluated for selected criteria in order to prove plausibility. Results identify computing process as a main criterion for quality management since it includes individuality of the investigator as well as the several factors due to the setting of investigation process (time, premises, computing, plausibility and individual factors). As a main influencing factor could be identified the time-span for investigation and commitment of the investigator. Selected training facilities for the investigators could improve quality and commitment and are qualified as an instrument for quality protection.

276 treatment records of patients who were undergoing high-frequent, outpatient, individual, psychoanalytic therapy were analysed with respect to the prevalence and patterns of childhood sexual abuse in the history of these patients. 22.8% of all patients experienced narrowly defined sexual abuse during childhood (the end of the 17th year); additionally, 35.2% of all patients reported minor forms of sexually abusive experiences. The gender distribution, the age at onset of sexual abuse, and the relationship to the perpetrator were analysed. Looking at psychoanalytic diagnoses, a significant correlation between a history of childhood sexual abuse and a diagnosis of hysterical neurosis was found.

The provisional trial was carried out in a sample of 133 second- and 139 fourth-graders from the Heidelberg area. The HD-LT was subjected to an item selection, test criteria were ascertained and temporary percentile norms for the second and fourth grades were established. High item difficulty resulted for both grades, i.e. the test was relatively easy. Test criteria were generally satisfactory. Significant correlations were found in both grades between the HD-LT and the children's spelling ability. The HD-LT accounted for 30% of the spelling variance among second-graders as compared to 10% of that among fourth-graders. This reflects the specific significance of phonetic discrimination ability in the first years of elementary school. Children with spelling difficulties were compared to those with good spelling abilities in respect to their ability to discriminate sound. Spelling-impaired children in both grades exhibited a significantly lower overall HD-LT score. No significant sex differences were found with regard to the auditory and kinesthetic phonetic discrimination ability. Since the HD-LT turns out to be well-suited to indicate a phonetic discrimination disability during the initial phases of acquisition of written language, its further development and extension of its application to the pre-school level are recommended.

In the inpatient treatment of acute psychiatric episodes in children and adolescents, the psychiatrist must set up an initial treatment plan incorporating one or more psychotherapeutic modalities and adapt this plan to the patient's clinical course. This article summarises the clinical experience of a model unit at the University of Heidelberg, the result of a collaboration between the Department of General Psychiatry and the Department of Child and Adolescent Psychiatry at the Clinic of Psychiatry. A series of 116 adolescent admissions was reviewed for clinical diagnosis, the nature and frequency of psychotherapeutic modalities, and the role of family involvement in patient care. Differential and adaptative approaches to the selection of treatment modalities in the context of an acute care setting are emphasised.

Adopting a therapeutic view on diagnosis in child and adolescent psychiatry a psychodynamic diagnostic manual seems to be necessary, that may provide reliability in the assessment of intrapsychic processes. Multiaxial diagnosis of children's and adolescent's psychiatric disturbances may thus be completed with additional psychodynamic assessment procedures. In adults an operationalized procedure of psychodynamic assessment (OPD) already exists. In child and adolescent psychiatry a working group for psychodynamic diagnostic (OPD-KJ) has been founded. In 4 areas (subjective experiences of disturbances, relationships, intrapsychic conflicts and psychic structure) diagnostic manuals are being worked out. Fundamental questions of developmental psychopathology and diagnostic procedures have to be addressed. The basic proposition takes into account that children should not be psychodynamically compared with adults, but normally have a basic capacity to adapt to environment on a high level of psychic organisation in all developmental stages. Reports of the ongoing work are being given.

Objective: With reference to an epidemiological sample of adolescents and young adults the impact of different models on the number of children classified as having specific spelling problems is investigated., Method: Using the same set of data, the effect of alternative definitions and methodological procedures on the prevalence of specific spelling retardation is shown. The virtual consequences of various norm-orientated definitions of cases is discussed with reference to external empirical criteria., Results: Particularly, obsolete norms lead to a large overestimation of cases. In the present study case definitions of specific spelling retardation based on substantial criteria result in prevalence rates between 6 and 9 percent. Academic achievement is considerably affected by persisting specific spelling problems and the attendance of secondary schools is rare, in spite of sufficient nonverbal intelligence., Conclusions: Because of the high impact of spelling ability for educational success, dyslexic children need help by early intervention. Furthermore scholastic promotion is necessary to enable a school carer appropriate to the intellectual possibilities of the child.

