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Biomedical subjects

M Bauer

Publications and source records attributed to M Bauer.

At least 109 records · Page 6Linked to original sources

Functional significance of endothelin B receptors in mediating sinusoidal and extrasinusoidal effects of endothelins in the intact rat liver.

Endothelins (ET) are important regulators of the hepatic microcirculation that act through different receptor subtypes. We investigated functional significance of ET(B) receptors in mediating microhemodynamic effects of ETs in normal and endotoxin (lipopolysaccharide [LPS])-primed rat liver. LPS priming (Escherichia coli O26:B6; 1 mg. kg(-1)) selectively increased ET(B) mRNA and led to a shift in available receptors to the ET(B) subtype. IRL 1620 (an ET(B) agonist) increased portal pressure in a dose-dependent manner, and the increase in ET(B) expression was associated with prolonged portal pressor response in isolated livers. However, lactate dehydrogenase (LDH) release was attenuated and sinusoidal blood flow was better maintained upon ET(B) stimulation in vivo. In isolated livers, portal constriction as well as release of LDH, were substantially increased in the presence of N(omega)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase (NOS). In vivo microscopic assessment of sinusoidal perfusion during ET(B) stimulation revealed a disruption of the flow pattern including frequent reversal of the flow direction without significant sinusoid constriction. Sinusoidal flow decreased even further after discontinuation of IRL 1620. Both effects were mediated at extrasinusoidal sites that probably included postsinusoidal sites. However, after pretreatment with L-NAME, IRL 1620 evoked a significant sinusoidal constriction that colocalized with the body of the stellate cell. We propose that ET(B1)-induced NOS activity attenuates ET(B2) (and presumably ET(A))-mediated portal pressor response and stellate cell constriction. Transcriptional activation of the ET(B) gene may have a permissive effect on liver blood flow and protect against hepatocellular damage under pathophysiological conditions associated with endotoxemia.

Animals↗

The correction of congenital heart defects with less invasive approaches.

BACKGROUND: The minimally and less invasive approaches for the surgical treatment of different heart diseases are rapidly increasing because of their cosmetic and recovery-related advantages. Presented here are the results of less invasive surgery in 51 patients with congenital heart defects. METHODS: From June 1996 to January 1999, we used less invasive techniques for the correction of congenital heart defects in 51 patients. In 32 patients, we performed right anterolateral thoracotomy (6-13 cm), and on the other 19 patients, we used the partial inferior sternotomy (4-7 cm). The ascending aorta and the caval veins were cannulated in all patients. RESULTS: The following congenital heart defects were corrected: ostium secundum atrial septal defect (n = 35), sinus venosus atrial septal defect with partial anomalous pulmonary venous connection (n = 7), ventricular septal defect (n = 7), tetralogy of Fallot (n = 1), and cor triatriatum sinistrum (n = 1). The average age of the patients was 15 years old ranging from 2 months to 48 years and the average weight 39.6 kg (range 3.8-86 kg). The patients were removed from artificial respiratory support on average 8 hours (range 1-48 hours) after surgery and left the hospital after 7 days (range 2-10 days). In 16 patients, blood transfusions were required, an average 5.7 ml/kg BW (range 1.45-19.75 ml/kg BW). The postoperative course was uneventful in all patients. Follow-up (range 3-33 months, mean 17.5 months) was complete with no late deaths or residual defects. CONCLUSION: The right anterolateral thoracotomy and the partial inferior sternotomy provide a safe approach for the correction of certain congenital heart defects. These techniques enable operative correction without any additional risks being incurred and can be performed with standard instruments and cannulation. Additional approaches for extracorporeal circulation are unnecessary.

Adolescent↗

Coexistence of intestinal trefoil factor (hITF) and oxytocin in magnocellular neurons in the human hypothalamus.

