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Biomedical subjects

B Pflug

Publications and source records attributed to B Pflug.

At least 19 recordsLinked to original sources

Stages of sleep pathology in spinocerebellar ataxia type 2 (SCA2).

BACKGROUND: Autosomal dominant spinocerebellar ataxia type 2 (SCA2) bears clinical and neuropathologic similarities to sporadic multisystem atrophy (MSA) or Parkinson disease, in which sleep pathology is well documented. However, those clinical entities have a marked variability of the reported sleep disturbances, and their etiology is heterogeneous. In contrast, the study of SCA2 provides an opportunity to examine a molecularly homogeneous patient group, in which disease stages can be defined not only based on disease duration and ataxia scores, but also with regard to modulatory effects of mutation size. OBJECTIVE: To examine the presence and progression of sleep pathology in SCA2. METHODS: We analyzed eight patients with disease durations of 3 to 31 years, all with medium size SCA2 expansions (CAG 38 to 49), using clinical scores, sleep interviews, and video-polysomnography (VPSG) recordings. RESULTS: Almost all patients reported good subjective sleep quality and negated incidents of REM behavior disorder (RBD). At early disease stages, however, REM without atonia in four patients' VPSG suggested subclinical RBD. This was accompanied by a consistent reduction of REM density. In three patients at later SCA2 stages, REM sleep was undetectable, whereas slow wave sleep (SWS) was markedly increased at the cost of light sleep. Periodic leg movements, apnea, or hypopnea were not prominent. CONCLUSIONS: Progressive loss of dream recall in spinocerebellar ataxia type 2 was found and correlated with stages of REM more than non-REM pathology in video-polysomnography. These stages correspond to the progressive atrophy from the pons, nigrostriatal projection, and locus ceruleus to the thalamus.

Adolescent↗

Dexamethasone reduces the expression of p75 neurotrophin receptor and apoptosis in contused spinal cord.

Apoptosis is an important cause of secondary cell death in spinal cord injury (SCI). SCI induces the expression of the low affinity neurotrophin receptor p75 (p75NTR), that in the absence of the high affinity component, TrkA, can promote cell death by apoptosis. We therefore hypothesized that a reduction of p75NTR expression in SCI may increase tissue sparing and therefore improve recovery of function. As a tool to test our hypothesis we used the synthetic glucocorticoid dexamethasone (DEX) to down-regulate p75NTR expression. A standardized thoracic spinal cord contusion injury was produced in female rats. Laminectomized and SCI rats received various doses of DEX immediately after injury and the treatment was continued daily for 7 days. DEX, given at high doses (20 mg/kg, s.c.) but not at low doses (1 or 8 mg/kg) prevented the increase in p75NTR mRNA and protein in SCI rats, without affecting the expression of TrkA. High doses of DEX also reduced cellular apoptosis both in white and gray matters. This effect correlated with the ability of DEX to accelerate behavioral recovery of function measured by a combined behavioral score. These data suggest that reduction of p75NTR in SCI may be a therapeutic strategy to limit cell and tissue damage and therefore to improve recovery of function in SCI patients.

Animals↗

[Effect of activation tasks on acute neuroleptic-induced akathisia].

In this study, we investigated experimentally the effects of different activation procedures on both motor and psychic symptoms in of 11 in-patients with acute neuroleptic-induced akathisia using the Hillside and Barnes akathisia rating scales and videotape rating technique. Motor activation was achieved by finger tapping. Cognitive activation tasks consisted of sequences of mental calculations which were designed either to be easy to perform or to produce stress due to a given time limit or to more difficult calculation operations, respectively. Motor as well as psychic symptoms of akathisia decreased during both motor and simple cognitive activation without stress. By contrast, stress-producing calculation tasks led to an increase in motor and psychic symptoms immediately following the task performance. These possibly specific effects of activation procedures on symptoms might be useful in differentiating acute neuroleptic-induced akathisia from other neuroleptic-induced and extrapyramidal movement disorders.

