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Biomedical subjects

S Thiemann

Publications and source records attributed to S Thiemann.

17 recordsLinked to original sources

Testing gene function early in the B cell lineage in mb1-cre mice.

The mb1 gene encodes the Ig-alpha signaling subunit of the B cell antigen receptor and is expressed exclusively in B cells beginning at the very early pro-B cell stage in the bone marrow. We examine here the efficacy of the mb1 gene as a host locus for cre recombinase expression in B cells. We show that by integrating a humanized cre recombinase into the mb1 locus we obtain extraordinarily efficient recombination of loxP sites in the B cell lineage. The results from a variety of reporter genes including the splicing factor SRp20 and the DNA methylase Dnmt1 suggest that mb1-cre is probably the best model so far described for pan-B cell-specific cre expression. The availability of a mouse line with efficient cre-mediated recombination at an early developmental stage in the B lineage provides an opportunity to study the role of various genes specifically in B cell development and function.

Animals↗

Prevalence of hormone replacement therapy and antidepressant use in peri- and postmenopausal women.

OBJECTIVE: To examine the prevalence of hormone replacement therapy (HRT) and antidepressant use in peri- and postmenopausal women. DESIGN: Prevalence survey. SUBJECTS: Peri- and postmenopausal outpatients (N = 253) at five medical clinics. METHODS: Participants completed a 47-item questionnaire requesting information on mood changes associated with menstruation, childbirth, oral contraceptive use, and menopause. Peri- and postmenopausal participants were asked to rate the severity of dysphoric symptoms experienced during the menopausal transition and to specify whether HRT, antianxiety medication, or antidepressant medication relieved the symptoms. RESULTS: Forty percent of respondents experienced more severe depression than anticipated during menopause, but only 8% were treated with antidepressants. Forty-six percent of respondents were treated with HRT. CONCLUSIONS: The data suggest that antidepressant and antianxiety medications are more helpful than HRT in relieving peri- and postmenopausal depression or anxiety. However, most women managed the mood changes associated with menopause without psychopharmacologic intervention. This is consistent with other reports on the transitory nature of peri- and postmenopausal depression for most women.

Adult↗

Are fluoxetine plasma levels related to outcome in obsessive-compulsive disorder?

OBJECTIVE: In obsessive-compulsive disorder, the relationship between blood levels of serotonin reuptake inhibitors and clinical outcome is unclear. In a multicenter trial, the authors examined the relationship between steady state plasma levels of fluoxetine and norfluoxetine (determined after 7 weeks of treatment), and their sum, and clinical outcome. METHOD: Ratings of symptom severity of obsessive-compulsive disorder (Yale-Brown Obsessive Compulsive Scale scores) were obtained at baseline and after 13 weeks for 200 adult outpatients with moderately severe obsessive-compulsive disorder treated with fluoxetine doses of 20 mg/day (N = 68), 40 mg/day (N = 64), and 60 mg/day (N = 68). RESULTS: Mean plasma levels of fluoxetine and norfluoxetine were statistically significantly higher with higher dose. Statistical analyses revealed no significant relationship for plasma level of either molecule or their sum in predicting endpoint percent change in obsessive-compulsive scores. Plasma levels of patients with a marked response (decrease of 50% or more in obsessive-compulsive score) did not differ significantly from those of nonresponders (less than a 25% decrease in obsessive-compulsive score). No hint was seen of a therapeutic window or of a relationship limited to one gender or within the lowest dose group (20 mg/day). However, since S-norfluoxetine is a much more potent serotonin reuptake inhibitor than R-norfluoxetine, the absence of chiral (stereospecific) assays in this study limits the results. CONCLUSIONS: Steady state plasma levels of fluoxetine and norfluoxetine are not related to clinical outcome in patients with obsessive-compulsive disorder. Individual patients can be told only that the optimum dose of fluoxetine for them will be the dose that produces the largest therapeutic effect with the smallest side effect burden. Future studies should examine the predictive utility of measures of serotonergic neuronal function and, if plasma levels of norfluoxetine are examined, the use of chiral assays.

Adolescent↗

Physician-patient sexual contact. Prevalence and problems.