Human intestinal trefoil factor hITF, a polypeptide of the P-domain family, was found to occur in hypothalamic neurons. With combined immunofluorescence and immunoperoxidase technique we investigated the coexistence of hITF with the neurohypophysial peptide oxytocin and the associated neurophysin I in sections of the human hypothalamus. In the supraoptic nucleus, 39.2% of magnocellular oxytocinergic perikarya show hITF immunoreactivity. A similar distribution was observed in perivascular hypothalamic oxytocinergic neurons, whereas in the paraventricular nucleus, 99% of the oxytocinergic neurons show hITF coexpression. In the periventricular nucleus (PEV), single, scattered neurons with both immunoreactivities occur. Our findings indicate that hITF and oxytocin are coexpressed in a portion of the magnocellular neurons in the human hypothalamus, and that hITF is among the neurohypophysial peptides.

Aged↗

A quick assay for monitoring recombinant hirudin during cardiopulmonary bypass in patients with heparin-induced thrombocytopenia type II : adaptation of the ecarin clotting time to the act II device.

BACKGROUND: Recombinant hirudin is increasingly advocated as a promising alternative anticoagulation for patients with heparin-induced thrombocytopenia type II during cardiopulmonary bypass. This requires monitoring of the ecarin clotting time. No commercial ecarin clotting time assay is available for clinical use. We adapted the ecarin clotting time to the easy-to-handle ACT II device. METHODS: Three different concentrations of the ecarin reagent (20, 10, 5 U/mL) were investigated as preliminary studies. Standard calibration curves were constructed for concentrations of recombinant hirudin ranging from 0 to 5 microgram/mL. In vivo samples were collected from patients with heparin-induced thrombocytopenia type II who underwent cardiopulmonary bypass, and the values were compared with the values obtained by the chromogenic method. The final concentration for the assay of 5 IU/mL ecarin was further assessed in vitro for reproducibility and the influence of variations in hematocrit, platelet count, and procoagulants. RESULTS: All three concentrations of ecarin revealed linearity to 5 microgram/mL concentrations of recombinant hirudin. The ecarin concentration of 5 U/mL revealed the best correlation (0.87) to the laboratory method, was reproducible over the whole recombinant hirudin range, and was not influenced by the variations in the in vitro setup. CONCLUSIONS: The ACT II/ecarin clotting time with an ecarin concentration of 5 U/mL is a simple and reliable assay for monitoring recombinant hirudin during cardiopulmonary bypass. Use of this assay allows a wider use of recombinant hirudin in patients with heparin-induced thrombocytopenia type II during bypass and thereby may contribute to the safer management of these patients.

Anticoagulants↗

Complicated chronic pancreatitis causing mycotic aortic aneurysm: in situ replacement with a cryopreserved aortic allograft.

Mycotic aortic aneurysm, which resulted from infected pancreatic pseudocysts with retroperitoneal abscess, developed in a patient with chronic pancreatitis. The aorta was approached through median laparotomy. Necrotic material was debrided from the pancreatic pseudocysts, and the mycotic aneurysm was resected. The aorta was replaced in situ with a cryopreserved aortic allograft. This report discusses the rare complication of pancreatic pseudocysts, which affect the infrarenal abdominal aorta and cause a large mycotic aneurysm. This case suggests that the use of cryopreserved allografts is promising for in situ reconstruction, even in a grossly infected field.

Aneurysm, Infected↗

Endotoxin desensitization of human mononuclear cells after cardiopulmonary bypass: role of humoral factors.