Adult↗

[Narcolepsy. An illness in transition].

The signs of narcolepsy have been known since the last century and the tetrad of symptoms was described 50 years ago: excessive sleepiness, cataplexy, sleep paralysis, and hallucinations. Polysomnography typically shows decreased sleep and REM sleep latency, and laboratory testing reveals a high association with the human leucocyte antigens (HLA) DQB1*0602 and DQA1*102. Actual studies suggest disturbances in the orexin (hypocretin) neurotransmitter system. However, the exact pathophysiology is still unclear. In Germany, about 1500 patients diagnosed with narcolepsy are known. The prevalence in Caucasian populations is estimated at 50/100,000. Thus, the number of undiagnosed patients is likely to be high.

Cross-Sectional Studies↗

Catatonia as a psychomotor syndrome: a rating scale and extrapyramidal motor symptoms.

BACKGROUND: Catatonia was first described by Kahlbaum as a psychomotor disease with motor, behavioral, and affective symptoms. In keeping with this concept, we developed a rating scale for catatonia (Northoff Catatonia Scale [NCS]) with three different categories of symptoms (i.e., motor, behavioral, affective). Furthermore, the question of the relationship among catatonic symptoms, extrapyramidal motor symptoms, and neuroleptics was addressed in the present study. METHOD: 34 acute catatonic patients and 68 age-, sex-, diagnosis-, and medication-matched psychiatric control subjects were investigated on days 0, 1, 3, 7, and 21 with the NCS, with other already validated catatonia rating scales by Rosebush, Bush (BFCRS), and Rogers (MRS), as well as with scales for hypokinetic (SEPS) and dyskinetic (AIMS) extrapyramidal motor features. Validity and reliability of the new scale, factor analysis, correlational analysis, and differences between catatonic patients and psychiatric control subjects were statistically calculated. RESULTS: NCS showed high validity (i.e., significant positive correlations [p <0.0001] with the other scales, significant differences between catatonic and control subjects), high intra-and interrater reliabilities (r = 0.80-0.96), and high affective subscores. Factor analysis revealed four factors best characterized as affective, hypoactive, hyperactive, and behavioral. Catatonic scores in NCS correlated significantly with AIMS on day 0 and SEPS on days 7 and 21. There were no significant differences in catatonic (i.e., NCS, MRS, BFCRS) and extrapyramidal (i.e., AIMS, SEPS) scores between neuroleptically treated and untreated catatonic subjects. CONCLUSIONS: The following conclusions were drawn: (1) the NCS has to be considered as a valid and reliable rating instrument for catatonia; (2) catatonia can be characterized by psychomotor symptoms encompassing motor, affective, and behavioral alterations; and (3) extrapyramidal hyperkinesias like dyskinesias are apparently closely related to catatonic symptoms which, in general, seem to be relatively independent of previous neuroleptic medication.

Acute Disease↗

[A survey of the psychosocial situation of homeless men in Frankfurt am Main].

In a current field-study a sample of 71 homeless men (mean age 35.4 years) was investigated with a semi-standardized interview. Sociodemographically, a low education level, a high unemployment rate and low income were noted. The income was gained mainly through regular social welfare support. Mostly unmarried and without children, the participants seldom lived in a stable partnership during their life. Psychosocial conflicts (59.2%) were one of the most important causes for homelessness at an average age of 28.1 years. Interpersonal conflicts, release from jail and loss of job were the most frequently reported causes of current homelessness. 42.3% had been treated in psychiatric hospitals in the past, the majority because of alcoholism. In summary the current findings indicate that homeless men experience social isolation early during their maturation and that the frequency of psychiatric disorders is high.

Adult↗

Expression of p75NTR in a human prostate epithelial tumor cell line reduces nerve growth factor-induced cell growth by activation of programmed cell death.