To document the current prevalence of physician-patient sexual contact and to estimate its effect on involved patients, 10,000 family practitioners, internists, obstetrician-gynecologists, and surgeons were surveyed. Of the 1,891 respondents, 9% acknowledged sexual contact with 1 or more patients. Even in the unlikely case that none of the nonrespondents had sexual contact with patients, its prevalence among all 10,000 physicians surveyed would still be 2%. Of respondents, 23% had at least 1 patient who reported sexual contact with another physician; 63% thought this contact was "always harmful" to the patients. Almost all (94%) responding physicians opposed sexual contact with current patients; 37% also opposed sexual contact with former patients. More than half of respondents (56%) indicated that physician-patient sexual contact had never been addressed in their training; only 3% had participated in a continuing education course focusing on this issue. Clear and enforceable medical ethics codes concerning physician-patient sexual contact are needed, as well as preventive educational programs for medical schools and residency programs.

Ethics, Medical↗

Retraction.

Explore the source record for details and available documents.

Retraction Notice↗

A strategy to use soft data effectively in randomized controlled clinical trials.

Soft data are defined as measures having substantial intrasubject variability due to errors of measurement or to the inconsistency of subjects' responses. Such data are often important measures of response in randomized clinical trials. In this context, we show that using an intensive design and the slope of response on time as the outcome measure (a) maximizes sample retention and (b) decreases within-group variability, thus (c) maximizing the power of test procedures without requiring increased sample sizes.

Clinical Trials as Topic↗

Rating scales in research: the case of negative symptoms.

Two measures of negative schizophrenic symptoms, the Scale for the Assessment of Negative Symptoms and the withdrawal-retardation subscale of the Brief Psychiatric Rating Scale, are found to be redundant when used together. Studies incorporating redundant measures have numerous disadvantages. Using multiple scales increases the cost and effort for the investigator, places a greater burden on research subjects, and compromises the interpretability of findings by increasing the probability of both Type I and Type II errors. A strategy for evaluating the use of multiple rating scales is suggested, and the theoretical basis of this strategy is discussed.

Humans↗

Depression, parkinsonian symptoms, and negative symptoms in schizophrenics treated with neuroleptics.

To determine whether depression and neuroleptic-induced parkinsonism confound the clinical assessment of negative symptoms in schizophrenics, we evaluated 45 outpatient schizophrenics for depression, parkinsonian symptoms, and negative symptoms using standard clinical rating scales. Neuroleptic and anticholinergic dose and plasma activity were also determined. Associations between negative symptoms and these clinical and drug variables were examined using a multivariate statistical model. Negative symptoms were significantly correlated with several parkinsonian symptoms, some vegetative features of depression, and with anticholinergic dose. No significant correlations were found between negative symptoms and cognitive features of depression, or neuroleptic and anticholinergic plasma activity. These findings suggest that assessment criteria for negative symptoms, depression, and drug-induced parkinsonism overlap in treated schizophrenics. Strategies for differentiating these clinical syndromes are discussed.

Adult↗

Neurochemistry of dopamine in Huntington's dementia and normal aging.

We measured the dopamine metabolite homovanillic acid (HVA) in cerebrospinal fluid (CSF) before and after probenecid administration in normal controls and in patients with Huntington's disease. Baseline CSF HVA concentrations correlated positively with age in normal control subjects. Baseline CSF HVA concentrations were reduced in patients with Huntington's disease, and the degree of this reduction correlated with the severity of dementia and with the duration of disease. These results suggest that changes in the metabolism of dopamine by dopaminergic neurons may be associated with the dementia of Huntington's disease as well as with normal aging. These changes in dopaminergic functioning are apparently different in Huntington's disease than in normal aging and can be detected by measuring CSF HVA concentration.

Adult↗

Central error-correcting behavior in schizophrenia and depression.

A previous study suggested that schizophrenic subjects exhibit an impaired ability to correct their own errors of movement without using exteroceptive signals. However, the performance of schizophrenic subjects was compared to that of only one other psychiatric group (alcoholic subjects), and a relatively small number of subjects was studied. To investigate the specificity of the postulated impairment, 9 schizophrenic, 11 depressed, and 8 normal subjects performed a tracking task designed to prevent the use of exteroceptive cues in correcting errors of movement. The depressed and normal groups did not differ significantly on any performance measure, but the schizophrenic subjects again demonstrated a gross impairment in correcting errors, yet no impairment in initiating correct responses. These findings suggest that the impaired ability to monitor ongoing motor behavior on the basis of internal, self-generated cues may be specific to schizophrenia among major psychiatric disorders.

