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Biomedical subjects

S Schmidt

Publications and source records attributed to S Schmidt.

At least 73 records · Page 4Linked to original sources

Continuous telemetric monitoring of fetal oxygen partial pressure during labor.

INTRODUCTION: Upright or ambulatory birth positions are favorable for fetal oxygenation. Studies of fetal oxygenation with regard to maternal position require free maternal mobility. Therefore, telemetry for a fetal sensor for such investigations is a pre-requisite. Telemetry-if technically feasible-could enable monitoring of fetal oxygen partial pressure using an existing sensor without restricting the mobility of the parturient woman. We have developed a telemetry system for use with a fetal transcutaneous partial oxygen pressure sensor (ttcpO(2)) and have studied effects of maternal position and position changes during normal labor. MATERIALS AND METHODS: The monitoring system consists of three parts: the telemetry unit with the ttcpO(2) sensor to transmit the tcpO(2) and the heating output telemetrically, a modified CTG monitor and a personal computer storing the measurements. All data were plotted on the CTG recording paper and fed into a new purpose-designed software, displaying fetal heart rate, the uterine contraction intensity, ttcpO(2) and the heating output. Three laboring women, randomly and successively adopting "classical birth positions" (supine or side positions), sitting or vertical or walking position, were studied. RESULTS: Fetal heart rate, uterine contractions, ttcpO(2) and heating output are influenced by the birth positions and by changes of the birth position. In the classical supine and side position there seemed to be lower fetal oxygenation. Sitting, standing and especially walking were more favorable. DISCUSSION: Telemetry is useful to study a possible clinical benefit of individual birth positions.

Equipment Design↗

[Coccidioidomycosis. Two case reports with discussion of current diagnostic and therapeutic issues].

Coccidioidomycosis is a systemic mycosis that is acquired by inhalation. It is endemic in desert-like areas of the southwest USA and neighboring regions, but is becoming increasingly prevalent in other regions of the world as a result of widespread travel. The clinical spectrum is broad, ranging from inapparent infections or symptoms of acute respiratory infection with spontaneous recovery to various manifestations of disseminated coccidioidomycosis. Since the majority of patients with disseminated coccidioidomycosis present with cutaneous manifestations, early diagnosis of this potentially life-threatening disease by dermatologists is important. Atypical skin changes, pulmonary infiltrates and a history of travel to areas where the disease is endemic are indicative of coccidioidomycosis. For conclusive diagnosis, identification of the fungus by histopathologic examination or culture is desirable. Serological tests can be helpful for establishing the diagnosis and monitoring the course of the disease. The treatment of choice for cutaneous coccidioidomycosis is currently oral azole antifungal agents, such as itraconazole 400 mg daily, continued for 6 months after clinical response. Since relapses are frequent after discontinuation of the treatment, close clinical, serological and radiological follow-up is required for years.

Administration, Oral↗

Escalating immunotherapy of multiple sclerosis--new aspects and practical application.

Recent clinical studies in multiple sclerosis (MS) provide new data on the treatment of clinically isolated syndromes, on secondary progression, on direct comparison of immunomodulatory treatments and on dosing issues. All these studies have important implications for the optimized care of MS patients. The multiple sclerosis therapy consensus group (MSTCG) critically evaluated the available data and provides recommendations for the application of immunoprophylactic therapies. Initiation of treatment after the first relapse may be indicated if there is clear evidence on MRI for subclinical dissemination of disease. Recent trials show that the efficacy of interferon beta treatment is more likely if patients in the secondary progressive phase of the disease still have superimposed bouts or other indicators of inflammatory disease activity than without having them. There are now data available, which suggest a possible dose-effect relation for recombinant beta-interferons. These studies have to be interpreted with caution, as some potentially important issues in the design of these studies (e. g. maintenance of blinding in the clinical part of the study) were not adequately addressed. A meta-analysis of selected interferon trials has been published challenging the value of recombinant IFN beta in MS. The pitfalls of that report are discussed in the present review as are other issues relevant to treatment including the new definition of MS, the problem of treatment failure and the impact of cost-effectiveness analyses. The MSTCG panel recommends that the new diagnostic criteria proposed by McDonald et al. should be applied if immunoprophylactic treatment is being considered. The use of standardized clinical documentation is now generally proposed to facilitate the systematic evaluation of individual patients over time and to allow retrospective evaluations in different patient cohorts. This in turn may help in formulating recommendations for the application of innovative products to patients and to health care providers. Moreover, in long-term treated patients, secondary treatment failure should be identified by pre-planned follow-up examinations, and other treatment options should then be considered.

