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Biomedical subjects

D Hartmann

Publications and source records attributed to D Hartmann.

At least 91 records · Page 5Linked to original sources
PubMed1994

Development of granule cells, and afferent and efferent connections of the dentate gyrus after experimentally induced reorganization of the supra- and infrapyramidal blades.

We have analyzed the development of the major afferent and efferent connections of the hamster dentate gyrus as well as the morphology of its granule cells, subsequent to a novel developmental defect. Following the selective destruction of the overlying meningeal cells by the neonatal administration of 6-hydroxydopamine, the majority of the glial and neuronal precursor cells destined for the infrapyramidal blade of the dentate gyrus are redirected into the suprapyramidal stratum granulosum, that subsequently becomes elongated and thickened. The remaining cells form a rudimentary infrapyramidal blade with a temporal delay of at least one week, the molecular layer of which is reduced in comparison to controls. This rudiment is either attached to the suprapyramidal blade by an apparently normal crest region or develops as a separate structure. Consecutive to this manipulation, the terminal field of the early-differentiating commissural and associational fibers expands in the suprapyramidal blade, whereas it is reduced in the late-forming infrapyramidal rudiment, the vacant space at the granule cell dendrites being taken over by entorhinal afferents. The efferent mossy fiber bundle does not show any differences along its course into the CA3 region, whereas hilar mossy fibers expand their intragranular distribution, sometimes contacting, but never invading the molecular zone. The morphology of the majority of the granule cells is entirely normal, however, a small but significant proportion maintains additional basal dendrites normally present only in immature, but not in adult rodents.

Animals↗
PubMed1994

Early modifications of biochemical markers of bone metabolism in spinal cord injury patients. A preliminary study.

Spinal cord injury is associated with the development of a rapid and severe osteoporosis which might reflect uncoupling between bone formation and resorption. A prospective study was made in 6 spinal cord injury patients followed up to 2-3 months after onset with various markers of a) bone formation: osteocalcin and C-terminal peptide of type I procollagen, b) bone resorption: pyridinolines and C-terminal telopeptide of type I collagen, c) connective tissue metabolism: amino-terminal propeptide of type III collagen (PIIINP). Preliminary results show that early after onset, bone formation was depressed as compared to dramatically increased bone resorption. Low bone formation rate lasted two weeks before it began to raise, while bone resorption showed a continuous tendency to increase. The dramatic increase in PIIINP levels might represent some attempt of bone to repair. This paper describes the evolution of various biochemical markers of bone and connective tissue metabolism after onset of paralysis and critically reviews the use of those markers in patients with spinal cord injury.

Adult↗
PubMed1994

Effect of a novel beta-adrenoceptor agonist (Ro 40-2148) on resting energy expenditure in obese women.

The aim of this single-blind, placebo-controlled study was to investigate the effects of the new beta-adrenergic compound Ro 40-2148 on resting energy expenditure (REE) at rest and after an oral glucose load in non-diabetic obese women before and after two weeks of treatment. After one week of placebo administration and after an overnight fast and one hour rest, REE and glucose and lipid oxidation rates were measured by indirect calorimetry (hood system) before and for 6 h after a single dose of placebo solution. A 75 g oral glucose tolerance test (OGTT) was performed during this period starting 90 min after the placebo administration. During the following two weeks, using a randomization design, six patients received Ro 40-2148 at a dose of 400 mg diluted in 100 ml water twice a day (i.e. 800 mg per day), while six others continued with the placebo administration. The same tests and measurements were repeated after two weeks, except for the treatment group which received the drug instead of the placebo. The 14-day period of drug administration did not increase REE measured in post-absorptive conditions. Similarly, there was no acute effect on REE of a 400 mg dose of Ro 40-2148. In contrast, glucose-induced thermogenesis was significantly increased after two weeks in the treatment group (means +/- s.e.m.: 3.7 +/- 1.3%, P = 0.047), while no change was observed in the placebo group (-0.8 +/- 0.7%, not significant). Since there was no significant change in the respiratory quotient, the increase in energy expenditure observed in the treatment group was due to stimulation of both lipid and glucose oxidation. The drug induced no variations in heart rate, blood pressure, axillary temperature or in plasma glucose, insulin and free fatty acid levels. In conclusion, this study shows that Ro 40-2148 activates glucose-induced thermogenesis in obese non-diabetic patients.

