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W Schmidt

Publications and source records attributed to W Schmidt.

At least 181 records · Page 10Linked to original sources
PubMed1999

Immunohistochemical evaluation of apoptosis in placentae from normal and intrauterine growth-restricted pregnancies.

OBJECTIVE: To investigate the extent of apoptosis within the human placenta in tissues from normotensive term pregnancies and those complicated by intrauterine growth-restriction (IUGR). METHODS: A total of 18 placentas, 10 obtained from uncomplicated term gestations and 8 from intrauterine growth restricted fetuses were included in this study. Apoptosis was identified using a terminal deoxynucleotidyl transferase-mediated deoxyuridine triophosphate nick end-labeling technique (TUNEL, Boehringer, Mannheim, Germany) in paraffin-embedded sections. RESULTS: Apoptosis was predominantly detected in the villous trophoblast and stromal tissue. There were no differences in the incidence of apoptosis in different parts of the same placenta. The apoptotic index in placental tissue from uncomplicated pregnancies was 0.93 +/- 0.12. Significantly more apoptotic nuclei were detected in the placental tissue from IUGR gestation (4.2 +/- 2.96, p < 0.01). CONCLUSION: These results might point toward a possible role of apoptosis in the pathophysiology of intrauterine growth-restriction.

Adolescent↗
PubMed1999

Influence of C1-esterase inhibitor on tissue oxygenation of jejunal mucosa during endotoxemia.

BACKGROUND: The complement system has been shown to play an important role in the pathogenesis of microcirculatory disturbances in trauma and sepsis. The intestinal mucosa is the most susceptible portion of the gut to impaired perfusion and oxygen delivery. The objective of this study was to investigate the effects of C1-esterase inhibitor (C1-INH) on arterial oxygenation (PaO2) and tissue oxygenation (PtiO2) of jejunal mucosa during endotoxemia. METHODS: Eighteen anesthetized and ventilated rats were laparotomized and a jejunal portion was exteriorized and fixed on a plexiglass stage. The jejunum was punctured and a Clark type microcatheter PO2 probe and a micro thermocouple were placed on the mucosa in order to measure PtiO2. The animals were randomly assigned to receive one of the three treatments: infusion of Escherichia coli lipopolysaccharides (LPS) without C1-INH pretreatment (LPS group); or infusion of LPS with C1-INH pretreatment (C1-INH group); the control group (n = 6) without treatment of either C1-INH or LPS. The mean arterial pressure (MAP), heart rate (HR), PaO2 and PtiO2 were measured at baseline, 60 and 120 min after induction of endotoxemia. RESULTS: Hemodynamic parameters (MAP, HR) in all the three groups showed no significant changes during the study period. PaO2 significantly decreased in the LPS group. This decrease could be attenuated by pretreatment with C1-INH. The mucosal PtiO2 of the jejunum in the control group remained stable. It significantly decreased in the LPS and in the C1-INH groups without showing a significant difference after 120 min of endotoxemia. CONCLUSIONS: Pretreatment with C1-INH was able to diminish a decrease in PaO2 during endotoxemia, indicating that pulmonary injury was attenuated. Endotoxin-induced tissue hypoxia of the intestinal mucosa could not be prevented suggesting a minor involvement of complement activation in this pathophysiological process.

Animals↗
PubMed1998

Phylogenetic analysis of nucleotide sequences: an algebraic approach.

In a previous paper Schmidt and Mueller [Bull. Math. Biosci. 58 (3) (1996) 449.] proposed a new method for calculating phylogenetic trees from dichotomous (present/absent) properties of the taxonomic units. The proposed method is based on a specified distance measure quantifying the phylogenetic information content of the selected properties with respect to the joint evolutionary history. Formally, the method can be applied to arbitrary property patterns and is not based on restricting evolutionary models and optimization principles looking forward in evolutionary time. Instead, its theoretical foundation is the retrospective postulate that properties which are present in any two (closely related) taxa were also present in their most recent common ancestor. The reliability of the derived trees depends essentially on the phylogenetic relevance of the chosen properties. To apply this method to related nucleotide sequences I have defined a set of biologically meaningful nucleotide properties which separate and evaluate the different substitution events. The proposed algorithm provides additive trees and needs no numerical constraints to avoid negative branch lengths or any other meaningless result. In a series of applications the method has been tested and compared with the outcomes of other established tree reconstruction methods. For demonstration, I report and discuss the results of the reanalysis of two families of genomic sequences. Here and in a series of further applications I obtained trees which are biologically acceptable and in good coincidence with the published trees. Thus, it can be concluded that the proposed method will be a useful alternative for the study of phylogenetic relationships.

