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Biomedical subjects

D Hartmann

Publications and source records attributed to D Hartmann.

At least 73 records · Page 4Linked to original sources

Seven years of experience with the centrifugal pump in patients with cardiogenic shock.

From September 1987 to September 1994 61 patients between 29 and 78 years of age received mechanical circulatory support by means of the Biomedicus centrifugal pump. The patients were divided into three groups by indication: Group I included 15 patients with early postcardiotomy cardiogenic shock and 24 patients with late postcardiotomy cardiogenic shock. Group II 11 patients with therapy-resistant cardiogenic shock following acute myocardial infarction, and Group III 11 patients with cardiogenic shock of other etiologies. Duration of support was 1 to 347 hours. Survival rates were 46.7% and 33.3% in patients with early and late postcardiotomy cardiogenic shock, respectively (Group I), 27.2% in Group II, and 18.1% in Group III. Most frequent complications were bleeding (40%, 58%) and acute renal failure (26.7%, 29.2%) in Group I and multiple organ failure in Groups II and III (64% and 45.5%). Major causes of death were bleeding and multiple organ failure in Group I (37.5%) and multiple organ failure in Groups II and III (87.5% and 50%). Groups II and III (87.5% and 50%).

Adult↗

Relevance of reversible inhibitors of monoamine oxidase type A and of reuptake inhibition for noradrenaline turnover.

Noradrenaline (NA) and serotonin, monoamines that increase neurotransmission at the monoaminergic synapses, remain primary targets for antidepressant drugs. To help elucidate NA's role in the action of antidepressants, a model was set up allowing for a simulation of NA turnover under various conditions examining 3 compartments: newly synthesized vesicular NA, released synaptic NA, and vesicular NA reuptake across neuronal membranes. We compared the influence of the reversible MAO inhibitor, moclobemide, and the NA reuptake inhibitor, desipramine, both useful in regaining baseline synaptic NA concentrations. Moclobemide appears less sensitive to fluctuations either in drug concentrations and/or physiological determinants of NA turnover; we conclude that it may influence brain function in a more regulatory way than reuptake inhibitors.

Animals↗

Distribution of somatostatin receptor subtype 1 mRNA in the developing cerebral hemispheres of the rat.

Somatostatin (SST) is one of the major peptide transmitters in the mammalian central nervous system and also seems to exert specific functions during brain development. In contrast to ligand binding experiments, by which two pharmacologically different binding sites were characterized, molecular cloning techniques have led to the identification of at least five different receptor subtypes (SSTR1-5), which according to RNA blot analyses seem to be differentially distributed and regulated in the developing brain. In order to provide more precise data on the distribution of SSTR1 during ontogenesis, we have performed an in situ hybridization analysis, using a 35S-labelled RNA probe, in the developing rat cortex between embryonic day (E)12 and adulthood. Within the cortical plate, expression of SSTR1 gene was first detected in parallel with the establishment of the deep laminae V/VI at E16, thereby following the characteristic morphogenetic gradients of cortical plate construction. Thus, with the subsequent addition of cells along the radial dimension, e.g. the deposition of the supragranular neurons beyond E18, the hybridization signal spreads as an uniform homogenous band through the entire cortical plate, whereby silver grains reach their peak density around birth. Similar developmental gradients were observed along the lateromedial and frontooccipital dimension, whereby SSTR1 transcripts were detected near the frontal pole and the lateral cortical areas roughly 2 days before they appeared in the occipital and medial cortical anlage, respectively. From the initially homogenous distribution, two distinct SSTR1 mRNA-positive bands coextensive with laminae V/VI and II/III, respectively, and sparing lamina IV evolved during the first postnatal week, the grain density of which decreased during further postnatal development. Within the hippocampal formation, SSTR1 transcripts were initially observed at E18 in the subicular complex, and after birth also extending into the neighboring CA1 region. During the 1st and 2nd postnatal week, silver grains were observed over the pyramidal cell layer of CA2 and CA3 and as a faint supragranular band in the dentate gyrus. Similar to the isocortex, grain density decreased thereafter. Hypothetically, the pronounced temporospatial regulation of SSTR1 gene expression during brain development can be correlated with (1) the establishment and eventual reduction of transient cortical SSTergic neuron populations described for late pregnancy and early postnatal development and (2) a receptor subtype exchange during maturation as evidenced by the late (from postnatal day 7 onward) appearance of e.g. SSTR3.

Animals↗

Human myofibroblastlike cells obtained by outgrowth are representative of the fibrogenic cells in the liver.

