Decreased myoblast differentiation in chronic binge alcohol-administered simian immunodeficiency virus-infected male macaques: role of decreased miR-206.

Skeletal muscle stem cells play a critical role in regeneration of myofibers. We previously demonstrated that chronic binge alcohol (CBA) markedly attenuates myoblast differentiation potential and myogenic gene expression. Muscle-specific microRNAs (miRs) are implicated in regulation of myogenic genes. The aim of this study was to determine whether myoblasts isolated from asymptomatic CBA-administered simian immunodeficiency virus (SIV)-infected macaques treated with antiretroviral therapy (ART) showed similar impairments and, if so, to elucidate potential underlying mechanisms. Myoblasts were isolated from muscle at 11 mo after SIV infection from CBA/SIV macaques and from time-matched sucrose (SUC)-treated SIV-infected (SUC/SIV) animals and age-matched controls. Myoblast differentiation and myogenic gene expression were significantly decreased in myoblasts from SUC/SIV and CBA/SIV animals compared with controls. SIV and CBA decreased muscle-specific miR-206 in plasma and muscle and SIV decreased miR-206 expression in myoblasts, with no statistically significant changes in other muscle-specific miRs. These findings were associated with a significant increase in histone deacetylase 4 (HDAC4) and decrease in myogenic enhancer factor 2C (MEF2C) expression in CBA/SIV muscle. Transfection with miR-206 inhibitor decreased myotube differentiation, increased expression of HDAC4, and decreased MEF2C, suggesting a critical role of miR-206 in myogenesis. Moreover, HDAC4 was confirmed to be a direct miR-206 target. These results support a mechanistic role for decreased miR-206 in suppression of myoblast differentiation resulting from chronic alcohol and SIV infection. The parallel changes in skeletal muscle and circulating levels of miR-206 warrant studies to establish the possible use of plasma miR-206 as an indicator of impaired muscle function.

[Structural dynamics and vulnerability models]. / Strukturdynamik und Vulnerabilitätsmodelle.

This paper links Janzarik's structural-dynamic coherence model with Zubin and Springs' vulnerability model and shows that Janzarik's model enables reduction of the multiple and partially speculative single factors of the vulnerability model to a functionally interpretable and coherent theory. We will then review the internal logic of the structural-dynamic coherence model concerning the explanatory power of pathogenetic models of schizophrenia and show that Janzarik is confirmed by the literature in the assumption that primary hypodynamism is present in the run-up to the schizophrenic prodrome and first manifestations. Structural dynamic derailment as a core phenomenon in psychotic disorders is also accepted and confirmed by the literature. On the other hand, the 'einheitspsychose', or unitary psychosis, basis of the structural dynamic model is controversial. In this context the author discusses his own Vienna school's Axes model, which suggests a variety of further determinants of the pathoplastic formation of the idiopathic psychosyndrome above and beyond Janzarik's model. Finally we discuss further questions which may arise out of the structural dynamic model.

[New concepts of schizophrenic sub-syndromes - consequences for treatment]. / Neuere Konzepte schizophrener Subsyndrome - Konsequenzen für die Therapie.

Etiopathogenetic research gives rise to the suspicion that the classifications on hand pool heterogeneous disturbances under the heading of schizophrenia. This has drawn increasing attention to the necessity of identifying schizophrenic subsyndromes. Investigations using factor analysis revealed convincingly three major groups of schizophrenic symptoms: 1. a "negative factor", 2. a "psychoticism factor", comprising delusions and hallucinations and 3. a "disorganization syndrome" whose cardinal item is formal thought disorder. These studies have not yet furnished final results, but already opened insights enabling the conceptualization of syndrom-oriented therapies. The observation that the psychoticism symptomatology occurs in the frame of a "dynamic instability", based on a thymopsychic hyperreactivity, is in this regard especially important. In schizophrenic patients this hyperreactivity may be caused by secondary biological compensation mechanisms - such as perhaps an "up-regulation" of postsynaptic dopamine receptors. "Classic" neuroleptics can only correct the dynamic instability and thus eliminate psychoticism symptoms and reduce the accentuation of disorganization symptoms. They have, however, no influence upon negative symptomatology and can moreover aggravate "secondary" negative symptoms and especially impede cognitive functions. New "atypical" neuroleptics do not produce these side effects. They seem to have a reducing influence on negative symptoms and to improve cognitive functions. In each neuroleptic therapy a stepwise drug withdrawal should make clear whether or not a continous treatment is necessary. In the first case the needed efficacious dosis must be identified. The patients must learn to recognize relapse prodromes and to prevent the appearance of acute episodes through appropriate modifications of the medication. This strategy requires the combination with adequate psychotherapeutic methods enabling the patient to master persistent negative and disorganization symptoms in the best possible way.