Algorithms↗
PubMed1998

Expression of interleukin 6 in the rat striatum following stereotaxic injection of quinolinic acid.

Stereotaxic intrastriatal injection of the naturally occurring N-methyl-D-aspartate (NMDA) agonist quinolinic acid (QA) serves as a valuable in vivo model to study excitotoxic cell damage in the central nervous system (CNS). Although morphological changes such as neuronal loss, glial activation and remote reactions following QA injection have been described in some detail, much less is known about the molecular mechanisms mediating the accompanying glial response. Cytokines are known to play a crucial role in almost all kinds of CNS alterations. We now demonstrate that IL-6, a multifunctional glycoprotein which belongs to the family of neurokines, is expressed endogenously in the rat striatum following QA injection. Using Northern blot analysis, a massive but transient upregulation of IL-6 mRNA could be detected. This started 3 h after QA injection, reached a maximum at 6 h and disappeared within 24 h. That activated microglia are the most likely cellular source of the observed corresponding IL-6 protein expression could be concluded by comparing the immunocytochemical pattern of IL-6 expression and microglial activation. Interestingly, astrocytes initially downregulate their expression of glial fibrillary acidic protein (GFAP) in the excitotoxically injured striatum, but show a delayed increase in GFAP immunoreactivity starting in the periphery of the striatum, subsequently expanding to the core. The early transient IL-6 expression may play an important role in initiating the delayed astrocytic response following excitotoxic cell injury.

Animals↗
PubMed1998

HIV-1 p24 but not proviral load is increased in the intestinal mucosa compared with the peripheral blood in HIV-infected patients.

OBJECTIVE: To investigate differences in viral and proviral load between the peripheral blood and the intestinal mucosal immune system in HIV-infected patients. DESIGN: HIV-1 p24 and HIV DNA content were compared in blood samples and intestinal biopsies from HIV-infected patients. METHODS: Intestinal biopsies and peripheral blood were simultaneously obtained from 27 HIV-infected patients undergoing diagnostic endoscopy. The p24 concentrations were measured in serum and homogenized intestinal biopsies by enzyme-linked immunosorbent assay after acid-dissociation of immune complexes. Proviral load was determined in blood and intestinal biopsies by a quantitative competitive polymerase chain reaction amplifying the HIV-1 nef gene from genomic DNA. RESULTS: No significant differences were found in proviral load comparing HIV copies per 1.5 x 10(5) cell equivalents in blood [2650 (600-44000)] and intestinal biopsies [4200 (1325-19 625)]. Paired analysis revealed a strong positive correlation between serum and mucosal proviral load. In contrast, HIV core protein p24 was detected in intestinal biopsies from 18 patients in much higher concentrations than in serum [858 (262-4111) pg/g versus 34 (9-242) pg/g; P < 0.005]. The p24 concentrations in serum and intestinal biopsies did not correlate and no significant correlation was observed in serum or intestinal biopsies between proviral load and p24 concentrations. No clear correlations were observed between clinical parameters and HIV DNA or HIV p24 levels in blood or biopsies. CONCLUSIONS: Our findings demonstrate a homogenous distribution of HIV proviral load in the peripheral blood and the intestinal mucosal immune system. The high viral antigen load in the intestine therefore indicates that mucosal HIV production is upregulated at the transcriptional and/or translational level. The intestinal mucosa is a major reservoir for HIV in HIV-infected patients.