The impact of premorbid social and intellectual functioning in childhood and early adolescence on the developmental course of schizophrenia is not sufficiently understood. In a retrospective case study (93 consecutive in-patients, 43 males and 50 females) of first-episode psychosis occurring in adolescence, the relationship between premorbid adjustment and short-term therapeutic outcome under treatment conditions was examined. All of the patients had a DSM-III-R diagnosis of schizophrenia (n = 56) or schizo-affective disorder (n = 37). The mean age of the patients at the time of the study was 15.8 (SD = 1.0). Premorbid functioning during childhood and early adolescence was assessed by using the Cannon-Spoor et al. Premorbid Adjustment Scale (PAS) and studied with respect to its prognostic relevance for short-term therapeutic outcome (eight weeks) under neuroleptic treatment (350-700 mg Chlorpromazin dose equivalent). Criteria for clinical outcome were obtained from the study by Pearlson et al. (1989) which defines three grades (complete remission, partial remission and no response), according to the degree of positive symptomatology. Statistical analysis was based on nonparametric variance analysis. Patients with complete remission of positive symptoms after eight weeks of therapy had experienced far better premorbid adjustment in early adolescence and in childhood. Diagnosis and gender did not bias this result. Our data suggest that premorbid social functioning is a crucial variable with regard to therapeutic outcome in first-episode psychosis. Previous studies have reported a relation between poor premorbid functioning and negative symptoms. We found premorbid adjustment related to the course of positive symptoms.

In a large epidemiological sample of young adults, predictions of the right-shift (RS) theory of Annett that cognitive abilities will vary with right-left hand skill were tested. Presenting a theory of a genetic balanced polymorphism with heterozygote advantage for laterality and ability, Annett & Manning (1989, 1990a) and Annett (1993c) claimed that probands at the right end of the R-L hand skill continuum would show lower general intelligence in IQ testing and that specific verbal abilities and educational success would be lower at both extremes of the R-L distribution, taking the form of an inverted U. Most of these predictions could not be confirmed by our study. In particular, our data contrast with the important and specific prediction of the RS theory that strong dextrals will be the most disfavoured group. In our sample, probands at the left end of the R-L continuum had significantly lower scores in spelling and educational success and showed a tendency to have lower non-verbal IQ scores, while strong dextrals tended to have average or even marginally higher ability scores. The effects, however, are small and decrease when controlling for other variables. Implications of these empirical findings for the right-shift theory are discussed.

The sense of shame seems to vanish for more than a decade now, manifested e.g. by an increasing tolerance toward the naked female body. However, it is supposed that shame has still its significance especially during female puberty. Psychological considerations referring to shame and to the puberty of girls are reported and the significance of feeling ashamed in this salient segment of female development is delineated. Finally a concept is proposed within which the feeling of shame is understood as a possibility to create accordance between the positive aspects of being ashamed and the tendency of going beyond the borders of shame usually guaranteed by social rules.

Handedness and cognitive abilities in a representative sample of adolescents and young adults. The relationship between laterality and cognitive ability was examined in a representative sample of adolescents and young adults between 16 and 30 years of age. The study was designed as a possible replication of Annett's data supporting her right-shift theory (rst), but included other measures of laterality as well. We found, as Annett did, that strong right-handedness was associated with a weak left hand rather than a strong right hand. However, we could not confirm two other predictions of the rst with our data: The nonverbal IQ was significantly lower in both extreme groups of handedness than in the two middle groups. Because of the sample size this rather small effect, explaining only 1.9% of the variance, is significant, but it disappears with other kinds of grouping for handedness. We could not find the linear decline in nonverbal IQ from the left to the right extreme of handedness as predicted by the rst. In spelling, too, there was a rather small, but significant effect of handedness, explaining 2.4% of the variance. Spelling in the first (left most) quartile of handedness was worse than in quartiles two and four. The predicted poorer spelling in the extreme groups than in the middle groups (inverted U) was not found in our sample. In multivariate analysis with variables explaining larger proportions of the variance in spelling (education, nonverbal IQ and sex) the small effect of handedness on spelling completely disappeared. A weak relationship between left-handedness and dyslexia was evident only with the strictest definition of dyslexia, regardless of how handedness was defined. The implications of these data for the rst are discussed.

