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Biomedical subjects

D Schmidt

Publications and source records attributed to D Schmidt.

At least 37 records · Page 2Linked to original sources
PubMed1997

Co-stimulatory pathways controlling activation and peripheral tolerance of human CD4+CD28- T cells.

Co-stimulation mediated by the CD28 molecule is considered critical in the activation of CD4+ T cells. In patients with rheumatoid arthritis and infrequently in normal individuals, CD4+ T cells lacking CD28 expression are expanded and contain clonogenic populations. To analyze whether these cells are independent of co-stimulatory requirements or whether they use co-stimulatory signals distinct from the CD28 pathway, we have compared CD4+ CD28+ and CD4+ CD28- T cell clones isolated from rheumatoid arthritis patients. Accessory cells supported the induction of CD25 expression as well as of proliferative responses after anti-CD3 cross-linking and prevented the induction of anergy in CD4+ CD28- T cell clones. In contrast to CD4+CD28+ T cells, the presence of accessory cells did not enhance the secretion of interleukin (IL)-2, interferon-gamma, or IL-4. The co-stimulatory signals did not involve CD28/CTLA-4-CD80/CD86 receptor-ligand interactions. The proliferative response of CD4+CD28- T cells could not be blocked by anti-CD2, anti-CD18, and anti-CD58 antibodies, suggesting that these receptor-ligand interactions cannot provide CD28- independent co-stimulation. Our data suggest that CD4+CD28- T cells require co-stimulatory signals for optimal induction of cell growth and CD25 expression as well as for the prevention of anergy. The co-stimulatory receptor-ligand interaction is independent of the CD28 pathway and may be involved in the oligoclonal expansion of the CD4+ CD28- T cell subset in rheumatoid arthritis.

Antigen-Presenting Cells↗
PubMed1997

Prenatal diagnosis of the fetus with cystic fibrosis and meconium ileus.

The sonographic finding of hyperechoic or dilated fetal bowel raises suspicion of a number of prenatal disorders including meconium ileus (MI), meconium peritonitis, congenital infection, neoplasm, or chromosomal trisomy. These findings may also represent transient normal variants. The following case report details the evaluation of one pregnancy with abnormal intestinal echogenic findings on serial sonograms (US), to demonstrate inherent diagnostic difficulties in such a case. A diagnostic algorithm is presented to aid in the proper use of US and DNA mutation analysis for cystic fibrosis (CF), so that the cause of an abnormal abdominal US can be established earlier and more accurately than suggested by previous management schemes. Earlier fetal diagnosis may help to anticipate postnatal problems associated with CF/MI, and therefore provide more optimal clinical management of the affected fetus.

Adult↗
PubMed1997

Whole-body kinetics and dosimetry of L-3--123I-iodo-alpha-methyltyrosine.

The synthetic amino acid L-3--123I-iodo-alpha-methyltyrosine (IMT) is currently under clinical evaluation as a single-photon emission tomography (SPET) tracer of amino acid uptake in brain tumours. So far, dosimetric data in respect of IMT are not available. Therefore we investigated the whole-body distribution of IMT in six patients with cerebral gliomas and the radiation doses were estimated. Whole-body scans were acquired at 1.5, 3 and 5 h after i.v. injection of 370-550 MBq IMT. The bladder was voided prior to each scan and the radioactivity excreted in the urine was measured. Based on the MIRD-11 method and the updated MIRDOSE3, the mean absorbed doses for various organs and the effective dose were calculated from geometric means of the anterior and posterior whole-body scans using seven source organs and the residence time. IMT was predominantly excreted by the kidneys (52.8%+/-11.5% at 1.5 h p.i., 63.0%+/-15.7% at 3 h p.i. and 74.6%+/-9.8% at 5 h p.i.). No organ system other than the urinary tract showed significant retention of the tracer. Early whole-body scans revealed slightly increased tracer uptake in the liver and in the bowel. Highest absorbed doses were found for the urinary bladder wall (0.047 mGy/MBq), the kidneys (0.010 mGy/MBq), the lower large intestinal wall (0.011 mGy/MBq) and the upper large intestinal wall (0.008 mGy/MBq). The effective dose according to ICRP 60 was estimated to be 0.0073 mSv/MBq for adults. This leads to an effective dose of 3.65 mSv in a typical brain SPET study using 500 MBq IMT. The MIRDOSE3 scheme yielded similar results. Thus, in spite of the relatively high tracer dose required for optimal brain scanning, radiation exposure in SPET studies with IMT is in the normal range of routine nuclear medicine investigations.

