Biomedical subjects

A Czernik

Publications and source records attributed to A Czernik.

At least 19 recordsLinked to original sources

PubMed2006

Improvement of cognitive functions in chronic schizophrenic patients by recombinant human erythropoietin.

Schizophrenia is increasingly recognized as a neurodevelopmental disease with an additional degenerative component, comprising cognitive decline and loss of cortical gray matter. We hypothesized that a neuroprotective/neurotrophic add-on strategy, recombinant human erythropoietin (rhEPO) in addition to stable antipsychotic medication, may be able to improve cognitive function even in chronic schizophrenic patients. Therefore, we designed a double-blind, placebo-controlled, randomized, multicenter, proof-of-principle (phase II) study. This study had a total duration of 2 years and an individual duration of 12 weeks with an additional safety visit at 16 weeks. Chronic schizophrenic men (N=39) with defined cognitive deficit (>or=1 s.d. below normal in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)), stable medication and disease state, were treated for 3 months with a weekly short (15 min) intravenous infusion of 40,000 IU rhEPO (N=20) or placebo (N=19). Main outcome measure was schizophrenia-relevant cognitive function at week 12. The neuropsychological test set (RBANS subtests delayed memory, language-semantic fluency, attention and Wisconsin Card Sorting Test (WCST-64) - perseverative errors) was applied over 2 days at baseline, 2 weeks, 4 weeks and 12 weeks of study participation. Both placebo and rhEPO patients improved in all evaluated categories. Patients receiving rhEPO showed a significant improvement over placebo patients in schizophrenia-related cognitive performance (RBANS subtests, WCST-64), but no effects on psychopathology or social functioning. Also, a significant decline in serum levels of S100B, a glial damage marker, occurred upon rhEPO. The fact that rhEPO is the first compound to exert a selective and lasting beneficial effect on cognition should encourage new treatment strategies for schizophrenia.

Adult↗

PubMed2002

[Personality, accentuated traits and personality disorders. A contribution to dimensional diagnosis of personality disorders].

A dimensional diagnostic system for personality disorders (PD) postulates continuous transition from normal to disordered personalities (continuity hypothesis) and universal validity of basic personality dimensions (universal hypothesis). The present study investigates the validity of Leonhard's concept of attenuated personalities that define a conceptual link between normal personality dimensions and PD. Nine possible continuous transitions between three conceptual levels (Big Five personality factors, nine attenuated personality traits, nine PD) were tested by questionnaire data obtained from a mentally healthy (n = 166) and a clinical sample (n = 78). Both samples differed significantly in nearly all variables. However, they showed substantial similarity concerning the (in)validity of single continua and the complex structure of all variables as analyzed by multidimensional scaling. The concept of attenuated personalities could be validated for six out of nine tested continua and can be recommended for application in dimensional models of personality and personality disorders.

Adult↗

PubMed2002

[Personality and personality disorders I. Universality and sensitivity of dimensional personality models as diagnostic systems for personality disorders].

OBJECTIVE: A dimensional diagnostic system for personality disorders (PD) postulates continuous transitions from normal to disordered personalities (continuity hypothesis) and universal validity of basic personality dimensions (universal hypothesis). In the present study three dimensional personality models that claim to provide a systematic representation of the overall domain of personality disorders were compared: the Big-Five model proposed by Costa and McCrae, the psychobiological model proposed by Cloninger and colleagues, and the "Dimensional Assessment of Personal Pathology (DAPP)" model proposed by Livesley and colleagues. METHOD: The "Six Factor Test" (SFT) measuring the Big-Five factors of personality, the "Temperament and Character Inventory (TCI)" measuring 4 temperament and 3 character dimensions, and the DAPP measuring 18 basic traits and 4 second ordered factors were administered to general population subjects (n = 156), and a clinical sample (n = 220) including a subsample of 69 patients with at least one diagnosis of DSM-IV PD. Group comparisons, regression analyses, and facet theoretical analyses were conducted. RESULTS: The nonmetric similarity analyses of the three personality models show a nearly identical radex-representation of the second ordered factors in the non-clinical and clinical sample reflecting an universal validity of 4 basic personality dimensions and confirming the universal hypothesis. In comparison with the BIG-Five concept and the psychobiological model the DAPP model seems to be more sensitive to differentiate PD patients from controls with a reclassification rate of 94.5 %. CONCLUSIONS: The Big-Five model, the DAPP and the TCI represent a substantially similar domain despite their different conceptualization. However, the DAPP was more sensitive to differences between PD patients and controls, offered a more comprehensive account of PD, and could differentiate the two groups more effectively.