A blunted thyrotropin (TSH) response is a predictor of a good response to antidepressant drug treatment in depressives and neuroleptic treatment in paraphrenic patients (Larger et al 1986). The aim of the following study was to elucidate possible relationships between different endocrine systems and to shed light on the pathogenetic hypotheses of TSH-blunting. In order to evaluate especially hypothalamic activity in severe depression we were interested in the vasopressin system as another hormonal system underlying hypothalamic control. Thirty-four patients who met the criteria for major depression according to DSM-III-R were subjected to the thyrotropin-releasing hormone (TRH) test. We also took baseline readings of the cortisol, neurophysinI (hNpI, reflecting vasopressin plasma levels), and neurophysinII (hNpII, reflecting oxytocin plasma levels) levels. Likelihood ratio tests were done with logistic regression models to analyze the phenomenon of TSH-blunting. We observed that the likelihood of a blunted TSH response increases with higher levels of hNpI and low levels of cortisol, but is unrelated to hNpII levels.

Self-mutilation as addictive behaviour has been mentioned in a few studies in recent years. We present the case of a girl with narcissistic borderline personality disorder (DSM III-R: 301.83, 301.81), who undertook multiple, repetitive self-mutilating acts. Self-mutilation is discussed as addictive behaviour in this case. We emphasize the evaluation of repetitive self-mutilating acts by applying criteria for addictive and dependence disorders, in order to achieve additional adequate strategies for treating patients showing this behaviour.

Three methods for prevention of perioperative spasm of the internal mammary artery were compared in 78 patients undergoing coronary artery bypass grafting. In group 1, internal mammary artery pedicles were divided distally, clamped, and placed under the upper sternum submerged in papaverine solution (1.5 mg/ml). In group 2, as in group 1 but before clamping, 2 ml of heparinized blood with 1.5 mg/ml papaverine added was injected into the vessel lumen. In group 3 treatment was as in group 2, but heparinized blood with papaverine was injected a second time just before extracorporeal bypass was begun. In a univariate analysis free flow from dilated internal mammary arteries was not significantly different among the groups (group 1, 58 ml/min; group 2, 82 ml/min; group 3, 68 ml/min; p < 0.1). When free flow from dilated internal mammary arteries was the dependent variable in a regression analysis, the use of intraluminal papaverine, high blood pressure during flow measurement, and high initial blood flow were predictors of high flow (all p < 0.01). Morphometric measurements on the resected distal portion of the dilated internal mammary arteries disclosed less folding of the internal elastic lamina and a larger luminal area in groups 2 and 3 compared with respective findings in group 1 (1.21 mm2 and 1.42 mm2 versus 0.77 mm2; p < 0.02). Mechanical vessel wall injury occurred in 8 of 52 internal mammary arteries treated with intraluminal papaverine. Intraluminal papaverine solution injected once or twice in addition to external papaverine exposure therefore provides a better blood flow rate and distal dilation than mere submersion in papaverine solution, but at a considerable risk of mechanical wall injury.

A critical review is given of modern psychotherapeutic and sociotherapeutic approaches used with children and adolescents with schizophrenic disorders. Therapeutic strategies are evaluated within the framework of emprical data on biological and psychosocial facets of schizophrenia. Major treatment goals are discussed that go beyond differences in psychotherapeutic methodology, e.g. attainment of biographical continuity, improvement of strategies for social interaction and conflict resolution, stabilization of self-structures, mastery of age-dependent developmental tasks and, finally, coordination of different therapeutic interventions. It is stressed that psychotherapy and sociotherapy are equally important in the treatment of children and adolescents with schizophrenia.

Based on a historical survey of the term "magic thinking" structural aspects of primary process and prelogical thinking will be elucidated. Developmental necessities for the emergence of magic interpretations in children of pre-school age are proposed. The thesis will be formulated, that magic interpretations may help the developing self in the management of life-circumstances during a period of cognitive egocentrism: feelings of non-competence may be compensated, and the locus of control may be held in the face of experiences of inferiority.

The following study on natural immunology in schizophrenic patients aims at elucidating differential effects of psychopathological status and neuroleptic treatment. Natural killer (NK-) cell activity and antibody dependent cellular cytotoxity (ADCC) were tested in 24 adolescent schizophrenic patients and compared to 27 adult schizophrenics and healthy controls. Twelve adolescent patients were tested before and after 2 weeks on neuroleptic treatment. Age or psychopathological status did not have a significant impact on NK-activity or ADCC. There were no significant general effects resulting from neuroleptic treatment on NK-activity detectable in patients tested before and during treatment. However, there was a significant negative correlation between the differences of NK-activity (before and during treatment) and the NK-activity before treatment.

