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Biomedical subjects

H Schmidt

Publications and source records attributed to H Schmidt.

At least 199 records · Page 11Linked to original sources
PubMed2000

Longitudinal change of white matter abnormalities.

A three year follow-up of 273 participants (mean age 60+/-6.1 years) of the Austrian Stroke Prevention Study provides first information on the rate, clinical predictors, and cognitive consequences of MRI white matter hyperintensity in elderly individuals without neuropsychiatric disease. Lesion progression was found in a total of 49 (17.9%) individuals. It was minor in 27 (9.9%) and marked in 22 (8.1%) participants. Diastolic blood pressure (odds ratio 1.07/mmHg) and early confluent or confluent white matter hyperintensities at baseline (odds ratio 2.62) were the only significant predictors of white matter hyperintensity progression. Lesion progression had no influence on the course of neuropsychologic test performance over the observational period.

Aged↗
PubMed2000

Genetic aspects of microangiopathy-related cerebral damage.

Microangiopathy related cerebral damage (MARCD) includes early confluent and confluent white matter hyperintensities (WMH) and lacunar lesions. It is expected to be the result of interactions between multiple genetic and environmental factors. The estimated proportion of genetic factors contributing to the interindividual variation seen in WMH volume is 73%. This estimate points to a significant genetic component in WMH development. In the setting of the Austrian Stroke Prevention Study we search for genes being associated with the presence, severity and progression of MARCD using the candidate gene approach. Defining susceptibility genes may allow to better identify individuals at high risk for MARCD and to target preventive measures.

Apolipoprotein E2↗
PubMed2000

Milrinone improves intestinal villus blood flow during endotoxemia.

PURPOSE: To determine whether the compromised intestinal villus blood flow in a rat model of endotoxemia could be improved by continuous infusion of the phosphodiesterase (PDE) inhibitor milrinone. METHODS: Twenty-four anesthetized and ventilated rats were laparotomized and an ileal portion was exteriorized and opened by an antimesenteric incision. The ileal segment was fixed with the mucosal surface upward. Microcirculatory parameters were assessed by intravital videomicroscopy. The animals were randomly assigned to receive one of three treatments: infusion of Escherichia coli lipopolysaccharides without phosphodiesterase inhibitor pretreatment (=LPS group); or infusion of LPS with milrinone pretreatment (= milrinone group), or without infusion of LPS or milrinone (=control group). Macrohemodynamic parameters (MAP, HR) and microhemodynamic parameters of ileal mucosa (mean diameter of central arterioles = D(A) and mean erythrocyte velocity within the arterioles= V(E)) were measured 30 min before and at 0, 60, and 120 min after induction of endotoxemia. Mucosal villus blood flow was calculated from D(A) and V(E). RESULTS: In the milrinone group MAP decreased 60 min after induction of endotoxemia whereas it remained stable in the control and the LPS group. In both groups given endotoxin V(E) decreased after start of LPS infusion. In contrast, D(A) decreased in the LPS group, but increased in the milrinone group after 120 min of endotoxemia. Thus, the endotoxin-induced decrease of intestinal villus blood flow was diminished but not fully restored by milrinone infusion. CONCLUSION: Our results indicate that milrinone has some beneficial microcirculatory effects during endotoxemia. Although it contributed to systemic hypotension, it attenuated intestinal mucosal hypoperfusion.

Animals↗
PubMed2000

Vascular risk factors in dementia.

This review describes differing profiles of vascular risk factors in different types of dementia. Although vascular risk factors are related to various types of strokes, their independent effect on the occurrence of poststroke dementia appears to be small. Various risk factors have been identified for microangiopathy-related cerebral abnormalities, such as white matter changes and lacunae, which are the core lesions for the development of a vascular dementia syndrome without stroke symptoms. Most consistently, arterial hypertension and diabetes mellitus have been found to be associated with such brain abnormalities. Diastolic blood pressure seems to be of particular importance as recent investigations demonstrate that this factor is related to the course of multiple lacunar strokes and the progression of white matter disease. Epidemiological studies report that various vascular risk factors including arterial hypertension, diabetes mellitus, and atrial fibrillation may also be associated with Alzheimer's disease. There is also evidence of a direct relationship between Alzheimer's disease and general atherosclerosis. Further investigations are needed to determine whether these associations are due to the weakness of diagnostic criteria, or whether vascular risk factors indeed modulate the clinical expression of primary degenerative dementia. Common susceptibility genes leading to shared risk factors may be one of the reasons for a higher coincidence of Alzheimer's disease and vascular dementia than can be expected by chance. A modulatory effect of vascular risk factors in the development of primary degenerative dementia may extend treatment options.

Aged↗
PubMed2000

Foreign body aspiration in children.

