Biomedical subjects

R Schlösser

Publications and source records attributed to R Schlösser.

At least 19 recordsLinked to original sources

PubMed2005

[Schizophrenia as a disconnection syndrome. Studies with functional magnetic resonance imaging and structural equation modeling].

Aside from characteristic psychopathological symptoms, cognitive deficits are a core feature of schizophrenia. These deficits can only be addressed within the context of widespread functional interactions among different brain areas. To examine these interactions, structural equation modeling (SEM) was used for the analysis of fMRI datasets. In a series of studies, both in antipsychotic-treated and drug-free schizophrenic patients, a pattern of enhanced thalamocortical functional connectivity could be observed as an indicator for possible disruptions of frontostriatal thalamocortical circuitry. Moreover, drug-free patients and those receiving typical antipsychotic drugs were characterized by reduced interhemispheric corticocortical connectivity. This difference relative to normal controls was less in patients under atypical antipsychotic drugs. The results could be interpreted as a beneficial effect of atypical antipsychotic drugs on information processing in schizophrenic patients. The present findings are consistent with the model of schizophrenia as a disconnection syndrome and earlier concepts of "cognitive dysmetria" in schizophrenia.

Antipsychotic Agents↗

PubMed2005

Oxidative stress related markers in the "VITA" and the centenarian projects.

Oxidative stress seems to play an important role in the pathophysiology of Alzheimer's disease (AD). At present there are no easily accessible biochemical markers for AD. We performed activity assays for platelet MAO-B and erythrocyte Cu/Zn-SOD as well as Western blotting for these two proteins. Moreover, we assessed plasma lactoferrin and performed RFLP-analysis for the MAO-B-intron-13-polymorphism in patients from the Vienna-Transdanube Aging (VITA) and from the so called centenarian project. The first one, VITA, is a community-based cohort study of all 75 years old inhabitants of a geographical region of Vienna. The centenarian project investigates chronic care in-old patients suffering from AD. In both sexes platelet MAO-B activity increased significantly in the AD group, and Cu/Zn-SOD activity decreased, but the latter effect was significant only in females. No significant difference was found regarding plasma lactoferrin. No correlation was found between MAO-Bi13 and MAO-B platelet activity or allele MAO-Bi13 and disease frequency. These results point to the possibility that a combination of MAO-B and SOD activity levels might be useful tools for an early diagnosis of AD.

Aged↗

PubMed2002

Long-term effects of the substituted benzamide derivative amisulpride on baseline and stimulated prolactin levels.

In the present study, we investigated the long-term effects of treatment with amisulpride, a substituted benzamide derivative, as compared with the effects of treatment with flupenthixol, a thioxanthene, on the prolactin levels in schizophrenic patients. After completing 6 weeks of medication with either amisulpride or flupenthixol, the patients entered a long-term maintenance treatment with amisulpride 200-600 mg/day or flupenthixol 5-15 mg/day for a maximum of 12 months with a subsequent drug-free follow-up until month 15. Eighteen initially included patients were still participating in the study at month 6. In the flupenthixol group, only 1 patient treated reached month 12, and none of the patients reached month 15. For the amisulpride treatment group, months 12 and 15 were completed by 9 and 6 patients, respectively. After 1, 3, 6, and 12 months of treatment, and finally 3 months after cessation of treatment, the basal and thyrotropin-releasing hormone-stimulated secretions of prolactin were investigated. The prolactin plasma levels were elevated in both treatment groups during the course of maintenance treatment with a maximum effect at month 1. Flupenthixol treatment initially raised the prolactin levels about two- or threefold, and a subsequent decline during months 3 and 6 occurred. However, only the changes for month 1 reached the level of a statistical trend. The prolactin secretion was initially increased over tenfold by amisulpride. The prolactin levels at months 1, 3, 6, and 12 were significantly elevated as compared with the baseline values. A continuous decline of prolactin levels in both treatment groups occurred over the course of the next months. The prolactin response after the thyrotropin-releasing hormone challenge was not significantly changed over the long-term course. Notably, in the amisulpride group, 3 months after cessation of treatment at month 12, the elevated levels of prolactin returned to baseline at month 15. In summary, amisulpride demonstrated more pronounced effects than flupenthixol on the prolactin levels. However, the findings indicate also that treatment with amisulpride at clinically effective doses can be achieved at significantly lower prolactin levels during the long-term maintenance phase than during the prior acute phase.