BACKGROUND: The ability of leukocytes to release proinflammatory cytokines on lipopolysaccharide stimulation in vitro is impaired after cardiopulmonary bypass (CPB). This study tested contribution and interaction of humoral factors in altered leukocyte responsiveness to lipopolysaccharide. METHODS: Whole blood and isolated peripheral-blood mononuclear cells (PBMCs) from 10 patients obtained after induction of anesthesia (T1) and 20 min (T2) and 24 h (T3) after CPB were cultured in the absence or presence of lipopolysaccharide and assessed for release of tumor necrosis factor alpha (TNF-alpha) and interleukin (IL)-1beta and their functional antagonists, IL-1 receptor antagonist (IL-1ra) and IL-10. In addition, dose-response characteristics and interaction of IL-10 and norepinephrine as modulators of TNF-alpha release were studied. RESULTS: Cardiopulmonary bypass induced release of antiinflammatory (T2: IL-10: median 25 pg/ml, 25th-75th percentile 9-42; IL-1ra: median 1,528 pg/ml, 25th-75th percentile 1,075-17,047; P < 0.05 compared with T1) but failed to induce proinflammatory cytokines (T2: TNF-alpha: median 0 pg/ml, 25th-75th percentile 0-6; IL-1beta: median 1 pg/ml, 25th-75th percentile 0-81; nonsignificant). Removal of plasma at T2 increased TNF-alpha response to lipopolysaccharide (+83.8%; P < 0.05), whereas it suppressed IL-10 (-36.8%; P < 0.05). Similarly, incubation of PBMCs (T1) with plasma obtained after CPB (T2) as well as addition of IL-10 or norepinephrine in concentrations present in plasma after CPB led to a reduced lipopolysaccharide-stimulated TNF-alpha and an increased IL-10 response. Coadministration of norepinephrine and IL-10 had synergistic effects. Although pretreatment with an anti-IL-10 antibody and labetalol before addition of plasma obtained at T2 largely restored the TNF-alpha response in vitro, their addition post-treatment failed to restore the monocytic TNF-alpha response. CONCLUSIONS: Plasma contains interacting factors that inhibit the release of TNF-alpha and increase the release of IL-10, presumably attenuating the inflammatory response to CPB. Although norepinephrine fails to induce a cytokine response in the absence of other stimuli, its administration seems to augment the antiinflammatory IL-10 response while attenuating the TNF-alpha response.

Adult↗

Cell viability in optical tweezers: high power red laser diode versus Nd:YAG laser.

Viability of cultivated Chinese hamster ovary cells in optical tweezers was measured after exposure to various light doses of red high power laser diodes (lambda = 670-680 nm) and a Nd:yttrium-aluminum-garnet laser (lambda = 1064 nm). When using a radiant exposure of 2.4 GJ/cm2, a reduction of colony formation up to a factor 2 (670-680 nm) or 1.6 (1064 nm) as well as a delay of cell growth were detected in comparison with nonirradiated controls. In contrast, no cell damage was found at an exposure of 340 MJ/cm2 for both wavelengths, and virtually no lethal damage at 1 GJ/cm2 applied at 1064 nm. Cell viabilities were correlated with fluorescence excitation spectra and with literature data of wavelength dependent cloning efficiencies. Fluorescence excitation maxima of the coenzymes NAD(P)H and flavins were detected at 365 and 450 nm, respectively. This is half of the wavelengths of the maxima of cell inactivation, suggesting that two-photon absorption by these coenzymes may contribute to cellular damage. Two-photon excitation of NAD(P)H and flavins may also affect cell viability after exposure to 670-680 nm, whereas one-photon excitation of water molecules seems to limit cell viability at 1064 nm.

Absorption↗

Double-blind, placebo-controlled trial of the use of lithium to augment antidepressant medication in continuation treatment of unipolar major depression.

OBJECTIVE: Use of lithium to augment antidepressant medication has been shown to be beneficial in the acute treatment of depression. The authors examined the efficacy of lithium augmentation in the continuation treatment of unipolar major depressive disorder. METHOD: Thirty patients with a refractory major depressive episode who had responded to acute lithium augmentation during an open 6-week study participated in a randomized, parallel-group, double-blind, placebo-controlled trial of lithium augmentation during continuation treatment. After a 2-4-week stabilization period following remission, patients were randomly assigned to receive either lithium or placebo for a 4-month period. Antidepressant medication was continued throughout the study. RESULTS: Relapses (including one suicide) occurred in seven (47%) of the 15 patients who received placebo in addition to antidepressants. None (0%) of the 14 patients who received lithium augmentation with antidepressants suffered a relapse during the double-blind phase of the study. Five of the seven relapsing patients in the placebo group developed a depressive episode, and the other two experienced a manic episode. CONCLUSIONS: Lithium augmentation in the continuation phase of treatment of unipolar major depressive disorder effectively protects patients against a relapse. Patients who respond to lithium augmentation should be maintained on lithium augmentation for a minimum of 6 months or even longer.

