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Biomedical subjects

H Schmidt

Publications and source records attributed to H Schmidt.

At least 415 records · Page 23Linked to original sources
PubMed1996

Frequent occurrence of p53 mutations in rhabdomyosarcoma and leiomyosarcoma, but not in fibrosarcoma and malignant neural tumors.

We have analyzed soft-tissue sarcomas (STS) molecularly for mutations in the tumor-suppressor gene p53 and immunohisto-chemically for expression of p53 and mdm2 proteins. In this study, tumor samples from 3 groups of soft-tissue sarcomas, i.e., fibrosarcomas, myogenic sarcomas and malignant neural tumors (MNT), were investigated. The methods applied encompass immunohistochemistry on 198 tumor samples using p53 antibodies (DO-1 and DO-7) and an mdm2 antibody (IF-2). Out of these, 100 samples were subjected to non-radioactive PCR-SSCP-sequencing analysis. Immunohistochemical detection rate for p53 (range of 57% to 67%) and for mdm2 proteins (range of 19 to 44%) was similar in all 3 groups. In higher tumor grades, an increased rate of immunopositivity was found for p53 but not for mdm2. Investigation of p53 mutational status revealed 6 mutations in myogenic sarcomas but none in malignant neural tumors or fibrosarcomas, suggesting different roles of p53 in the 3 STS groups. Interestingly, a G-->A transition in codon 245 (a CpG site) was found in 3 myogenic sarcomas. Our results and those of others suggest p53 codon 245 as a mutational hotspot in sarcomas, as recognized in carcinomas.

Base Sequence↗
PubMed1996

[Clinical criteria for acute maxillary sinusitis in general practice].

The purpose of the investigation was to examine the diagnostic value of various symptoms, clinical findings, erythrocyte sedimentation rate (ESR) and serum C-reactive protein (CRP) in acute maxillary sinusitis using the aspiration of purulent or mucopurulent from the sinus of a patient with a pathological CT-scanning as the golden standard. Of 174 patients with suspected acute maxillary sinusitis seen in general practice we found 70% to have a pathological CT-scanning and 53% to have pus or mucous pus in the sinus aspirate. Only the ESR and CRP level were found to be significantly and independently associated with a positive diagnosis as defined by the golden standard. A clinical criterion based on either an elevated ESR and/or CRP level in a patient with pain related to the maxillary sinus region had sensitivity of 0.82, a specificity of 0.57, a positive predictive value of 0.68 and a negative predictive value of 0.75, and was diagnostically superior to the clinical examination. The investigation also confirms that this disease is most likely overdiagnosed in general practice.

Acute Disease↗
PubMed1996

The Pasteur effect in facultative anaerobic metazoa.

The existence and the regulatory mechanisms of the Pasteur effect in facultative anaerobic metazoa are discussed. There are three reasons for the controversy surrounding this phenomenon. 1) The different definitions of the Pasteur effect, 2) the antagonistic effect of metabolic depression and its species specific response to hypoxia, as well as 3) the laboratory-specific differences in the experimental procedures for analyzing the Pasteur effect and its regulation. This review aims to clarify the confusion about the existence of the Pasteur effect in facultative anaerobic metazoa and to offer possible molecular mechanisms.

Adenosine Triphosphate↗
PubMed1996

Polynucleobacter necessarius, an obligate bacterial endosymbiont of the hypotrichous ciliate Euplotes aediculatus, is a member of the beta-subclass of Proteobacteria.

An almost full length 16S rRNA gene of the obligate bacterial endosymbiont Polynucleobacter necessarius was amplified using the polymerase chain reaction in combination with site-specific primers. The amplified DNA was directly sequenced and compared with other bacterial 16S rRNA sequences. P. necessarius belongs to the beta-subclass of Proteobacteria and shows the closest relationship to Alcaligenes eutrophus, Burkholderia solanacearum, and B. pickettii. In Proteobacteria and shows the closest relationship to Alcaligenes eutrophus, Burkholderia solanacearum, and B. pickettii. In situ hybridization with a specific oligonucleotide probe corroborated the assignment of the retrieved sequence to P. necessarius.

Animals↗
PubMed1996

Influence of the platelet-activating factor receptor antagonist BN52021 on endotoxin-induced leukocyte adherence in rat mesenteric venules.

