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Biomedical subjects

S Schmidt

Publications and source records attributed to S Schmidt.

At least 289 records · Page 16Linked to original sources

Investigations of breast tumors with fluorine-18-fluorodeoxyglucose and SPECT.

METHODS: We designed a prospective study to investigate the feasibility of combined FDG-SPECT and whole-body acquisition in the diagnostic work-up of breast tumors applying visual analysis. We studied 50 patients with breast tumors of unknown histology. RESULTS: All malignant diseases were accurately detected in tumors > 2.3 cm, while the smallest FDG-positive lesion was 1.4 cm. In a subgroup of these patients, quantitative evaluation (tumor-to-back-group ratios) was added, which improved the sensitivity. Lymph node metastases were accurately indicated in 9 of 13 patients, while the detection of distant metastases depended on the location and size. False-positive FDG scans were observed in inflamed tissue, in a rapidly growing phylloides tumor and in supposedly healthy breasts. CONCLUSION: These results are comparable with prior investigations of other groups using PET. Therefore, FDG-SPECT and whole-body acquisition may be an adequate and less expensive technique to meet the increasing demand of FDG examinations.

Breast Neoplasms↗

[Comparison of miniplate and lag screw osteosynthesis in treatment of collum fractures].

The question whether- and if by which means-operative reconstruction of condylar process fractures is appropriate is still unresolved. This study was initiated to compare osteosynthesis of low dislocated and/or luxated condylar fractures by means of miniplates or lag screws according to Eckelt. 22 patients participated, 16 being treated with miniplate osteosynthesis, 6 with lag screws. Investigation concentrated on the parameters TMJ-function (side shift in dynamic and static occlusion, maximum interincisal distance, impairment of pro- and laterotrusion), radiologic post-operative fragment position, intra- and postoperative complications, and evaluation by the patients. Miniplate osteosynthesis showed better results leading in 80% to an unimpaired TMJ function compared to 50% of the lag screw group. Miniplate osteosynthesis was performed faster. No intra- or postoperative problems occurred in contrary to the lag screw, where one fracture of the screw intra- and one post-operatively were noted. Even if the numbers are too small for statistical calculations, trends are shown favouring miniplate osteosynthesis for operative reconstruction of condylar fractures.

Adolescent↗

[Falloposcopy for preoperative evaluation before microsurgery].

In order to optimize the preoperative evaluation prior to microsurgery falloposcopy was performed in 105 patients using the Imagyn-System. In 28% of the patients the indication for operative intervention was confirmed. The pregnancy rate in the group of patients with normal falloposcopy pattern was 69% whereas a rate of only 17% was registered in patients with intratubal pathology. The rate of ectopic pregnancies was 2%. We conclude that the preoperative use of falloposcopy will be beneficial during evaluation of microsurgery candidates.

Adult↗

Angiotensinogen gene M235T polymorphism is not associated with diabetic nephropathy. The Diabetic Nephropathy Study Group.

BACKGROUND: There is agreement that a family history of hypertension (HT), is a predictor for the risk of diabetic nephropathy (DN) in patients with type 2 diabetes, and possibly also type 1 diabetes. It follows that genes related to the risk of hypertension must also be considered candidate genes for DN. The 235T allele of the angiotensinogen gene was found to be related to primary HT. METHODS: To examine whether it is predictive for DN as well, we examined the angiotensinogen gene polymorphism in 230 healthy local controls, 423 patients with type 1 diabetes (n = 180 with DN; n = 243 without DN) and 663 patients with type 2 diabetes (n = 310 with DN; n = 353 without DN). The angiotensinogen gene M235T polymorphism was determined using PCR amplification. RESULTS: The following results were obtained (i) no significant difference of genotype distribution (type 1: MM/MT/TT (%) 27.6/57.2/15.2 vs 27.2/56.1/16.7 (P = 0.92); type 2; MM/MT/TT (%) 31.7/48.2/2/20.1 vs. 32.9/46.8/20.3 (P = 0.93) or allele frequencies (type 1: M 0.56 vs. 0.55 (P = 0.795); type 2; M 0.56 vs. 0.56 (P = 0.86)) was found, between diabetic patients with or without DN, (ii) no difference was found between normotensive and hypertensive diabetic patients. CONCLUSION: The data argue against a role of the angiotensinogen gene M235T polymorphism in the manifestation of diabetic nephropathy or hypertension in diabetic patients.