Dose variation due to differences in applicator placement used for intracavitary brachytherapy of cervical cancer.

The prognosis for women with early stage cancers of the cervix is excellent. The cervix and proximal vagina are relatively radioresistant structures; dose limiting critical structures for radiation treatment in this area are tissues such as the bladder and rectum. The high dose rate gradient of brachytherapy allows high doses to the tumor volume, while doses to the neighboring structures are lower. Intracavitary treatment of cervical cancer is performed by insertion of tandem and ovoid applicators. Correct tandem and ovoid placement is verified and documented with orthogonal radiographs. If placement of the tandem and ovoid is not acceptable, the packing is removed, and the tandem or ovoid is repositioned or exchanged as necessary. To examine the difference in dose to specific reference points when tandem or ovoid placement was changed by the physician, three patients' initial insertion radiographs were compared to those that were accepted to treat. Points of comparison selected for the patients on each of the insertions were: point A (L and R), external iliac nodes (L and R), bladder, and rectum. Each of the placement changes for the three patients resulted in differences in distance, and therefore, differences in dose. Changes as high as 823 cGy resulted from the adjustment of only one component. In the cases examined, repositioning improved dose distribution to the cervix, and lowered the dose to adjacent critical structures.

Conceptualization of schizophrenia: the symptom-oriented approach.

E. Bleuler proposed to establish the diagnosis of schizophrenia on the basis of fundamental symptoms which he presumed to be particularly linked with the primary deficiency. K. Schneider, on the other hand, based his diagnosis on the presence of symptoms recognizable without difficulty. Modern classifications include both Bleuler's fundamental and Schneider's first-rank symptoms in their diagnostic criteria. This may lead to erroneous attributions in view of the possibility that most first-rank and some of the symptoms Bleuler suspected to be fundamental may be unspecific reactions to different basic disturbances. It can therefore be expected that research on symptoms is better suited for aetiopathogenetic investigations than research based on diagnoses. Strategies to select those symptoms on which research should focus are described and recent findings of symptom-oriented studies are discussed.

[French translation of the Frankfurt Complaint Questionnaire (Frankfurter Beschwerde-Fragebogen, FBF, Süllwold, 1986)]. / Traduction française du questionnaire de plaintes de Francfort (QPF) (Frankfurter Beschwerde-Fragebogen, FBF, Süllwold, 1986).

Observable behaviors play the predominant role in the clinical assessment of schizophrenia, while only secondary emphasis is placed on exclusively subjective complaints. Huber employed the phenomenological approach to obtain subjective symptoms that he named "basic symptoms". Subjective symptoms constitute an important component of the schizophrenic symptomatology. They may play a predominant role during the prodromal or early phases of the disease, they may be useful in elucidating cognitive and perceptual disturbances in schizophrenia. In the last decade, the assessment of patients' subjective experiences has acquired significance with the development of several instruments for their specific evaluation. The Frankfurt Complaint Questionnaire (FCQ, Süllwold, 1986) is the instrument most widely used in Europe for assessing subjective experiences. It covers a wide range of complaints of cognitive deficits that Süllwold compiled from the complaints of schizophrenic patients. We present the French translation of the FCQ. The availability of the FCQ in French could be an important step in promoting the study of subjective experiences in research and clinical activities.

[Suggestion and hypnosis in hysteria]. / Suggestion et hypnose dans l'hystérie.

Suggestive influences allow to resolve ambiguities. Normally they are only accepted if they correspond with the knowledge and believes of the subject. Under hypnosis or under the impact of serious psychic perturbations one may take up reality constructions which are not in conformity with these criteria. The restriction of consciousness and the ignoring of certain functions permitting this are the common basis of hypnosis and hysteria. But suggestions do not cause the later; they may only shape the symptomatology. Hypnosis can create a terrain facilitating the resolution of the problems underlying hysteria but it does not represent the treatment of hysteria.

[Diagnostic criteria and European nosology]. / Critères diagnostiques et nosologie européenne.

