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Biomedical subjects

W Schmidt

Publications and source records attributed to W Schmidt.

At least 145 records · Page 8Linked to original sources

Heterologous mullerian mixed tumor after whole body irradiation because of Hodgkin's disease in stage IV.

PURPOSE: With an incidence of 1.5% of all malignant diseases of the uterus as specified in the literature, the mullerian mixed tumor is a rarity amongst the malignancies of the female genital tract. METHODS: A retrospective analysis of an individual case report with the occurrence of heterologous mullerian mixed tumor years after irradiation because of Hodgkin's disease. RESULTS: This case reports describes the occurrence of a mullerian mixed tumor 12 years after the treatment of Hodgkin's disease by whole body irradiation. To our knowledge, the incidence of a mullerian mixed tumor after the treatment of Hodgkin's disease has rarely been described up to now in the literature. CONCLUSION: This case report appears to indicate the possible carcinogenic potency of radiotherapy when administered many years before. A causal connection between the administration of whole body irradiation and the development of a mullerian mixed tumor cannot be established.

Aged↗

Nucleated red blood cell count and doppler ultrasound in low- and high-risk pregnancies.

OBJECTIVE: The aim of this study was to evaluate the influence of circulatory deterioration in small-for-gestational-age fetuses (SGA) on the nucleated red blood cell count (NRBC). PATIENTS AND METHODS: During a 12-month period 194 patients with a complete NRBC count post-partum were enrolled in the study. Using pulsed wave colour Doppler ultrasound we recorded blood flow velocity waveforms from both uterine arteries and from the umbilical artery and/or from the fetal aorta. Patients were assigned to seven groups according to the results of the Doppler examination. Mean outcome measures were birthweight, gestational age at delivery, NRBC count, incidence of preeclampsia or SGA and need of neonatal intensive care. RESULTS: Significantly higher nucleated red blood cell counts than in all other groups were found in cases with abnormal Doppler findings in both uterine arteries and the umbilical artery and/or fetal aorta (p<0.001). These newborns had significantly lower birth weights (p<0.01, p<0.001), lower gestational age (p<0.001), an increased likelihood of caesarean section for clinical signs of fetal distress (p<0.001) and had to be transfered more frequently to the neonatal intensive care unit (p<0.01, p<0.001). CONCLUSION: Patients with abnormal Doppler velocimetry waveforms of the uterine arteries in the presence of an abnormal umbilical artery or fetal aorta Doppler findings have a high risk of prematurity, preeclampsia or delivering a small-for-gestational-age newborn. Fetal response to uteroplacental insufficiency may lead to elevated nucleated red blood cells in the fetal blood. This fact might help to discriminate the small-for-gestational-age fetus who is growth-retarded and suffers from chronic placental insufficiency from the small but healthy fetus.

Birth Weight↗

The clinical significance of antenatal pathological Doppler findings in fetal middle cerebral artery compared to umbilical artery and fetal aorta.

PURPOSE: To compare the diagnostic capacity of fetal Doppler velocimetry in fetal middle cerebral artery to umbilical artery and fetal aorta to the prediction of fetal outcome. METHODS: 229 patients between 28 weeks of gestation (weeks) and 40 weeks were examined by Doppler ultrasound in relationship to complications in gestation and labor, and fetal outcome. One thousand two hundred and seventy doppler blood flow velocity waveforms in the middle cerebral artery, umbilical artery and fetal aorta were recorded. Sensitivity of these vessels with regard to the prediction of intrauterine growth retardation, rate of cesarean section, preterm delivery and new-born depression was calculated. In all Doppler measurements there were no cases with absence of end-diastolic flow. RESULTS: The differences between pathological fetal outcome were not statistically significant, but diagnostic capacity of the middle cerebral artery velocimetry with regard to the prediction of pathological fetal outcome was on average 11% below the diagnostic capacity of the fetal aorta and umbilical artery. CONCLUSION: There is no benefit in examining fetal middle cerebral artery Doppler measurements in clinical routine in patients with normal velocity waveforms in the umbilical artery and fetal aorta.