Epithelial expression of the 75-kDa low-affinity neurotrophin receptor (p75NTR) is inversely associated with the malignant progression of the human prostate. To elucidate the function of p75NTR in the prostate, the human prostate epithelial tumor cell line TSU-pr1, which does not express p75NTR, was stably and transiently transfected with the cDNA for the receptor. The stably transfected cells were assessed for levels of p75NTR expression and categorized into low, intermediate, and high receptor-expressing clones by immunocytochemical and immunoblot analyses. Incorporation of [3H]thymidine was used to assess nerve growth factor (NGF)-induced changes in cell proliferation. TSU-pr1 epithelial cells transfected with a neomycin-resistance vector alone demonstrated a dose-dependent increase in the rate of NGF-stimulated [3H]thymidine uptake. Expression of p75NTR decreased the dose-dependent NGF-mediated proliferation of the TSU-pr1 prostate epithelial cells. The greater the degree of expression of p75NTR in the transfected clones, the less the stimulatory effect of exogenous NGF on cell proliferation. Furthermore, the ratio of p75NTR to tropomyosin receptor kinase for each clone was inversely correlated with the ability of NGF to stimulate growth of the TSU-pr1 transfectants. To determine whether p75NTR-mediated growth inhibition of prostate epithelia occurs by induction of programmed cell death, transiently transfected clones were analyzed by an in situ DNA nick-translation assay. NGF deprivation and anti-NGF treatment of transiently transfected TSU-pr1 cells significantly increased the proportion of epithelial cells undergoing programmed cell death by approximately fourfold above control levels. Conversely, addition of NGF was able to rescue p75NTR-expressing clones from undergoing programmed cell death at levels not significantly different from those of mock-transfected clones. These results demonstrate that p75NTR is a negative regulator of human prostate epithelial cell growth by induction of programmed cell death. Hence, loss of p75NTR expression in human prostate epithelia eliminates a growth-inhibitory pathway, thereby contributing to the malignant progression of the prostate.

Apoptosis↗

Double-blind, multicenter comparative study of sertraline and amitriptyline in hospitalized patients with major depression.

Sertraline is a selective serotonin reuptake inhibitor (SSRI) for which marketing approval has been obtained recently in Germany. The results of several double-blind, placebo-controlled studies have demonstrated that sertraline has a clear antidepressive effect. However these studies have been conducted in outpatient populations. In the context of this multicenter study, a total of 160 inpatients were treated with sertraline 50-150 mg or amitriptyline 75-225 mg over a period of 6 weeks in a double-blind fashion. Sixty-two patients in the sertraline and 59 patients in the amitriptyline group were evaluated for efficacy in the according-to-protocol (ATP) population; 80 sertraline and 75 amitriptyline patients were evaluated for safety in the Intention-to-treat population (ITT). No statistically significant differences were detected between the two groups in the efficacy analysis performed on the basis of the Hamilton Depression Scale (HAM-D) total score and Clinical Global Impression (CGI). Due to its sedating properties, amitriptyline was found to be significantly more effective with regard to the HAM-D factor "sleep disturbance". The safety analysis, which was based on the CGI, the global assessment at the end of study and a score for somatic adverse events (FSUCL) revealed statistically significant advantages of sertraline over amitriptyline. Amitriptyline was associated with more autonomic and circulatory side effects, while epigastric complaints occurred more often with sertraline. The incidence of nausea - a typical SSRI side effect - was the same in both groups.

Adrenergic Uptake Inhibitors↗

[Subjective experiences of patients with acute neuroleptic-induced akathisia].