Clinical Trials as Topic↗

[Value of CT in small-bowel obstruction].

Small bowel obstruction is a leading cause of admission in surgical and emergency units. During the last two decades, the classical philosophy of "never let the sun set or rise on small-bowel obstruction" has been succeeded by a new management based especially on the cause and the severity of the obstruction. It most often allows a correct choice between medical therapy and surgery using laparotomy or laparoscopy. This changing attitude is still in progress and is mainly related to the high accuracy of computed tomography. This review will discuss the semiology and value of computed tomography compared with clinical examination and other imaging modalities.

Humans↗

Glucocorticoid receptor heterozygosity combined with lack of receptor auto-induction causes glucocorticoid resistance in Jurkat acute lymphoblastic leukemia cells.

Glucocorticoids (GC) induce apoptosis in malignant lymphoblasts, but the mechanism of this process as well as that of the clinically important GC resistance is unknown. We investigated GC resistance in Jurkat T-ALL cells in which ectopic GC receptor (GR) restores GC sensitivity, suggesting deficient GR expression. Jurkat cells expressed one wild-type and one mutated (R477H) GR allele. GR(R477H) ligand-binding-dependent nuclear import, as revealed by live-cell microscopy of YFP-tagged GR, was unaffected. Transactivation and transrepression were markedly impaired; however, GR(R477H) did not act in a dominant-negative manner, that is, did not prevent cell death, when introduced into a GC-sensitive cell line by retroviral gene transfer. Contrary to another GR heterozygous, but GC-sensitive, T-ALL model (CCRF-CEM), Jurkats expressed lower basal GR levels and did not auto-induce their GR, as revealed by 'real-time' RT-PCR and immunoblotting. Absent GR auto-induction could not be restored by transgenic GR and, hence, was not caused by reduced basal GR levels. Thus, inactivation of one GR gene results in haploinsufficiency if associated with lack of GR auto-induction.

Animals↗

Glucocorticoid-induced apoptosis and glucocorticoid resistance: molecular mechanisms and clinical relevance.

The ability of glucocorticoids (GC) to efficiently kill lymphoid cells has led to their inclusion in essentially all chemotherapy protocols for lymphoid malignancies. This review summarizes recent findings related to the molecular basis of GC-induced apoptosis and GC resistance, and discusses their potential clinical implications. Accumulating evidence suggests that GC may induce cell death via different pathways resulting in apoptotic or necrotic morphologies, depending on the availability/responsiveness of the apoptotic machinery. The former might result from regulation of typical apoptosis genes such as members of the Bcl-2 family, the latter from detrimental GC effects on essential cellular functions possibly perpetuated by GC receptor (GR) autoinduction. Although other possibilities exist, GC resistance might frequently result from defective GR expression, perhaps the most efficient means to target multiple antileukemic GC effects. Numerous novel drug combinations are currently being tested to prevent resistance and improve GC efficacy in the therapy of lymphoid malignancies.

Animals↗

[Dynamics of thrombin-antithrombin-III complex (TAT-III) and prothrombin fragments F1 + 2 during labour with and without aprotinin administration].