Adult↗

PubMed2001

Congenital nemaline myopathy due to ACTA1-gene mutation and carnitine insufficiency: a case report.

A premature boy with a congenital form of nemaline myopathy due to mutation in the ACTA1-gene showed decreased carnitine levels in the eighth week of life. After sufficient oral carnitine substitution he improved gradually. In the first 15 months of life he made good progress; he reached full head control, learned to sit unsupported and was able to raise objects. At that time the carnitine levels were normal without substitution. Nemaline myopathy is clinically and genetically heterogenous. The pathogenesis of the muscle weakness is poorly understood. Disturbances of carnitine metabolism in this group of patients as one possibility are conceivable. Further investigations of carnitine metabolism in patients with nemaline myopathy may shed light on the pathogenesis of this entity.

Bacterial Proteins↗

PubMed2001

Functional magnetic resonance imaging research in psychiatry.

Advanced functional imaging techniques now make it possible to study in vivo the relationship between altered cerebral activation patterns and the psychopathologic and cognitive features of psychiatric disorders. Functional MR imaging (fMRI) offers new approaches to research questions in psychiatry that could not have been addressed earlier by positron emission tomography and single photon emission CT. Basic features of the biology of psychiatric disorders now can be elucidated by means of fMRI. Study designs involving fMRI capitalize on the technique's enhanced spatial and temporal resolution, noninvasive nature, and absence of radiation exposure.

Arousal↗

PubMed2000

[Detection of neurotransmitter interactions with PET and SPECT by pharmacological challenge paradigms].

Functional brain imaging with positron emission tomography (PET) and single photon emission computerized tomography (SPECT) enables the in vivo study of specific neurochemical processes in the context of normal regulatory mechanisms and pathophysiological alterations of the brain. By combining these methods with pharmacological challenge-paradigms, the study of functional interactions of different neurotransmitter systems is possible. This review will present data from animal and healthy volunteer studies as well as first data from investigations in different patient populations with regard to this research direction. Especially, interactions of different neurotransmitter systems with the dopaminergic and the cholinergic system will be discussed. The database acquired so far confirms existing models of neuronal feedback-circuits, and the first clinical results are consistent with the hypothesis of an increased dopaminergic responsivity in schizophrenic patients. These results open up new perspectives for a further evaluation of treatment response predictors from drug-challenge studies and for the development of new drug treatments for neuropsychiatric disorders.

Animals↗

PubMed2000

Effects of subchronic paroxetine administration on night-time endocrinological profiles in healthy male volunteers.

To evaluate the subchronic effects of paroxetine, a selective serotonin reuptake inhibitor, on nocturnal endocrinological profiles, eight healthy male volunteers with no personal or family history of a psychiatric or neurological disease were administered paroxetine (30 mg/day) or placebo in a double-blind cross-over design. Drugs were given as a single dose at 10:00 h for a period of 4 weeks each. Between days 21 and 28 of each treatment period, sleep EEG was registered for four consecutive nights from 23:00 to 07:00 h. During the last night, hormonal profiles for prolactin, growth hormone (GH), cortisol, corticotropin (ACTH), luteinizing hormone (LH), testosterone and melatonin were determined, and area-under-the-curve values were calculated. None of the endocrinological parameters revealed any statistically significant changes. A trend could be found for an increased cortisol production under paroxetine (P = 0.069). ACTH, LH, and melatonin showed slight and non-significant decreases. Prolactin release was only marginally elevated (+7%). The mean sleep onset GH release (as measured for a time period of 180 min after sleep onset) was decreased by about 30% under paroxetine. However, statistical significance could not be reached. For hGH, there was a delayed mean GH-peak under paroxetine. Nocturnal testosterone secretion remained almost unaltered. The lack of significant endocrinological alterations might be partially explained by both adaptational phenomena under subchronic treatment conditions and the extended time span between the single morning dose and the registration period, respectively.