Adrenergic beta-Agonists↗
PubMed1994

[New avenues in therapy of postoperative low output syndrome].

The present definitions of low-output syndrome (LOS) associated with cardiac surgery are based on data obtained via the Swan-Ganz-catheter. However, further important data such as signs of chronic renal insufficiency, arterial vascular disease, and perioperative volume overload have hardly been considered. At the Heart Center NRW, FRG, the Swan-Ganz-Catheter is not used routinely to monitor patients following cardiac surgery. According to our experience, the definition of low-output syndrome includes a wider spectrum of relevant criteria. In addition to the data obtained by means of a central venous catheter the clinical aspect of the patient as well as laboratory analysis should be regarded as well. In 1259 consecutive patients (pts) (914 with coronary surgery and 318 with valve surgery) the incidence and mortality of low-output syndrome were determined. In 49 of the 941 coronary surgery pts (5.2%) a postoperative low-output syndrome occurred. Nine pts (0.95%) died as a result of this complication. According to our therapeutical strategy, the low-output syndrome was treated medically in 28 pts (2.9%); in 14 pts (1.5%) IABP implantation was necessary, and 7 pts needed mechanical circulatory support. Surprisingly, the same incidence of LOS occurred in the valve surgery group of pts as in the coronary group. We saw a low-output syndrome in 17 of the 318 pts (5.3%), with fatal outcome in three pts. In 14 of these pts (4.4%) the LOS was treated medically, while the remaining three pts (0.9%) required diastolic augmentation of the IABP.

Adult↗
PubMed1994

Biotin kinetics in serum of cattle after intravenous and oral dosing.

Single oral (p.o.) or intravenous (i.v.) doses of biotin were given to four cattle (400-450 kg body weight) in two consecutive tests two weeks apart. Dosages were p.o. 20, 40, 80 or 160 and i.v. 5, 10, 20, 40 mg biotin per 300 kg body weight. A three-compartment model was used to describe the course of serum concentrations with time. After i.v. administration, terminal half-lives of about 8 h were found. Areas under the curves were linearly related to both the p.o. and the i.v. doses. The systemically available fraction of the p.o. dose was 50 to 60%. On the basis of kinetic parameters, the biotin uptake via the feed was estimated to be 2.5 mg/day, which was about half of that estimated to be in the hay consumed. The data suggest that there was no relevant ruminal synthesis of biotin.

Administration, Oral↗
PubMed1993

The anti-tumor arotinoid Ro 40-8757 protects bone marrow from the toxic effects of cyclophosphamide.

The arotinoid Ro 40-8757 is a novel compound that has significant therapeutic activity against chemically induced breast tumors in rats. The results of combination therapy with cyclophosphamide, plus the arotinoid showed that the anti-tumor effects were additive. However, all of the rats given CPA alone died between week 6 and week 10 of treatment. None of the animals in the group treated with the combination died. Administration of a single dose of Ro 40-8757 to non-tumor bearing mice resulted in a transient increase in bone-marrow-progenitor cells after 2 days and a decrease in splenic progenitors at day 4. Treatment of mice with the combination demonstrated that the marrow progenitors were protected from the toxic effects of CPA by the arotinoid. Direct addition of Ro 40-8757 to mouse bone-marrow cells in clonogenic assay cultures containing WEHI-3-conditioned medium plus erythropoietin showed no significant enhancement by the arotinoid. The results suggest that this compound may exert its protective effect through the hemopoietic micro-environment.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1993

Historical aspects of the oral use of retinoids in acne.

A number of investigations of the effects of vitamin A deficiency in animals and man and its treatment with natural products containing vitamin A were carried out in the twenties and thirties. In 1942, a clinical study in patients with acne treated with vitamin A yielded encouraging results. Further trials in the forties and fifties, trying to confirm the beneficial effect of oral vitamin A in acne, met with equivocal success. In the sixties, all-trans retinoic acid (tretinoin) became clinically available, and its topical efficacy in acne could be demonstrated. In 1971, oral tretinoin also was shown to be active in patients with acne. Coincidentally, the efficacy of oral 13-cis retinoic acid (isotretinoin) became evident in a series of unpublished studies in Europe. Then, in 1978, a trial carried out at the NIH, Bethesda, Maryland, yielded convincing evidence that isotretinoin is a potent new drug for the treatment of severe cystic acne. In 1982, isotretinoin was registered in the United States and one year later in Europe for the treatment of severe, recalcitrant, cystic acne. Since then, many thousands of patients suffering psychologically and physically from the severity of their disease have been treated successfully with this drug. However, the main concern of physicians prescribing isotretinoin has to focus on its potentially severe side effects, particularly its teratogenicity.