Neuroleptic-induced akathisia is a clinically important neuropsychiatric syndrome with mainly subjectively experienced psychic symptoms on the one hand and well-observable motor signs on the other. There is no general consensus of opinion on the relative importance of these two aspects for diagnosing akathisia. Hence, differential diagnosis is difficult and in the absence of a biological marker it depends crucially on clinical judgement. Systematic investigation of 27 in-patients via a semistructural interview, a self-assessment scale (20 in-patients) and established akathisia rating scales (Hillside, Barnes, Prince Henry Hospital and Chouinard) revealed four characteristics of subjective experience in acute neuroleptic-induced akathisia: 1. perception of a foreign but nevertheless inner compulsion to move; 2. lack of control over motor behaviour; 3. feeling of inhibition of purposeful actions and 4. subjectively close or inseparable relationship between inner restlessness and restless movements. These features are strongly interrelated and correlate with severity of akathisia. They could be useful in differentiating akathisia from other states of restlessness. The results of this study are discussed in context of the literature on clinical phenomenology of akathisia. We propose a symptom-severity model of akathisia emphasizing psychodynamic aspects with considerable consequences for diagnosis and quantification of the disorder. The model points to the relevance of patient exploration for optimizing diagnostic reliability and should be taken into account when developing new and valid akathisia rating instruments.

Adolescent↗

Can response to partial sleep deprivation in depressed patients be predicted by regional changes of cerebral blood flow?

The possible predictive value of regional cerebral perfusion patterns with respect to the response to partial sleep deprivation (PSD) was evaluated in 15 major depressive patients (mean age = 54.9 years, mean Hamilton depression score = 21.6). Patients were studied with single photon emission computed tomography with technetium-99 m-D,L-hexamethyl-propylene amine oxime. Scans were performed on the morning before and after (at 08.00 h) PSD. Responders to PSD had significantly higher perfusion in the right orbitofrontal cortex than did non-responders before PSD. Multiple regression analysis indicated that right orbitofrontal/basal cingulate perfusion (r = -0.77, P < 0.001) before PSD, and left inferior temporal perfusion (r = 0.59, P = 0.01) after PSD, were fairly accurate predictors of change in Hamilton depression scores. Thus, it appears that the orbitofrontal cortex and the cingulate are involved in PSD and may serve as predictors of therapeutic response.

Adult↗

Loss of low-affinity nerve growth factor receptor during malignant transformation of the human prostate.

BACKGROUND: The low-affinity nerve growth factor receptor (LNGFR) exhibits an inverse association of epithelial expression with the degree of differentiation of prostate adenocarcinoma tissue. However, the stage at which loss of LNGFR expression is first manifested in the malignant prostate has not been determined. METHODS: In order to characterize loss of LNGFR expression in the clinically localized malignant prostate of untreated patients, the pattern of expression of the LNGFR was examined in nonmalignant tissues, consisting of normal and prostatic intraepithelial neoplastic tissues, and in malignant tissues that had been graded by Gleason's scores and categorized into well, moderately, and poorly differentiated adenocarcinomas. In order to determine whether there was an inverse correlation between LNGFR expression and prostate-specific antigen (PSA) secretion, preoperative concentrations of PSA in the serum were also analyzed in relation to the differentiative state of the adenocarcinomas. RESULTS: Premalignant prostate tissues exhibited expression of the LNGFR on all epithelia, whereas in malignant prostate tissues a proportion of epithelia exhibited loss of expression of the LNGFR. An increase in Gleason score of the adenocarcinoma tissue was associated with an increase in the proportion of epithelia that exhibited loss of expression of the LNGFR. Moreover, the proportion of epithelia expressing the LNGFR was inversely correlated with an increase in the concentration of serum PSA. The loss of LNGFR expression was first manifested in epithelia that occurred toward the center of adenocarcinoma tissue. Furthermore, extensive loss of expression of the LNGFR of approximately 63% occurred in well-differentiated adenocarcinomas. CONCLUSIONS: These observations demonstrate that loss of LNGFR expression is first observed in well-differentiated malignant epithelia. Hence, loss of the LNGFR may be indicative of the initial stages of malignant transformation of prostate epithelia, as well as all subsequent stages of prostate adenocarcinomas.

Adenocarcinoma↗

Two peptides derived from the nerve growth factor precursor are biologically active.