Adult↗
PubMed1998

Duodenal biopsies of HIV-infected patients with diarrhoea exhibit epithelial barrier defects but no active secretion.

OBJECTIVES: To characterize diarrhoeal mechanisms in HIV-infected patients, epithelial transport and barrier function of the duodenal mucosa was investigated in vitro. PATIENTS: Twenty-one HIV-seropositive patients (13 asymptomatic and eight with diarrhoea) and 12 controls from an urban referral-based tertiary care centre in Berlin who underwent duodenoscopy. METHODS: A new miniaturized Ussing chamber allowed measurements on duodenal forceps biopsies. Epithelial barrier function was characterized by alternating current impedance analysis, which allows differentiation of epithelial and subepithelial resistance and by 3H-lactulose and 3H-mannitol flux measurements. Na+-glucose cotransport was quantified as phlorizin-sensitive short circuit current (Isc) and active ion secretion by baseline and bumetanide-sensitive Isc. RESULTS: Duodenal biopsies from asymptomatic HIV-infected patients were no different from controls, whereas biopsies from HIV-infected patients with diarrhoea showed a decrease in epithelial resistance from 21.2+/-1.9 to 12.9+/-1.3 omega cm2 (P<0.01). Concomitantly, mucosal-to-serosal lactulose flux increased from 0.29+/-0.02 to 0.40+/-0.03 micromol (hcm2) (P<0.01). Phlorizin-sensitive Isc indicating Na+-glucose cotransport, as well as baseline and bumetanide-sensitive Isc indicating active electrogenic chloride secretion were not different between the three groups. CONCLUSIONS: A miniaturized Ussing device was developed for electrophysiological investigations of duodenal forceps biopsies, which allowed characterization of active ion transport mechanisms and epithelial barrier function. Duodenum of HIV-infected patients with diarrhoea showed no evidence for active ion secretion or Na+-glucose malabsorption, but showed an impaired epithelial barrier function, which could contribute to diarrhoea by a leak flux mechanism.

Adult↗
PubMed1998

Relaxation training and breast milk secretory IgA.

OBJECTIVE: To evaluate the hypothesis that breast-feeding women who participate in relaxation training will have increased secretory IgA (sIgA) levels in their breast milk compared with women not receiving training. DESIGN: Nonrandomized control trial of a convenience sample. SETTING: Women were recruited from the postpartum floor of a university teaching hospital. The intervention took place in the women's homes. PARTICIPANTS: Women in the first 48 hours after delivery who were planning to breast-feed their healthy newborn infants for at least 8 weeks were approached for enrollment. Women were excluded if they had previous experience with relaxation training. At 4 to 6 weeks postpartum, we enrolled 38 women still breast-feeding their infants. INTERVENTIONS: Women were allocated into 3 groups. Women in group 1 were taught relaxation and had breast milk samples collected before and after the teaching. Women in group 2 had conversation with similar breast milk sample collection, and women in group 3 had 1 breast milk sample collected. Women in group 1 were encouraged to practice the relaxation once or twice a day for 2 weeks, and a second visit was made to all mothers with repeated breast milk collections. Women who were still breast-feeding at 6 to 8 weeks after study end had a final breast milk sample collected. Breast milk was analyzed for secretory IgA levels. Stress was assayed using the Symptom Checklist-90-R and open-ended questions. RESULTS: There was no difference in sIgA levels among the 3 groups at any time. Women who reported stress present between visit 1 and visit 2 increased their sIgA levels at the final sample collection (+0.16 g/L) compared with women who reported no stress (-0.09 g/L; P= .03). The ratings of success in relaxation in women in group 1 were related to the following sIgA levels in sample 4: poor relaxation, 0.67 g/L; fair relaxation, 0.41 g/L; good relaxation, 0.35 g/L; and very good, 0.30 g/L (P= .006). CONCLUSIONS: Self-reported stress appears to increase breast milk sIgA levels. Success at relaxation was inversely related to sIgA levels in the group learning relaxation.

Adult↗
PubMed1998

Influence of N-acetylcysteine treatment on endotoxin-induced microcirculatory disturbances.