The aim of this study was to investigate the influence of the platelet-activating factor (PAF) antagonist BN52021 on endotoxin-induced leukocyte-endothelium interactions and on venular microcirculation. The rates of leukocyte adherence and changes in red cell velocity, volumetric blood flow, vessel diameter, and venular shear rate were monitored in rat mesenteric venules following intravenous lipopolysaccharide (LPS) exposure (15 mg/kg body wt). The experiments were performed in LPS-treated control animals and in animals pretreated with the PAF receptor antagonist BN52021. LPS exposure induced a marked increase in adherent leukocytes in the control group compared to the BN52021-pretreated group. Thirty minutes after LPS injection, 6.1 +/- 0.8 leukocytes were adherent to 100 microns of venule in the control group compared to 2.5 +/- 0.5 in BN52021-pretreated animals (P < 0.01). The increased leukocyte adherence in the control group was accompanied by leukocytopenia. Red cell velocity, volumetric blood flow, vessel diameter, and venular shear rate did not differ between groups, indicating that increased leukocyte adherence in the control group was not due to diminished hydrodynamic dispersal forces. The attenuation of leukocyte adherence by the PAF receptor antagonist BN52021 suggests that PAF is involved in the mediation of the initial process of leukocyte sticking to the endothelium after LPS stimulation.

Animals↗
PubMed1996

Effect of endotoxemia on intestinal villus microcirculation in rats.

Intestinal mucosal hypoperfusion with subsequent ischemia during endotoxemia might cause a breakdown of the gut barrier with translocation of bacteria and their toxins into the systemic circulation, thus maintaining a "gut-derived" septic state. The aim of this study was to investigate the influence of endotoxin on the microcirculation of intestinal villi, which represent the most vulnerable part of the mucosa. The changes in blood flow and in the diameters of the central villus arterioles located in the distal ileum were monitored in control rats without lipopolysaccharide (LPS) exposure (n=7), and in rats receiving 1.5 mg/kg b.w. LPS (n=7) or 15 mg/kg b.w. LPS (n=7) over 60 min. The blood flow and the arteriolar diameters were determined using in vivo videomicroscopy at baseline, and 60 min and 120 min later. In control animals, no change in blood flow and arteriolar diameters were observed during the entire experiment. Administration of 1.5 mg/kg b.w. LPS reduced the blood flow to 69.5 +/- 9.0% of the baseline value at the end of the study period. This decrease in blood flow was associated with a decrease in the villus arteriolar diameters by 17.4 +/- 2.5% from the baseline values. In animals exposed to 15 mg/kg b.w. LPS, the decrease in villus blood flow at 60 min was 64.8 +/- 10.9% of baseline, and at 120 min 66.9 +/- 12.6% of baseline. The diameters of the villus arterioles were reduced by 11.5 +/- 2.4% and 15.1 +/- 1.7%, respectively. In the control group and in the 1.5-mg/kg LPS group, the mean arterial blood pressure did not change during the entire study period. In the 15-mg/kg LPS group, the mean arterial pressure tended to decrease after 60 min. These data suggest a reduction of villus blood flow due to vasoconstriction in the central villus arterioles during normotensive endotoxmia, which might represent the mechanism for the mucosal ischemia observed in critically ill patients.

Animals↗
PubMed1996

Thalidomide inhibits TNF response and increases survival following endotoxin injection in rats.

Sepsis is a leading cause of death following major trauma and complicated abdominal surgery. Tumor necrosis factor-alpha (TNF) is believed to be a central mediator in the inflammatory response syndrome. Numerous methods of blunting the TNF response in sepsis have been attempted with suggestion of increased survival and decreased organ injury. Thalidomide, shown in vitro to selectively inhibit TNF production, has been used clinically in states of chronic TNF elevation with encouraging results. In this study, we examined the effect of thalidomide administration in a rat model of acute septic shock. Femoral artery cannulation was performed and baseline TNF measured. Dose response was determined by giving varying doses of thalidomide by gavage. Rats were injected intraarterially with endotoxin and serial samples drawn. TNF was measured by ELISA. For survival, thalidomide was given by gavage and endotoxin injected intraperitoneally. Serum TNF elevation occurred after endotoxin injection with peak levels at 90 min. Thalidomide treated rats had lower TNF levels at all time points (P = <0.01 at 90 and 120 min), with the inhibition being dose dependent. Survival in treated rats exceeded that of untreated rats (53% vs 19%, P = <0.05) at 48 and 72 hr. In conclusion, we found that thalidomide administration leads to increased survival following acute endotoxemia, which may be due to the observed TNF inhibition.

