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Biomedical subjects

Andreas Meier

Publications and source records attributed to Andreas Meier.

14 recordsLinked to original sources
PubMed2006

The atypical antipsychotics olanzapine and quetiapine, but not haloperidol, reduce ACTH and cortisol secretion in healthy subjects.

RATIONALE: Increased activity of the hypothalamic-pituitary-adrenal (HPA) axis is an important aspect of the pathophysiology of major depression and schizophrenia. Despite the usefulness of atypical antipsychotics in the treatment of depression and their positive influence on cognitive functioning possibly related to their impact on cortisol, little is known about their effect on HPA axis function. OBJECTIVE: Therefore, this double-blind, placebo-controlled, randomized cross-over study investigated the influence of the atypical antipsychotics quetiapine and olanzapine in comparison with haloperidol and placebo on plasma adrenocorticotropic hormone (ACTH), cortisol, and prolactin levels. Eleven healthy male volunteers were studied during four sessions one week apart, orally receiving placebo, quetiapine (50 mg), olanzapine (5 mg), or haloperidol (3 mg). Blood samples were taken at hourly intervals from 0900 until 1700 hours. For ACTH, cortisol, and prolactin a significant effect of treatment condition (p < or = 0.005; p < or = 0.035; p < or = 0.0001, respectively) for area under the curve (AUC) was found. In comparison to placebo, quetiapine and olanzapine significantly reduced ACTH (p < or = 0.002; p < or = 0.05, respectively) and cortisol (p < or = 0.005; p < or = 0.03, respectively). No effect of haloperidol on AUC of ACTH or cortisol levels was observed. In comparison with placebo, haloperidol (p < or = 0.0001) and olanzapine (p < or = 0.0001) elevated AUC of prolactin plasma levels, whereas no significant effect was observed for quetiapine as a main effect of treatment condition. The atypical antipsychotics' strong influence on HPA-function with pronounced ACTH and cortisol lowering is possibly related to the atypicals' blockade of serotonergic receptors, but blockade of adrenergic or histaminergic receptors may play a role as well. The observed HPA-axis down-regulation may be clinically important for the atypicals' effects on depressive symptomatology and cognitive functioning.

Adrenocorticotropic Hormone↗
PubMed2005

Normal hypocretin-1 (orexin-A) levels in the cerebrospinal fluid of patients with Huntington's disease.

A significant atrophy and loss of hypocretin neurons in the brains of human patients with Huntington's disease (HD) and in R6/2 mice have been reported. We included 10 patients with HD and 12 patients with chorea-like hyperkinetic movement disorders (non-HD). All patients of the HD group and eleven patients of the non-HD group showed normal hypocretin-1 levels. Thus, hypocretin-1 may not serve as an additional diagnostic marker for HD.

Biomarkers↗
PubMed2005

Developing the young academic surgeon.

In the past, the process of developing the young academic surgeon was arguably less strategic, one that was often not deliberately managed and monitored, leading in some cases to academic drift and disillusionment. Once upon a time it was assumed that greatness was genetic and that the next triple threat would emerge when a pre-programmed set of genes was turned on. Today, as the complexities and vicissitudes of our work increase, it is practically impossible for even the most gifted young person to be successful without careful attention to career development. Faculty development must be deliberate and strategic--every junior faculty member is unique and will require a customized career development plan that is well thought out, linked to measurable goals, monitored routinely and buttressed by effective mentoring. This approach will require time and commitment--precious commodities that are in short supply as the demands on our time are only escalating. By recruiting the right people (those who fit with the organization's values and goals) and providing the right environment, we can optimize the growth and satisfaction of our young faculty and, in so doing, create departments that are leaders in carrying out our missions of research, education and patient care. We cannot afford to have our young people fail--it is simply too costly, both from a financial and a human perspective.

Academic Medical Centers↗
PubMed2005

Ziprasidone decreases cortisol excretion in healthy subjects.