OBJECTIVES: To determine the influence of N-acetylcysteine (NAC) in a treatment model, its effects on endotoxin-induced leukocyte-endothelial cell adhesion, vascular leakage, and venular microhemodynamics in postcapillary venules of rat mesentery. DESIGN: Prospective, randomized, controlled, experimental study. SETTING: Animal research laboratory. SUBJECTS: 40 male Wistar rats. INTERVENTIONS: The rats randomly received one of four treatments: infusion of saline (SAL) or Escherichia coli lipopolysaccharides (LPS) followed by treatment with saline (SAL) or NAC (150 mg.kg-1 body weight) 30 min after induction of endotoxemia. MEASUREMENTS AND MAIN RESULTS: Leukocyte adherence, red blood cell velocity, and vessel diameters in postcapillary venules of rat mesentery were evaluated every 30 min over a period of 120 min using in vivo videomicroscopy. Vascular permeability was determined by measuring the extravasation of fluorescence-labeled albumin. Venular wall shear rate was calculated from red cell velocity, and vessel diameter. NAC in rats without endotoxemia (SAL + NAC group) compared to the control group (SAL + SAL) did not change microcirculatory parameters in postcapillary venules of rat mesentery. In both LPS-treated groups (LPS + SAL and LPS + NAC), leukocyte adherence increased after just 30 min. NAC treatment prevented a further increase in leukocyte adherence and attenuated the extravasation of fluorescence-labeled albumin during endotoxemia. Venular diameters remained unchanged, while erythrocyte velocity decreased in the LPS + SAL group. This led to a lower venular wall shear rate in this group. CONCLUSIONS: Treatment with NAC attenuates endotoxin-induced leukocyte adherence and macromolecular leakage in postcapillary venules of rat mesentery, showing that NAC is also effective after the onset of endotoxemia.

Acetylcysteine↗
PubMed1998

Regulatory considerations for preclinical development of anticancer drugs.

The entry of new anticancer treatments into phase I clinical trials is ordinarily based on relatively modest preclinical data. This report defines the battery of preclinical tests important for assessing safety under an Investigational New Drug application (IND) and outlines a basis for extrapolating starting doses of investigational anticancer drugs in phase I clinical trials from animal toxicity studies. Types of preclinical studies for the support of marketing of a new anticancer drug are also discussed. This report addresses differences and similarities in the preclinical development of cytotoxic drugs (including photosensitizers and targeted delivery products), drugs used chronically (chemopreventive drugs, hormonal drugs, immunomodulators), and drugs intended to enhance the efficacy (MDR-reversing agents and radiation/chemotherapy sensitizers) or diminish the toxicity of currently used anticancer therapies. Factors to consider in the design of preclinical studies of combination therapies, alternative therapies, and adjuvant therapies in the treatment of cancer, and to support changes in clinical formulations or route of administration, are also discussed.

Animals↗
PubMed1998

[The intraoperative measured stimulation impedance of pacemaker electrodes is not a predictor for their longevity].

UNLABELLED: As pacing impedance is inversely related to pacing current, the increase of pacing impedance additionally decreases pacing current. Whether the impedance measurement at implantation predicts the outcome during follow-up, was studied in 87 patients who received the VDD-single lead UniPass 425 connected to the pacemaker Unity (Sulzer Intermedics). The impedance changes between implantation and 6 months follow-up were assessed for each patient. Similar impedance values were defined, if the two measurements were within a range < or = -100 to +100 omega. Six-months impedance was lower or higher compared to implantation, if the difference exceeded > -100 or > +100 omega. At implantation, impedance was 535 +/- 98 omega (range: 333-811 omega) and significantly increased to 604 +/- 160 omega (range: 361-1150 omega) after 6 months. Mean difference between the two measurements was 69 +/- 162 omega (range: -336 bis + 560 omega). Similar impedance had 43 (implantation: 527 +/- 75 omega, 6 months: 531 +/- 87 omega), lower values 11 (implantation: 660 +/- 83 omega, 6 months: 494 +/- 73 omega) and higher values 33 patients (implantation: 503 +/- 99 omega, 6 months: 735 +/- 168 omega). Compared to the patients with similar impedance patients with lower impedance had a significantly higher impedance values at implantation. CONCLUSIONS: Pacing impedance increased significantly within 6 months after implantation. Pacing impedance changed > 100 omega in 51% of the patients. The long-term follow-up of pacing impedance can be predicted generally, but not for the individual patient.