This report provides evidence that the proregion of the NGF precursor protein contains two novel bioactive peptides. The presence of pairs of basic amino acid (aa) residues in the NGF proregion suggests that two or three peptides other than NGF may be generated by proteolytic cleavage. Synthetic peptides of 29 aa (LIP1) and 38aa (LIP2) corresponding to the sequences -71 to -43 and -40 to -3 of the proNGF, respectively, were used in this study. ELISA specific for these two peptides revealed their presence in the rat intestine. LIP1 was localized by immunohistochemistry in endocrine cells of the intestinal epithelium, and LIP2 was immunoprecipitated from an intestinal extract. We also provide evidence for the presence of specific receptors for LIP2 in several cell lines. Scatchard analysis indicated the presence of a low affinity binding site with a Kd of approximately 10(-7) M and a high affinity binding site of 10(-9) M. Cross-linking studies revealed receptor forms of about 140 kD and 93 kD in a prostatic adenocarcinoma cell line. LIP1 and LIP2 induced rapid F-actin redistribution in PC12 cells within 2 min of incubation, which suggests a role of LIP1 and LIP2 in the process of neurite outgrowth. Furthermore, both propeptides induced rapid tyrosine phosphorylation of the Trk protein in both prostatic adenocarcinoma cells and PC12 cells, thus implicating trk in their mechanism of action. These results support our hypothesis that two peptides within the NGF precursor protein are biologically active.

Actins↗

Plasma homovanillic acid concentrations in catatonia.

We investigated the dopamine metabolite plasma homovanillic acid (plasma HVA) levels in 37 catatonic patients on the day of admission before initial medication as well as in 17 healthy controls. In a prospective study catatonic syndrome was diagnosed according to criteria of Lohr and Wiesniwski (1987) and Rosebush et al (1990) whereas comorbid diagnosis was made by Diagnostic and Statistical Manual of Mental Disorders, 3rd ed, revised (DSM III/R) (APA 1987). On the day of admission blood samples were taken before initial medication. Compared to controls (80.1 +/- 40.1 pmol/mliter) catatonic patients showed significantly (P = 0.0286) increased plasma HVA (140.9 +/- 53.6 pmol/mliter). Catatonic patients free of neuroleptic medication (n = 21) differed significantly (p = 0.0416) from controls whereas neuroleptically treated catatonics (n = 16) did not. Our findings of increased plasma HVA in catatonia are explained by an alteration in either mesolimbic or mesocortical dopaminergic function, as is assumed in the case of schizophrenia. As an alternative, it may be due to increased nigrostriatal function, which can lead, as shown in animal experiments with the dopamine agonist amphetamine, to hypokinetic states resembling catatonia in humans.

Adolescent↗

Increase of serum creatine phosphokinase in catatonia: an investigation in 32 acute catatonic patients.

We investigated serum creatine phosphokinase (CPK) and associated parkinsonic (SEPS) and dyskinetic (AIMS) movements in 32 hospital admitted acute catatonic patients. Thirty-two (N = 24 without neuroleptics on admission) catatonic patients were compared with 32 non-catatonic dyskinetic psychiatric patients, 32 non-catatonic non-dyskinetic psychiatric patients and 32 healthy controls. CPK was significantly higher (P = 0.015) in catatonics (mean 255.75, S.D. +/- 226.54) than in healthy controls (38.6, +/- 27.4) and non-catatonic non-dyskinetic psychiatric patients (57.1, +/- 120.8) whereas there was no significant difference between catatonics and non-catatonic dyskinetic psychiatric patients (453.4, +/- 128.5). There were significantly positive correlations between CPK and AIMS, as well as significantly negative correlations between CPK and SEPS, in all three groups. Our results suggest that increased serum CPK in catatonia may be related to occurrence of dyskinetic movements. Furthermore, we were able to distinguish a parkinsonic (low CPK, low AIMS, high SEPS) and a dyskinetic (high CPK, high AIMS, low SEPS) subtype in catatonia.

Acute Disease↗

[The subjective experience in catatonia: systematic study of 24 catatonic patients].

