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M Hirschmann

Publications and source records attributed to M Hirschmann.

12 recordsLinked to original sources
PubMed2000

Melting of the Earth's lithospheric mantle inferred from protactinium-thorium-uranium isotopic data

The processes responsible for the generation of partial melt in the Earth's lithospheric mantle and the movement of this melt to the Earth's surface remain enigmatic, owing to the perceived difficulties in generating large-degree partial melts at depth and in transporting small-degree melts through a static lithosphere. Here we present a method of placing constraints on melting in the lithospheric mantle using 231Pa-235U data obtained from continental basalts in the southwestern United States and Mexico. Combined with 230Th-238U data, the 231Pa-235U data allow us to constrain the source mineralogy and thus the depth of melting of these basalts. Our analysis indicates that it is possible to transport small melt fractions--of the order of 0.1%--through the lithosphere, as might result from the coalescence of melt by compaction owing to melting-induced deformation. The large observed 231Pa excesses require that the timescale of melt generation and transport within the lithosphere is small compared to the half-life of 231Pa (approximately 32.7 kyr). The 231Pa-230Th data also constrain the thorium and uranium distribution coefficients for clinopyroxene in the source regions of these basalts to be within 2% of one another, indicating that in this setting 230Th excesses are not expected during melting at depths shallower than 85 km.

Journal Article↗
PubMed1999

Neurophysiological testing in long-standing cystinosis.

Neurophysiological data of two brothers with long-standing cystinosis are presented. Both patients showed a distally symmetrical myopathy affecting the arms more than the legs. Myopathy occurred before the onset of polyneuropathy or signs of central nervous involvement.

Adult↗
PubMed1998

Sleep endocrine effects of megestrol acetate in healthy men.

Synthetic and naturally occurring steroids exert a variety of neural effects that include modulation of nocturnal sleep. The present study focuses on the effect of progesterone receptor (PR) activation on the nocturnal sleep electroencephalogram (EEG) in male volunteers. As a PR ligand, the synthetic progesterone megestrol was used, which has the advantage over progesterone in that it is not metabolized into other steroid compounds which could cloud the progesterone-mediated effects through their own neuroactive properties. Nine healthy male volunteers were investigated in a prospective single-blind randomized study design. They received either placebo tablets or megestrol acetate dosages of 160, 320 or 480 mg at 14.00 h and 19.00 h. Blood samples were drawn half-hourly from 22.00 h until 07.00 h. After 320 mg megestrol, plasma adrenocorticotropin secretion was lower and growth hormone secretion was higher than after 160 mg and 480 mg megestrol or placebo. Similarly, the reduction in the relative amount of rapid eye movement sleep was most pronounced after 320 mg. Thus, progesterone receptor activation, as reflected by the sleep EEG and associated pituitary hormone secretion, follows a nonlinear U-shape dose dependency of a well-defined PR ligand, which may explain the unresolved inconsistencies of neuroendocrine progesterone effects to date. Moreover, employing a CV1 cell line, contransfected with a human glucocorticoid receptor expression vector and a reporter gene-based detection system for transcriptional activity, revealed that a PR agonist such as megestrol may also activate glucocorticoid receptors. This may account for some of the neuroendocrine effects of megestrol and other progestins.

Adrenocorticotropic Hormone↗
PubMed1998

Sleep-endocrine effects of mifepristone and megestrol acetate in healthy men.

Administration of steroid hormones was demonstrated to modulate the sleep electroencephalogram (EEG) and sleep-associated hormonal secretion in specific ways. The present study was conducted to compare the effects of mifepristone (Mif), a mixed glucocorticoid (GR) and progesterone receptor (PR) antagonist, and megestrol acetate (Meg), a PR agonist. Nine healthy men were pretreated with either placebo or 200 mg Mif or 320 mg Meg, or a combination of both. Changes in plasma adrenocorticotropic hormone (ACTH), cortisol, and growth hormone concentrations were registered every 30 min; sleep EEG recordings were obtained continuously. Administration of Mif increased the morning plasma ACTH and cortisol surges, whereas Meg had the opposite effect. Growth hormone secretion was lowered by Mif pretreatment and enhanced by Meg. Simultaneous administration of both compounds led to largely compensated effects. The sleep EEG changes induced by Mif were a slight increase in the time awake and a delayed onset of slow-wave sleep. Meg led to a reduction of rapid-eye-movement sleep. Simultaneous administration of Mif and Meg showed a synergism in increasing time awake and shallow sleep: it therefore may be concluded that the sleep EEG effects are mediated by an interaction of GR and PR in unknown mechanisms.