A retrospective study was conducted of 53 consecutive inpatients (through 1990) with psychotic disorders. The patients were between 13 and 18 years of age. In all cases this was the first time they had been treated with clozapine. The adverse effects seen under clozapine are discussed. During the use of clozapine assessments were made of liver enzymes, leukocytes, blood pressure and body temperature. There was an increase in liver enzyme values in 37.7% of the patients, leukopenia under 4000/mm3 in 15.1%, an increase in body temperature in 3.8% and bradycardia together with hypotensive dysregulation in 1.9%.

Aortocaval fistula is an uncommon complication of ruptured abdominal aortic aneurysm and is only seen in 4% of all ruptured aneurysms. The symptoms may vary from one patient to another but the characteristic physical findings are high output heart failure, widened pulse pressure with low diastolic blood pressure and venous hypertension. When these signs are combined with an abdominal aortic aneurysm and a continuous abdominal bruit, the diagnosis of aortocaval fistula must be seriously considered. It is important to diagnose the fistula before surgical intervention, so as to prevent intraoperative bleeding and complications. In our surgical department we have operated 103 ruptured abdominal aortic aneurysms but only one with an aortocaval fistula. This case is discussed in the light of the literature on the subject.

Based on a phenomenological analysis of psychotic interpretation of the world concretism is supposed to represent an important mechanism of schizophrenic thinking: Schizophrenic concretism is the result of an ontological regression of cognitive functioning onto the archaic level of actional representation. Following Jean Piaget's theories about the children's constructions of reality a hypothesis about the structure of psychotic interpretations of the world is being proposed: In psychotic thinking the knowledge about the world is structured in an adualistic way which is characterized by an alloy of significance and notion, inner and outer world, physis and psyche. The structural similarity of psychotic thinking and thinking in early developmental stages is illustrated concretely on the basis of examples. Fundamental differences between childish and schizophrenic ways of interpreting the world will be presented, showing the specificity of cognitive representation in schizophrenic thinking.

A patient with primary Hodgkin's disease of the lung is described. Special features of this case were alcohol-induced chest pain as the main presenting clinical symptom and the documentation of the evolution of the pulmonary mass by serial X-rays. Complete remission was achieved by lobectomy and subsequent MOPP-therapy. Since then the patient has been in unmaintained remission for 36 months.

This study was designed to investigate the possible common patterns of neuroendocrine mechanisms, which may be involved in the therapeutic effects of antidepressant drugs in depressive and of neuroleptic drugs in schizophrenic patients. Sixty-three depressed women (major depressive disorder) and 21 paranoid-hallucinatory women have been studied while on antidepressant (clomipramine) or neuroleptic (haloperidol) treatment, respectively. The neuroendocrine test (TRH-test) was performed at weekly intervals. The change of TSH-response to TRH during treatment, i.e. the treatment associated normalization of a former blunted TSH-response, can tentatively be regarded as a predictor of outcome for depressive and paranoid-hallucinatory patients to their respective drug treatments. Antidepressant and neuroleptic drugs appear to involve the normalization of the TSH-response in their therapeutic effects in that proportion of patients (40%) which showed a blunted TSH-response at admission.

A newly developed pulsed ultrasound Doppler meter was used for measurement of blood flow in aortocoronary vein grafts during operation. The results were compared with measurements obtained with conventional electromagnetic flowmetry. In 27 grafts, excellent agreement was found between electromagnetic flow probes thoroughly calibrated for varying hematocrit on fresh veins in vitro, and a clip-on type of Doppler probe (r = 0.86). In vitro calibration showed a close correspondence (r = 0.98) with the Doppler technique with no dependency on hematocrit and no need for zero calibration. The use of a conventional electromagnetic flowmeter showed strong dependency on recent calibration, both for saline and for varying hematocrit. Zero-calibration was necessary for every single graft measurement. The application of ultrasound Doppler meters of high quality together with clip-on probes of proper design proved to be superior to electromagnetic flowmetry for intraoperative blood flow measurements.

Valve thrombosis and its prevention was studied in 33 Labrador retriever dogs who received Hall-Haster mitral disc valves during extracorporeal circulation with extreme hemodilution. Three antithrombotic regimes were used. (1) 12 dogs received 1 g heparin preoperatively, and Warfarin tablets from the first postoperative day. Anticoagulation was controlled with thrombotest (TT), aiming at 20-25% of normal coagulation activity. (2) 9 dogs received 10 mg of heparin intravenously hourly for 10 h, and intravenous injections of Warfarin daily, aiming at TT values of 15-20%. (3) The last 12 dogs had continuous heparin infusion for 24 h, and Warfarin injections before as well as after the operation in doses sufficient to reduce the TT to 10-15% of normal. Stable anticoagulation was very difficult to maintain. Only 15 dogs survived the first postoperative day, 7 were alive after 4 weeks. 7 early and 5 late deaths were due to valve thrombosis. All three antithrombotic regimes were equally ineffective in preventing thrombosis, and more intensive antithrombotic prophylaxis is needed to make the canine model suitable for experimental open-heart surgery.