Adult↗
PubMed1997

Cerivastatin: pharmacology of a novel synthetic and highly active HMG-CoA reductase inhibitor.

The pyridine derivative cerivastatin is a new entirely synthetic and enantiomerically pure inhibitor of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase. As a sodium salt cerivastatin is present in the active, open ring form. Cerivastatin inhibited the membrane-bound (non-solubilized) HMG-CoA reductase of the native microsomal fraction isolated from rat liver with a Ki value of 1.3 x 10(-9) M. The reference compound lovastatin was 100-fold less potent and exhibited a Ki value of 150 x 10(-9) M. Cerivastatin inhibited the cholesterol synthesis in the human hepatoma cell line HepG2 cells with a similar IC50 value of 1.0 x 10(-9) M. In vivo studies reflected its high in vitro activity. In both rats and dogs, cerivastatin inhibited the hepatic [14C]cholesterol synthesis from [14C]acetate with an oral ED50 value of 0.002 mg/kg body weight, while lovastatin exhibited an oral ED50 value of 0.3 mg/kg in rats, showing again the ratio of 100 or more between cerivastatin and lovastatin. In the small intestine and testes, cerivastatin was at least 50-fold less active with oral ED50 values higher than 0.1 mg/kg, which is indicative for a high liver selectivity of cerivastatin. In cholestyramine-primed dogs cerivastatin dose-dependently lowered the serum cholesterol concentrations by up to 59% with 0.1 mg/kg after 20 days. Interestingly, the serum triglycerides were markedly reduced by 53 and 76% with 0.03 and 0.1 mg/kg, respectively. In normal chow fed dogs the low density lipoprotein (LDL) concentrations were reduced by up to 75% after 0.1 mg cerivastatin/kg. The ratio of HDL/LDL increased by 81% compared with a change of only 14% in the placebo treated control group. The antiatherogenic effect of cerivastatin was shown in rabbits fed a diet enriched with 0.2% cholesterol. After 9 weeks on diet 0.1 mg cerivastatin/kg decreased the accumulation of cholesterol ester in the arterial tissue by 73%. In summary, these data as compared to published data on other HMG-CoA reductase inhibitors demonstrate cerivastatin to be the most active compound in this class. Vastatins used in therapy are effective in mg doses, while cerivastatin offers a new low dose therapy in the microg range.

Administration, Oral↗
PubMed1997

Macular-threatening traction detachment of the retina in diabetic proliferative retinopathy, treated by laser.

PURPOSE: To treat patients with traction detachment of the central retina by laser in order to avoid vitrectomy. METHODS: Focal treatment of and around the flat detached retinal area with the argon laser. RESULTS: Seven patients were treated for macular-threatening traction detachment of the retina. The non-rhegmatogenous traction detachment was flat and circumscribed. Panretinal photocoagulation (PRP) with the argon laser was performed prior to treatment of the traction in three of the cases, in four it was carried out in addition to PRP. In each of the seven patients partial or complete reattachment and stabilization for many years was achieved, rendering vitrectomy unnecessary (mean follow-up after therapy: 40.1 months). In no case was a laser-induced hole produced, and in no patient did the visual acuity decrease. CONCLUSION: The favourable results following photocoagulation can be explained by the tight retinal/choroidal scar formation (laserpexy). Laserpexy is only recommended for eyes with slight initial detachment.

Adult↗
PubMed1997

A case of localized retinal damage in thallium poisoning.