During human fibrogenesis, myofibroblastlike cells proliferate and are the main source of fibrosis components. We have used cultured myofibroblastlike cells obtained by outgrowth from explants of human liver to study the expression of extracellular matrix (ECM) components and matrix-metalloproteinase-2 (MMP-2) These cells contained types I, III, IV, and V procollagen messenger RNAs (mRNAs). They also expressed mRNAs for laminin B1 chain and for cellular and plasma fibronectin. The corresponding proteins were detected by immunocytochemistry. MMP-2 expression was shown by Northern blot and gelatin zymography. Because transforming growth factor beta 1 (TGF beta 1) is considered an important mediator in liver fibrogenesis, we examined its effect on expression of ECM components by cultural human myofibroblastlike cells. TGF beta 1 increased collagen mRNAs steady-state levels and total collagen secretion in the culture medium. It also increased fibronectin mRNA levels but had no effect on laminin mRNA or MMP-2 expression. In summary, cultured human myofibroblastlike cells express those ECM components that accumulate during hepatic fibrogenesis, indicating the usefulness of this model to study mechanisms of human liver fibrogenesis. In addition to the mitogenic effect of TGF beta 1 on human myofibroblastlike cells, we now demonstrate its stimulation of ECM accumulation in these cells, thus emphasizing the central role of TGF beta 1 and myofibroblastlike cells in the pathophysiology of human hepatic fibrosis.

Cells, Cultured↗

Study on the possible interaction between tenoxicam and atenolol in hypertensive patients.

Sixteen hypertensive male out-patients (33-54 y), whose blood pressure (BP) had been normalized (diastolic BP < 90 mmHg) by treatment with a daily dose of 50 mg atenolol (CAS 29122-68-7), participated in this double-blind, placebo-controlled, parallel group study, which investigated the possible influence of the non-steroidal anti-inflammatory drug tenoxicam (CAS 59804-37-4) on the control of BP by atenolol. After a run-in of 10 days, to assess the stability of BP control by atenolol, and to determine baseline parameters, 8 patients in group A received 20 mg tenoxicam (2 x 20 mg on days 1 and 2), and 8 patients in group B received placebo, daily over 15 days (days 0-14), concomitantly with their atenolol regimen. BP was measured under standardized conditions on several days. Heart rate (EHR) after 5 min of exercise by bicycle ergometry (constant 75W), and parameters of renal function were assessed before (baseline) and during concomitant dosing of atenolol and tenoxicam. On day 14 the mean changes (delta A, delta B) from baseline of pre-dose BP (mmHg) and EHR (beats/min) in groups A and B, and the one-sided 95% confidence regions (R) for delta A, respectively, were (delta A, delta B, R): 4.4, 1.6, < 9.5 for sitting systolic BP, 2.8, -0.3, < 4.5 for sitting diastolic BP, -0.3, -0.6, < 5.5 for standing systolic BP, -0.6, -1.9, < 3.0 for standing diastolic BP, 0.4, -7.5, < 0.4 for EHR at pre-dose, 3.1, 0.6, < 7.8 for EHR at 3.5 h post-dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Left ventricular function in heart valve surgery: a multidisciplinary challenge.

Between January 1988 and December 1994, 4,097 patients underwent heart valve replacement at the Heart Center North Rhine-Westfalia, Bad Oeynhausen, 1,388 (33.8%) of them suffered from impaired left ventricular (LV) function. Overall hospital mortality was 2.3% (n = 95). In the poor LV function group it was 1.8% (n = 25). There was a significant increase of mortality from 1.5% in patients younger than 60 years to 4.9% in patients 80 years of age and older. Reoperations and emergency operations showed an additional increase of mortality each: 6.2% and 18.2%, respectively. Medium term survival (maximum 48 months) was assessed in a group of 2,006 patients operated between January 1991 and December 1993. The cumulative mortality for patients with poor LV function (n = 148) was 12.8%, whereas for those with normal LV function it was 6.1%. Our data suggest that left ventricular function is of minor importance as far as primary operative results are concerned. In long term follow up patients with valve replacement and poor LV function show an increased mortality mainly due to cardiac causes.

Adolescent↗

[Changes in the polymorphism and concentrations of components of the class II complement after orthotopic transplantation of the liver].