The study was designed to investigate, by weekly thyrotropin-releasing hormone tests, possible patterns of thyroid-stimulating hormone (TSH) responses which may indicate therapeutic mechanisms of antidepressant and neuroleptic drugs in patients with depressive and paranoid-hallucinatory syndrome during their process of recovery (3-9 weeks). 65 depressed women and 33 paranoid-hallucinatory women have been studied while on antidepressant (clomipramine) or neuroleptic (haloperidol) treatment, respectively. Four patterns of TSH response were observed. Patients with a pattern of a 'disblunting TSH response' (normalization of an abnormal low response) during drug treatment had a significantly higher chance to recover compared to patients with other TSH response patterns. This finding was independent of psychopathological features and drugs used for treatment. A hypothesis of 'malactivation' as a pathogenetic indicator of various psychotic states is being presented.

Natural killer (NK) cell activity and antibody-dependent cellular cytotoxicity (ADCC) were tested in patients with schizophrenia or depression. It was found that NK activity as well as ADCC were significantly lower in both groups, as compared to healthy control individuals (P less than 0.001). Psychopharmacologic treatment with neuroleptics and antidepressives resulted in a significant increase in NK activity and ADCC (P less than 0.005) in patients with schizophrenia but not in treated patients with depression. In patients with schizophrenia, no correlation could be established between the dose of neuroleptic given and the increase in NK activity. Lithium also did not produce an increase in NK activity and ADCC. The addition of serum, derived from untreated patients with schizophrenia, to cell cultures in concentrations of 10 and 20% had an inhibitory effect upon the ADCC and, to a lesser degree, upon NK activity (20% serum concentration only); sera from treatment schizophrenics produced no inhibition of NK activity, but did affect ADCC. No serum-derived inhibitory effect upon either NK activity or ADCC was found to be present in sera from patients with depression. We conclude that lytic effector mechanisms are impaired in patients with schizophrenia or depression and that this defect is reversed in schizophrenic patients on treatment, but not in depressives on therapy. Patients with schizophrenia also tend to have a reversible serum-mediated inhibition of NK activity which is absent in patients with depression.

Epidemiological, clinical and therapeutic aspects obtained from 38 cases of intoxication with the antiemetic drug "cyclizine" in children and adults are discussed. The relative frequency of accidentally or purposely performed overdosage shows a decreasing tendency. The introduction of regulations after the prescription of cyclizine compounds, leaving a limited dose available without prescription and the introduction of a safety package to prohibit misuse by children are reported in their relationship with the epidemiologic data. A toxic dose of 5 mg/kg body weight, a minimal lethal dose (MLD) of about 80 mg/kg are evaluated and compared with previous published data. Differences of age in the development of the clinical picture of the cyclizine-intoxication with a disposition for the evolvement of convulsions in children compared to the total lack of convulsions in adults have to be pointed out. The management of overdoses follows general principles of treatment like gastric lavage, supporting care and includes the specific treatment with the antidote "physostigmin-salicylate", which causes a shortening of the time of recovery.

Based on retrospective investigation using hospital records of 44 schizophrenic patients of a rehabilitation department, who committed suicide between 1966 and 1986, the paper discusses demographic and psychological features of schizophrenic suicide in comparison with international literature. Subjects who committed suicide were found to be accumulated within age-range 25 to 30 years and between one or two years of duration of illness. 20% of subjects died in an acute psychotic state, 58% had been found within a depressive episode and 66% had confronted themselves with their social situation and/or future in the light of their illness.

The present study was designed for long-term evaluation of the recently developed Hall-Kaster heart valve prosthesis. Mitral valve replacement was performed in 33 dogs. A detailed description of the operative procedure used is given. Extracorporeal circulation was instituted using a nonhemic priming volume resulting in an extreme hemodilution with hematocrit of about 15%. 19 of the animals died within 24 h, while 7 survived the observation period of 4--6 weeks. Thrombus on the valve was the major cause of early and late deaths. Anticoagulants were therefore given, and the therapy was made more extensive as the study progressed. The anticoagulation regime finally comprised warfarin administration preoperatively and throughout the experiment, and heparin infusion during the first 24 h postoperatively. Neomycin was used for preoperative sterilization of the gut. Later, cephalotin and penicillin were given. The use of these anticoagulants and antibiotics was found to be of major significance in providing us with a satisfactory canine model for long-term in vivo evaluation of the prosthesis.