Adult↗

Monoamine interactions in narcolepsy and hypersomnia: a preliminary report.

Principal component analysis was performed on data obtained for the concentrations of 3,4-dihydroxyphenylacetic acid, 3-methoxy-4-hydroxyphenylethylene glycol, homovanillic acid, and 5-hydroxyindoleacetic acid in lumbar cerebrospinal fluid from a group of normal volunteers (n = 40), hypersomniac patients (n = 13), and narcoleptic patients (n = 8). All four compounds were shown to be highly intercorrelated in the normal volunteers. In the hypersomniac patients, 3-methoxy-4-hydroxyphenylethylene glycol did not appear to be correlated with the other three compounds. In the narcoleptic patients, homovanillic acid and 3,4-dihydroxyphenylacetic acid appeared not to be correlated with the other two metabolites. The results provide tentative support for a neurochemical distinction between narcolepsy and hypersomnia and suggest that attention should be given to a possible malfunction of the dopamine system in narcolepsy and norepinephrine in hypersomnia.

3,4-Dihydroxyphenylacetic Acid↗

Serotonin and schizophrenia: correlations between serotonergic activity and schizophrenic motor behavior.

Increased serotonergic activity in animals has been associated with a variety of stereotyped motor behaviors. In addition, serotonin facilitates brainstem, reticular, and spinal motor neuronal activity implicated in the expression of these behaviors. This report presents positive correlations between both peripheral (platelet serotonin levels) and central (cerebrospinal concentrations of 5-hydroxy-indoleacetic acid) measures of serotonin metabolism and the symptom of peculiar or unusual mannerisms and posturing in schizophrenic patients. The findings are discussed in light of the animal behavioral correlates of increased serotonergic activity and the stereotyped affectomotor behavior seen in some schizophrenic patients.

Adult↗

Desglycinamide-9-arginine-8-vasopressin (DGAVP, Organon 5667) in patients with dementia.

Vasopressin peptides have been shown to facilitate learning and memory in both animals and humans; however, the effectiveness in humans is controversial. In a double blind parallel group study, 17 demented subjects (either Alzheimer's or alcoholic) were given either desglycinamide-9-arginine-8-vasopressin (DGAVP) 92 micrograms intranasally TID or an identical placebo for 1 week after having received 1 week of placebo. To our knowledge, this is the first report of DGAVP being used in subjects with dementia. The DGAVP group had a statistically significant improvement on the Buschke list learning of low imagery words. However, for various reasons discussed in the paper, we feel this finding needs to be replicated before any definite conclusions can be drawn. Since there were no other appreciable behavioral effects of this DGAVP regimen, our results should be considered negative. There was no evidence of any DGAVP-related adverse effects, except for possible weight gain.

Affect↗

[Improved osseointegration and periprosthetic bone volume around cementless metal implants under bisphosphonate treatment].

AIM: The effects of a systemic treatment with the bisphosphonate ibandronate on osseointegration of uncoated and hydroxyapatite-coated titanium implants and on periprosthetic bone volume have been evaluated and the dosage of medication had to be defined. METHOD: We used an animal model of the rat, the animals were assigned to three treatment groups receiving 1 microg, 5 microg and 25 microg/kg body weight and one control group receiving NaCl 0.9%. An uncoated and a hydroxyapatite-coated titanium rod were inserted into the medullary canal of the femur. After 28 days the specimens were harvested and histomorphometric evaluation revealed extend of osseointegrated implant surface and changes of periprosthetic bone volume. RESULTS: Treatment groups receiving 5 microg and 25 microg ibandronate showed significant improvement of osseointegrated implant surface compared to the control group. Enhancement of periprosthetic bone volume was revealed in all treatment groups but only application of 25 microg ibandronate was significantly improved compared to the control group. CONCLUSION: A minor dose of 1 microg ibandronate is not effective to improve osseointegration. A high dosed bisphosphonate treatment with 5 microg or 25 microg ibandronate is potent to improve osseointegrated implant surface significantly compared to an untreated control in both uncoated and hydroxyapatite-coated titanium implants and to enhance periprosthetic bone volume. By that, improved secondary stability and prolonged survival time of cementless metal implants can be expected.

Animals↗