Acne Vulgaris↗
PubMed1993

Effect on dietary fat absorption of orlistat, administered at different times relative to meal intake.

Orlistat (O) is a potent and selective inhibitor of gastrointestinal lipases. The effect on dietary fat absorption following dosing of O at different times relative to meals was investigated in a placebo (P) controlled study in 24 hospitalized healthy males. After a 5-day run-in, to accustom the subjects to a diet of 2400 kcal and 77 g fat per day and to establish baseline faecal fat excretion, subjects received, in four parallel groups of 6. over 8 days three times daily doses of 80 mg O.P.P (group A) or P. 80 mg O.P (group B) or P.P. 80 mg O (group C) or P.P.P (group D) at mid-meal. 1 h and 2 h after mid-meal respectively. Faeces were collected to measure total fat excretion. The mean (s.d.) of faecal fat in percent of dietary fat, after deduction of pre-treatment faecal fat, was (%) 32.8 (8.1), 34.0 (8.8), 26.9 (4.0) and -1.4 (1.7) in groups A. B. C and D respectively. It was concluded that, within the time period investigated, the pharmacological effect of O is not critically dependent on the time of dosing relative to meals.

Adult↗
PubMed1993

[Serum hyaluronic acid in osteoarthritis].

In this prospective study, serum hyaluronate (SH) was assayed using a radiometric method (Pharmacia) in 73 osteoarthritis patients and 39 controls. All assays were performed between 8 h 00 and 9 h 00 a.m. because SH levels exhibit circadian variations. SH levels were significantly higher in patients with osteoarthritis than in controls (92 +/- 66 micrograms/l and 39 +/- 21 micrograms/l, respectively, p = 0.0001). Among 50 patients with osteoarthritis, including 29 with knee involvement and 21 with hip involvement, SH levels were not correlated with morning stiffness, duration of symptoms, Lequesne's algofunctional index, erythrocyte sedimentation rate, C-reactive protein, severity of roentgenographic changes in the affected knee or hip, disease extension, or severity. The lack of any relationship between changes in SH levels and Lequesne's is index values in 25 patients or between SH levels and joint space narrowing evaluated retrospectively in 16 patients, as well as the prompt return to high SH levels after arthroplasty and synovectomy in 14 patients with hip joint osteoarthritis, suggest that this potential marker is not useful for monitoring osteoarthritis in a single joint.

Adult↗
PubMed1993

Establishment and characterization of B-like lymphoblastoid cell lines by long-term culture of primary explants from human myasthenic thymus.

Using a simple method of long-term culture, it was possible to obtain B-like lymphoblastoid cell lines (LyCLs) from myasthenic thymuses. Successful cultures were carried out from 14 out of 15 hyperplastic thymuses and in 1 out of 3 myasthenic thymoma, whereas none of the 8 control thymuses, nor the 2 Myasthenia gravis-associated normally involuted thymuses, nor the Myasthenia gravis-associated lymphoma gave rise to LyCL. All the LyCLs secreted immunoglobulins (Ig), either IgG or IgM. None of these Ig reacted with acetylcholine receptor or with other antigens known to be often involved in autoimmune diseases. EBV antigens were found in all the LyCLs as well as in the corresponding donors at the time of thymectomy. HLA characterization of some LyCLs and the corresponding donors showed that class II MHC antigens were expressed normally or with mild differences. However, 86% of the LyCL tested did not express class I MHC antigens.

B-Lymphocytes↗
PubMed1993

The bioavailability of supplemental biotin in cattle.