In a double-blind placebo-controlled study, the effects of tenilsetam, a novel antihypoxidotic/nootropic agent, on spontaneous and event-related activity of the central and autonomous nervous system were studied in 15 elderly subjects of both sexes aged 58-77 years by means of the Viennese Psychophysiological Test-System (VPTS). The VPTS includes a special selection and combination of experimental situations, physiological measurements, behavioral measurements and data analysis. At weekly intervals, the subjects received randomized single oral doses of placebo, 150 mg, 300 mg and 900 mg tenilsetam (TEN) and 5 mg co-dergocrine-mesylate (CDM) as reference drug. Psychophysiological testings were carried out before and 2 h after drug administration. Evaluation of the spontaneous EEG-activity demonstrated no significant drug effects as compared to placebo. In contrast, TEN showed a dose-dependent augmentation of the N1-P2 and N2-P300 amplitudes of the event-related potentials (ERPs) in specific experimental conditions. In reference to placebo, the increase of N2-P300 amplitude after the highest dosage of TEN, as well as after CDM, amounted to approximately 5 microV, which confirms the hypothesis that nootropic drugs may influence the P300 amplitude in the sense of an improved availability of cognitive processing resources. There was no effect on ERP latencies, on mean amplitudes of contingent negative variation and of post-imperative negative variation, on autonomous nervous system, on psychological measurements, nor on reaction time. However, specific improvements were observed in psychomotor measures, such as synchronization accuracy and rhythmicity. These findings highlight the importance of using EEG and ERP measures in different experimental situations in conjunction with behavioral, psychological and autonomous nervous system measures to study nootropic drug effects.

The present study aimed at elucidating lytic effector cell function in 32 schizophrenic patients and comparing the results with data obtained in 27 normal probands. Natural killer cell (NK) activity and antibody dependent cellular cytotoxicity (ADCC) were tested. Schizophrenics did not differ from normal controls in either test system. Within the schizophrenic group, higher NK activity was detected in patients with neuroleptic monotherapy (p less than 0.05). Patients given a combination of neuroleptics, antidepressants and/or lithium did not differ from drug-free patients in either test system. There was no influence of psychopathological variables on lytic effector cell function.

The following pharmacokinetic study was aimed at a comparison of the bioavailability of two different preparations of diazepam (Gewacalm and a further wellknown formulation). 40 healthy volunteers were subjected to a cross-over design in which plasma levels of diazepam were assayed after oral and intramuscular application of 10 mg of a preparation. In the comparison (N = 30) of oral bioavailability (rate and completeness of enteral absorption) no statistical difference between both preparations was observed. In the study of intramuscular bioavailability (N = 10), a trend of quicker and more complete resorption of Gewacalm was of statistical significance (p less than 0.05), however, because of the small number of subjects tested in the intramuscular study a replication study is advisable.

Inotropic effects via cardiac alpha-adrenoceptors were studied in electrically driven auricular strips (1 Hz, 37 degrees C) from patients treated with beta-blockers for months prior to open heart surgery. Marked alpha-mediated positive inotropic effects were demonstrated with adrenaline (A), noradrenaline (NA) and phenylephrine (PHE) in the presence of beta-blocker and with blockers of the muscarinic receptor and of the neuronal and extraneuronal uptake mechanisms for the catecholamines. In the presence of approximately 10(-6) M propranolol the maximal effects as well as the potencies (pD2-values) for A and NA were not significantly different while higher than for PHE. The alpha 1-blocker, prazosin (10(-6) M), markedly reduced the pD2-values but not the intrinsic activities (alpha-values) for A, NA and PHE in the beta-blocked preparations. Methoxamine, however, induced negative inotropic responses at normal and low frequencies (1, 0.5 and 0.1 Hz) of stimulation, suggestive of non-specific, cardiodepressant effects. Other agonists with alpha-effects in other types of tissue (oxymethazoline, xylomethazoline and clonidine) were without effects on the force and velocity of contraction in the auricular strips under the present experimental conditions. The results show alpha 1-type of adrenoceptor-induced inotropic effects for A, NA and PHE during beta-blockade in human auricular strips, indicating that cardiac alpha 1-receptors may have clinical importance by increasing the inotropy of the human myocardium treated with beta-blocking agents.