PURPOSE: To determine the cause of visual impairment and to document the late eye disturbances in a case of thallium poisoning. PATIENT: A 44-year-old woman presented with a history of repeated attacks of complete alopecia over a period of several months, diffuse pain in both legs, transient gastrointestinal disturbances, abasia with a progressive paraparesis, paresthesia in the fingertips, and polyneuropathy. She complained of slowly progressive visual deterioration in both eyes which began about six months after the first attack of alopecia. The optic discs showed distinct signs of temporal atrophy together with a deep temporal excavation. The Goldmann perimetry revealed an absolute central scotoma. Traces of thallium were found in the urine and in the serum. The district attorney later discovered that her husband had been trying to poison her with thallium. METHODS: The clinical and electrophysiological examinations included visual evoked potentials (VEP) and electroretinography (flash ERG, multifocal ERG and pattern ERG). RESULTS: The VEP showed a reduction in amplitude and a prolonged latency indicating a conduction block. The pattern ERG was initially normal. At a follow-up examination 6 years later, a slight amplitude reduction in the pattern ERG was found. The multifocal ERG showed a diminished amplitude in the center of the retina (up to +/- 10 degrees visual angle). CONCLUSIONS: The electrophysiological investigations in our patient--who had an optic atrophy--indicated a conduction block of the retinal nerve fibers (VEP) and an additional lesion at or before the retinal bipolar cells (multifocal ERG), localized in the central +/- 10 degrees. These findings suggest that thallium poisoning can lead to a combined lesion of the retinal nerve fibers and the neural retina.

Adult↗
PubMed1997

Polymorphism of the tumour necrosis factor-alpha and lymphotoxin-alpha genes in chronic lymphocytic leukaemia.

The neoplastic cells of CLL are able to produce TNF which is known to stimulate the proliferation of CLL cells in an autocrine and paracrine manner. Genetic polymorphism of molecules of the TNF ligand superfamily has been described and certain alleles were suspected to predispose to variant biological responses. Previously, the rare allele TNFB*1 of the TNF-beta/lymphotoxin (LT)-alpha gene (NcoI, asparagine at amino acid position 26) was found to be associated with a stronger LT-alpha response of PBMC in vitro. We now report on a significant increase of the allele TNF1 (TNFA -308 G) of the TNF-alpha promoter/enhancer polymorphism in a group of 73 CLL patients when compared to healthy individuals (RR = 3.18, 95% confidence interval 1.57-8.3; P = 0.006). The allelic distribution of the TNF-beta/LT-alpha NcoI polymorphism did not differ significantly from randomized healthy controls. On the other hand, the frequency of the allele TNFB*2 was increased in CLL patients with advanced clinical stage (P = 0.004). These findings indicate immunogenetic associations involving polymorphisms of cytokine genes serving as paracrine and autocrine growth factors, which thus can contribute to the pathogenesis of the TNF/LT-sensitive haematological malignancy CLL.

Adult↗
PubMed1997

Localization of the motor hand area to a knob on the precentral gyrus. A new landmark.

Using functional magnetic resonance imaging (fMRI) we have evaluated the anatomical location of the motor hand area. The segment of the precentral gyrus that most often contained motor hand function was a knob-like structure, that is shaped like an omega or epsilon in the axial plane and like a hook in the sagittal plane. On the cortical surface of cadaver specimens this precentral knob corresponded precisely to the characteristic 'middle knee' of the central sulcus that has been described by various anatomists in the last century. We were then able to show that this knob is a reliable landmark for identifying the precentral gyrus directly. We therefore conclude that neural elements involved in motor hand function are located in a characteristic 'precentral knob' which is a reliable landmark for identifying the precentral gyrus under normal and pathological conditions. It faces and forms the 'middle knee' of the central sulcus, is located just at the cross point between the precentral sulcus and the central sulcus, and is therefore also visible on the cortical surface.

Aged↗
PubMed1997

Color vision tests for early detection of antiepileptic drug toxicity.

A previous suggestion that antiepileptic drugs may induce color vision deficiencies prompted us to examine whether color vision deficiencies may occur at lower drug serum concentrations than those associated with symptoms of neurotoxicity. Eighty patients presenting with epilepsy received monotherapies of valproic acid, phenytoin, or carbamazepine; 18 patients did not receive antiepileptic drug therapy. Color vision was tested by the Farnsworth-Munsell 100-hue test, spectral sensitivity, and the newly developed tritan screening plates. Patients treated with phenytoin or carbamazepine developed blue-yellow color vision deficiencies. In contrast, patients exposed to valproic acid or receiving no drug treatment showed normal color vision. There was a significant correlation (p < 0.0001) between signs of neurotoxicity induced by phenytoin or carbamazepine and blue-yellow color vision deficiencies. In contrast, we found no correlation between these signs of neurotoxicity and the drug serum concentrations (p = 0.0637). Color vision testing in epileptic patients treated with phenytoin or carbamazepine appears to be a sensitive method for early detection and monitoring of clinical neurotoxicity.