Analysis of Variance↗
PubMed1996

Anaerobic metabolism in the leech (Hirudo medicinalis L.): direct and indirect calorimetry during severe hypoxia.

Anaerobic metabolism in the limnic annelid Hirudo medicinalis L. was investigated by direct and indirect calorimetry. During long-term severe hypoxia, the rate of heat dissipation was reduced up to 13% of the aerobic rate. At the same time, the rate of ATP turnover was reduced to about 30% of the aerobic rate, indicating that metabolic depression is an important mechanism to ensure survival of the leech during environmental anaerobiosis. Heat dissipation during hypoxia was monitored under two experimental conditions, favouring either concomitant hypocapnia (continuous N2 bubbling) or hypercapnia (self-induced hypoxia). The reduction in heat dissipation during hypocapnic hypoxia was less pronounced than during hypercapnic hypoxia, indicating that the different experimental conditions may influence anaerobic metabolism and the extent of metabolic depression. Biochemical analysis of known anaerobic substrates and endproducts provided the basis for indirect calorimetry during self-induced hypoxia. From changes in metabolites, the expected heat dissipation was calculated for initial (0-8 ,h) and long-term severe hypoxia (8-72 h). During the initial period, the calculated heat dissipation fully accounted for direct calorimetric determination. During long-term hypoxia, only 71% of the measured heat production could be explained from biochemical analysis of metabolites. Therefore, an additional unknown endproduct cannot be excluded, especially when anaerobic ammonia production and analysis of the carbohydrate balance are considered.

Aerobiosis↗
PubMed1996

Pulmonary alveolar microlithiasis in children.

Two asymptomatic Turkish sibs are presented, a 4-year-old boy and his 7-year-old sister, with pulmonary alveolar microlithiasis (PAM) confirmed by transbronchial lung biopsy and bronchoalveolar lavage. Chest radiographs and high resolution CT demonstrated widespread intra-alveolar calcifications in both lungs. The lesions were sharply defined and less than 1 mm in diameter. CT documented a high concentration of microliths along the bronchovascular bundles, the intralobular fissure and the (sub)pleural lung parenchyma. The combination of bronchoalveolar lavage and roentgenographic appearance in high resolution CT are characteristic and pathognomonic, and can confirm the diagnosis. The more severe changes in the elder sib and the radiographic controls suggest that the pulmonary disease may be progressive in our patients. The described family of consanguineous, unaffected parents with two affected and one healthy child confirmed the autosomal recessive inheritance of PAM (McKusick 265100). In addition, the affected girl had autosomal recessive Waardenburg-anophthalmia syndrome (McKusick 206920), raising the question of whether this is a chance occurrence or possibly a contiguous gene syndrome.

Biopsy↗
PubMed1996

Prevalence and clinical manifestations of Shiga toxin-producing Escherichia coli infections in Austrian children.

The prevalence and clinical manifestations of infections associated with Shiga toxin-producing Escherichia coli (STEC) among Austrian children were assessed. Stool samples from 280 pediatric patients were analyzed by enzyme immunoassay (EIA) for the presence of free fecal Shiga toxin (Stx) 1 and 2, and by culture on sorbitol MacConkey agar. Specimens testing positive by the EIA were subjected to a cytotoxicity assay, polymerase chain reaction analysis, and a colony hybridization test. Direct culture on MacConkey agar demonstrated the presence of three Escherichia coli O157:H7-positive stools. These were also positive by EIA and by the DNA-based methods. An additional six samples were positive by EIA, and in four of these, non-O157 STEC of serotypes O111H-, O146:H-, and O113:H53 could be isolated. Analysis of stools for a variety of enteric pathogens demonstrated that STEC was the third most common bacterial pathogen. The clinical manifestations of STEC infections were difficult to distinguish from those of infections caused by other enteric pathogens, as most patients presented with watery diarrhea. The median age of children with STEC infections was 27.6 months (range, 7 months to 5.75 years); children with Salmonella or Campylobacter infections were younger on average, while those with Rotavirus infections were older. This study demonstrated that although Escherichia coli O157:H7 could be identified with the same sensitivity by both EIA or agar-based methods, the identification of non-O157 STEC strains was enhanced by the use of EIA followed by colony hybridization. Analysis of overnight cultures from 53 STEC isolates revealed that all strains producing Stx1, Stx2, or Stx2c reacted in the EIA. However, culture supernatants from Stx2e-producing Escherichia coli O101 were negative in the EIA. Despite this disadvantage, the EIA is easy to perform and time efficient and can be recommended as a screening test for non-O157 STEC in children with diarrhea.