Adrenocorticotropic Hormone↗

PubMed1999

Occupancy of striatal D(2)-like dopamine receptors after treatment with the sigma ligand EMD 57445, a putative atypical antipsychotic.

RATIONALE: EMD 57445 (panamesine) is a high affinity sigma ligand with the profile of an atypical antipsychotic in animal studies. It has been reported recently to have antipsychotic activity in schizophrenia. However, its metabolite, EMD 59983, binds also to D(2) and D(3) dopamine (DA) receptors. OBJECTIVES: The aim of this study was to test, using single photon emission computed tomography (SPECT) and [(123)I]iodobenzamide (IBZM) as the radiotracer, whether EMD 59983 would pass the blood-brain barrier and to what extent it would contribute to the effects of EMD 57445 in schizophrenia. METHODS: Two IBZM SPECT-scans were performed in five neuroleptic-free schizophrenic patients (DSM IV), one before and one after treatment with 60 mg panamesine daily for a treatment duration of 12-26 days. RESULTS: A high occupancy of striatal D(2)-like DA receptors similar to that induced by typical neuroleptics was observed in all patients treated with EMD 57445. CONCLUSIONS: Our results suggest that a possible antipsychotic activity of EMD 57445 in schizophrenia is not necessarily attributable to its affinity for sigma receptors, but could be simply due to the potent antidopaminergic effects of EMD 59983, its main metabolite.

Adult↗

PubMed1999

Neuroendocrine response to antipsychotics: effects of drug type and gender.

BACKGROUND: To study the influences of drug type and gender on the neuroendocrine response to neuroleptic treatment, we compared the endocrine actions of two neuroleptics with different receptor affinity profiles--a substituted benzamide, amisulpride, a selective D2-like dopamine antagonist; and a thioxanthene, flupenthixol, a mixed D1/D2-like antagonist also blocking serotonin, H1, and D1 receptors--on anterior pituitary hormone secretion in schizophrenic patients (DSM-III-R). METHODS: Blood was withdrawn at 15-min intervals to assess basal secretion of prolactin, growth hormone (GH), and thyroid-stimulating hormone (TSH). Four hundred micrograms of thyrotropin-releasing hormone (TRH) was injected i.v. to investigate drug effects on TRH-stimulated secretion of prolactin, TSH, and GH. RESULTS: Prolactin plasma levels were markedly elevated in both treatment groups. In female, but not in male patients, this elevation was significantly more pronounced under amisulpride than under flupenthixol. The prolactin response to TRH was significantly blunted by amisulpride only in male subjects. While basal TSH secretion was significantly increased by both compounds, TRH-stimulated TSH secretion was elevated only in patients treated with amisulpride. Low basal prolactin levels predicted improvement of negative symptoms in patients treated with amisulpride. CONCLUSIONS: Amisulpride's more pronounced endocrine effects may be a reflection of its distinguished pharmacology and pharmacokinetics.

Adult↗

PubMed1999

Congenital unilobar pulmonary lymphangiectasis.

A premature female infant is described in whom a cystic malformation of the left lung was observed on the second day of life. A lobectomy was carried out on day 31 of life, and histological examination revealed congenital pulmonary lymphangiectasis with isolated left upper lobe involvement.

Cystic Adenomatoid Malformation of Lung, Congenita↗

PubMed1999

[Threshold value retinopathy of prematurity. Visual outcome of 2-year-old children after cryocoagulation].