Character↗

PubMed2002

[Personality and personality disorders II. The Specificity of the DAPP-model as a diagnostic system for personality disorders].

The 'Dimensional Assessment of Personality Pathology - Basic Questionnaire' (DAPP) measures 18 traits to provide a systematic representation of the overall domain of personality disorders (PD). The present study investigated the relationships between DAPP personality profiles and dimensional assessments of DSM-IV PD in general population subjects (n = 156), and a sample of 220 nonpsychotic psychiatric patients (including n = 67 PD patients). Using nonmetric multidimensional scaling models the similarities between the 18 DAPP-factors and the dimensional scores of the 12 DSM-IV PD (inclusive appendix) were graphically represented in a 2-dimensional similarity-system. Here each DSM-IV PD dimension could be described by a distinct profile of DAPP-factors. Overall results support the assumption that PD can be represented by a dimensional system of personality traits with sufficient sensitivity and specificity.

Humans↗

PubMed2001

Altered expression of a-type but not b-type synapsin isoform in the brain of patients at high risk for Alzheimer's disease assessed by DNA microarray technique.

Using a cDNA microarray representing 6794 distinct human genes, we identified candidate genes whose expression is altered in cerebral cortex of cases of early Alzheimer's disease (AD); among these was the synaptic vesicle protein synapsin II, which plays an important role in neurotransmitter release. While other candidate genes are presently under investigation in our lab, in this study we discuss the regulation of synapsin gene expression during the transition from normal cognitive function to early AD. We found a selective decrease in the expression of the synapsin splice variants I-III of the a-type isoform in the entorhinal (EC, BM36) but not visual cortex (VC, BM17) of cases characterized by the earliest clinically detectable stage of AD. In contrast, we found no changes in synapsin splice variant II of the b-type isoform. Alteration of synapsin expression at the earliest clinical stage of AD may suggest novel strategies for improved treatment.

Aged↗

PubMed2000

Stimulation of unitary T-type Ca(2+) channel currents by calmodulin-dependent protein kinase II.

The effect of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) stimulation on unitary low voltage-activated (LVA) T-type Ca(2+) channel currents in isolated bovine adrenal glomerulosa (AG) cells was measured using the patch-clamp technique. In cell-attached and inside-out patches, LVA channel activity was identified by voltage-dependent inactivation and a single-channel conductance of approximately 9 pS in 110 mM BaCl(2) or CaCl(2). In the cell-attached patch, elevation of bath Ca(2+) from 150 nM to 1 microM raised intracellular Ca(2+) in K(+)-depolarized (140 mM) cells and evoked an increase in the LVA Ca(2+) channel probability of opening (NP(o)) by two- to sixfold. This augmentation was associated with an increase in the number of nonblank sweeps, a rise in the frequency of channel opening in nonblank sweeps, and a 30% reduction in first latency. No apparent changes in the single-channel open-time distribution, burst lengths, or openings/burst were apparent. Preincubation of AG cells with lipophilic or peptide inhibitors of CaMKII in the cell-attached or excised (inside-out) configurations prevented the rise in NP(o) elicited by elevated Ca(2+) concentration. Furthermore, administration of a mutant recombinant CaMKIIalpha exhibiting cofactor-independent activity in the absence of elevated Ca(2+) produced a threefold elevation in LVA channel NP(o). These data indicate that CaMKII activity is both necessary and sufficient for LVA channel activation by Ca(2+).

Animals↗

PubMed1999

[Quality of life. Construct validation and the development of a modular system].

The construct Quality of Life (QoL) is investigated by metaanalysis of eight (inter)nationally validated questionnaires in a multicenter study. Data have been collected in a mentally healthy (n = 479), a depressed (n = 171) and a schizophrenic (n = 139) sample. Conventional psychometric criteria and a facet analytical methodology have been applied. The resulting questionnaire "Modular System for Quality of Life" (MSQoL) consists of a core module with 47 items (one "G-factor" and six subdimensions), which is sufficiently valid for all three samples. Additionally, there are four specific modules (demography, family, partnership, profession). No specific modules can be identified for the psychopathological subgroups. The validated radex structure for subjective QoL offers the opportunity for a cumulative research design and for adaptations to the actual setting.