Age Factors↗
PubMed1996

Effects of continuous (CPAP) and bi-level positive airway pressure (BiPAP) on extravascular lung water after extubation of the trachea in patients following coronary artery bypass grafting.

OBJECTIVE: To evaluate the effects of continuous positive airway pressure (CPAP) and bi-level positive airway pressure (Bi-PAP) on extravascular lung water during weaning from mechanical ventilation in patients following coronary artery bypass grafting. DESIGN: Prospective, randomized clinical study. SETTING: Intensive care unit at a university hospital. PATIENTS: Seventy-five patients following coronary artery bypass grafting. INTERVENTIONS: After extubation of the trachea, patients were treated for 30 min with CPAP via face mask (n = 25), with nasal BiPAP (n = 25), or with oxygen administration via nasal cannula combined with routine chest physiotherapy (RCP) for 10 min (n = 25). MEASUREMENTS AND RESULTS: Extravascular lung water (EVLW), pulmonary blood volume index (PBVI) and cardiac index (CI) were obtained during mechanical ventilation (T1), T-piece breathing (T2), interventions (T3), spontaneous breathing 60 min (T4) and 90 min (T5) after extubation of the trachea using a combined dye-thermal dilution method. Changing from mechanical ventilation to T-piece breathing did not show any significant differences in EVLW between the three groups, but a significant increase in PBVI from 155 +/- 5 ml/m2 to 170 +/- 4 ml/m2 could be observed in all groups (p < 0.05). After extubation of the trachea and treatment with BiPAP. PBVI decreased significantly to 134 +/- 6 ml/m2 (p < 0.05). After treatment with CPAP or BiPAP, EVLW did not change significantly in these groups (5.5 +/- 0.3 ml/kg vs 5.0 +/- 0.4 ml/kg and 5.1 +/- 0.4 ml/kg vs 5.7 +/- 0.4 ml/kg). In the RCP-treated group, however, EVLW increased significantly from 5.8 +/- 0.3 ml/kg to 7.1 +/- 0.4 ml/kg (p < 0.05). Sixty and 90 min after extubation, EVLW stayed at a significantly higher level in the RCP-treated group (7.5 +/- 0.5 ml/kg and 7.4 +/- 0.5 ml/kg) than in the CPAP-(5.6 +/- 0.3 ml/kg and 5.9 +/- 0.4 ml/kg) or BiPAP-treated groups (5.2 +/- 0.4 ml/kg and 5.2 +/- 0.4 ml/kg). No significant differences in CI could be observed within the three groups during the time period from mechanical ventilation to 90 min after extubation of the trachea. CONCLUSIONS: Mask CPAP and nasal BiPAP after extubation of the trachea prevent the increase in extravascular lung water during weaning from mechanical ventilation. This effect is seen for at least 1 h after the discontinuation of CPAP or BiPAP treatment. Further studies have to evaluate the clinical relevance of this phenomenon.

Aged↗
PubMed1996

Phenylalanine hydroxylase genotypes, predicted residual enzyme activity and phenotypic parameters of diagnosis and treatment of phenylketonuria.