OBJECTIVES AND METHODS: The genes of complement factor B, C2 and C4 are located within the major histocompatibility complex class III region on chromosome 6 in man. These components demonstrate a genetic polymorphism which, when determinated, can be used to define complotypes (association of C2, factor B, C4A and C4B allotypes). On the other hand the liver is the main source of the circulating complement component synthesis. The aim of this study was to analyse the kinetics of several complement component (C3, factor B and C4) concentrations in the plasma and to assess changes in the polymorphic pattern of the complotypes after orthotopic liver transplantation. Nephelometry was used for plasma level measurements and factor B, C2 and C4 typings were performed with high voltage electrophoresis or isofocalisation and immunofixation at intervals before, during and after orthotopic liver transplantation in eleven patients. RESULTS: Complotypes changes were observed 24 hours after liver transplantation in all patients. A slight decrease in C3, C4, and factor B plasma levels was observed in the first hours after transplantation. A rapid increase in the levels of these components was observed subsequently, with normalization in less than 15 days. CONCLUSION: These results demonstrate a rapid synthesis of complement components and the changes in complement polymorphic patterns after liver transplantation.

Adult↗

The anti-tumor arotinoid Ro 40-8757 protects bone marrow from the toxic effects of 5-fluorouracil.

Combination therapy with 5-fluorouracil (5-FU) and the arotinoid Ro 40-8757 (mofarotene) of established chemically induced mammary tumors in rats was examined. The cytotoxic drug was administered weekly and Ro 40-8757 was given daily. The dose of Ro 40-8757 used in this study did not have an effect on tumor burden but, in combination with 5-FU, significantly enhanced the reduction in tumor burden and tumor number. In order to determine if Ro 40-8757 had a protective effect on 5-FU-treated animals, several studies were performed with non-tumor-bearing mice. The 5-FU was given once a week for 3 weeks at a dose that was lethal only after the third administration. When this treatment was combined with Ro 40-8757 given 5 times/week, approximately 50% of the mice survived. Examination of the progenitor cell contents of femur and spleens of treated mice indicated that the protective effect of Ro 40-8757 was manifested at the primitive hemopoietic progenitor cell level. Studies with murine bone marrow cells and human breast-cancer cell lines in vitro demonstrated that there was no interaction between the 2 drugs at the cellular level, indicating that the arotinoid does not enhance the ability of cells to metabolize 5-FU. This protective effect of the arotinoid makes it a useful potential partner for combination therapy with 5-FU.

Animals↗

Comparison of the inhibition of dietary fat absorption by full versus divided doses of orlistat.

Orlistat is a potent and selective inhibitor of gastrointestinal lipases. The drug is designed for the treatment of obesity. The effect on dietary fat absorption of orlistat after administration of divided doses spread over 2 hours from mid-meal, in comparison with that after administration of a full dose mid-meal, was investigated in a randomized, single-blind study including 16 hospitalized healthy males. After a 5-day run-in, to accustom the subjects to a diet of 2350 kcal and 76 g fat per day and to establish baseline fecal fat excretion, subjects received, in two parallel groups of eight over 8 days, three times a day 80 mg orlistat at mid-meal, and placebo at mid-meal and 0.5, 1, and 2 hr after mid-meal (group A), or placebo at mid-meal, and 20 mg orlistat at mid-meal and 0.5, 1, and 2 hr after mid-meal (group B). Feces were collected to measure total fat excretion. The mean (SD) of fecal fat in percent of dietary fat, after deduction of pretreatment fecal fat, was (%) 36.1 (4.2) and 37.0 (9.3) in groups A and B, respectively. Changing the mode of administration of orlistat, within the dose regimens investigated, does not affect its pharmacologic efficacy.

Absorption↗

The development of the radial glial scaffold of the cerebellar cortex from GFAP-positive cells in the external granular layer.