Aorta↗

Reference ranges and standard percentile-curves for the Doppler indices RI and S/D ratio of the fetal middle cerebral artery. Color Doppler measurements in a perinatal centre.

PURPOSE: To perform reference ranges and standard percentile-curves for the Doppler indices resistance index (RI) and systolic/diastolic (S/D) ratio of the fetal middle cerebral artery, periodical color doppler sonographic measurements of 70 pregnant women in the 3rd trimester of pregnancy were done. METHODS: 600 Doppler flow measurements of the fetal middle cerebral artery between 28 and 40 weeks of gestation were performed. The patients had no previous obstetric complications, no apparent medical problems and no complications in pregnancy and labor. Percentiles curves were performed for the RI and the S/D ratio from the 10th percentile up to the 90th percentile. RESULTS: In the 3rd trimester of pregnancy fetal cerebral circulation shows an increase of the diastolic component and simultaneous decrease in cerebral resistance. The average S/D ratio in week 29 is 8.0, in week 34 6.0 and in the 40th week 3.5. The RI decrement is from 0.88 to 0.67. Other groups demonstrated similar ranges however absolute data are different. CONCLUSION: The increase in the diastolic component in the middle cerebral artery of the last third of the pregnancy demands reference ranges by using percentile curves. Knowledge of the reference range helps to discriminate between a normal fetal situation and disease. Because of different absolute ranges in the literature each perinatal centre should develop their own data.

Adolescent↗

Falsely increased HbA1c values by HPLC and falsely decreased values by immunoassay lead to identification of Hb Okayama and help in the management of a diabetic patient.

A falsely increased HbA1c value of 47.1% was determined by cation exchange chromatography during a routine HbA1c measurement of the blood sample from a 63-year-old diabetic male patient living in Hamburg, Germany. In former determinations by immunological assays falsely decreased values in the range of 5.0 to 5.5% were obtained. The sample was inconspicuous in alkaline hemoglobin electrophoresis. But acid hemoglobin electrophoresis confirmed the falsely increased value. These facts let us consider the existence of a heterozygous "silent hemoglobin variant", such as hemoglobin Okayama, with an amino acid substitution in one of the first four amino acids of the beta chain, representing the epitope of common immunoassays. DNA analyses confirmed this presumption and we found the heterozygous mutation hemoglobin Okayama [beta 2 (NA 2) His (CAC)-->Gln (CAA)]. Knowing that an immunological assay only detects about half of the present HbA1c, the obtained values can be used for therapeutic management of this diabetic patient.

Amino Acid Substitution↗

Transfection of immature murine bone marrow-derived dendritic cells with the granulocyte-macrophage colony-stimulating factor gene potently enhances their in vivo antigen-presenting capacity.

Ag presentation by dendritic cells (DC) is crucial for induction of primary T cell-mediated immune responses in vivo. Because DC culture from blood or bone marrow-derived progenitors is now clinically applicable, this study investigated the effectiveness of in vitro-generated murine bone marrow-derived DC (Bm-DC) for in vivo immunization protocols. Previous studies demonstrated that GM-CSF is an essential growth and differentiation factor for DC in culture and that in vivo administration of GM-CSF augments primary immune responses, which renders GM-CSF an attractive candidate to further enhance the effectiveness of DC-based immunotherapy protocols. Therefore, immature Bm-DC were transiently transfected with the GM-CSF gene and tested for differentiation, migration, and Ag-presenting capacity in vitro and in vivo. In vitro, GM-CSF gene-transfected Bm-DC were largely unaltered with regard to MHC and costimulatory molecule expression as well as alloantigen or peptide Ag-presenting capacity. When used for in vivo immunizations, however, the Ag-presenting capacity of GM-CSF gene-transfected Bm-DC was greatly enhanced compared with mock-transfected or untransfected cells, as determined by their effectiveness to induce primary immune reactions against hapten, protein Ag, and tumor Ag, respectively. Increased effectiveness in vivo correlated with the better migratory capacity of GM-CSF gene-transfected Bm-DC. These results show that GM-CSF gene transfection significantly enhances the capacity of DC to induce primary immune responses in vivo, which might also improve DC-based vaccines currently under clinical investigation.