BACKGROUND: The results of the Cryo-ROP group showed that cryotherapy significantly reduces the rate of adverse morphological and functional outcome of eyes with threshold retinopathy of prematurity. Structural status and visual acuity of 48 eyes which consecutively underwent cryocoagulation in our hospital between 1990 and 1994 were examined at 2 years corrected gestational age. METHOD: Visual acuity and fundus morphology were examined by Teller acuity-cards test, retinoscopy, orthoptic status and fundus examination. A favourable grating acuity was defined as > or = 2.2 cy/degree, a favourable morphology as no pathological or mild findings at the level of the posterior pole or stage 4 a. RESULTS: Fifty-six % of cases reached a quantifiable grating acuity between 0.32 and 13.0 cy/degree, 42% reached a favourable functional outcome, and 69% of the eyes had a morphologically favourable outcome. Fifty-five % of the measurable eyes were myopic, and 29% had a high myopia > or = -6.0 D. 47% showed a heterotropia. CONCLUSIONS: Our results show a discrepancy between morphological and functional outcome. Especially for zone 1 eyes, cryocoagulation of the avascular retina does not seem to allow a favourable morphological and functional outcome.

Child, Preschool↗

PubMed1999

Lamellar body counts in amniotic fluid for prediction of fetal lung maturity.

OBJECTIVE: Comparison of three different methods of fetal lung maturity (FLM) testing in amniotic fluid (AF) to predict fetal respiratory distress syndrome (RDS): phospholipid concentration, phosphatidylglycerol (PG) and lamellar body count (LBC). STUDY DESIGN: 315 amniotic fluid (AF) samples were tested, 291 by determination of phospholipid, 237 by PG and 68 by LBC. Eighty one patients (26%) delivered within 3 days, incidence of RDS was 7% (n = 6). Correlation of phospholipids and LBC to gestational age was analyzed as well as correlation of LBC and PG versus phospholipid concentration. Sensitivity and specificity for all three methods were calculated. RESULTS: Phospholipids and LBC increased exponentially with gestational age (rregr = 0.54, p < 0.01, rregr = 0.76, p < 0.01) showing a curvilinear function. There was a linear correlation between both methods (rcorr = 0.51, p < 0.01, n = 47). Sensitivity for prediction of RDS was 80% for phospholipids compared to 83% for LBC and 67% for PG. Specificity was best for PG (92%) followed by phospholipids (85%). While positive predictive value was low (27% for phospholipids and 50% for LBC), negative predictive value varied between 97% and 100%. CONCLUSIONS: LBC is a simple and reliable method for FLM testing, with a sensitivity comparable to phospholipid testing and a somewhat lower specificity (67% vs. 85%). It may be useful for screening of FLM in a cascade approach.

Amniotic Fluid↗

PubMed1999

Neonatal sepsis: a challenge in hemostaseology.

Several therapeutic approaches to sepsis and disseminated intravascular coagulation (DIC) have shown promising results in animal models. Large controlled trials in humans, however, have failed to show a clearly beneficial effect of a single drug or substance on outcome and survival so that treatment remains uncertain. As one researcher stated: ". . . sepsis is a classical example of a disease greater than the sum of its parts; it is a complex process in which intervention in one area might have only a modest effect on the final outcome." We believe that the complex pathophysiological setting of septic shock will undoubtedly require a multifaceted approach. Consequently, we attempt to arrest DIC and restore adequate tissue perfusion by intervention with heparin, AT and if possible protein C (PC) in the earliest stage of the disease, with the aim of blocking ongoing microthrombus formation and to support fibrinolysis. Growing understanding of the basic underlying mechanisms teaches us how to successfully stabilise the individual decompensated sub-systems like coagulation in septic patients. We should learn to accept these steps to reach the goal of a better outcome in terms of survival in this devastating illness.

Animals↗

PubMed1999

[Value of fetal lung maturity assessment in maternal diabetes].