OBJECTIVE: The aim of this study was to determine if aprotinin could affect postpartal fibrinolysis when given at the latest 15 min before delivery and if there is a difference between normal delivery and caesarean section. Furthermore we wanted to examine if the thrombin-antithrombin-III-complex (TAT-III) and prothrombin fragments F1 + 2 changed in the peripartal period and if prethrombotic stages could be recognized. PATIENTS AND METHODS: 84 patients (15 - 44 years of age) have been examined (41 normal deliveries, 43 cesarean sections). After giving informed consent and randomization, 30 of these patients were administered 1 Mio KIE aprotinin (Trasylol(R)) at the latest 15 min before delivery (15 normal deliveries, 15 cesarean sections). The results of TAT-III, prothrombin fragments F1 + 2, factor VIII and partial thromboplastin-time (PTT) were collected shortly before and after delivery and 30 and 120 min after detachment of the placenta. RESULTS: Normal deliveries without aprotinin showed a significant increase of TAT-III and an evident increase of prothrombin fragments F1 + 2. After administration of aprotinin this increase was significantly lower. The increase of TAT-III and prothrombin fragments F1 + 2 in patients with caesarean sections was evidently lower than in normal deliveries and was not influenced significantly by aprotinin. Factor VIII and partial thromboplastin time (PTT) showed no relevant changes in all study groups. DISCUSSION AND CONCLUSION: The consumption of coagulation and fibrinolysis factors induced by delivery of the child and detachment of the placenta can be reduced after administration of aprotinin given at the latest 10 - 18 min before partus. This could be used in therapy and prophylactic treatment in high-risk patients (e. g., pre-eclampsia, HELLP syndrome, etc.).

Adolescent↗

[Variations of superficial nerves at the pelvis considering orthopaedic surgical approaches].

PROBLEM: Intraoperative injuries of vessels and nerves are common risks and repeatedly described in orthopaedic pelvic surgery. Especially in pelvic osteotomies or bone harvesting procedures subcutaneous nerves are at risk for damage. In this study we elucidated the variations of subcutaneous nerves by anatomic preparation exposure with regard to the anterior and posterior spines. METHODS: To investigate the different anatomic variations the iliohypogastrical, lateral cutaneous, subcostal and the cluneal nerves of 10 human cadavers were prepared and exposed bilaterally at the anterior, lateral and posterior pelvic region. For determination of anatomically important reference points the distance of these structures to the anterior superior spine was measured and compared with present datas in literature with respect to the ilioinguinal (Letournel) and iliofemoral (Smith- Petersen) approach. RESULTS: We found a high variability of superficial pelvic nerves. Our findings differ somehow with datas of recent papers. CONCLUSION: The findings of our study stress the importance of basic knowledge and thorough preparation in surgical procedures at the pelvis including harvesting bone grafts to minimize donor site morbidity.

Bone Transplantation↗

[Differential diagnosis of a polyhydramnion in hyperprostaglandin E syndrome: a case report].

INTRODUCTION: A polyhydramnion is diagnosed in 0.4 to 3.3 % of all pregnancies. The most common causes of increased amniotic fluid include maternal diabetes mellitus, fetal malformations and chromosomal aberrations, twin-to-twin transfusion syndrome, rhesus incompatibility syndrome, and congenital infections. After exclusion of other etiologies for polyhydramnion, the very rare, autosomal-recessive transferred hyperprostaglandin E syndrome (HPS) has to be considered. PATIENTS AND METHODS: We report on a 31-year-old women who visited our obstetrical outpatient clinics at 22 + 4 weeks of gestation for prenatal ultrasound scanning and amniocentesis. This, the patient's third pregnancy had been without complications so far. She had delivered two children before, one of them bearing the HPS. The women herself suffered from epilepsy. At 26 + 0 weeks of gestation the pregnancy was complicated by a polyhydramnion requiring serial amniocentesis for reducing amniotic fluid load. Among others, her amniotic fluid was analyzed for chloride concentration and for genetic aberrations regarding HPS. Serological investigations and an oral glucose tolerance test (oGTT) were performed. RESULTS: Amniocentesis revealed a normal chromosomal pattern. The oGTT demonstrated values in the normal range. Serological investigations regarding TORCH infections were without pathological findings. The chloride concentration was highly increased in the amniotic fluid, which is suspicious for HPS. Finally, molecular analysis proved an NKCC2-mutation responsible for HPS. A cesarean section was performed at 33 + 3 weeks of gestation. CONCLUSION: If HPS is suspected to be the cause of polyhydramnions, the chloride concentrations in the amniotic fluid and molecular analysis for HPS should be performed. Interdisciplinary care, diagnostics and therapy in an experienced perinatal center are essential for an optimal outcome of the pregnancy and the newborn infant.

