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Biomedical subjects

C Schmidt

Publications and source records attributed to C Schmidt.

At least 217 records · Page 12Linked to original sources
PubMed1998

Assessment of cardiovascular volume status by transoesophageal echocardiography and dye dilution during cardiac surgery.

Conventional evaluation of cardiovascular volume status by filling pressures is unreliable in critically ill patients. Measurements of left ventricular end diastolic area index by transoesophageal echocardiography and of intrathoracic blood volume index by dye indicator dilution are new approaches to this problem. In this study, different indices of cardiovascular volume status were analysed to define their relation during the pronounced haemodynamic changes associated with systemic inflammation after cardiopulmonary bypass. Correlations were performed with left ventricular end diastolic area index, intrathoracic blood volume index, central venous pressure (CVP) and pulmonary capillary wedge pressure (PCWP). Data from 15 patients receiving coronary artery bypass grafts were compared after induction of anaesthesia and in the intensive care unit. Spearman's correlation coefficient for perioperative absolute changes in left ventricular end diastolic area index and intrathoracic blood volume index was 0.87 (P < 0.05). However, an increase in intrathoracic blood volume index by 125 mL m-2 was necessary to maintain a baseline left ventricular end diastolic area index. Absolute values of all variables varied widely, with the only significant correlation found between CVP and PCWP. Changes in CVP and PCWP did not correlate with changes in left ventricular end diastolic area index or intrathoracic blood volume index. Provided simultaneous baseline measurements are available and a supranormal intrathoracic blood volume index compensates for the haemodynamic changes in systemic inflammation, left ventricular end diastolic area index and intrathoracic blood volume index may substitute for each other during the evaluation of cardiovascular volume status in patients with stable cardiac function.

Anesthesia↗
PubMed1998

Transoesophageal echocardiography in the critically ill.

Echocardiography offers real-time bedside diagnosis and monitoring of a variety of structural and functional abnormalities of the heart. Transoesophageal echocardiography, in particular, provides information on cardiac contractility, filling status and output, valvular morphology and function and on the structure of the ascending and descending aorta in the critically ill patient. The full range of modalities of echocardiography, including M-mode, 2-D-mode, colour Doppler and spectral Doppler, is at the disposal of the intensive care specialist. In this review, the indications for and the clinical impact of transoesophageal echocardiography and Doppler are discussed.

Cardiac Output↗
PubMed1998

Baroreflex sensitivity and heart rate variability in coronary disease compared to dilated cardiomyopathy.

This study was designed to compare baroreceptor sensitivity and heart rate variability as measures of cardiac autonomic tone in patients with coronary disease (CAD, n = 49) and idiopathic dilated cardiomyopathy (IDC, n = 130). Time domain heart rate variability, including SDNN, SDANN, and pNN50, was determined during 24-hour Holter ECG. Baroreflex sensitivity was analyzed nonivasively using the phenylephrine method. Baroreflex sensitivity and heart rate variability were comparable between patients with CAD versus IDC (baroreflex sensitivity: 6.1 +/- 3 vs 6.9 +/- 5 ms/mmHg; SDNN: 97 +/- 40 vs 114 +/- 41 ms; SDANN: 83 +/- 33 vs 99 +/- 41 ms; pNN50: 3.9 +/- 4 vs 9.6 +/- 13 ms, P = NS for all comparisons). Likewise, a subgroup analysis of patients with a left ventricular ejection fraction (LVEF) < or = 30% showed no significant difference in baroreceptor sensitivity and heart rate variability between IDC and CAD patients. Patients with CAD and an LVEF > 30% had a decreased heart rate variability but not a decreased baroreflex sensitivity compared to patients with IDC and LVEF > 30% (baroreflex sensitivity: 6.4 +/- 4 vs 8.3 +/- 6 ms/mmHg, P = NS; SDNN: 98 +/- 19 vs 128 +/- 42 ms, P < 0.05; SDANN: 86 +/- 21 vs 112 +/- 43 ms, P < 0.05; pNN50: 4.2 +/- 3 vs 12.3 +/- 8 ms, P < 0.05). Patients with a markedly depressed LVEF show comparable alterations in cardiac autonomic tone whether they have CAD or IDC. Patients with CAD and preserved LV function, however, have a decreased heart rate variability compared to patients with IDC and preserved LV function. The prognostic significance of these findings will be determined prospectively in a large patient cohort at our institution.