Adolescent↗

PubMed1999

Identification of the putative mammalian orthologue of Sec31P, a component of the COPII coat.

The regulation of intracellular vesicular trafficking is mediated by specific families of proteins that are involved in vesicular budding, translocation, and fusion with target membranes. We purified a vesicle-associated protein from hepatic microsomes using sequential column chromatography and partially sequenced it. Oliogonucleotides based on these sequences were used to clone the protein from a rat liver cDNA library. The clone encoded a novel protein with a predicted mass of 137 kDa (p137). The protein had an N terminus WD repeat motif with significant homology to Sec31p, a member of the yeast COPII coat that complexes with Sec13p. We found that p137 interacted with mammalian Sec13p using several approaches: co-elution through sequential column chromatography, co-immunoprecipitation from intact cells, and yeast two-hybrid analysis. Morphologically, the p137 protein was localized to small punctate structures in the cytoplasm of multiple cultured cell lines. When Sec13p was transfected into these cells, it demonstrated considerable overlap with p137. This overlap was maintained through several pharmacological manipulations. The p137 compartment also demonstrated partial overlap with ts045-VSVG protein when infected cells were incubated at 15 degrees C. These findings suggest that p137 is the mammalian orthologue of Sec31p.

Amino Acid Sequence↗

PubMed1997

Lithium vs carbamazepine in the maintenance treatment of schizoaffective disorder: a randomised study.

In a randomised multicentre study, the prophylactic efficacy of lithium and carbamazepine was compared in schizoaffective disorder. A total of 90 ICD-9 schizoaffective patients were included in the maintenance phase (2.5 years). They were also diagnosed according to RDC and DSM-III-R and classified into subgroups. Mean serum levels were 0.58 +/- 0.12 mmol/l for lithium and 6.4 +/- 1.5 micrograms/ml for carbamazepine (mean dose 643 +/- 179 mg/d). Outcome criteria were hospitalisation, recurrence, concomitant psychotropic medication and adverse effects leading to discontinuation. There were more non-completers under carbamazepine than under lithium (p = 0.02). Survival analyses demonstrated no significant differences between lithium and carbamazepine in treatment outcome. Patient's ratings of side effects (p = 0.003) and treatment satisfaction (p = 0.02) favoured carbamazepine. Following the RDC criteria, patients of the schizodepressive and non-classifiable type did better under carbamazepine (p = 0.055 for recurrence), whereas in the schizomanic patients equipotency of both drugs was found. Applying DSM-III-R, carbamazepine demonstrated a superiority in the patient group with more schizophrenia-like or depressive disorders (p = 0.040 for recurrence), but not in patients fulfilling the DSM-III-R criteria of bipolar disorder. Lithium and carbamazepine seem to be equipotent alternatives in the maintenance treatment of broadly defined schizoaffective disorders. However, in subgroups with depressive or schizophrenia-like features and regarding its long-term tolerability carbamazepine seems to be superior.

Adult↗

PubMed1997

Personality differences between patients with major depression and bipolar disorder--the impact of minor symptoms on self-ratings of personality.

The study explores whether minor symptoms of patients in recovery from a mood disorder have an impact on self-ratings of personality with special consideration of potential differences between diagnostic groups. 90 recovered DSM-III-R major unipolar depressives and 167 recovered bipolars were compared with respect to scale values of the Munich Personality Test (MPT). Major depressives showed significantly higher scores on the MPT scales Rigidity and Orientation towards Social Norms, and lower scores on Extraversion than the bipolar patients. Using a LISREL-model, psychopathology was found to have a significant impact on Neuroticism and Extraversion, but not on Rigidity and on Orientation towards Social Norms. Controlling for symptomatology, the differences in the MPT scale values of the two diagnostic groups remained significant and can hardly be sufficiently explained by residual symptomatology.

Adult↗

PubMed1997

Lithium versus carbamazepine in the maintenance treatment of bipolar disorders--a randomised study.