A trial using 12 yearling heifers was carried out to test whether biotin metabolism and bioavailability are influenced by continuous dietary supplementation with biotin. Six of these heifers received no biotin supplementation (controls), while six received a daily dietary supplement of 20 mg biotin over the whole experimental period of four months. During each of three test periods (on days 14 and 21, 56 and 63, and 118 and 124), single test dosages of 40 mg (oral) and 5 mg (intravenous) biotin were given to each animal in a crossover test design. Blood samples were collected up to 72 h after each of these single doses, and at approximately two-weekly intervals for the assessment of baseline values. Serum biotin levels were determined by an ELSA test. Areas under the curves (AUC) were calculated as the target parameter for the assessment of the bioavailability of orally administered biotin. Serum biotin baseline levels were 300-800 ng/l in the controls and 3000-8000 ng/l in the supplemented animals. In both groups, AUC values in the first test period (days 14 and 21) were significantly higher than in subsequent periods. However, the biotin supplementation showed no significant effect. There was no significant difference in elimination half-lives between groups with and without biotin supplementation. The range was 5-18 h. Furthermore, there was no significant difference in the bioavailability of biotin between the test periods or between the biotin-supplemented and unsupplemented animals. Overall bioavailability was 48%.

Administration, Oral↗
PubMed1992

Development of astroglial cells in the proliferative matrices, the granule cell layer, and the hippocampal fissure of the hamster dentate gyrus.

The histogenesis of the hamster dentate gyrus was studied with light and electron microscopy and antisera against the astrocyte-associated antigens vimentin and GFAP, in order to follow the differentiation of radial glial cells and astrocytes. The formation of the stratum granulosum is preceded by the establishment of successive dentate matrices, which are formed by cells that leave the ventricular neuroepithelium and occupy positions above the fimbria (suprafimbrial), below the pial surface (subpial), and within the dentate hilus (hilar dentate matrix). The subpial dentate matrix invades the marginal zone of that region of the cerebral wall, where the stratum granulosum will later develop. From the beginning of its existence on embryonal day 13 (E13) up to its disappearance about postnatal day 7 (P7), it is characterized by a high content of GFAP-positive cells and mitoses. This indicates early gliogenesis in the dentate anlage, long before the appearance of the stratum granulosum. Many of the bipolar GFAP-positive cells are oriented parallel to the pial surface and have focal contacts to the pial basement membrane. The establishment of the subpial dentate matrix splits the primordial radial glial scaffold of the hippocampal/dentate anlage into two bundles: 1) the suprafimbrial bundle that retains its original radial position between ventricle and pial surface; and 2) the dorsal glial bundle that traverses the ventral tip of the pyramidal cell layer of future CA3. The latter is pushed dorsolaterally, away from the pial surface, by the enlargement of the subpial dentate matrix and, later, by the suprapyramidal blade. The latter emerges around birth as small radial columns of granule cells located between the bent basal parts of the ventralmost fibers of the dorsal glial bundle and the subpial dentate matrix. From the beginning of its existence it is traversed by unipolar "secondary" radial glial fibers that appear to originate from the subpial dentate matrix. Both the supra- and the infrapyramidal blades seem to elongate by the addition of postmitotic granule cells and "secondary" radial glial cells from the subpial dentate matrix to the growing end of the primordial stratum granulosum. The hilar dentate matrix that is localized in the prospective hilar region, inside the growing stratum granulosum, also contains glial cells that seem to be incorporated into the stratum granulosum. The dentate gyrus is demarcated from the CA1 region of the hippocampus proper by GFAP-positive cells that populate the hippocampal fissure, and that also originate from the subpial dentate matrix.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Destruction of meningeal cells over the medial cerebral hemisphere of newborn hamsters prevents the formation of the infrapyramidal blade of the dentate gyrus.