Baroreflex↗
PubMed1998

Mapping of candidate genes for hypertension by fluorescence in situ hybridization on the genome of transgenic rats and mice.

Transgenic animals are new and important models for the study of candidate genes in hypertension research as well as in other fields of medicine. For detailed genetic characterization of the transgenic animals, and to account for the symptoms arising from the insertion of transgenes in the genome, it is essential to identify these insertion sites. In this study, the insertion sites of the transgenes of candidate genes for hypertension were identified by fluorescence in situ hybridization (FISH) after G-banding of the chromosomes in transgenic rats and mice. This technique combines high resolution G-banding and fluorescence in situ hybridization for the mapping of four different candidate genes in six different transgenic rats as well as three different mouse transgenic lines. The presented results will help to draw conclusions about the influence of the respective integration site on transgene expression.

Angiotensinogen↗
PubMed1998

Basic neuroscience: critical issues for understanding psychiatric disorders.

Recent scientific advances in understanding the function and plasticity of the central nervous system have opened fundamental insights into the pathophysiology of various mental disorders. This chapter reviews the basic physiology of the central nervous system, and further focuses on the applications of the new knowledge to clinical psychiatry.

Antidepressive Agents↗
PubMed1998

An update on adolescent psychopharmacology.

Adolescent pediatricians are being asked to assume a larger role in the management of psychiatric disorders. Therefore, dissemination of the knowledge base regarding the use of psychotropic medications to treat these disorders in children and adolescents is critical. This chapter is an update to the previous "Primer on Adolescent Psychopharmacology" by Bailey and Hendren. Many of the disorders that occur in adolescence are associated with significant morbidity and functional impairment. While the evaluation of adolescents involves a careful assessment of the psychosocial milieu and the implementation of an intervention that involves the use of multiple modalities, pharmacotherapy can diminish symptom severity and thereby assist in the process of recovery. Successful pharmacotherapy begins with the development of an active and reciprocal alliance with the patient and family that allows for sharing of critical information and provision of support. The initiation of treatment should include a clear definition of target symptoms, the potential risks and benefits of the proposed intervention, and a discussion that includes a review of the current treatment experiences in both adult and child psychiatry. The establishment of a method that allows for adequate monitoring of both response and side effects is critical. Clearly, this is a field in its infancy. Thus, practitioners must be acutely aware of both the extent and limitations of the existing knowledge base as well as critical need for more controlled studies of these interventions in adolescence.

Adolescent↗
PubMed1998

Selection and outcome of ventricular assist device patients: the Muenster experience.

BACKGROUND: Because the number of patients on the waiting list for transplantation is increasing and the stagnation in the number of organs donated has led to a more restrictive listing for transplantation, an increased fraction of patients needs to be bridged mechanically. We examined the hypothesis that selection of these patients with regard to urgency status is critical in determining outcome. METHODS: A cohort of 631 patients referred for transplantation to our center between January 1, 1990, and December 31, 1996, was analyzed. Two hundred ninety-seven patients were listed for transplantation and 157 were given transplantation. Forty-one patients had to undergo ventricular assist device implantation (n=34, Novacor; n=6, TCI Heartmate; n=1, Medos), 39 for bridging to transplantation and 2 for permanent support. Initial transplantation evaluation data were analyzed in 3 subgroups (elective bridging, urgent bridging, emergency bridging) and compared with another and with other patients referred for transplantation, specifically those who did not have to be bridged on the waiting list. RESULTS: Patients who underwent elective or urgent assist device bridging were younger and more compromised than the rest of patients accepted on the waiting list (higher functional class, lower mean arterial pressure, lower cardiac index, lower serum sodium, higher pulmonary capillary wedge pressure). In the elective group, overall survival including perioperative mortality rate was better than in the urgent/emergency group and at least as good as in patients who were stable on the waiting list and did not undergo heart transplantation during follow-up. This should prompt cardiologists and cardiac surgeons to consider assist device implantation earlier.

Adult↗
PubMed1997

Redundancy of class III POU proteins in the oligodendrocyte lineage.