The first in vivo haemodynamic observations of the recently developed Hall-Kaster central flow prosthetic heart valve are reported. Haemodynamic evaluation of valve function was performed both in acute and chronic experiments following implantation of the Hall-Kaster prosthesis in the mitral position in dogs. These studies showed a low transvalvular pressure gradient, an effective opening angle of about 70 degrees and good diastolic flow through both the large and small orifices of the prosthesis. A slow rotational movement was depicted by the disc during opening and closure.

The effect of celiprolol at a daily dosage of 300 mg (19 patients) was compared with that of propranolol at a daily dosage of 120 mg (14 patients) on peripheral blood flow of the calf and foot in a randomized double-blind trial. Altogether 33 patients (47 extremities) suffering from arterial occlusive disease (stage II according to Fontaine) and hypertension, were treated for 25 days. Blood flow was measured by strain-gauge plethysmography. Celiprolol led to a small, insignificant increase in resting blood flow of the muscle. Propranolol produced a small decrease in resting blood flow of the muscle, and a significant fall in resting blood flow of the skin of the foot. At the completion of treatment with celiprolol there was a small increase in the initial value of reactive hyperaemia of the calf. Propranolol led to a decrease in the initial, and in the maximum values of reactive hyperaemia of the calf and foot. Celiprolol and propranolol led to a comparable decrease in resting blood pressure.

12 Labrador retriever dogs had mitral disc valves implanted during cardiopulmonary bypass (CPB) with extreme hemodilution, obtained with preoperative blood withdrawal, the use of blood-free priming fluid during perfusion, and retransfusion of autologous blood. Before operation, platelet adhesiveness as well as the reactivity of the intrinsic and extrinsic coagulation systems were markedly higher than in man. During CPB, the number of functioning platelets was very low, but increased after retransfusion, and were after 4 h twice as high as in 7 human patients who received aortic disc valves during CPB with extreme dilution. The extrinsic coagulation system also reacted much faster during and after CPB in the dogs, and heparin activity was rapidly neutralized and intrinsic coagulation normalized in them. Intravascular coagulation did not occur, and more hemolysis was induced in the dogs than in the patients. 3 of the dogs died from valve thrombosis within 24 h. The high reactivity of platelets and coagulation systems in the dog makes the canine model a very difficult one for experimental open-heart surgery because of a strong tendency to thrombosis.

A new temporary pacemaker lead, Medtronic 6400, with a solid defined electrode surface area of 7.5 mm2, has been implanted in 50 patients after open-heart surgery. One electrode was inserted intramyocardially on the right ventricle, while another was placed extracardially and served as a reference lead. Forty-six of the patients were followed postoperatively with measurements of myocardial stimulation threshold and resistance. In 25 of the patients, electrograms were recorded on magnetic tape for further computer analysis of amplitudes, slew rates, and signal source impedance. During constant current pacing, myocardial stimulation threshold increased from a median of 0.4 mA one hour postoperatively to a maximum value of 2.3 mA. In two patients (4.3%) intermittent pacing failure was seen. Stimulation resistance fell from a median of 875 omega to a minimum of 487 omega, with a subsequent increase of 598 omega before electrode removal. Both mean electrogram amplitude (7.35 mV) and slew rate (0.82 V/s) had their minimum values on the sixth postoperative day. Intermittent sensing failure was observed in 2/25 patients (8%). Signal source impedance was of a magnitude not likely to contribute to sensing failure. No complications were seen from the use of this lead. The new electrode is an important improvement in temporary pacemaker lead design.

We determined whether the response of thyrotropin (TSH) to thyrotropin-releasing hormone could predict the outcome of treatment with antidepressant and neuroleptic drugs. We studied 114 female patients diagnosed as having major and minor depressive, manic, schizoaffective, and schizophrenic disorders. A blunted TSH response (less than 5 microU/mL [less than 5 mU/L]) at admission was associated with recovery after nine weeks of inpatient treatment using clomipramine hydrochloride for depression and haloperidol for psychosis. A blunted TSH response at discharge was associated with early relapse in depressives receiving clomipramine maintenance therapy. Our findings support the notion that the thyrotropin-releasing hormone test is a "state" marker that may be of use in predicting the outcome of treatment with antidepressant and neuroleptic drugs.