AIMS: To determine the influence of the atypical antipsychotic ziprasidone on cortisol excretion. METHODS: In a double-blind, placebo-controlled, randomized cross-over design 11 healthy male subjects were studied twice for 2 consecutive nights (N1, undisturbed sleep conditions; N2, exposure to acoustic stress) 5 days apart. Placebo or ziprasidone 40 mg was administered orally 2 h before bedtime on N1 and N2. Urine was collected during three fractionated collection periods (evening; night; morning) for the later determination of cortisol concentrations by standard radioimmunoassays. RESULTS: Ziprasidone decreased the total amount of cortisol excreted by 4.9 (95% CI 3.3, 6.5) microg during N1 and by 10.8 (95% CI 5.7, 15.8) microg during N2 (P < 0.002). This effect was still detectable in the morning (P < 0.02), with decreases of 5.8 (95% CI -2.8, 14.4) microg after N1 and by 12.1 (95% CI 2.8, 21.4) microg after N2. The effect subsided in the evening. A significant intervention-condition interaction (P < 0.02), was found. The significant increase in cortisol excretion during acoustic stress observed with placebo was absent after treatment with ziprasidone. CONCLUSIONS: The significant decrease in nocturnal cortisol excretion following ziprasidone reflects a decreased activity of the HPA-axis in healthy subjects. This effect may be an important contributor to the mode of action of ziprasidone in different patient populations, particularly in the treatment of depression and in cognitive impairment in schizophrenia.

Acoustic Stimulation↗
PubMed2005

RNA polymerase I transcription factors in active yeast rRNA gene promoters enhance UV damage formation and inhibit repair.

UV photofootprinting and repair of pyrimidine dimers by photolyase was used to investigate chromatin structure, protein-DNA interactions, and DNA repair in the spacer and promoter of Saccharomyces cerevisiae rRNA genes. Saccharomyces cerevisiae contains about 150 copies of rRNA genes separated by nontranscribed spacers. Under exponential growth conditions about half of the genes are transcribed by RNA polymerase I (RNAP-I). Initiation of transcription requires the assembly of the upstream activating factor (UAF), the core factor (CF), TATA binding protein, and RNAP-I with Rrn3p on the upstream element and core promoter. We show that UV irradiation of wild-type cells and transcription factor mutants generates photofootprints in the promoter elements. The core footprint depends on UAF, while the UAF footprint was also detected in absence of the CFs. Fractionation of active and inactive promoters showed the core footprint mainly in the active fraction and similar UAF footprints in both fractions. DNA repair by photolyase was strongly inhibited in active promoters but efficient in inactive promoters. The data suggest that UAF is present in vivo in active and inactive promoters and that recruitment of CF and RNAP-I to active promoters generates a stable complex which inhibits repair.

Chromatin↗
PubMed2005

Improved sleep continuity and increased slow wave sleep and REM latency during ziprasidone treatment: a randomized, controlled, crossover trial of 12 healthy male subjects.

OBJECTIVE: Ziprasidone, an atypical antipsychotic, is a potent dopamine (D(2)) and serotonin (5-HT(2A/C)) receptor blocker, has agonistic properties at the 5-HT(1A) receptor, and blocks serotonin and norepinephrine reuptake. These transmitter systems are closely related to the regulation of sleep. METHOD: The aim of this double-blind, placebo-controlled, randomized, crossover study was to investigate the effects of ziprasidone on polysomnographic sleep structure and subjective sleep quality. Twelve healthy male subjects were randomly assigned to receive ziprasidone 40 mg or placebo for 2 sessions each composed of 2 consecutive nights (night 1, standard sleep conditions; night 2, acoustic stress) 5 days apart. Treatment was administered orally 2 hours before bedtime. The study was conducted from April 2004 to July 2004. RESULTS: Ziprasidone significantly increased total sleep time, sleep efficiency, percentage of sleep stage 2, and slow wave sleep; decreased the number of awakenings; and significantly affected tonic and phasic REM sleep parameters, i.e., it decreased percentage of REM and REM density and profoundly increased REM latency. CONCLUSION: Ziprasidone's effects on the sleep profile are somehow opposite to what is known about sleep of depressed patients (e.g., disturbances of sleep continuity, a reduciton of slow wave sleep, and a disinhibition of REM sleep). Its REM sleep-suppressing properties resemble those of most, although not all, antidepressants and may be clinically relevant. The drug also demonstrates sleep-consolidating properties under both standard routine and acoustic stress conditions. These effects are most likely related to ziprasidone's 5-HT(2C) antagonism, 5-HT(1A) agonism, and serotonin and norepinephrine reuptake inhibition.