Catatonic patients are often not able to communicate their subjective experiences behind their "fassade of immobility." Therefore was retrospectively (3 weeks later) investigated subjective experiences in 24 catatonic patients with a self-assessment-scale especially for catatonia developed by us. Our results showed that catatonic patients subjectively experience less their altered movements but rather cognitive, i.e. ambivalence, or affective, i.e. intense emotions which couldn't be controlled, alterations. According to our results we were able to distinguish an emotive (intense anxiety) from a non-emotive, i.e. cognitive (predominating ambivalence), subtype in catatonia with regard to subjective experience.

Adult↗

[Benzodiazepine withdrawal with carbamazepine].

Seventeen patients who had been dependent on benzodiazepines for more than 0.5 years were subjected to abrupt withdrawal with carbamazepine (CBZ, 400 mg twice a day). Most patients were had been taking benzodiazepines because of panic disorder or neurosis. In 2 cases the patients were regarded as having high dose dependency. In 2 others withdrawal was discontinued because of loss of motivation or medical problems (HIV infection). During the withdrawal the patients were rated daily for anxiety, mood alterations, perception disturbances, neurological symptoms, and vegetative signs. Perception disturbances were noted in 14 patients. Most patients showed sleep disturbances, mood alterations or anxiety. Epileptic seizures, a well known complication of benzodiazepine withdrawal, did not occur. The CBZ treatment was well tolerated by all patients and caused no severe problems. Compared with a gradual tapering off of benzodiazepines, abrupt withdrawal plus CBZ medication seems to be better tolerated; in particular, the period of hospitalization for these patients can be shorter. Because anxiety, the reason for the benzodiazepine treatment in many cases, often recurs, the patients must be offered continuous after-care to prevent a new dependence.

Adult↗

[Subjective diurnal fatigue and sleep deprivation response].

29 major depressive patients, the majority suffering from a melancholic subtype and typical diurnal variation of mood, rated subjective tiredness on a 100 mm analogous scale before and after total sleep deprivation (TSD). In study A every four hours during the day before and after TSD and every 2 hours during the TSD-night ratings were performed, in study B at 8.00 a.m. before and after TSD. The mean response rate was 55.2% in the 2 studies. In study A subsequent responders were less tired during the afternoon before TSD. Responding patients were more alert the morning after sleep deprivation than non-responders. A higher inter-individually variability of tiredness ratings in responders before and after sleep deprivation was found in study B, assuming an arousing property and a greater variability in subjective arousal at least during the morning hours. In summary the determination of the subjective arousal level may help to predict response.

Adult↗

Ball experiments in 32 acute akinetic catatonic patients: deficits of internal initiation and generation of movements.

We undertook ball experiments in 32 akinetic catatonic patients in order to determine specific functional deficits in the motor system in akinetic catatonia. Standardized ball experiments (catching, throwing, stopping, kicking) were conducted in 32 acute akinetic catatonic patients (23 without neuroleptics on admission), diagnosed according to Lohr, Rosebush, and the Diagnostic and Statistical Manual of Mental Disorders (3rd ed, revised) on days 0 and 21. Additionally, associated psychopathology was evaluated using different scales on days 0 and 21: the Global Assessment Scale, the Brief Psychiatric Rating Scale, the Hamilton-Anxiety Scale, the scale for the assessment of negative symptoms (SANS), and the Simpson scale for extrapyramidal side effects (SEPS). Significantly more patients were able to perform more externally guided tasks (catching, stopping) than internally guided tasks (throwing, kicking). Patients showed significantly more posturing and awkward movements on day 0 than on day 21. There was a significantly positive correlation between hypokinetic extrapyramidal features (SEPS) and negative symptoms with their cognitive alterations (SANS) on day 0. The findings suggest a deficit of internal initiation, as in parkinsonism, as well as a dysfunction in the generation of voluntary movements in akinetic catatonia. We assume an underactivity in the dorsolateral prefrontal cortex and the supplementary motor area with consecutive down-regulation of the cortical-striatal-thalamic circuit, the "motor loop," in catatonia.

Acute Disease↗