The elaboration of a-theoretical comprehensive classifications has become a main concern of American psychiatry. European psychiatrists are frequently reluctant to join this consensus-based endeavour. Their nosological approaches have largely been guided by the theoretical distinction between genuine mental diseases and quantitative psychic deviations: Jasper' warning that the dismemberment of the latter leads astray incited them to concentrate mainly on the classification of the former. Thus, European psychiatrists developed several concepts of functional psychoses which differ in regard to the subdivision of these disorders and their delimitation from mere quantitative deviations. The American classifications have partially abandoned or distorted traditional european views. In order to examine the reliance of their concepts the European schools should more systematically provide operational diagnostic criteria and submit them to polydiagnostic validation-studies.

A multicenter double-blind study of three different doses of the new cAMP-phosphodiesterase inhibitor rolipram in patients with major depressive disorder.

A multicenter randomized 4-week interindividual double-blind study was carried out in 58 hospitalized patients with major depressive disorder (DSM III 296.23, 296.22, 296.33, 296.32, 296.53 and 296.52) to test the dose-effect relationship of three different doses of the new cAMP-phosphodiesterase inhibitor rolipram: 3 x 0.25 mg, 3 x 0.50 mg and 3 x 1.00 mg rolipram/day. With respect to the desired effect, the 3 x 0.50 mg dosage stood out from the others in almost all relevant parameters. With respect to the response rate, the efficacy of the 3 x 0.25 mg dosage was about the same as that reported in the literature for placebo. The inferior performance of the 3 x 1.00 mg dosage compared to the 3 x 0.50 mg dosage might indicate a reverse U-shaped dose-effect relationship. There was good tolerance to all three dosages. There were no findings that might cast doubt on the safety of the dosages tested.

[Development of the manic-depressive concept in German language psychiatry]. / Devenir du concept maniaco-dépressif dans la psychiatrie de langue allemande.

German language psychiatry has had and still has much difficulty in getting rid of the dichotomy of endogenous psychosis as set by Kraepelin. The concept which makes a distinction between schizophrenic psychosis and manic-depressive psychosis grants the former a predominant position by applying Jasper's hierarchic rule: the presence of symptoms regarded as schizophrenic indubitably attributes the disorder to schizophrenia. Such classification, however, does not necessarily imply that schizophrenia and cyclothymia (word proposed by K. Schneider for manic-depressive psychosis) represent separate nosological entities. It is admitted that it is possible for each group to include diseases whose hereditary transmission is not necessarily due to the same genetic predisposition. Thus, German language psychiatry has well accepted the possibility that bipolar manic-depressive psychosis and unipolar depressions represent separate etiologies. For most German-speaking psychiatrists, however, the distinction between endogenous and psychogenic depressions still remains a current assumption. The distinction between these two types of depression is generally made with reference to an "endogenous item profile" or to a depressive endogenomorphous axial syndrome. Only a few authors have accepted the model of continuity between these two types of depression proposed by the London school. The Hamburg school gave a new dimension to the conceptualization of manic-depressive psychosis by drawing attention on the existence of "rapidly alternating mixed states" which are much more common than the stable mixed conditions described by Kraepelin. On the basis of this concept and by questioning the validity of Jaspers' hierarchic rule, the Vienna school has considerably extended the limits of affectives psychosis to the detriment of the wide concept of schizophrenia described by K. Schneider.(ABSTRACT TRUNCATED AT 250 WORDS)

[Evolution of diagnostic criteria for schizophrenia]. / Evolution des critères diagnostiques pour la schizophrénie.

Many operational diagnostic criteria for schizophrenia, which are rooted to various degrees in the concepts of Kraepelin, E. Bleuler and K. Schneider, have been developed during the last two decades. They often incorporate prognostic factors to which Langfeldt in particular had drawn attention. These recent criteria vary considerably according to the attitude taken with regard to Jasper's hierarchical principle, which accords a diagnostic superiority to schizophrenic symptoms over affective symptomatology. Attribution to schizophrenia is very different depending upon whether the systems uphold, reject or reverse this principle. One should distinguish between classifications based upon a consensus of experts or experienced clinicians on the one hand and diagnostic research criteria destined to test etiopathogenetic hypotheses on the other. The important principles of attribution of DSM III and DSM III-R are outlined as well as their shortcomings, the latter leading to the conclusion that one should not restrict oneself to employ solely the American classification, but utilize it along with other classifications, such as the French empirical criteria or the Vienna research criteria, in order to see more clearly whether the very broad definitions of schizophrenia do not camoufly particular etiopathogenetic entities which ought to be identified.