Acoustic Stimulation↗
PubMed2004

Developing the young academic surgeon.

In the past, the process of developing the young academic surgeon was arguably less strategic, one that was often not deliberately managed and monitored, leading in some cases to academic drift and disillusionment. Once upon a time it was assumed that greatness was genetic and that the next triple threat would emerge when a pre-programmed set of genes was turned on. Today, as the complexities and vicissitudes of our work increase, it is practically impossible for even the most gifted young person to be successful without careful attention to career development. Faculty development must be deliberate and strategic--every junior faculty member is unique and will require a customized career development plan that is well thought out, linked to measurable goals, monitored routinely and buttressed by effective mentoring. This approach will require time and commitment--precious commodities that are in short supply as the demands on our time are only escalating. By recruiting the right people (those who fit with the organization's values and goals) and providing the right environment, we can optimize the growth and satisfaction of our young faculty and, in so doing, create departments that are leaders in carrying out our missions of research, education and patient care. We cannot afford to have our young people fail--it is simply too costly, both from a financial and a human perspective.

Academic Medical Centers↗
PubMed2004

Sleep-promoting properties of quetiapine in healthy subjects.

The aim of this study was to investigate the effects of quetiapine, an atypical antipsychotic, on polysomnographic sleep structure and subjective sleep quality. This double-blind, placebo-controlled, randomized cross-over study investigated the polysomnographic sleep structure and subjective sleep quality of 14 healthy male subjects given placebo, quetiapine 25 mg or quetiapine 100 mg. Volunteers were studied 3 times for 3 consecutive nights (N0, adaptation; N1, standard sleep conditions; N2, acoustic stress) 4 days apart. Treatment was administered orally 1 h before bedtime on nights 1 and 2. Quetiapine 25 mg and 100 mg significantly improved sleep induction and continuity under standard and acoustic stress conditions. Increases in total sleep time, sleep efficiency, percentage sleep stage 2 and subjective sleep quality were seen. A significant increase in periodic leg movements during sleep was observed with quetiapine 100 mg. The sleep-improving properties of quetiapine may be important in counteracting different aspects of psychopathology in schizophrenia and other disorders. These sleep-inducing and sleep-modifying properties are probably related to quetiapine's receptor-binding profile, including its antihistaminergic, antidopaminergic and antiadrenergic properties. Other mechanisms might be relevant as well and further investigation is required.

Acoustic Stimulation↗
PubMed2004

Functional 5-HT receptors in human occipital artery.

5-HT receptors were studied in human occipital arteries, obtained from patients during neurosurgery. We detected mRNA for the following receptors (incidence): 5-HT(1B) (14/18), 5-HT(1D) (15/18), 5-HT(2A) (16/18), 5-HT(2B) (8/8), 5-HT(4(a)) (13/18), 5-HT(4(b)) (5/18), 5-HT(4(g)) (7/18), 5-HT(4(i)) (1/18), 5-HT(7(a/b)) (10/18) and 5-HT(7(d)) (12/18). 5-HT contracted and relaxed arterial rings at low (-logEC(50) M=7.0) and high (-logEC(50) M=4.2) concentrations, respectively. 5-HT-evoked contractions were antagonized partially by both 5-HT(1B)-selective SB224289 (200 nM) and 5-HT(2A)-selective ketanserin (1 microM) but not by 5-HT(1D)-selective BRL15572 (500 nM) or prazosin (1 microM). Sumatriptan caused contractions (-logEC(50) M=6.8, intrinsic activity with respect to 5-HT=0.3). Sumatriptan-evoked contractions were antagonized by SB224289 with high potency (pK(B)=9.4) but not by BRL15572. 5-HT-induced relaxations were resistant to blockade by 5-HT(1B)-selective SB224289 (1 microM), 5-HT(1D)-selective BRL15572, 5-HT(2B)-selective SB204741 (1 microM), 5-HT(4)-selective GR113808 (100 nM) and 5-HT(7)-selective SB269970 (1 microM), and a combination of SB204741 and SB269970, inconsistent with an involvement of 5-HT(1B), 5-HT(1D), 5-HT(2B), 5-HT(4) and 5-HT(7) receptors. Triton X-100 treatment of the arteries abolished acetylcholine-induced relaxations of rings precontracted by prostaglandin F(2alpha), but a reduction of the relaxant effects of 5-HT did not reach significance. Nitro-L-arginine (1 mM) reduced 5-HT-induced relaxations, suggesting a contribution of nitric oxide released from endothelial cells. Ketanserin (1 microM) prevented the relaxant effects of 5-HT. We conclude that 5-HT contracts human occipital artery through 5-HT(1B) receptors at low concentrations and through 5-HT(2A) receptors at high concentrations. Sumatriptan contracts mostly through 5-HT(1B) receptors. These results are consistent with the 5-HT(1B) and 5-HT(2A) mRNA data. 5-HT-induced relaxation is mediated, in part, through ketanserin-sensitive receptors, but 5-HT(1B), 5-HT(1D), 5-HT(2B), 5-HT(4) and 5-HT(7) receptors appear not to be involved.