Adult↗

Computed tomography-guided pulmonary nodule localization before thoracoscopic resection.

PURPOSE: To assess the success rate and complication rate of a CT-guided pulmonary nodule-marker system before thoracoscopic resection. MATERIAL AND METHODS: In 24 patients (15 M, 9 F; age range, 18-71 years) a total of 25 pulmonary nodules (in 1 patient 2 lesions simultaneously) were marked with a special wire under CT-guidance and then thoracoscopically resected. We evaluated lesion size, lesion distance to the pleura, the time of intervention, complications, and thoracoscopic success rate. RESULTS: Mean lesion size was 7 mm (range 4-15 mm) and mean lesional distance to the pleura was 13 mm (range 2-31 mm). The pulmonary nodule-marker system was positioned successfully in all 25 pulmonary nodules within 5-11 min (mean 7.5 min). Minimal pneumothoraces were observed in five patients with no requirements of chest drains. In addition, no bleeding complications or hematothorax were observed. All 25 pulmonary nodules could be resected thoracoscopically. However, in one patient (4%), the guide-wire dislocated during thoracoscopy, but the lesion could be successfully resected during thoracoscopy. CONCLUSION: The CT-guided placement of the pulmonary nodule-marker system used here offers a safe and accurate guide for the localization of small pulmonary nodules during thoracoscopic resection.

Adolescent↗

Synthesis of 5-alkynylated d4T analogues as potential HIV-1 reverse transcriptase inhibitors.

A series of 2',3'-didehydro-2',3'-dideoxynucleosides substituted with an alkynylhydroxy- (6, 7, 12 and 13) and alkynylamino- (20) groups at the C-5 position were synthesized. All these five target modified nucleosides were tested for anti-human immunodeficiency virus type 1 activity in CEM-SS and MT-4 cells and unfortunately displayed no improvement in antiviral activity.

Alkynes↗

Interleukin-5 receptors on human lung eosinophils after segmental allergen challenge.

BACKGROUND: IL-5 is a specific cytokine for eosinophil accumulation, activation and prolongation of survival and can be recovered in elevated concentrations from the bronchoalveolar compartment in atopic asthma following allergen challenge. OBJECTIVE: The action of IL-5 is mediated via the specific IL-5 receptor-alpha (IL-5Ralpha). Although in vitro data suggest that IL-5R expression is regulated by cytokines such as IL-3, IL-5 and GM-CSF, IL-5R regulation in vivo and its kinetics following allergen provocation are incompletely understood. METHODS: We investigated IL-5R regulation in vivo following segmental allergen provocation (SAP) with an individually standardized dose of allergen in 12 patients with atopic asthma. Lavage was performed 10 min and 18 h (eight patients) and 10 min and 42 h (eight patients) after allergen challenge. In addition to differential cell counts, IL-5Ralpha was measured by flow cytometry and IL-5 concentrations in bronchoalveolar lavage (BAL) fluid were determined by ELISA. RESULTS: IL-5Ralpha expression decreased significantly on peripheral blood and on BAL eosinophils 18 and 42 h after SAP. In contrast, IL-5 concentrations increased significantly in BAL fluid 18 and 42 h after SAP. In four and two patients, respectively, there were detectable IL-5 concentrations in serum 18 or 42 h after allergen exposure. CONCLUSIONS: Although there was no correlation between IL-5 concentrations and IL-5Ralpha expression on eosinophils in BAL, our data support previous in vitro and in vivo findings of a negative feedback mechanism between IL-5 concentrations and IL-5Ralpha expression on eosinophils.

Adult↗

Increase in granzyme B+ lymphocytes and soluble granzyme B in bronchoalveolar lavage of allergen challenged patients with atopic asthma.