Adjuvants, Immunologic↗

The tumorigenicity of IL-2 gene-transfected murine M-3D melanoma cells is determined by the magnitude and quality of the host defense reaction: NK cells play a major role.

Transfection of a variety of tumor lines with the IL-2 gene strongly reduces their tumorigenic potential when applied to either euthymic or athymic animals. To elucidate the mechanisms underlying this phenomenon, we inoculated IL-2-transfected M-3D melanoma (M-3D-IL-2) cells into DBA/2 mice immunosuppressed by gamma-irradiation. Animals thus treated developed pigmented tumors, suggesting that IL-2 transfection of melanoma cells, instead of altering their neoplastic growth properties, renders them capable of evoking a tumoricidal host response. To define the critical effector cell, we injected M-3D-IL-2 and, for control purposes, nontransfected M-3D cells into DBA/2 recipients and analyzed the injection site. We found that 1) IL-2-expressing M-3D cells induce a much stronger inflammatory reaction than wild-type cells, 2) in both instances the infiltrate consists mainly of macrophages (40-60%) and granulocytes (30-40%), and 3) only the infiltrate of M-3D-IL-2 cell deposits contains a minor fraction of NK cells (approximately 1-2%). When we reconstituted sublethally irradiated animals with various leukocyte subsets, we found that unfractionated as well as macrophage-depleted peritoneal lavage cells but not NK cell-depleted peritoneal lavage cells were able to suppress the growth of IL-2-expressing M-3D cells. In vivo leukocyte depletion experiments showed that the NK cell-depleting asialo-GM1 antiserum, but not anti-macrophage and/or anti-granulocyte reagents, restored the tumorigenicity of M-3D-IL-2 cells. Our results indicate that the inflammatory tissue response evoked by IL-2-transfected cancer cells includes the attraction and/or activation of NK cells and that, in the experimental system used, these cells are critically needed for successfully controlling cancer growth in vivo.

Animals↗

Immunotherapy of metastatic malignant melanoma by a vaccine consisting of autologous interleukin 2-transfected cancer cells: outcome of a phase I study.

We performed a phase I trial to evaluate the safety and tolerability of repeated skin injections of IL-2-transfected autologous melanoma cells into patients with advanced disease. Cell suspensions, propagated from excised metastases, were IL-2 gene transfected by adenovirus-enhanced transferrinfection and X-irradiated prior to injection. Vaccine production was successful in 54% of the patients. Fifteen patients (37%) received two to eight skin vaccinations of either 3 x 10(6) (intradermal) or 1 x 10(7) (half intradermal, half subcutaneous) transfected melanoma cells per vaccination (secreting 140-17,060 biological response modifier program units of IL-2/10(6) cells/24 hr). Analyses of safety and efficacy were carried out in 15 and 14 patients, respectively. Overall, the vaccine was well tolerated. All patients displayed modest local reactions (erythema, induration, and pruritus) and some experienced flu-like symptoms. Apart from newly appearing (4 of 14) and increasing (5 of 14) anti-adenovirus and newly detectable anti-nuclear antibody titers (1 of 15), recipients developed de novo or exhibited increased melanoma cell-specific delayed-type hypersensitivity (DTH) reactions (8 of 15) and vitiligo (3 of 15) and showed signs of tumor regression (3 of 15). This supports the idea of a vaccine-induced or -amplified anti-cancer immune response. None of the patients exhibited complete or partial regressions, but five of them experienced periods of disease stabilization. Three of these individuals received more than the four planned vaccinations and their mean survival time was 15.7 +/- 3.5 months as compared to 7.8 +/- 4.6 months for the entire patient cohort. These data indicate that IL-2-producing, autologous cancer cells can be safely administered to stage IV melanoma patients and could conceivably be of benefit to patients with less advanced disease.

Adult↗

[Imaging diagnosis in suspected inflammatory rheumatoid axial skeleton diseases (sacroilitis)].