Adolescent↗
PubMed2004

Quetiapine reduces nocturnal urinary cortisol excretion in healthy subjects.

RATIONALE: Hypothalamic-pituitary-adrenal (HPA) axis dysfunction is a frequent finding in psychiatric disorders, including psychotic depression and schizophrenia. Conflicting results exist concerning the influence of antipsychotics on the HPA-axis. OBJECTIVE: Therefore, this double-blind, placebo-controlled, randomized cross-over study investigated the effect of quetiapine on nocturnal urinary cortisol and melatonin excretion in 13 healthy male subjects under conditions of undisturbed and experimentally disturbed sleep. METHODS: Volunteers were studied 3 times for 3 consecutive nights (N0, adaptation; N1, standard sleep conditions; N2, acoustic stress) 4 days apart. Placebo, quetiapine 25 mg or quetiapine 100 mg was administered orally 1 h before bedtime on nights 1 and 2. Urine produced during the 8-h bedtime period was collected for later determination of cortisol and melatonin concentrations by standard radioimmunoassays. RESULTS: MANOVA showed a significant effect for N1 vs. N2 with elevated total amount of cortisol ( p<0.005) and melatonin ( p<0.05) excretion after acoustic stress. Both quetiapine 25 mg and 100 mg significantly ( p<0.0005) reduced the total amount of cortisol excretion in comparison to placebo. No interaction effect of stress condition was observed. There was no effect of quetiapine on melatonin levels. CONCLUSION: The significant reduction of nocturnal cortisol excretion following quetiapine reflects a decreased activity of the HPA-axis in healthy subjects. This finding may be an important aspect in quetiapine's mode of action in different patient populations.

Acoustic Stimulation↗
PubMed2004

The relationship of pulmonary artery pressure and survival in congenital diaphragmatic hernia.

BACKGROUND/PURPOSE: Pulmonary hypertension is an integral part of the pathophysiology of the respiratory failure associated with congenital diaphragmatic hernia. Hypothesizing that the evolution of the pulmonary hypertension would determine clinical outcome, the authors examined pulmonary artery pressures in relation to survival in their CDH patients. METHODS: The authors performed a retrospective chart review of all neonates with the CDH from 1991 to 2002 at their institution eliminating infants with complex congenital heart disease, prematurity, or limited treatment. Cardiac ECHO data were used to estimate pulmonary artery pressures as a ratio to systemic pressure. Statistical analyses of estimated pulmonary pressure ratios stratified by survival status and time were performed using chi2 and Fisher's Exact Test methods. RESULTS: Forty-seven full-term CDH infants with 428 cardiac ECHO evaluations were studied. Long-term survival rate was 74%. Forty-nine percent of patients had normal pulmonary artery pressure estimates within the first 3 weeks of life. All patients survived. Seventeen percent had persistent systemic or suprasystemic pressure estimates unrelieved by treatment interventions resulting in 100% mortality rate. Thirty-four percent had intermediate reductions in pressure estimates over time with 75% survival rate. Systemic pulmonary artery pressures were associated with decreased survival at all time-points when compared with normal-pressure survivors: week 1, 60% (P <.003); week 3, 38% (P <.007); week 6, 0% (P <.02). CONCLUSIONS: The evolution of pulmonary hypertension is a critical determinant of survival in CDH patients with current treatment strategies. Three groups can be modeled with markedly different clinical performance patterns. Using serial cardiac ECHO examinations, pulmonary artery pressure estimations can be used to predict clinical outcome.