Asthma has been linked to a chronic, T-cell-mediated bronchial inflammation. Because other T-lymphocyte-mediated, chronic inflammatory disorders have been associated with elevated granzyme B (grB) expression we tested the hypothesis that atopic asthma might be associated with elevated grB levels in the bronchoalveolar compartment. Therefore we performed intracellular grB staining in lymphocytes from bronchoalveolar lavage (BAL) collected 42 h after segmental allergen provocation (SAP) in allergic patients with bronchial asthma. There was a significant increase in CD3(+), CD8(+), and CD16/56(+) lymphocytes expressing grB in BAL 42 h after SAP as compared to saline challenged controls. However, compared to peripheral blood the percentages of these lymphocyte subsets detected as grB(+) in BAL remained significantly lower. Measurement of extracellular grB in BAL fluids by a particle immunoassay revealed significantly elevated grB levels in the allergen challenged bronchoalveolar compartment 42 h following SAP in six of the eight patients (range, <1.0-348.1 pg/ml) as compared to saline challenged controls (range, <1.0-70.5 pg/ml). We conclude that total cell numbers of grB(+) lymphocyte subsets increase 42 h after SAP in the lower respiratory tract. In addition there is evidence to suggest that grB is released into the airways of asthmatic patients. This suggests a role for grB in the pathophysiological processes following SAP but its definitive role in allergic bronchial asthma needs to be established.

Adolescent↗

Comparative responses of three rat strains (DA/Han, Sprague-Dawley and Wistar) to treatment with environmental estrogens.

The rat uterotrophic assay is a widely used screening test for the detection of estrogenic, endocrine-disrupting chemicals. Although much attention has been paid to identifying protocol variables and reproducibility between laboratories the question whether toxicodynamic and toxicokinetic variations of different strains may affect their sensitivity to estrogenic stimuli has been rarely addressed. We have compared the estrogenic activity of the environmental chemicals genistein (GEN), bisphenol A (BPA) and p- tert-octylphenol (OCT) in DA/Han (DA), Sprague-Dawley (SD) and Wistar (WIS) rats after repeated oral application. Rats were treated per os for 3 days with different doses of these weakly estrogenic compounds and the potent reference estrogen ethinylestradiol (EE). Then uterine wet weight, thickness of the uterine epithelium, uterine gene expression of clusterin (CLU), and thickness of the vaginal epithelium were examined as parameters for estrogenic potency of the test compounds in the three strains of rats. The uterotrophic response to treatment with BPA, OCT and GEN was similar in the three strains, and allowed us to rank them as GEN being more potent than OCT, and BPA being the weakest estrogen. This was confirmed by analysis of other biological endpoints, despite some differences in the magnitude of their response among strains and to distinct compounds. For instance, the uterus wet weight response to EE treatment indicated lower sensitivity of SD rats than that of DA and WIS rats, but this was not observed for responses of the uterine or vaginal epithelium. Moreover, blood concentrations were assessed at the time of killing and related to biological responses: plasma levels of total and unconjugated BPA and GEN depended upon the dose administered and varied to some extent within treatment groups and among the three rat strains. However, there was no good correlation in the three strains between individual compound concentrations analysed 24 h after the last dose and the uterotrophic wet weights. Summarising our results, we conclude that the sensitivity of various biological endpoints can differ slightly between strains of rats. On the other hand, our data demonstrate that the choice of the rat strain does not lead to pronounced differences in the evaluation of estrogenic activities of chemicals, especially when different biological endpoints are included in the analysis.

Administration, Oral↗

Electron-phonon coupling and its evidence in the photoemission spectra of lead.

We present a detailed study of the influence of strong electron-phonon coupling on the photoemission spectra of lead. Representing the strong-coupling regime of superconductivity, the spectra of lead show characteristic features that demonstrate the correspondence of physical properties in the normal and the superconducting state, as predicted by the Eliashberg theory. These features appear on an energy scale of a few meV and are accessible for photoemission only by using modern spectrometers with high-resolution in energy and angle.

Journal Article↗