Involvement of the sacroiliac joints is a hallmark of the spondyloarthropathies, especially in ankylosing spondylitis. The conventional diagnostic imaging of sacroiliitis in early stages might cause problems, because sensitivity of conventional radiographic methods is known to be too low in early stages of the disease. Magnetic resonance imaging of the sacroiliac joints certainly enables one to detect acute as well as chronic inflammatory changes in all stages of the disease. The potential disadvantages of this method are the dependency on the examiner, the lack of standardization, and the relatively high costs. Therefore, the "Workgroup of Diagnostic Imaging in Rheumatology of the Regional Center of Rheumatology of Berlin" including experienced rheumatologists, skeletal radiologists, and orthopedists acquired an imaging graduation for detection of sacroiliitis in consideration of the clinical background, the technical details of the methods, questions of ionizing radiation exposure, and cost effectiveness.

Cost-Benefit Analysis↗

Effects of general anaesthesia vs. sedation on fertilization, cleavage and pregnancy rates in an IVF program.

Anaesthetic management for oocyte retrieval may interfere with the results and success rate of an in vitro fertilization (IVF) program. This study was conducted to compare the effects of two different anaesthetic techniques (general anaesthesia versus sedation) used for oocyte retrieval on IVF outcome. For general anaesthesia we used a combination of remifentanil (Ultiva) with either propofol or isoflurane in hypnotic concentrations. For sedation the protocol included midazolam, diazepam or propofol according to clinical needs. In total, 202 women were enrolled in the study. 96 women opted for sedation and 106 for general anaesthesia. The number of collected oocytes was significantly higher with general anaesthesia (10.54+/-5.43 [mean+/-SD]) than with sedation (6.25+/-3.65, p<0.0001), whereas the number of fertilized oocytes was not different (4.70+/-3.57 vs. 4.23+/-2.90). There were no significant differences in cleavage and pregnancy rates. We therefore believe that remifentanil-based general anaesthesia without nitrous oxide is a suitable alternative to sedation and may be recommended for IVF oocyte retrieval if general anaesthesia is requested.

Anesthesia, General↗

Carbon dioxide storage and nonbicarbonate buffering in the human body before and after an Himalayan expedition.

Before and 7-12 days after an Himalayan expedition CO2 equilibration curves were determined in the blood plasma of 12 mountaineers by in vitro and in vivo CO2 titration; in vivo osmolality changes (delta Osm x deltaPCO2(-1), deltaOsm x delta pH(-1), where PCO2 is the partial pressure of CO2) during the latter experiments yielded estimates of whole body CO2 storage. In vitro -delta[HCO3-] x delta pH(-1) [nonbicarbonate buffer capacity (beta) of blood] was increased 7 days after descent [before 31.3 (SEM 0.4) mmol x kgH2O(-1), after 38.3 (SEM 3.9) mmol x kgH2O(-1); P<0.05] resulting from an increased proportion of young erythrocytes; in additional experiments an augmented beta was found in young (low density cells) compared to old cells [<1.097 g x ml(-1): 0.216 (SEM 0.028) mmol x gHb(-1), >1.100 g x ml(-1): 0.145 (SEM 0.013) mmol x gHb(-1), where Hb is haemoglobin; P < 0.02]. In spite of increased Hb mass in vivo delta[CO2total] x deltaPCO2(-1) [0.192 (SEM 0.010) mmol x kgH2O(-1) x mmHg(-1)] and -delta[HCO3-] x delta pH(-1) [17.9 (SEM 1.0) mmol x kgH2O(-1)] as indicators of extracellular beta rose only slightly after altitude (7 days +16%, P<0.02; +7%, NS) because of haemodilution. The deltaOsm x deltaPCO2(-1) [0.230 (SEM 0.015) mosmol x kgH2O(-1) x mmHg(-1)] remained unchanged. Prealtitude differences in deltaOsm x delta pH(-1) between hypercapnia [-41 (SEM 5) mosmol x kgH2O(-1)] and hypocapnia [-20 (SEM 3) mosmol x kgH2O(-1); P<0.01] disappeared temporarily after return since the former slope was reduced. The high value during hypercapnia before ascent probably resulted from mechanisms stabilizing intracellular pH during moderate hypercapnia which were attenuated after descent.