We have reinvestigated the origin and genesis of the radial glia of the cerebellar cortex in the hamster using three astroglial markers, vimentin, GFAP, and S-100 protein antibodies. On embryonic day 12 (E12), before the emergence of the external granular layer, the cerebellar anlage is traversed from the ventricle to the pial surface by a primordial radial glial scaffold which is vimentin-positive, but GFAP and S-100 negative. With the formation of the external granular layer on E13, a few GFAP positive cells appear among the unstained external granular layer cells. First seen within the germinal trigone and caudalmost part of the external granular layer, they then develop rostrally, amongst the cells of the expanding external granular layer, proliferating adjacent to the basement membrane. Beginning on E15, cells that are positive for the S-100 protein also appear within the external granular layer and the molecular zone. In later stages, S-100 is strongly expressed in Golgi epithelial cells, so we have considered it to be a marker for these cells. By contrast, the primordial radial glial cells were not stained with this marker. On the day of birth (E16/PO) many S-100 positive cells also appear at intermediate levels between the EGL and the Purkinje cell plate. They are unipolar and bear a single radial process that is directed towards the pial surface. The caudorostral appearance of S-100-positive cells firstly in the external granular layer, then in the molecular zone and finally in the Purkinje cell plate is identical to the temporal sequence of development of these layers, and suggests that S-100-positive cells are at first integral constituents of the external granular layer, but later descend through the molecular zone, to colonize the Purkinje cell plate. Here they proliferate and ultimately differentiate into Golgi epithelial cells, their numerous short radial glial processes traversing the molecular zone and the external granular layer to fill the interstices between the primordial radial glial fibres. At birth, S-100-positive Golgi epithelial cells have progressively colonized the Purkinje cell plate from the germinal trigone rostrally, up to a region midway between primary fissure and anterior medullary velum and, between P2 and P3, the rostralmost part of the cerebellum has become populated. GFAP- and S-100-positive cells remain in the external granular layer up to the end of the first postnatal week. In the same interval, the number of Golgi epithelial cells and Bergmann glial fibres increases rapidly in the expanding cerebellar cortex.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Complete inherited deficiency of the fourth complement component in a child with systemic lupus erythematosus and his disease-free brother in a north African family.

Although null alleles of complement C4 genes (C4A*Q0 and C4B*Q0) are frequent in the normal population, the occurrence of two null alleles on the same chromosome is very rare and therefore complete C4 deficiency is exceptional. We describe a 16-year-old North African boy who presented with systemic lupus erythematosus with renal involvement and persistent undetectable classical pathway activity and C4 protein and hemolytic activity in plasma, with normal C3 levels. Similar complement abnormalities were observed in his healthy 12-year-old brother. Complete C4 deficiency was documented in the two brothers by investigation of the family and the lack of C4A and C4B bands upon phenotyping of C4. Southern blot analysis of the C4/CYP21 gene organization in the family indicated that the deficiency resulted from a deletion of the C4B/CYP21A genes associated with nonexpression of a C4A gene. The double-null haplotype was found to be associated with homozygous A2 B17 C2C BFF C4 AQ0 BQ0 DR7 HLA haplotype. Thus, similar C4 deficiencies with HLA identity may lead to different clinical presentations.

Adolescent↗

Analysis of collagens solubilized from cartilage of normal and spontaneously osteoarthritic rhesus monkeys.

Osteoarthritis (OA) is a disorder which results in the destruction of the articular cartilage and the remodeling of the subchondral bone in synovial joints. We have analyzed the cartilage collagen from normal and osteoarthritic free-ranging rhesus monkeys from the Cayo Santiago colony. The cartilage samples were assigned a severity score based on histological staging system and were divided into four groups (normals, mild OA, moderate OA and severe OA). After a 4.0 M guanidinium chloride (GuCl) extraction, the remainder of the cartilage was digested with pepsin and the collagen was salt precipitated at 2.5 M and 4.3 M NaCl. The GuCl solubility of the osteoarthritic cartilage increased compared to normals. Collagen extractability by GuCl also increased with the severity of disease. Pepsin digestion followed by salt precipitation shows that collagen from rhesus osteoarthritis cartilage is more easily extracted than from normal cartilage. With an anti-type I collagen antibody we have detected the presence of type I collagen in the severe OA cartilage samples but not in the milder OA groups or in normal cartilage. Total collagen content decreases with severity of OA, which is not due to changes in propyl hydroxylation because examination of collagen hydroxylation, based on hydroxyproline analysis, shows no difference between OA and normal cartilage.

Animals↗

The influence of storage on cytotoxic drug activity in an ATP-based chemosensitivity assay.

The use of viability assays to assess the effect of antineoplastic agents on cell lines and tumor cells is an important investigative tool and may have clinical relevance. Such assays require very small quantities of drugs and it is the practice of many laboratories to freeze aliquots of drugs for use in these assays as required. We have investigated the stability of 11 different agents in an ATP-based chemosensitivity assay which is being evaluated for clinical use. The results show that most drugs maintain their biological activity well when frozen at -20 degrees C for periods up to 24 months, or occasionally at room temperature. However, 4-hydroperoxycyclophosphamide and mitomycin C are exceptions to this rule, and should not be kept frozen for more than 2-3 months. Cisplatin is unstable when frozen and then thawed, but maintained activity at room temperature for at least 6 months. Since biological activity may not correlate completely with chemical stability, further studies on the effect of storage are required, but it seems unlikely that the appropriate use of frozen aliquots is a major source of error in tumor chemosensitivity assays.

Adenosine Triphosphate↗

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↗

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↗