This study was aimed at disclosing possible relationships between short term therapeutic outcome and certain ranges in plasma concentrations of haloperidol and of prolactin. Acutely psychotic patients (n = 28) were diagnosed (by RDC) as schizophrenics acute subtype (n = 17), schizoaffectives manic type, acute subtype (n = 8) and manics (n = 3). Parenteral haloperidol was the pharmacological treatment mostly given; the dose was kept constant intraindividually but varied between patients from 5 to 40 mg/d (median 15 mg/d). Data for statistical analyses of possible psychobiological relationships were analyzed at 12 days (median) of haloperidol regimen, that is at a relatively early cut-off in treatment. Keeping the methodological difficulties in mind, certain ranges in plasma concentrations of haloperidol (16-26.9 mg/ml; (Fig. 1) and of prolactin (64-159.9 mg/ml; (Fig. 2) were found to be associated-statistically independently-with a favourable therapeutic outcome. The rate of recovery was best if a patient came to lie with both plasma levels within these therapeutic ranges (Fig. 3). It is concluded that the combination of pharmacological and neuroendocrinological techniques in psychiatric research may be of substantial use for clinical purposes.

A new temporary pacing lead. Medtronic Model 6400, with a defined electrode surface area of 7.5 mm2, has been clinically and electrophysiologically evaluated during bipolar atrial application in 20 patients after cardiac operations. A silicon disc was used for fixation of the electrodes to the right atrium in 10 patients, and an atrial plication technique was used in the other 10. Myocardial stimulation threshold and resistance were measured throughout the postoperative period. Atrial electrograms were recorded on magnetic tape for computer analysis of amplitudes, slew rates, and signal source impedance. No significant differences (p greater than 0.1) were found in myocardial stimulation threshold between the two fixation modes. During constant-current pacing, median threshold rose from 0.65 mA to 2.3 mA. Stimulation resistance, measured during constant-voltage pacing, fell from 567 to 365 omega, with a subsequent rise to 425 omega before electrode removal. Again no difference was found between silicon disc and plication fixation of the electrodes. P-wave amplitudes were significantly higher with plication than with silicon disc fixation (2.26 versus 0.86 mV, p less than 0.01), as were slew rates (0.34 versus 0.18 V/s, p less than 0.05). Signal source impedance had a magnitude of 6 k omega. The electrodes were used successfully in 12 (60%) of the patients for diagnosis and/or treatment of arrhythmias. We find the new lead well suited for atrial application.

Functional beta-adrenoceptor populations in the human heart were studied in vitro in electrically-paced strips of the right auricular and ventricular myocardium. The relative potency of selected agonists in producing inotropic responses (Tmax, T'max) in the presence of blockers for neuronal and extraneuronal uptakes was found to be as follows: isoprenaline greater than noradrenaline = adrenaline = salbutamol greater than dobutamine. Prenalterol had a negative inotropic effect in these preparations. The selective beta 1-(practolol) and beta 2-(H 35/25) blockers reduced inotropic responses to adrenaline (Tmax, T'max) and noradrenaline (T'max) in the auricular strips. These results indicate the participation of beta 2-adrenoceptors in inotropic responses in the human auricular and ventricular myocardium. For comparison, inotropic responses of electrically-paced rat myocardium to beta-adrenergic agonists in the presence of blockers for neuronal and extraneuronal uptakes were likewise studied. The relative potencies for Tmax were: noradrenaline = adrenaline greater than prenalterol greater than dobutamine = salbutamol. Given the high relative potency of salbutamol in the human myocardial strips (analogous to that previous shown in the beta 2-dominated atria of the frog and trout) and the low relative potency of salbutamol in the rat tissue, these findings indicate a greater population of functionally active beta 2-adrenoceptors in the human than in the rat myocardium.

In order to find a psychophysiological paradigm for clinical application we have developed the Viennese Psychophysiological Test-System (VPTS), which includes a special selection and combination of experimental situations, physiological measurements, behavioral measurements and data analysis. This study presents detailed information concerning these four aspects. Experimental situations are related to the human model of information processing, where short changes of stimulus-reaction-correlated processes are selected: resting conditions (eyes open, eyes closed), habituation-orienting test, psychomotor-performance test, signal-detection test and reaction-time test. Physiological measures include central and peripheral activity of the cerebrospinal and autonomic nervous system: cortical activity (spontaneous electroencephalogram, auditory evoked potentials, late positive components, slow potentials), ocular activity (eye and eyelid movements), electrodermal activity (skin conductance), cardiac activity (heart rate measurement), respiratory activity (rate of respiration) and peripheral vascular activity (finger pulse volume). Behavioral measurements extend from micro behavior to complex diagnostic systems: psychomotor measurements, self-reported mood, arousal and visceral perception, psychological and psychiatric interviews. The application of this test system in 15 elderly subjects of both sexes aged 58-77 years gives information which exceeds the sum of the singular constructing elements of the VPTS.