BACKGROUND: There is still considerable controversy about the diagnostic procedure, the endoscopic approach, and the complication rate with foreign body aspiration in children. METHODS: Review of our data for 98 children suspected for foreign body aspiration between January 1990 and December 1998 was performed. RESULTS: In this data review, 78% of the children studied were younger than 2 years. A foreign body aspiration was identified in 70%, and 67% had a definite history of aspiration. Predominant clinical features were fever (46%), pneumonia (39%), and coughing (29%). Pathologic chest radiographs were found in 84% of the children. Sixty-two percent of the foreign bodies were trapped in the right lung, and 87% were of organic in origin. In 93%, a single endoscopic procedure was successful in removing the foreign bodies. The mean time between aspiration and bronchoscopic extraction was 5.4 days (range, 1 h to 36 weeks). The procedure-related morbidity rate was 0.96% and the mortality 0. CONCLUSIONS: Outcome and complications were found to depend mainly on the time the foreign body stayed in the tracheobronchial system. Early bronchoscopy is paramount in any case of suspected foreign body aspiration, and it is mandatory to increase the awareness of the population and medical professionals.

Bronchoscopy↗
PubMed2000

Relationships between thought-action fusion, thought suppression and obsessive-compulsive symptoms: a structural equation modeling approach.

Research has shown that there are strong similarities in content between the obsessions and compulsions that characterize obsessive-compulsive disorder and nonclinical obsessions and compulsions. However, clinical and nonclinical obsessions and compulsions do differ with respect to characteristics like frequency, intensity, discomfort and elicited resistance. Two separate concepts have been invoked to explain how normal obsessions and compulsions may develop into clinical phenomena. First, it is suggested that thought-action fusion (TAF) contributes to obsessive-compulsive symptoms. Second, thought suppression may intensify obsessive-compulsive symptoms due to its paradoxical effect on intrusive thoughts. Although both phenomena have been found to contribute to obsessive-compulsive symptoms, possible interactions between these two have never been investigated. The current study explored how TAF and thought suppression interact in the development of obsessive-compulsive symptoms. Undergraduate psychology students (N = 173) completed questionnaires pertaining to TAF, thought suppression and obsessive-compulsive symptoms. Covariances between the scores on these questionnaires were analyzed by means of structural equation modeling. Results suggest that TAF triggers thought suppression, while thought suppression, in turn, promotes obsessive-compulsive symptoms.

Adolescent↗
PubMed2000

Recurring chromosomal abnormalities in non-Hodgkin's lymphoma: biologic and clinical significance.

Non-Hodgkin's lymphomas (NHLs) are a group of clinically important neoplasms with a complex biology that makes their classification and treatment difficult. Their incidence is increasing and they cause significant morbidity and mortality. NHLs result from transformation of B and T/natural killer (NK) cells. Their genetic hallmark is chromosomal translocations resulting from aberrant rearrangements of IG and TCR genes, which lead to inappropriate expression of genes at reciprocal breakpoints that regulate a variety of cellular functions, including gene transcription, cell cycle, apoptosis, and tumor progression. Cytogenetics followed by molecular genetic analysis of some of the recurring translocations continues to provide new insights into lymphomagenesis and cell biology. More recently, chromosomal and gene amplification and gene deletion have been recognized as frequent genetic changes that may play a role in lymphoma progression and clinical behavior. In this review, cytogenetic data pertaining to recurring chromosomal changes on lymphomas are reviewed and examined in relation to their relevance to lymphoma development, classification, and clinical behavior.

Chromosome Aberrations↗
PubMed2000

Detection of nucleic acid sequences from bacterial species with molecular genetic methods.

While blood products become more safe in terms of viral contamination, the risk of transfusion-related bacterial infection has re-emerged to one of the major hazards in transfusion medicine. In recent prospective studies the rate of contaminated platelets ranged from 0.04 to 0.5%, and a rate of transfusion reactions between 0.007% and 0.046%. It is generally agreed that most of the organisms isolated from donated blood originate from the normal skin flora or from the environment. As it is unlikely that antiseptic methods can achieve absolute sterilization of the skin before venepuncture, blood banks have to rely on laboratory tests to detect contaminated blood products before release. But most of the currently available methods detecting bacterial contaminations do not have the potential to be sensitive and fast enough for a routine contamination screening in transfusion services. Here we present two alternative strategies based on molecular genetic techniques (Real-Time-PCR and Haystack processing) that detect or semi-quantify bacterial rRNA gene sequences for the majority of bacterial species. In addition we discuss some aspects on target selection, routine preparation and residual 16S-rDNA-contamination of enzymes.

Bacteria↗
PubMed2000

Heterogeneity of the prtC gene of Porphyromonas gingivalis.