Blood Pressure↗
PubMed2004

Patterns of tissue remodeling after placement of ITI dental implants using an osteotome technique: a longitudinal radiographic case cohort study.

The aim of this prospective study was to document radiographically tissue remodeling patterns around ITI implants placed according to an osteotome technique. In 19 consecutive patients from a private practice, 25 implants of the ITI Dental Implant System were placed subjacent to the sinus floor. Implant beds were pre-prepared with pilot drills and/or using the Summers Osteotome Kit. Bio Oss particles were mixed with autologous bone and inserted into the apex area. Implants were placed self-tapping. The sinus floors were thereby pushed up with attempts not to sever the Schneiderian membrane. Healing occurred submerged or semi-submerged and was uneventful in 24/25 implants. At 1 year, all implants had been restored with crowns or short fixed partial dentures. One implant was lost in the first 3 weeks, but was replaced 6 months later in a second attempt. Intraoral radiographs were obtained presurgically and postsurgically at 3 and 12 months. The mean preoperative distance between the sinus floor and the crest was 7.0 mm (range 2.3-10.3 mm). The mean distances between the implant apex and the initial sinus floor were: 3.66 +/- 1.74 mm mesially and 4.44 +/- 1.62 mm distally. The mean height of the new bone reaching apically and mesially to the implants was 1.52 +/- 2.48 mm at surgery, but was reduced significantly to 1.24 +/- 1.30 mm at 3 months and 0.29 +/- 1.91 mm after 12 months (Hotelling's test P< or =0.01). Similar values were obtained at the disto-apical aspects. In an attempt to assess periapical bone/graft remodeling, a novel index was applied: 0=no bone/graft visible, 1=cloudy appearance of new bone/graft, 2=clearly visible new bone/graft disappearing structures of original sinus floor, 3=new bone/graft with new cortical plate and the former boundary of the sinus floor disappearing. This index increased statistically significantly from baseline to 12 months (Hotelling's test P< or =0.02). In conclusion, this study shows that in areas with reduced bone height subjacent to the sinus, an osteotome technique may provide a minimally invasive way to obtain implant abutments predictably. The grafted area apical to the implants undergoes shrinkage and remodeling. The original boundary of the sinus is eventually consolidated and replaced by a new cortical plate. In addition to the linear measurements, the novel index may assist in assessing periapical remodeling at implants placed with an osteotome technique.

Adult↗
PubMed2002

Repair of active and silenced rDNA in yeast: the contributions of photolyase and transcription-couples nucleotide excision repair.

DNA repair by photolyase (photoreactivation) and nucleotide excision repair (NER) are the major pathways to remove UV-induced cyclobutane-pyrimidine dimers (CPDs). The nucleolus is a nuclear subcompartment containing the ribosomal RNA genes (rDNA) of which a fraction is transcribed by RNA polymerase I (RNAP-I), and the rest is silenced. Here yeast was used to investigate how photoreactivation and NER contribute to repair of active and inactive rDNA. Cells were irradiated with UV light and exposed to different repair conditions. Nuclei were isolated, and the active genes were separated from the inactive genes by restriction endonuclease digestion. CPDs were measured in total rDNA, in both fractions, and in the GAL10 gene. Repair in rDNA was as efficient as in GAL10 indicating that both pathways have unrestricted access to the nucleolus. Photoreactivation was much faster than NER and therefore was the predominant repair pathway. Active genes were faster repaired by photolyase than were silenced genes providing evidence for an open chromatin structure during repair. The transcribed strands of active genes, but not of inactive genes, were slightly faster repaired by NER providing evidence for transcription-coupled repair by RNAP-I. There was no pronounced inhibition of photoreactivation by RNAP-I in the transcribed strand, which is in contrast to genes transcribed by RNAP-II and suggests different stabilities of RNAP-I and RNAP-II stalled at CPDs.

Chromatin↗