OBJECTIVE: Results of antepartal fetal lung maturity (FLM) testing in diabetics were compared to control patients. We analysed 274 patients by phospholipid profile and 219 by phosphatidylglycerol (PG), consisting of 73, respectively 54 diabetic and 201, resp. 165 normal control subjects. MATERIAL AND METHODS: Phospholipid concentration increased exponentially with gestational age (rreg = 0.44 for diabetic and 0.57 for normal control patients). There was no significant difference between both groups. Measurement of PG showed a trend towards lung immaturity in diabetic infants for preterm and term gestations, which did not reach significance (chi-square [chi 2] test 0.07, resp. 0.06). RESULTS: Diabetic and non-diabetic pregnancies did not differ significantly in FLM and RDS frequency. Both methods show a high rate of falsely immature results. Antepartal FLM testing by measurement of phospholipids and PG does not play a role in clinical management of diabetic patients.

Amniocentesis↗

PubMed1998

Long-term stability of neurotransmitter activity investigated with 11C-raclopride PET.

There is evidence for the shift of regulatory setpoints of functionally linked neurotransmitter systems as a basis of psychiatric disorders. 11C-raclopride PET, which has been shown to be sensitive to changes in endogenous dopamine and has a high short-term test-retest reliability, can be used to investigate different regulatory states of the dopaminergic system with respect to psychiatric diseases and pharmacological influences. Prior to these studies, the reliability of the method over time has to be established. The current study was performed in order to evaluate the long-term stability of the striatal dopaminergic system. Eight normal healthy subjects (mean age: 48.1 years; range: 24-75) were studied twice with 11C-raclopride PET two times under resting conditions with a mean time interval between the scans of 11.3 months (range: 1-19). The ratio of basal ganglia (BG) to cerebellar (CB) distribution volumes (DVs) revealed a mean absolute change of 6.94 (range: 0.0-12.87%) between study A and B. BG DVs mean absolute change was 6.30% (range: 0.55-30.46%), CB DVs mean absolute change was 8.65% (range: 3.51-16.33%). The mean change of the BG/CB ratio was -0.33% (range: 12.87-12.34%). BG DVs mean change was 4.55% (range: 4.2-30.46%), CB DVs mean change was 5.10% (range: -10.71-16.33%). The intraindividual differences between the two scans in our study were not significantly different as compared to the 24 hour interval test-retest data, which have been published earlier (repeated measures ANOVA with df = 11; F = 0.49; P = 0.50) [Volkow et al. (1993) J. Nucl. Med., 34:609-613]. The intraclass correlation of the DV ratio index was r = 0.81. The binding potential in the baseline scans and repeated scans showed a non-significant correlation with age (r = -0.58, P = 0.13). Interindividually, the DV ratio index revealed a mean of 3.18 (range = 2.55-3.68, SD = 0.42 in study A and of 3.16 (range 2.37-3.57, SD = 0.41) in study B. The intrasubject stability of the 11C-raclopride binding over a long-term period in normal human subjects suggests the feasibility of study designs investigating the long-term changes of the dopaminergic responsivity after pharmacological challenges. The baseline stability will also serve as a necessary reference for further dose-response studies and investigations of subchronical pharmacological interventions.

Adult↗

PubMed1998

A prospective, randomized, multicenter trial of high-frequency oscillatory ventilation compared with conventional ventilation in preterm infants with respiratory distress syndrome receiving surfactant.