Acclimatization↗

Light-induced absorbance changes in Phycomyces: evidence for cryptochrome-associated flavosemiquinones.

Light-induced absorbance changes (LIACs), which are associated with early photochemical events of blue-light transduction, were detected in growing zones of Phycomyces sporangiophores. The novel LIACs meet all the essential requirements for a spectrophotometric photoreceptor assay which was previously unavailable for blue-light receptors (cryptochromes). In-vivo absorption spectra of growing zones were derived from reflection spectra which were measured with a novel rapid-scan spectrophotometer. To detect photoreceptor-associated absorbance changes white mutants were employed which lack the interfering bulk pigment beta-carotene. Blue and white light, not however red light, induced in these strains absorbance changes near 460-490 and 600-620 nm. The LIACs were absent in light-insensitive mutants with defects in the genes madA, madB and madC. Because these genes affect photosensory adaptation and the blue-light receptor itself, the novel in-vivo LIACs must be associated with photochemical events which occur early in the transduction chain. The spectral characteristics of the LIACs are in accordance with a blue- and red-light absorbing flavosemiquinone which is generated upon light absorption by an oxidized flavin receptor. It is proposed that the flavosemiquinone functions itself as photoreceptor which mediates several red-light responses of Phycomyces.

Cryptochromes↗

Monoclonal antibody MAb-170 for immunoscintigraphic detection of ovarian tumors.

OBJECTIVE: The technetium Tc 99m-labeled monoclonal antibody MAb-170 was designed for diagnostic use in patients with gynecologic adenocarcinoma. Our investigation was initiated to verify its usefulness for radioimmunoscintigraphy of ovarian tumors. STUDY DESIGN: Most of the 82 patients participating in this study underwent immunoscintigraphy before first-look surgery. RESULTS: Radioimmunoscintigraphy recognized 36 of 41 patients with adenocarcinoma of the ovaries, corresponding to an overall sensitivity of 88%. Specificity was 90% (38/42). The calculation of accuracy gave a result of 89% (74/83). Of 110 known lesions, 92 were visualized successfully; thus the local-regional sensitivity was 84%. Of 160 benign tumor sites, 154 showed no evidence of tracer accumulation, corresponding to a local-regional specificity of 96%. The smallest lesion visualized was an adenocarcinoma of the corpus uteri with a diameter of 1.5 cm. CONCLUSION: The monoclonal antibody MAb-170 is a promising radiopharmaceutical for immunoscintigraphy of ovarian adenocarcinoma.

Adenocarcinoma↗

Carcinosarcoma, endometrial intraepithelial carcinoma and endometriosis after tamoxifen therapy in breast cancer.

The fourth case of heterologous mesodermal tumour of the uterine corpus, that developed, years following tamoxifen therapy for breast cancer in a postmenopausal woman with no previous pelvic irradiation, is presented with coincidental endometriosis and endometrial intraepithelial carcinoma. This coincidence after tamoxifen treatment appears to be an indication for the possible carcinogenic potency of tamoxifen.

Aged↗

Omphalocele and gastroschisis: prenatal diagnosis and peripartal management. A case analysis of the years 1989-1997 at the Department of Obstetrics and Gynecology, University of Homburg/Saar.