Adrenocorticotropic Hormone↗
PubMed1997

Delayed colonic transit times in amyotrophic lateral sclerosis assessed with radio-opaque markers.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder, characterized by progressive loss of motor neurons. However, ALS has been recognized to involve several non-motor systems, subclinically. Cardiac and sudomotor autonomic involvement in ALS has been described. Recently, delayed gastric emptying was reported. The aim of this study was to assess colonic transit time in patients with ALS. Therefore, measurement of total and segmental colonic transit times using radio-opaque markers was performed in 14 patients with ALS and 14 healthy age-matched volunteers. Multiple-ingestion, single-radiograph technique was used. Segmental and colonic transit times were calculated from the number of retained markers. Nine of 14 patients with ALS showed markedly delayed colonic transit times if compared to healthy controls. Colonic transit in ALS patients was significantly delayed in the right and left colon; the rectosigmoid transit did not show major delay. The colonic transit times did not correlate with bulbar involvement, Norris score, walking disability or duration of the disease. In summary, colonic dysfunction in ALS may be a result of inactivity or inadequate fiber intake. However, it also may represent a gastrointestinal autonomic involvement due to nerval degeneration. Considering ALS as a multisystem disorder including the autonomic nervous system may have implications for research into pathogenesis and therapy of neurodegenerative disease.

Abdominal Pain↗
PubMed1997

Increased stress-induced adrenocorticotropin response after long-term intracerebroventricular treatment of rats with antisense mineralocorticoid receptor oligodeoxynucleotides.

Brain corticosteroid receptors, the type 1 mineralocorticoid receptor (MR) and the type 2 glucocorticoid receptor (GR), are involved in the regulation of neuroendocrine and behavioral responses during ongoing and stressful conditions. To further investigate the role of MR in these responses, we treated male Wistar rats intracerebroventricularly (icv) for 1 week with an 18-base end-capped phosphorothioate-protected antisense oligodeoxynucleotide (ODN) directed against MR mRNA (MR-AS). A mixed bases sequence (MR-MB) and vehicle (0.9% saline) served as controls. The ODN solution was administered by continuous infusion (1 microgram/0.5 microliter/h) via an icv cannula connected with polyethylene tubing to a subcutaneously implanted Alzet miniosmotic pump. No nonspecific effects of the ODNs, such as signs of sickness behavior or loss of body weight, were observed at any time during the treatment. The MR-AS treatment produced a 21% decline in hippocampal MR concentrations. Hippocampal GR levels were not affected by the treatment. MR and GR levels after MR-MB treatment were similar to those found after treatment with the vehicle. In situ hybridization experiments using an [35S]-labeled antisense MR probe showed that hippocampal MR mRNA levels were increased in MR-AS-treated rats. No changes were found in basal early morning levels of plasma ACTH and corticosterone which is consistent with the lack of any changes in adrenal and thymus weight. When rats were socially defeated for 10 min by a male and female resident and then placed for 5 min in the elevated plus-maze, no changes in the anxiety-like behavior were observed in MR-AS-treated animals. However, MR-AS-treated rats killed immediately after the behavioral test had markedly higher plasma ACTH, but not corticosterone, levels than the MR-MB and saline controls. In conclusion, down-regulation of the brain MR produces an enhanced responsiveness of ACTH to stressful situations which appears to be accompanied by a reduced sensitivity of the adrenal gland to ACTH.

Adrenocorticotropic Hormone↗
PubMed1988

[Radioimmunotherapy of solitary liver metastases using intratumor instillation of 131I-labeled monoclonal antibodies--initial results of a clinical study].

Solitary liver metastases (carcinoembryogenic antigen positive) in two patients suffering from colon carcinoma were multifocally injected with 131I-labelled monoclonal antibodies (131I-MAb) against the carcinoembryogenic antigen (CEA). The 131I activity in the metastases decreased biexponentially. The 131I serum concentration declined triexponentially in patient 1 and monoexponentially in patient 2. The radiation dose to the whole tumor volume amounted to 358 Sv and 762 Sv, respectively; the whole-body radiation dose was 87.5 mSv for patient 1 and 39.0 mSv for patient 2. Complications did not occur. Before treatment there had been a volume doubling time of the metastases of 1.5 and 0.9 months, respectively; this contrasts with a constant tumor volume after treatment as observed over the follow-up period of 3.5 and 2 months, respectively. The CEA serum concentration decreased after 131I-MAb instillation within 1.5 and 2.5 months to 66% and 58%, respectively, when compared with values immediately before treatment. On the basis of these results the intratumoral application of 131I-MAb appears in selected cases to be a suitable method of slowing down growth of liver metastases from gastrointestinal tumors.

Antibodies, Monoclonal↗
PubMedDate not supplied

Panic attacks caused by temporal tumors: an exemplary new case and a review.

A patient is described with a ruptured temporal cavernous hemangioma clinically presenting with recurrent panic attacks mimicking panic disorder. The role of temporal lobe structures in the pathogenesis of anxiety spells is highlighted, reviewing the published cases of temporal tumors leading to panic attacks.

Aged↗