Aged↗
PubMed1998

[Concomitant dermatitis herpetiformis Duhring, arthritis and Sjögren syndrome in a patient with celiac disease].

We report on a 26 year old woman with dermatitis herpetiformis Duhring, diagnosed at 10 years of age, who developed arthritis, symptoms of celiac disease, and Sjögren's syndrome 15 years later. Clinical symptoms, biopsies of duodenal mucosa and salivary glands as well as serological findings established the diagnoses. A coincidence of these pathologies has not been reported before. Gluten-free diet alleviated severity of clinical symptoms very quickly indicating the basic pathology of celiac enteropathy in the immunological disorders.

Adult↗
PubMed1998

Accurate and cost-effective evaluation of breast masses in males.

BACKGROUND: Because the majority of breast masses in males are benign and need not be excised if asymptomatic, we studied the combination of physical examination (PE) and fine needle aspiration (FNA), with or without mammography, as a diagnostic alternative to routine surgical biopsy of these lesions. METHODS: A diagnostic test study and cost-effectiveness analysis was performed in three participating multidisciplinary breast clinics, involving a consecutive sample of 51 males with unilateral breast masses. Each lesion was tested with both PE and FNA; 13 were also studied with mammography, and each test was scored as benign or suspicious. Lesions for which all tests were benign were followed up clinically (mean 19 months). Lesions for which any test was suspicious were excised. RESULTS: All tests were benign in 38 cases. No cancers developed at the index sites during follow-up of these lesions, including 8 excisional biopsies done for symptoms (negative predictive value and specificity 100%). Open biopsy confirmed malignancy in all 6 cases for which all tests were suspicious (positive predictive value and sensitivity 100%). In all 7 cases where the tests were not in agreement, open biopsy was benign. In these cases FNA (2 false positives) proved more accurate than PE (5 false positives). Mammography added no additional diagnostic information to the combination of PE and FNA. Compared with routine open biopsy, the combination of PE and FNA avoided surgical biopsy in 30 of the 51 lesions, and was associated with an average decrease in charges of up to $510 per case. CONCLUSIONS: The combination of PE and FNA for the evaluation of breast masses in males is diagnostically accurate and results in a reduction in patient charges compared with routine open biopsy.

Biopsy, Needle↗
PubMed1998

Tamoxifen and proliferation of vaginal and cervical epithelium in postmenopausal women with breast cancer.

OBJECTIVE: The estrogenic effect of tamoxifen on vaginal and cervical epithelium in postmenopausal women with breast cancer is evaluated. STUDY DESIGN: The tamoxifen group consisted of 92 postmenopausal breast cancer patients, the control group I of 30 postmenopausal women with breast cancer receiving no endocrine therapy and the control group II of 40 postmenopausal women without primary breast cancer taking no hormones. We determined the maturation index and the incidence of endocervical cell hyperplasia and metaplasia in cervical and vaginal smears. RESULTS: The maturation index increased under tamoxifen within the first 24 months from 0.4011 before taking tamoxifen (n=56) to 0.6039 (n=138, P<0.0001). The maturation index in the group treated with tamoxifen was statistically significantly higher (P<0.0001) than in the control groups (control group I: 0.3975, P<0.0001; control group II: 0.4102, P<0.0001). Under therapy with tamoxifen endocervical cell hyperplasia (P=0.00156) and metaplasia (P=0.00123) appeared significantly more often. CONCLUSION: An apparent increase not only of the incidence of endocervical cell hyperplasia and metaplasia but also of the maturation of the vaginal epithelium caused by the estrogenic effect of tamoxifen could be demonstrated.

Aged↗