OBJECTIVE: The article presents a retrospective analysis (1989-1997) of the prenatal diagnosis, the course and completion of pregnancy of 26 fetuses with omphalocele and 18 fetuses with gastroschisis. SUBJECTS: 44 pregnancies with anterior fetal wall defect diagnosed by prenatal ultrasound, clinical or patho-anatomic examination between 1989 and 1997 at the Department of Obstetrics and Gynecology, University of Homburg/Saar. RESULTS: In 40 of 44 pregnancies (91%) the fetal ventral abdominal wall defect could be detected antenatally with ultrasound. Associated malformations in fetuses with omphalocele were seen in 18 cases (69%), whereas only five fetuses with gastroschisis (28%) had an associated malformation. Nineteen of 26 fetuses (73%) with omphalocele had a normal karyotype. Seven of 26 fetuses (27%) with omphalocele had an abnormal karyotype. Eleven fetuses with omphalocele were live born, three of them with minor anomalies. Ten babies with omphalocele survived. No chromosomal anomalies were detected in fetuses with gastroschisis. There were four gastrointestinal malformations and one lethal associated malformation in fetuses with gastroschisis. There were 15 live born babies with gastroschisis, all of whom have survived. In 20 of 44 cases (45%) with ventral abdominal wall defect oligohydramnios could be detected by ultrasound. In 28 of 44 cases (64%) we found fetal growth retardation <10th percentile for gestational age. CONCLUSION: In case of a fetal ventral abdominal wall defect, the detection and appropriate classification of associated fetal anomalies is of great importance for the further course of pregnancy. Fetal karyotyping should be offered in case of a fetal abdominal wall defect. Early and close prenatal consultation of the neonatologist and the pediatric surgeon will favorably influence the perinatal outcome.

Adult↗

Influence of epinephrine and norepinephrine on intestinal villous blood flow during endotoxemia.

PURPOSE: The objective of this study was to determine the effects of epinephrine and norepinephrine on mucosal villous blood flow in a normotensive model of endotoxemia. MATERIALS AND METHODS: Thirty-two anesthetized rats were laparotomized, and a jejunal portion was exteriorized and opened by an antimesenteric incision. The jejunal 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 four treatments: infusion of Escherichia coli lipopolysaccharides (LPS, 2 mg/kg/h) without catecholamine pretreatment (LPS group); or infusion of LPS with epinephrine pretreatment (0.2 microg/kg/min, start 30 minutes before LPS infusion) (E group), or infusion of LPS with norepinephrine pretreatment (0.2 microg/kg/min, start 30 minutes before LPS infusion) (NE group). The control group did not receive either catecholamines or LPS. Mean diameter of central arterioles (D(A)) and mean erythrocyte velocity within the arterioles (V(E)) were measured 30 minutes before and at 0, 60, and 120 minutes after induction of endotoxemia. Mucosal villous blood flow was calculated from D(A) and V(E). RESULTS: LPS infusion alone and norepinephrine plus LPS infusion led to a significant vasoconstriction of central arterioles, which was associated with a similar decrease in mucosal villous blood flow. Epinephrine infusion alone led to a vasodilation and an increase in villous blood flow within the first 30 minutes. After induction of endotoxemia, D(A) returned to baseline values and villous blood flow was as low as in the LPS and the norepinephrine group after 120 minutes. CONCLUSION: In this experimental rat model, the catecholamines epinephrine and norepinephrine in a dosage of 0.2 microg.kg(-1).min(-1) neither diminish nor improve mucosal villous blood flow during the early phase of endotoxemia.

Animals↗

Expression patterns of complex glycoconjugates and endogenous lectins during fetal development of the viscerocranium.

Experimental evidence suggests that carbohydrates and their corresponding receptors (endogenous lectins) decode biological information. Therefore, the expression of complex oligosaccharides--the potential ligand part of this recognition system--during chondrogenesis and osteogenesis was determined in the viscerocranium of fetal rats by mapping the staining patterns of exogenous lectins. Results were compared with the expression of bone- and/or cartilage-specific core proteins and the binding profiles of neoglycoconjugates. These synthetic tools make possible the localization of sugar-ligand-binding sites. The spatial and temporal distribution patterns of glycoconjugates were highly dynamic and demonstrated a clear correlation with characteristic morphological modifications. The glycobiological characterization of precartilage mesenchymal cells revealed distinct differences compared to prospective bone anlagen. Especially the binding of the exogenous lectin from Griffonia simplicifolia II, that selectively visualized prechondral aggregations, reveals that regulation of early chondral growth is at least phenomenologically correlated with a relatively atypical oligosaccharide composition terminating with N-acetylglucosamine.

Animals↗