Adolescent↗
PubMed1997

Prognostic significance of the proliferative activity in neuroblastoma.

The prognostic significance of the immunohistochemically assessed growth fraction in neuroblastomas was determined in relation to tumor grade and tumor stage. A total of 101 cases of neuroblastoma were examined with the monoclonal antibodies PC10 against proliferating cell nuclear antigen (PCNA) and Ki-S5 against the Ki-67 protein. Patients were followed for a mean time of 4.8 years. Expression of both PC10 and Ki-S5 was found to be significantly linked to tumor grade and tumor stage. Prognostically favorable stage IVs was associated with low PCNA and Ki-S5 levels. For ganglioneuroblastoma, significant differences were found between the diffuse and the composite type. In univariate analysis of stage III and IV tumors, Ki-S5 and PCNA scores were significantly correlated with disease-free survival (P < 0.0015), allowing definition of a subset of cases with favorable outcome. As to Shimada's group with poor prognosis, significant differences in the clinical course were found for low and high Ki-S5 scores (P = 0.036) but not for PCNA. In multivariate analysis, only patient age, Shimada's grade, and Ki-S5 scores achieved prognostic significance. We conclude that proliferation marker Ki-S5 may provide substantial prognostic information and might become a useful adjunct for predicting the clinical courses of neuroblastoma.

Adolescent↗
PubMed1997

[Cellular and humoral functions in acute pancreatitis].

Infectious complications are the leading cause of death in acute pancreatitis. Individual factors of immune defence could be of significance, whether or not a patient develops a severe course with infectious complications. In a prospective 5-year trial including 72 patients, we investigated 29 cellular and humoral markers of the body's defence system for their potential to indicate the severity and course of acute pancreatitis. Complement factors C3 and C4 as well as immunoglobulins IgG, IgM and IgA were normal, in general. Measurable levels of IL-1 alpha, IL-1 beta, IL-2 and sIL-2R could be detected only occasionally. Values of alpha 1-AT, TNF-alpha, TNF alpha-Rp75, neopterin, sICAM-1, IL-8, IL-1RA and sIL-6R did not correlate with a severe course. Due to the high magnitude of increase, CRP, IL-6 and granulocyte elastase were the best indicators of the inflammatory process. Delayed-type hypersensitivity response was the only early predictor of a severe course. It was superior over other cellular markers such as monocyte count or CD4+/CD8+ ratio. In vitro function of polymorphonuclear granulocytes (PMN) was not adequate to the severity of the disease already during the first week of illness. During further course, PMN motility and capacities to produce reactive oxygen species even worsened. The compromized PMN function could explain the frequent development of infectious complications in patients suffering from severe pancreatitis. These results should encourage new concepts of infection prophylaxis using stimulants of cellular defence.

Acute Disease↗
PubMed1997

BARE-1 insertion site preferences and evolutionary conservation of RNA and cDNA processing sites.

The BARE-1 copia-like retrotransposon constitutes nearly 7% of the barley (Hordeum vulgare L.) genome as a family of more than 2 x 10(4) mostly full-length copies dispersed on all chromosomes. BARE-1 elements are transcribed in barley tissues from promoters within the LTR (long terminal repeat). The predicted, translated polyprotein contains conserved domains for GAG, aspartic proteinase, integrase, reverse-transcriptase, and RNase H. Here, we have used inverse PCR with LTR-based primers to establish the consensus sequences for the terminal region of the LTR, the external dinucleotides of the cDNA integration intermediate, and the minus- and plus-strand priming sites. These key functional entities are well-conserved in the BARE-1 family, including wheat Wis2, but differ from those of other plant retrotransposons. The target site duplication was established as 5 bp. Of the 13 integration sites identified here, 8 were other BARE-1 elements and 1 another retrotransposon; 59% of the total 17 identified BARE-1 insertion sites are retrotransposons. This nested insertion pattern may represent a basic feature of plant retrotransposons.