Adolescent↗

[The "difficult" patient in community psychiatry].

The "difficult patient" does not exist in psychiatric textbooks but rather in every day practice. A solely diagnostic description is not very useful, the categorisation into three separate subgroups by Sheets et al. (1982) on the contrary helps a lot. Three case studies describes typical treatment-situations with "difficult patients" in a community psychiatric setting.

Adult↗

[Cloning of partial cDNA of rat connective tissue growth factor and expression of its mRNA in experimental liver fibrosis].

OBJECTIVE: To clone the partial cDNA sequence of rat connective tissue growth factor (CTGF) and investigate the mRNA expression of CTGF and transforming growth factor-beta 1 (TGF-beta 1) in rat experimental liver fibrosis. METHODS: A 430-base pair sequence of rat CTGF Cdna was cloned by reverse transcription-polymerase chain reaction. Sixteen female Wistar rats were allocated into bile duct occlusion group (n=8) and sham-operated group (n=8). The liver tissue mRNA levels of CTGF and TGF-beta 1 were measured by multiprobe ribonuclease protection assay (RPA). RESULTS: The cloned partial cDNA sequence of rat CTGF was 95% homology (at nucleic acid level) with the mouse counterpart. In the liver of rats with biliary fibrosis mRNA levels of TGF-beta 1 and CTGF were 4 and 7 times as high as in those of sham-operated rats, respectively. CONCLUSION: The mRNA expression of CTGF is remarkably upregulated in rat liver fibrogenesis.

Animals↗

Chromosome 17 loss-of-heterozygosity studies in benign and malignant tumors in neurofibromatosis type 1.

Neurofibromatosis type 1 (NF1) is a common autosomal dominant condition characterized by benign tumor (neurofibroma) growth and increased risk of malignancy. Dermal neurofibromas, arising from superficial nerves, are primarily of cosmetic significance, whereas plexiform neurofibromas, typically larger and associated with deeply placed nerves, extend into contiguous tissues and may cause serious functional impairment. Malignant peripheral nerve sheath tumors (MPNSTs) seem to arise from plexiform neurofibromas. The NF1 gene, on chromosome segment 17q11.2, encodes a protein that has tumor suppressor function. Loss of heterozygosity (LOH) for NF1 has been reported in some neurofibromas and NF1 malignancies, but plexiform tumors have been poorly represented. Also, the studies did not always employ the same markers, preventing simple comparison of the frequency and extent of LOH among different tumor types. Our chromosome 17 LOH analysis in a cohort of three tumor types was positive for NF1 allele loss in 2/15 (13%) dermal neurofibromas, 4/10 (40%) plexiform neurofibromas, and 3/5 (60%) MPNSTs. Although the region of loss varied, the p arm (including TP53) was lost only in malignant tumors. The losses in the plexiform tumors all included sequences distal to NF1. No subtle TP53 mutations were found in any tumors. This study also reports the identification of both NF1 "hits" in plexiform tumors, further supporting the tumor suppressor role of the NF1 gene in this tumor type.

Adolescent↗

Hirudin monitoring using the TAS ecarin clotting time in patients with heparin-induced thrombocytopenia type II.

OBJECTIVE: To assess the reliability of the TAS/ecarin clotting time (ECT) for on-line monitoring of r-hirudin in cardiovascular surgery with and without cardiopulmonary bypass (CPB). DESIGN: Samples were spiked with r-hirudin (0 to 5 microg/mL) and calibration curves constructed. Reproducibility was evaluated by measurement of the sample five times at each concentration. The influence of variations in hematocrit, plasma factors, and platelet count on the test results was examined. Samples were obtained from patients during cardiovascular surgery with CPB (n = 8), without CPB (n = 3), and from volunteers (n = 5) and compared with the laboratory reference tests. All tests were performed in duplicate. SETTING: Deutsches Herzzentrum Berlin. PARTICIPANTS: Five healthy volunteers and 11 patients undergoing cardiovascular surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The TAS/ECT showed linearity and reliability to an r-hirudin concentration of 5 microg/mL and was not influenced (p < 0.005) by the varying conditions of the in vitro setup. The correlation to the laboratory method was 0.74 for the CPB group and 0.87 for the non-CPB group. CONCLUSIONS: The TAS/ECT is a reliable assay for monitoring r-hirudin at the point of care. With this information, the use of r-hirudin during surgery or angioplasty should become more effective and safer.