The interdependence of the predicted in vitro residual enzyme activity (PRA), as deduced from the complete genotypes of 64 hyperphenylalaninaemic patients, and parameters for diagnosis of hyperphenylalaninaemic disorders, the fluctuation of the phyenlylalanine (Phe) values during treatment, long-term dietary control during treatment, and a parameter for the outcome of therapy (IQ) was investigated by correlation analysis. A highly significant correlation was found between the PRA and diagnostic parameters, as well as the fluctuation of the Phe values during treatment. Significant correlations were also observed between the parameter describing the fluctuation of the Phe values and the IQ, as well as between the quality of dietary control and IQ. The PRA is a valuable tool for the differential diagnosis of hyperphenylalaninaemic disorders and for the prediction of one aspect of the course of the disease which is related to the intellectual outcome of therapy. The quality of dietary control was independent of the genotype, indicating that the outcome of therapy can be successfully manipulated in spite of the genetic make-up.

Alleles↗
PubMed1996

Magnetic resonance imaging of the brain in adolescents with phenylketonuria and in one case of 6-pyruvoyl tetrahydropteridine synthase deficiency.

White matter abnormalities on MRI have been observed in phenylketonuria (PKU) patients with late onset neurological symptoms as well as in neurologically inconspicious patients. We investigated 14 early treated adolescents at an age between 12 and 17 years (mean age 14.3 years) with classical PKU as well as one retarded patient with atypical PKU by cranial MRI with spinecho T1-, T2- and proton density sequences. Clinical examination was normal. Visual evoked potential (VEP) examination showed a prolonged latency of peak P100 (mean 122.6 ms; control mean 115.9) and IQ testing showed a mean IQ of 101.1. To investigate the influence of plasma phenylalanine (Phe) levels three approaches were used: Phe was determined for the day of MRI, for a period of 6 months prior to MRI and for lifetime up to 12 years. MRI scans revealed areas of abnormally increased signal intensity on T2-weighted and proton density images in 12 (86%) patients, preferably involving the parieto-occipital lobes. MRI of the patient with atypical PKU was normal. MRI findings correlated most strongly to long-term dietary control up to 12 years. We found no correlation with the other parameters of biochemical control, IQ or VEP latency. The nature and prognosis of MRI abnormalities in neurologically normal PKU patients remain unclear although abnormalities in VEPs which were not associated with the degree of MRI abnormalities in our sample indicate a disturbance in myelination along the visual pathways.

Adolescent↗
PubMed1996

Intelligence and professional career in young adults treated early for phenylketonuria.

The intellectual status and professional careers of 51 young adults with phenylketonuria whose treatment started before 3 months of age are described. Their mean IQ was 97 (SD = 16). Of the IQs, 4% were more than 2 SD below the norm. The distribution of types of schooling of the patients was comparable to that in the German population. The professional careers of nearly all the patients were according to their educational level. Within the sample the outcome was significantly correlated with phenylalanine (Phe) control, even when the patients' social background was statistically taken into account. The main influence of Phe on intelligence seems to occur during the first decade of life since IQ data remain stable even after Phe levels increased during adolescence.

Adult↗
PubMed1996

Evaluation of procollagen-III peptide as a marker for veno-occlusive disease after bone marrow transplantation.

Procollagen-III peptide (PIIIP) has been suggested as a marker for hepatic veno-occlusive disease (VOD) after bone marrow transplantation (BMT). Using the RIA-gnost PIIIP assay, we examined frozen plasma samples from three groups of patients. The groups included (A) four patients with clinically proven VOD, (B) nine patients with remarkably uneventful post-BMT courses, and (C) patients with either early complications other than VOD or pulmonary fibrosis in their later course. In group A, PIIIP levels increased parallel to the clinical course, with maximum values of 2.7-5.5 units/ml. In group B, values did not exceed 1.4 units/ml. In group C, higher values were occasionally observed. In one patient with early relapse of a lymphoma PIIIP peaks correlated with episodes of fever and graft versus host disease (GVHD). In another patient mild VOD seems possible retrospectively. The highest levels ( > 15 units/ml) occurred in one patient with ileus. Several patients with interstitial pneumonia (IP), adult respiratory distress syndrome (ARDS), or lung fibrosis showed increases in PIIIP levels corresponding to the clinical course; most of these events occurred later than day 30 after BMT. One patient with severe GVHD of the liver showed a maximum of only 1.4 units/ml. PIIIP elevation correlated with clinical VOD and may help to differentiate it from hepatic GVHD. In the presence of other complications (pulmonary, gastrointestinal), some caution in interpreting the results may be advisable.

Adult↗