Meningeal cells participate in the development of the cerebellum both by stabilizing the extracellular matrix of the pial surface and by organizing the radial glial scaffold and the lamination of the cerebellar cortex. In the present study we investigated possible influences of meningeal cells on the development of the dentate gyrus, whose ontogenesis has many similarities to that of the cerebellum. Meningeal cells were selectively destroyed by injecting newborn hamsters with 25 micrograms 6-hydroxydopamine (6-OHDA) into the interhemispheric fissure. Twenty-four hours postinjection (p.i.) the meningeal cells over the medial cerebral hemispheres were completely destroyed. Thirty days p.i. the infrapyramidal blade of the dentate gyrus was almost completely missing, while the suprapyramidal blade was hypertrophied, extending with its medial tip almost up to the medial surface of the cortex. In order to ascertain that this maldevelopment was caused by the destruction of meningeal cells, another group of hamsters was pretreated with normetanephrine (NMN) which inhibits the extraneuronal uptake of 6-OHDA into meningeal cells. In this group the meningeal cells were unaffected by the treatment, and the morphology of the dentate gyrus was normal 30 days p.i. of 6-OHDA plus NMN. When the meningeal cells were destroyed in later stages of development (postnatal days 1-5), alterations of the dentate gyrus could be induced only up to the fourth postnatal day; thereafter, 6-OHDA treatment left it unchanged. This indicates a critical period of meningeal cell influence that coincides with the period of existence of the subpial dentate matrix. Analysis of the time course of the defective development revealed that in the first 5 days p.i. 1) meningeal cells over the medial cerebral hemisphere were destroyed and removed, 2) the pial basement membrane over both the dentate anlage and the diencephalon thinned and ruptured, and the adjacent brain parts fused focally, 3) many cells of the subpial dentate matrix disappeared from their subsurface position, 4) the number of "immature" cells increased in the hilus and the subgranular zone of the suprapyramidal blade, 5) the suprapyramidal blade elongated and thickened considerably, while the infrapyramidal blade did not form. Beyond 5 days p.i. those parts of the pial surface of the dentate anlage that had not fused with the diencephalon were repopulated with meningeal cells. This reappearance of meningeal cells was accompanied by 1) the restitution of the normal morphology of the basement membrane, 2) the reappearance of neuronal and glial cells below the pial surface, and 3) the formation of fragments of the infrapyramidal blade which later developed a normal appearing lamination.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Effect of acitretin on the response to an intravenous glucose tolerance test in healthy volunteers.

The effect of the synthetic retinoid acitretin (A) on the disposition of blood glucose and on the serum insulin response following the IV infusion of 139 mmol glucose over 10 min (IGTT) has been investigated in six healthy subjects. The IGTT was performed on Days 1, 10 and 24. On Days 3 to 10 A 50 mg/d was administered. Several parameters of glucose disposition and insulin response (K-values, AUC) were assessed. As a methodological variant, the profiles over time of blood glucose and serum insulin were evaluated by model calculations using the 'minimal model'. Acitretin did not influence any parameter of glucose disposition. The area under the insulin-time curve (baseline corrected) was significantly decreased from 1.20 mU.min.l-1 on Day 1 to 0.89 mU.min.l-1 on Day 10, and was 0.91 mU.min.l-1 on Day 24. The model-derived 'insulin sensitivity' increased from 13.10(-4) l.mU-1.min-1 on Day 1 to 20.10(-4) l.mU-1.min-1 on Day 10 and was 18.10(-4) l.mU-1.min-1 on Day 24. The results suggest that A increased sensitivity to endogenous insulin. It supports a recent report showing greater insulin sensitivity in patients treated with the synthetic retinoid etretinate.

Acitretin↗
PubMed1992

Effect of tumor burden and route of administration on the immunotherapeutic properties of polyinosinic-polycytidylic acid stabilized with poly-L-lysine in carboxymethyl cellulose [Poly(I,C)-LC].

We examined the immunomodulatory and therapeutic activities of poly(I,C)-LC. Mice received a subcutaneous (s.c.) injection of sufficient numbers of MBL-2 lymphoma cells to produce in 1 week either a high or low tumor burden. A week after tumor cell injection, poly(I,C)-LC treatment was initiated; the agent was administered intraperitoneally (i.p.) at 5 mg/kg twice a week or at 2.5 or 0.5 mg/kg every day or as an intravenous (i.v.) injection at 0.5, 0.05, or 0.005 mg/kg three times a week. Poly(I,C)-LC treatment significantly increased antitumor effector cell functions in a variety of organs (including spleen, lungs, and peritoneum), as shown by increased killing of MBL-2 cells in vitro and increased tumor cell killing by natural killer cells and macrophages. Furthermore, prolongation of survival correlated with peritoneal macrophage tumoricidal activity when poly(I,C)-LC was given i.p. and with pulmonary effector cell function (including natural killer, cytolytic T-lymphocyte and macrophage tumoricidal activity) when the agent was administered i.v.

Animals↗