Adult↗

Phosphorylation-dependent proline isomerization catalyzed by Pin1 is essential for tumor cell survival and entry into mitosis.

Pin1, a member of the parvulin family of peptidyl-prolyl cis-trans isomerases (PPIases) has been implicated in the G2-M transition of the mammalian cell cycle. Pin1 interacts with a series of mitotic phosphoproteins, including Polo-like kinase-1, Cdc25C, and Cdc27, and is thought to act as a phosphorylation-dependent PPIase for these target molecules. Pin1 recognizes phosphorylated serine-proline or threonine-proline peptide-bonds in test substrates up to 1300-fold better than in the respective unphosphorylated peptides. To test directly whether Pin1 regulates the G2-M transition and/or progression through mitosis by catalyzing phosphorylation-dependent prolyl isomerization of essential mitotic targets, we examined the consequences of Pin1 depletion, achieved by (a) overexpression of Pin1 antisense RNA, (b) overexpression of dominant-negative Pin1, and (c) by a known small-molecule Pin1-PPIase inhibitor, juglone. The results of all of the three lines of investigation show that the catalytic activity of Pin1 is essential for tumor cell survival and entry into mitosis.

Antineoplastic Agents, Phytogenic↗

[Expression of collagen XVIII mRNA in rat liver fibrosis].

OBJECTIVE: To measure and study quantitatively the collagen XVIII mRNA in normal and fibrotic rat livers. METHODS: We used ribonuclease protection assay to investigate the collagen XVIII mRNA expression in rat liver fibrosis induced by complete bile duct occlusion (BDO). The expression level of procollagen 1 (XVIII) mRNA was compared with that of procollagen 1 (I) and tissue inhibitor of metalloproteinase 1 (TIMP1). RESULTS: mRNA levels of procollagen and TIMP 1 increased 20- and 4-fold in BDO rat livers, respectively. In contrast, hepatic procollagen 1 mRNA level increased only 1.8-fold in fibrotic rat livers. CONCLUSION: C XVIII mRNA is upregulated slightly in liver fibrosis, which is probably correlated with the fact that CXVIII is mainly expressed by hepatocytes.

Animals↗

[Cost control in anesthesiology--regulating net costs exemplified by anesthetics].

German hospitals are beginning to feel more and more pressure due to rising costs in health care. These are due to continuous increase in health care expenditure and decrease in state insurance contributions. A change in the state insurance system (GKV) is well and truly overdue; the source of income needs to be increased by either raising the compulsory insurance wage base or making other forms of income liable for insurance contributions. Unfortunately, the government is still reluctant to take action. The ruling coalition feels that it is better to limit the increase in expenditure on hospital care by introducing a case-related payment system. Unfortunately, they do not recognize that the main reason for the increase in health care expenditure is the growing medical potential and the higher morbidity of an, on average, older population. These cuts in financial means demand an efficient allocation of the available funds. As far as hospital in-patient care is concerned, this means that hospitals need to reconsider their expenditure and that economic success is dependent on their potential to recognize ways of reducing overall costs. This article illustrates that before the "Diagnosis Related Groups" (DRG) become effective in 2003, one needs to establish the cost price of individual hospital cases. The economic principles of cost-benefit ratios and methods to prevent cost inflation are presented. The methods of making a cost-effectiveness analysis of anaesthetic costs are explained in detail. The aim of this paper is to give the clinician a better understanding of cost management and to motivate staff to initiate cost-control studies.

Anesthesiology↗