Base Sequence↗
PubMed1997

[Current status and analysis of diagnostic and therapeutic guidelines in the area of chronic obstructive respiratory tract diseases in adulthood].

UNLABELLED: GOAL OF THE INVESTIGATION: It was investigated (1) whether guidelines for the treatment of bronchial asthma and chronic obstructive pulmonary diseases (chronic obstructive bronchitis and lung emphysema) are distributed in Germany, (2) whether they are accepted by general practitioners and physicians for internal medicine without subspecialty, and (3) how much they are used. METHODS: (1) The mostly read medical journals have been screened. (2) 1200 physicians have been questioned with regard to the main criteria of these guidelines. (3) 600 physicians were asked to write a documentation for two patients each with bronchial asthma and chronic obstructive pulmonary disease. 344 of the questionnaires (28.7%) and 544 of the documentations could be analyzed (22.7%). RESULTS: Guidelines for the treatment of bronchial asthma are published in all leading journals. Substantially less references were found for the therapy of chronic obstructive bronchitis. The main concepts of training, diagnosis of the disease's severity, and physical therapy are all known by the practitioners. The training plays a sufficient role in only half of the questioned physicians. The self-measurement of the patient is not every where accepted. The treatment according to a stage by stage pharmacological therapy cannot be seen in one third of the questioned physicians. CONCLUSIONS: Differential diagnosis and therapy are not sufficiently emphasized in the current guidelines. Practitioners should participate in the development of guidelines, to include the aspects of realization.

Adult↗
PubMed1997

Uncoupling of serotonergic and noradrenergic systems in depression: preliminary evidence from continuous cerebrospinal fluid sampling.

We used the technique of continuous cerebrospinal fluid (CSF) sampling to test the following hypotheses regarding CNS monoaminergic systems in depression: (1) absolute concentrations of the informational substances tryptophan and 5-hydroxyindoleacetic acid (5-HIAA) are altered in the CNS of depressed patients (2) abnormal rhythms of tryptophan and/or 5-HIAA, or defective conversion of tryptophan to serotonin (5HT), exist in the CNS of depressed patients, and (3) the relationship between the CNS 5HT and norepinephrine (NE) systems is disrupted in depressed patients. We obtained 6-h concentration time series of tryptophan, 5-HIAA, NE, and 3-methoxy-4-hydroxyphenylglycol (MHPG) in the CSF of 10 patients with major depression and in 10 normal volunteers. No significant differences in CSF tryptophan, 5-HIAA, NE, or MHPG concentrations or rhythms were observed between normal volunteers and depressed patients. Neither were there differences in the mean tryptophan-to-serotonin ratio. However, a negative linear relationship was observed between mean concentrations of 5-HIAA and NE in the CSF of the normal volunteers (r = 0.916 [r2 = 0.839], df = 9, P < 0.001) while, in contrast, depressed patients showed no such relationship (r = +0.094 [r2 = 0.00877], df = 9, n.s.). Furthermore, the correlation coefficients expressing the relationship between CSF MHPG and CSF 5-HIAA within the normal and depressed groups were significantly different. These data support the hypothesis that a disturbance in the interaction between the serotonergic and noradrenergic systems can exist in depressive illness in the absence of any simple 5HT or NE deficit or surplus.

Adult↗
PubMed1997

Neuroendocrine tumors of the uterus.

Neuroendocrine tumors of the uterus are rare. When present, the majority is found in the uterine cervix. Several theories on the histogenesis of these tumors have been proposed including an origin from local neuroendocrine cells or from reserve cells. The latter hypothesis is supported by the fact that not too seldom uterine neuroendocrine tumors contain other histological components including adenocarcinoma and squamous cell carcinoma or even both. A firm diagnosis can usually the rendered when immunostainings and/or electron microscopy are performed, in addition to conventional light microscopy and Grimelius stain. The tumors react positively for a diversity of so-called neuroendocrine markers and several hormonal substances. Ultrastructurally, they contain dense- core neurosecretory granules. Prognosis is usually poor with most patients dying within one year from diagnosis. Survival can only be achieved in patients who present with early disease.

Endometrial Neoplasms↗