Predicting course and outcome in delusional psychoses.

Eighty-four of 90 patients with delusional syndromes of different nosological attribution underwent a 7-year follow-up. From 179 items covering the whole spectrum of psychiatric description of index examination, 20 were found to be statistically significant in predicting different aspects of course and outcome by stepwise discriminant analysis. Course and outcome were defined by 6 criteria (course of illness, course of delusion, development of deficiency, length of inpatient care, adequate activity and social adjustment) encompassing separate (but only partly independent) aspects of a disorder. In contrast to the literature, clinical and psychopathological variables have major prognostic weight for different psychopathological as well as psychosocial aspects of outcome. Ten of the 20 significant items cover psychopathology, 4 pre-index course, 3 precipating events, 2 data from childhood, and 1 premorbid personality. Our results stress the importance of sensitive data collection and a clear separation of different outcome variables.

Methodological aspects of follow-up studies on psychotic patients in a polydiagnostic perspective.

Polydiagnostic follow-up studies should explore whether certain definitions of a given disorder permit better prediction of the illness course than others and whether this good predictive validity is related to specific etiopathogenetic conditions. In order to carry out such studies successfully they should be based on broadly defined samples and comprise provisions for additional validation such as genetic data, neuropsychological testing etc. After an assessment at baseline and at discharge from hospital, the follow-up assessments should comprise five steps: (1) Identification of successful and unsuccessful diagnostic systems; (2) identification of features determining successful attribution; (3) analysis of successful systems; (4) analysis of unsuccessful systems, and (5) analysis of cases which have changed diagnostic attribution. The conclusions drawn from these analyses are intended to refine classification in psychiatry.

Temporal stability of diagnostic criteria for functional psychoses. Results from the Vienna follow-up study.

200 first admissions with functional psychoses were interviewed with PSE and rated simultaneously according to different diagnostic criteria (ICD-9, RDC, DSM-III, St. Louis, Taylor, Vienna Research Criteria). At follow-up 7 years later 186 patients could be traced and a course diagnosis was applied to each patient. Temporal stability of diagnostic criteria was calculated for ICD-9, RDC and DSM-III by stability coefficient and kappa values and was used as a criterion for validity. Schizophrenia and affective disorder display considerable stability over time, no matter whether one uses ICD-9, RDC or DSM-III. The data for schizoaffective disorder are less impressive, the stability coefficient is much higher for schizoaffective bipolar than for schizoaffective depressive patients.

Clinical and epidemiological aspects of dementia in the elderly.

Dementia of the Alzheimer's type (DAT) is the most significant disease of the aging brain. Descriptive epidemiology of DAT found a constant doubling of prevalence rates every 5 years. Analytic epidemiology so far failed to reliably detect risk factors for DAT other than age. This might depend on the difficulties encountered in the clinical diagnosis and differential diagnosis of dementia in the elderly, which are discussed with special reference to 1) the definition of dementia, to 2) the grading of severity of dementia, to 3) the differentiation between dementia and depression, and to 4) the differentiation between multi-infarct dementia and DAT.

Neurotic, stress-related and somatoform disorders (section F4) and physiological dysfunction associated with mental or behavioural factors (section F5): results of the ICD-10 field trial.

The results of the ICD-10 field trial in German-speaking countries relevant to sections F4 (neurotic, stress-related and somatoform disorders) and F5 (physiological dysfunction associated with mental or behavioural factors) show a comparatively low level of acceptance. Interrater-reliability in various diagnostic categories is not always adequate. In particular the allocation of some of the "old" diagnostic entities of ICD-9 to various sections of ICD-10, and in part unsatisfactory classificatory distinctions gave rise to certain problems.

[Treatment of negative symptoms in schizophrenia with neuroleptics]. / Traitement des symptômes déficitaires de la schizophrénie par les neuroleptiques.

Different concepts of negative symptoms in schizophrenia are reviewed. The beneficial effects of neuroleptics are discussed. The results of a pharmacokinetic and pharmacodynamic study with Amisulpride in healthy volunteers are reported. Preliminary findings of a study with Amisulpride in schizophrenic patients with predominately negative symptoms are presented. The utility of various rating scales for documenting the clinical state of these patients during therapy, and correlations of negative symptoms with psychometric and psychophysiological data are discussed. Finally, therapeutic consequences suggested by different hypothesized etiological factors causing negative symptoms are considered.