In this study, the nucleotide sequences of the prtC genes of six clinical Porphyromonas gingivalis isolates obtained from patients with periodontitis and from reference strain 53977 were determined. All analyzed genes were heterogeneous in their nucleotide composition and differed in up to 13 nucleotides. Moreover, substantial differences were found in comparison to prtC of reference strain 53977. The prtC genes of 45 Porphyromonas gingivalis isolates were amplified by polymerase chain reaction (PCR) and the PCR products were also digested with restriction endonucleases Tsp509I, NlaIII and DraII (PCR-restriction fragment-length polymorphism). Nine different restriction pattern combinations were observed, with four being most frequent (28.9%, 26.7%, 17.8% and 11.1%). The data presented here demonstrates that prtC genes are heterogeneous in their nucleotide sequence and therefore may be used as a target for molecular epidemiological studies. The observed heterogeneity of prtC genes may be a result of microevolution processes.

Bacterial Proteins↗
PubMed2000

LMNA, encoding lamin A/C, is mutated in partial lipodystrophy.

The lipodystrophies are a group of disorders characterized by the absence or reduction of subcutaneous adipose tissue. Partial lipodystrophy (PLD; MIM 151660) is an inherited condition in which a regional (trunk and limbs) loss of fat occurs during the peri-pubertal phase. Additionally, variable degrees of resistance to insulin action, together with a hyperlipidaemic state, may occur and simulate the metabolic features commonly associated with predisposition to atherosclerotic disease. The PLD locus has been mapped to chromosome 1q with no evidence of genetic heterogeneity. We, and others, have refined the location to a 5.3-cM interval between markers D1S305 and D1S1600 (refs 5, 6). Through a positional cloning approach we have identified five different missense mutations in LMNA among ten kindreds and three individuals with PLD. The protein product of LMNA is lamin A/C, which is a component of the nuclear envelope. Heterozygous mutations in LMNA have recently been identified in kindreds with the variant form of muscular dystrophy (MD) known as autosomal dominant Emery-Dreifuss MD (EDMD-AD; ref. 7) and dilated cardiomyopathy and conduction-system disease (CMD1A). As LMNA is ubiquitously expressed, the finding of site-specific amino acid substitutions in PLD, EDMD-AD and CMD1A reveals distinct functional domains of the lamin A/C protein required for the maintenance and integrity of different cell types.

Amino Acid Sequence↗
PubMed2000

The p53 status in juvenile chronic arthritis and rheumatoid arthritis.

The aim of this study was to investigate the p53 status in two autoimmune diseases; juvenile chronic arthritis (JCA) and rheumatoid arthritis (RA). In a PCR-sequencing analysis of exons 4-9 of the p53 gene, no mutation was identified, except for the case of an RA synovectomy sample with two mutations of intron 7. p53 gene polymorphisms for codons 36, 47, and 213 were not detected. Codon 72 polymorphism showed an indication of an increased occurrence of the Pro/Pro allelotype in JCA. Expression of P53 protein was comparable for JCA and RA synovectomy samples. For all RA samples P53 protein was detectable, whereas one sample of a JCA patient failed to express P53 protein.

Adolescent↗
PubMed2000

Involvement of mitogen-activated protein kinase in agonist-induced phosphorylation of the mu-opioid receptor in HEK 293 cells.

Agonist exposure of many G protein-coupled receptors stimulates an activation of extracellular signal-regulated protein kinases (ERKs) 1 and 2, members of the mitogen-activated protein kinase (MAPK) family. Here, we show that treatment of human embryonic kidney (HEK) 293 cells stably transfected to express the rat micro-opioid receptor (MOR1) with [D-Ala2,MePhe4,Gly5-ol]enkephalin (DAMGO) stimulated a rapid and transient (3-5-min) activation and nuclear translocation of MAPK. Exposure of these cells to the MAPK kinase 1 inhibitor PD98059 not only prevented MAPK activation but also inhibited homologous desensitization of the mu-opioid receptor. We have therefore determined the effect of PD98059 on agonist-induced mu-receptor phosphorylation. DAMGO stimulated a threefold increase in MOR1 phosphorylation within 20 min that could be reversed by the antagonist naloxone. PD98059 produced a dose-dependent inhibition of agonist-promoted mu-receptor phosphorylation with an IC50 of 20 microM. DAMGO also induced MOR1 internalization that peaked at 30 min. Confocal microscopy revealed that DAMGO-induced MOR1 internalization was also largely inhibited in the presence of PD98059. U0126, another chemically unrelated inhibitor of the MAPK cascade, mimicked the effect of PD98059 on mu-receptor phosphorylation and desensitization. MOR1 itself, however, appears to be a poor substrate for MAPK because mu-receptors immunoprecipitated from stably transfected HEK 293 cells were not phosphorylated by exogenous ERK 2 in vitro. The fact that morphine also triggered MAPK activation but did not induce MOR1 internalization indicates that receptor internalization was not required for MOR1-mediated mitogenic signaling. We conclude that MOR1 stimulates a rapid and intemalization-independent MAPK activation. Activation of the MAPK cascade in turn may not only relay mitogenic signals to the nucleus but also trigger initial events leading to phosphorylation and desensitization of the mu-opioid receptor.