OBJECTIVES: To compare high-frequency oscillatory ventilation (HFOV) and intermittent positive pressure ventilation (IPPV) as a primary ventilation mode in preterm infants with respiratory distress syndrome. Primary end points were survival and maintenance of the randomized ventilation mode. STUDY DESIGN: Prospective, multicenter, randomized clinical trial. SETTING: Level III neonatal intensive care units at three university children's hospitals. PATIENTS: Ninety-six premature infants (gestational age < 32 weeks) randomly assigned to HFOV or IPPV within the first 2 hours of life. All patients received a natural surfactant. No differences were found between the study groups with respect to the demographic data or the severity of respiratory distress syndrome. Infants were stratified at randomization, by birth weight, into two groups: 750 to 1000 gm (n = 32) and 1001 to 1500 gm (n = 64). The centers involved complied with a study protocol that planned a reduction in respiratory pressures when the infant's oxygen requirement had reached a fractional concentration of inspired oxygen of 0.6. RESULTS: Five patients in the HFOV group died, and eight patients did not respond to the randomized ventilation mode; whereas four patients in the IPPV group died, and nine were switched to HFOV. No differences were found in gas exchange or ventilator support over the first 72 hours. Premature infants with a birth weight < 1000 gm had a significantly shorter course to reach fractional concentration of inspired oxygen of 0.21 while receiving IPPV than those receiving HFOV (9.3+/-4.5 days vs 27.5+/-10.2 days, p = 0.01). No differences were found between the groups in extraalveolar air (HFOV seven; IPPV, seven) and intracranial bleeding (HFOV, nine; IPPV, eight). CONCLUSION: After surfactant treatment, HFOV, as a primary ventilation mode in premature infants with respiratory distress syndrome, is as safe and efficacious as conventional ventilation.

Female↗

PubMed1998

Conventional and spectral power analysis of all-night sleep EEG after subchronic treatment with paroxetine in healthy male volunteers.

Paroxetine is a selective and potent serotonin reuptake inhibitor with reported antidepressant properties. Since changes in the regular sleeping pattern were described as side effects under treatment with paroxetine, the impact of the drug on the sleep architecture is of major interest. The present study addressed the question of subchronic effects of paroxetine medication (30 mg/day) in eight healthy male volunteers in a double blind, placebo-controlled crossover-design. Conventional sleep EEG parameters and additionally computed spectral power analysis based on FFT of 20-s time epochs in the delta, theta, alpha, beta and gamma frequency range for different sleep stages after 4 weeks of treatment were investigated. Subchronic paroxetine administration in healthy subjects led to a prolonged REM latency and a decrease in the number of REM phases, whereas sleep efficiency, total sleep time, sleep onset latency, number of awakenings, and awake during sleep period time were not altered by paroxetine medication. Moreover, we could not detect any alterations of the spectral power values in certain frequency bands during NREM or REM sleep following subchronic paroxetine medication.

Adult↗

PubMed1998

Functional magnetic resonance imaging of human brain activity in a verbal fluency task.

OBJECTIVES: Functional MRI (fMRI) holds the promise of non-invasive mapping of human brain function in both health and disease. Yet its sensitivity and reliability for mapping higher cognitive function are still being determined. Using verbal fluency as a task, the objective was to ascertain the consistency of fMRI on a conventional scanner for determining the anatomic substrate of language between subjects and between sexes. Comparison was made with previous PET studies. METHODS: Using a 1.5 Tesla magnet and an echoplanar pulse sequence, whole brain fMRI was obtained from 12 normal right handed subjects (6 males and 6 females) as they performed a verbal fluency task. RESULTS: A broadly consistent pattern of response was seen across subjects. Areas showing activation changes included the left prefrontal cortex and right cerebellum, in agreement with previous PET 15O-H2O studies. In addition, significantly decreased responses were seen in the posterior cingulate and over an extensive area of mesial and dorsolateral parietal and superior temporal cortices. The male cohort showed a slight asymmetry of parietal deactivation, with more involvement on the right, whereas the female cohort showed a small region of activation in the right orbitofrontal cortex. There were individual task related regional changes in all 12 subjects with the area showing the most significant change being the left prefrontal cortex in all cases. CONCLUSIONS: Magnetic resonance scanners of conventional field strength can provide functional brain mapping data with a sensitivity at least that of PET. Activation was seen in left prefrontal and right cerebellar regions, as with PET. However, decremental responses were seen over a much larger area of the posterior cortex than had been anticipated by prior studies. The ability to see a response in each subject individually suggests that fMRI may be useful in the preinterventional mapping of pathological states, and offers a non-invasive alternative to the Wada test for assessment of hemispheric dominance. There were no gross differences in the pattern of activation between male and female subjects.

Adult↗