Class III POU proteins are prominent regulators of neural development. Tst-1/Oct6/SCIP, for instance, is essential for terminal differentiation of myelinating Schwann cells in the peripheral nervous system. Although Tst-1/Oct6/SCIP is also expressed in the myelin forming oligodendrocytes of the central nervous system, targeted deletion of Tst-1/Oct6/SCIP failed to reveal a gross alteration of myelination in the central nervous system. To better understand this apparent discrepancy, we examined the expression of POU proteins in both cultured primary oligodendrocytes and in the oligodendrocyte-like CG-4 cell line. These cells expressed Tst-1/Oct6/SCIP, Brn-1, and Brn-2 in significant amounts, indicating that Brn-1 and Brn-2 might have the capacity to compensate loss of Tst-1/Oct6/SCIP. We show that Tst-1/Oct6/SCIP, Brn-1, and Brn-2 were all down-regulated during the early phases of oligodendrocyte development both on RNA and protein level. All three POU proteins exhibited similar DNA binding characteristics. When promoters consisting of a single POU protein-binding site adjacent to a TATA box were used as reporters in transient transfections, Brn-1 proved to be a weaker transcriptional activator than Tst-1/Oct6/SCIP. In agreement with this, we found the transactivation domain of Brn-1, which we mapped between amino acids 119 and 237, significantly weaker than the transactivation domain of Tst-1/Oct6/SCIP. Taken together, our data imply a partial, but not complete redundancy between POU proteins in oligodendrocytes.

Amino Acid Sequence↗
PubMed1997

Topoisomerase-I inhibitors for human malignant glioma: differential modulation of p53, p21, bax and bcl-2 expression and of CD95-mediated apoptosis by camptothecin and beta-lapachone.

Beta-lapachone and camptothecin are structurally unrelated agents thought to inhibit topoisomerase-I activity through distinct mechanisms. We find that beta-lapachone is much more potent than camptothecin in inducing acute cytotoxic effects on human malignant glioma cells. Acute cytotoxicity induced by both drugs is apoptotic by electron microscopy, but not blocked by inhibitors of RNA or protein synthesis and not associated with changes in the expression of bcl-2, bax, p53, p21 or GADD45 proteins. In contrast, prolonged exposure of glioma cells to both drugs for 72 hr results in growth inhibition and apoptosis, with EC50 values around 1 microM. None of 7 glioma cell lines tested were resistant to either drug. LN-229 cells which have partial p53-wild-type activity show enhanced expression of p53, p21 and bax protein, whereas bcl-2 levels decrease, after exposure to camptothecin. In contrast, beta-lapachone increases bax protein expression in the absence of p53 activation. T98G cells are mutant for p53. In these cells, p53 levels do not change and p21 is not induced. bax accumulation in T98G cells is induced by both drugs, with bcl-2 levels unaltered. Surprisingly, ectopic expression of murine bcl-2 fails to abrogate the toxicity of either drug. Camptothecin, but not beta-lapachone, sensitizes human malignant glioma cells to apoptosis induced by the cytotoxic cytokines, tumor necrosis factor-alpha and CD95 ligand. Thus, both drugs have potent anti-glioma activity that may be mediated by enhanced bax expression but is not inhibited by ectopic bcl-2 expression. Camptothecin-like agents are particularly promising for immunochemotherapy of malignant glioma using cytotoxic drugs and CD95 ligand.

Apoptosis↗
PubMed1997

A metalloprotease-inhibitor reduces pain associated behavior in mice with experimental neuropathy.

Tumor necrosis factor-alpha (TNF) is involved in the generation of inflammatory and neuropathic pain. The synthetic hydroxamic acid based metalloprotease inhibitor TAPI blocks cleavage of cell surface TNF and thus reduces levels of the mature 17-kDa TNF polypeptide in activated macrophages and T-cells. We have previously shown that pharmacologic inhibition of TNF production reduces pain related behaviors in mice with chronic constriction injury (CCI). Here we investigated whether blockage of TNF shedding by administration of TAPI would diminish hyperalgesia in animals with partial nerve injury. We injected 0.5 mg of the inhibitor epineurially once daily to mice with CCI for 7 days. The animals were tested for withdrawal thresholds to heat to test for thermal hyperalgesia and to von Frey hairs to assess mechanical allodynia. Mice with CCI developed thermal hyperalgesia and mechanical allodynia by day 3 after the injury. In mice treated with TAPI, a reduction of thermal hyperalgesia and mechanical allodynia of up to 50% occurred. Endoneurial TNF-immunoreactivity was reduced, but not immunoreactivity for IL-1alpha or IL-1beta. The numbers of degenerating axons and endoneurial macrophages were not affected by the treatment as compared to controls. We conclude that the metalloprotease inhibitor TAPI specifically reduces endoneurial TNF-levels after nerve injury and thereby may diminish neuropathic pain in the CCI-model.