Butadienes↗
PubMed2000

Early events leading to renal injury in obese Zucker (fatty) rats with type II diabetes.

UNLABELLED: Early events leading to renal injury in obese Zucker (fatty) rats with type II diabetes. BACKGROUND: More than half of the new patients admitted to dialysis therapy in some centers are diagnosed with type IIb diabetes, that is, diabetes associated with obesity. This study searched for a common final pathway of renal damage in this progressive renal disease. METHODS: The evolution of biochemical and morphological renal changes was examined in 6- to 60-week-old Zucker rats (fa/fa-rats), a model of obesity associated with type II diabetes. RESULTS: fa/fa-rats exhibited pronounced hyperinsulinemia and hyperlipidemia at 6 weeks and became diabetic after 14 weeks of age. Significant focal segmental glomerulosclerosis was first noted in 18-week-old fa/fa-rats and tubulointerstitial damage and proteinuria in 40-week-old fa/fa-rats. A comparison of kidneys of six-week-old fa/fa-and lean control (Fa/?) rats by immunohistology revealed a 1.8-fold increase in glomerular monocyte/macrophage counts in fa/fa-rats and a significant increase in de novo desmin expression in podocytes. Electron microscopy demonstrated an increase in the number of podocyte mitochondria and intracytoplasmic protein and fat droplets. Podocyte desmin scores markedly increased until week 18 in fa/fa-rats, whereas glomerular monocyte/macrophage counts peaked at 3.2-fold at week 14. Podocyte desmin expression, but not glomerular macrophage infiltration, correlated with damage in adjacent tubular cells, as evidenced by their de novo expression of vimentin. Progressive glomerular hypertrophy was detected in fa/fa-rats after 10 weeks. GBM width was significantly increased in 14-week-old fa/fa-rats as compared with lean controls. Mesangial cell activation (de novo expression of alpha-smooth muscle actin) and proliferation was low to absent throughout the observation period in fa/fa-rats. Renal cell death counts (TUNEL) remained unchanged in 6- to 40-week-old fa/fa-rats. Tubulointerstitial myofibroblast formation and matrix accumulation occurred late during the study duration in fa/fa-rats. CONCLUSION: These data suggest that early progressive podocyte damage and macrophage infiltration is associated with hyperlipidemia and type IIb diabetes mellitus, and antedates both the development of glomerulosclerosis and tubulointerstitial damage.

Aging↗
PubMed2000

Influence of amrinone on intestinal villus blood flow during endotoxemia.

PURPOSE: The objective of this study was to determine the effects of a continuous infusion of the phosphodiesterase (PDE) inhibitor amrinone on mucosal villus blood flow in a normotensive model of endotoxemia. MATERIALS AND METHODS: Twenty-four anesthetized and ventilated rats underwent laparotomy, and an ileal portion was exteriorized and opened by an antimesenteric incision. The ileal segment was fixed on a plexiglass stage with the mucosal surface upward. Microcirculatory parameters were assessed by intravital videomicroscopy. The animals were randomly assigned to receive one of three treatments: infusion of Escherichia coli lipopolysaccharides (LPS, 2 mg/kg/h) without phosphodiesterase inhibitor pretreatment (LPS group); or infusion of LPS with amrinone pretreatment (40 microg/kg/min, start 30 minutes before LPS infusion) (amrinone group), or infusion of equivalent volumes of NaCl 0.9% (control group). Macrohemodynamic parameters (MAP, HR) and microhemodynamic parameters of ileal mucosa (mean diameter of central arterioles = D(A) and mean erythrocyte velocity within the arterioles = VE) were measured 30 minutes before and at 0, 60, and 120 minutes after induction of endotoxemia. Mucosal villus blood flow was calculated from D(A) and VE. RESULTS: In this normotensive endotoxemia model, MAP remained stable in the control and the LPS group but significantly decreased in the amrinone group.The endotoxin-induced decrease of V(E) and D(A) of central arterioles of mucosal villi could be attenuated and prevented, respectively. Thus, the endotoxin-induced decrease of mucosal villus blood flow was diminished but not fully restored by amrinone infusion. CONCLUSION: Our results indicate that amrinone during an early stage of sepsis is of limited value. It attenuates mucosal hypoperfusion but contributes to systemic hypotension.

Amrinone↗