In a randomised multicentre study, the prophylactic efficacy of lithium and carbamazepine was compared in 144 patients with bipolar disorder (74 vs. 70 patients; observation period: 2.5 years; lithium serum level: 0.63 +/- 0.12 mmol/l, carbamazepine dose: 621 +/- 186 mg/day). Hospitalisations, recurrences, need of psychotropic comedication and adverse effects prompting discontinuation were defined as treatment failures. Survival analyses regarding hospitalisations and recurrences showed no statistically significant differences between both drugs. Results were distinctly in favour of lithium, considering recurrences combined with comedication (P = 0.041) and/or adverse effects (P = 0.007). Whereas adverse effects prompting discontinuation were more frequent under carbamazepine (9 vs. 4, ns), lithium patients reported more often slight/moderate side effects (61% vs. 21% after 2.5 years; P = 0.0006). In completers, recurrences occurred in 28% (lithium) vs. 47% (carbamazepine) of the patients (P = 0.06). Lithium seems to be superior to carbamazepine in maintenance treatment of bipolar disorder, in particular when applying broader outcome criteria including psychotropic comedication and severe side effects.

Adult↗

PubMed1997

5-HT brain function in affective disorder: d,l-fenfluramine-induced hormone release and clinical outcome in long-term lithium/carbamazepine prophylaxis.

Prolactin (PRL) and Cortisol (CORT) responses to d,l-fenfluramine (FEN) challenge (60 mg) were examined in patients with affective disorders on two occasions under euthymic conditions: drug-free before admission to prophylactic treatment and after about 9 months of medication with lithium or carbamazepine. Response to treatment was assessed by a complex algorithm using continuous ratings in outpatient clinic over a period of 2 years. In general, treatment resulted in a delayed and diminished CORT release (n.s.); subgroup analysis revealed an attenuated CORT response (P < 0.05) in responders, whereas nonresponders showed no change in CORT secretion pattern except an enhanced CORT baseline value (P < 0.05). Cross-sectional comparison of responders with nonresponders under medication yielded a trend for greater CORT stimulation in nonresponders. This result was not affected by FEN/NorFEN or lithium/carbamazepine serum levels, baseline CORT values, age, sex, diagnostic distribution, number of appointments to the outpatient clinic or duration of medication at the time of FEN test session. Before onset of prophylactic medication responders and nonresponders could not be discriminated significantly regarding stimulated hormone release, probably due to the small sample size (n = 17). CORT response to FEN was increased in drugfree unipolar patients compared to bipolar (P < 0.05) and to schizoaffective patients (P < 0.1). In accordance with its well-documented presynaptic 5-HT-agonistic action lithium medication resulted in a significantly greater increase in CORT release than carbamazepine (P < 0.05). Evaluation of PRL stimulation showed patterns of secretion quite similar to those of CORT, without reaching statistical significance in most cases. Perhaps due to methodological differences in assessing treatment response, these data do not confirm former results, which supposed an enhanced 5-HT net activity in long-term prophylactic lithium treatment. Because of high interindividual variances of hormone parameters, the FEN-test procedure is not a useful tool for the prediction of therapeutical outcome in terms of clinical routine use. Relations of stimulated hormone response as a marker of central serotoninergic activity and clinical outcome are discussed.

Adult↗

PubMed1996

Comparative efficacy of lithium and amitriptyline in the maintenance treatment of recurrent unipolar depression: a randomised study.

The present study, including 81 depressive patients, compares the prophylactic efficacy of lithium and amitriptyline in recurrent unipolar depression over a treatment period of 2.5 years in a randomised multicentre design. Hospitalisation, re-emergence of depressive or subdepressive recurrences, unwanted side-effects and need of concomitant psychotropic medication were considered to indicate treatment failures. Average dosage for amitriptyline was 98 +/- 37 mg/day, average lithium blood level was 0.59 +/- 0.12 mmol/l. Survival analyses demonstrated a significant superiority of lithium (P = 0.015) regarding the outcome criteria 'recurrences and/or subclinical recurrences' and non-significantly better results of lithium compared to amitriptyline concerning 'recurrence' (P = 0.059) or 'recurrence and/or concomitant medication' (P = 0.066).

Adolescent↗

PubMed1993

The recruitment process for a multicenter study on the long-term prophylactic treatment of affective disorders.

The paper reports on the process of patient recruitment for a controlled clinical multicenter study on the treatment of affective disorders. Two thirds of the patients screened did not participate because prophylactic treatment was either unnecessary or not justified for medical reasons. Further, a number of patients equal to that eventually allocated to the trial refused to participate for personal, idiosyncratic reasons. In spite of this, the patients in the trial were very similar to those not participating with respect to relevant variables such as age, sex, number of and intervals between previous episodes or severity of the present episode.

Adult↗

PubMed1987