Animals↗
PubMed1997

T promoter activity in the absence of functional T protein during axis formation and elongation in the mouse.

The T (Brachyury) gene, which encodes a transcription factor, is involved in the formation of posterior mesoderm. Although studies in Xenopus have shown that T gene expression is responsive to mesoderm inducing factors and furthermore suggest the existence of an autoregulatory loop involving T itself, eFGF, and the FGF receptor, little is known about the regulation of T expression in the mouse. We report here that in the mouse the expression of fgf-4, the putative homologue of Xenopus efgf, is not dependent on the presence of T protein during the first 48 hr of gastrulation. Furthermore, we address the question of autoregulation using a chimeric approach. Introduction of a T promoter-lacZ construct into T/T ES cells results in T promoter activity in the primitive streak and tail bud in the absence of functional T protein. Therefore, we suggest that a direct FGF and T autoregulatory loop is unlikely to operate during gastrulation and axis elongation in the mouse.

Animals↗
PubMed1997

Characterization of the human homologue of RAD54: a gene located on chromosome 1p32 at a region of high loss of heterozygosity in breast tumors.

A search of the Human Genome Sciences database of expressed sequence-tagged DNA fragments, for sequences containing homology to known yeast DNA recombination and repair genes, yielded a cDNA fragment with high homology to RAD54. Here we describe the complete cDNA sequence and the characterization of the genomic locus coding for the human homologue of the yeast RAD54 gene (hRAD54). The yeast RAD54 belongs to the RAD52 epistasis group and appears to be involved in both DNA recombination and repair. The hRAD54 gene maps to chromosome 1p32 in a region of frequent loss of heterozygosity in breast tumors and encodes a protein of M(r) 93,000 that displays 52% identity to the yeast RAD54 protein. The hRAD54 protein sequence additionally contains all seven of the consensus segments of a superfamily of proteins with presumed or proven DNA helicase activity. Mutations in genes with consensus helicase homology have been found in cancer-prone syndromes such as xeroderma pigmentosum and Bloom syndrome as well as Werner's syndrome, in which patients age prematurely, and the X-linked mental retardation with alpha-thalassemia syndrome, ATR-X. We have examined the hRAD54 gene in several breast tumors and breast tumor cell lines and, although the gene region appears to be deleted in several tumors, at present we have found no coding sequence mutations.

Amino Acid Sequence↗
PubMed1997

Regulation of paraxis expression and somite formation by ectoderm- and neural tube-derived signals.

During vertebrate embryogenesis, the paraxial mesoderm becomes segmented into somites, which form as paired epithelial spheres with a periodicity that reflects the segmental organization of the embryo. As a somite matures, the ventral region gives rise to a mesenchymal cell population, the sclerotome, that forms the axial skeleton. The dorsal region of the somite remains epithelial and is called dermomyotome. The dermomyotome gives rise to the trunk and limb muscle and to the dermis of the back. Epaxial and hypaxial muscle precursors can be attributed to distinct somitic compartments which are laid down prior to overt somite differentiation. Inductive signals from the neural tube, notochord, and overlying ectoderm have been shown to be required for patterning of the somites into these different compartments. Paraxis is a basic helix-loop-helix transcription factor expressed in the unsegmented paraxial mesoderm and throughout epithelial somites before becoming restricted to epithelial cells of the dermomyotome. To determine whether paraxis might be a target for inductive signals that influence somite patterning, we examined the influence of axial structures and surface ectoderm on paraxis expression by performing microsurgical operations on chick embryos. These studies revealed two distinct phases of paraxis expression, an early phase in the paraxial mesoderm that is dependent on signals from the ectoderm and independent of the neural tube, and a later phase that is supported by redundant signals from the ectoderm and neural tube. Under experimental conditions in which paraxis failed to be expressed, cells from the paraxial mesoderm failed to epithelialize and somites were not formed. We also performed an RT-PCR analysis of combined tissue explants in vitro and confirmed that surface ectoderm is sufficient to induce paraxis expression in segmental plate mesoderm. These results demonstrate that somite formation requires signals from adjacent cell types and that the paraxis gene is a target for the signal transduction pathways that regulate somitogenesis.

Amino Acid Sequence↗