Adult↗

[Outcome of structured asthma education in childhood and adolescence].

From 1988 onwards inpatient asthma training courses have been conducted in Berlin and Osnabrück. A controlled study on asthma training was carried out from 1990 to 1992 at both centres with the support of the Robert Bosch Foundation. In the first intervention group a subsequent training course of 6 months' duration was conducted with the inclusion and participation of the relevant family doctors in addition to the main training course. Scrutiny of the result was done before (T1), directly after (T2) and 12 months subsequent to the training course (T3). Improvements are seen in somatic data or cost-relevant data (emergency referral to the hospital or family physician, inpatient hospital periods, referral because of mild obstruction, days of non-attendance in school due to illness, severity of asthma, incidence of symptoms, stress endurance in sports). There is also a marked improvement in the self-assessment ability of the children and in the management of asthma, as well as a decrease in the asthma-specific feeling of anxiety. Self-reliance and independence, as well as early intervention, are improved as seen by the parents, whereas on the other hand unfavourable factors such as arguments on the proper asthma therapy are diminished. Especially with regard to confidence in controls on the state of health or disease there are significant changes that are more marked in the group subjected to subsequent training than in the group without such additional training, compared with the control group. Structured asthma training exercises a strongly positive effect on the daily management of asthma bronchiale by the families on different planes of coping with the disease. These effects are enhanced by subsequent aftercare by the family physician. Intensive care in the asthma outpatient wards alone does not sufficiently modify the factors contributing to good coping with the disease.

Absenteeism↗

A fraction enriched in a novel glucocorticoid receptor-interacting protein stimulates receptor-dependent transcription in vitro.

Glucocorticoids influence numerous cell functions by regulating gene activity. The glucocorticoid receptor (GR) is a ligand-activated transcription factor and, like any other transcription factor, does not modulate gene activity just by binding to DNA. Interaction with other proteins is probably required to enhance the establishment of a functional transcription initiation complex. To identify such proteins, we analyzed the in vitro interaction of the glucocorticoid receptor bound to a double glucocorticoid response element with nuclear proteins and describe here three interacting proteins with different molecular weights. One of them, which we named GRIP 170 (GR-interacting protein), was purified and microsequenced, and it turned out to be an unknown protein. When tested in a cell-free transcription assay, the fraction highly enriched for GRIP 170 does not influence basal promoter activity but does enhance GR induction.

Carrier Proteins↗

Neurofibromatosis 2 gene in human colorectal cancer.

Colon cancers commonly have allelic losses of chromosome 22q, which suggests the presence of a tumor suppressor gene on 22q. The candidate tumor suppressor gene on 22q is the neurofibromatosis 2 (NF2) gene. Using single strand conformation polymorphism (SSCP) analysis, we screened 24 pairs of colorectal cancer and adjacent normal mucosa, as well as 10 colon cancer cell lines from non-NF2 patients, for mutations in the coding sequence of the NF2 gene. Two SSCP variants, one in exon 14 and another one in exon 16, were detected in two of the sporadic colorectal cancers, but not in adjacent normal mucosa samples. Sequencing of these variants in one tumor detected an A-to-G transition in bp 1459 of the NF2 cDNA, resulting in the change of Ile to Val at codon 487 of merlin, the NF2 protein product. The other tumor showed a 2-bp (CT) deletion in the intronic sequence of the alternatively spliced exon 16. These results suggest that the NF2 gene is probably involved in some colorectal tumors, but is not the critical chromosome 22q tumor suppressor gene involved in colon tumorigenesis.

Base Sequence↗

The interaction of DNA duplexes containing 2-aminopurine with restriction endonucleases EcoRII and SsoII.

Oligonucleotides containing 2-aminopurine (2-AP) in place of G or A in the recognition site of EcoRII (CCT/AGG) or SsoII (CCNGG) restriction endonucleases have been synthesized in order to investigate the specific interaction of DNA with these enzymes. Physicochemical properties (CD spectra and melting behaviour) have shown that DNA duplexes containing 2-aminopurine exist largely in a stable B-like form. 2-Aminopurine base paired with cytidine, however, essentially influences the helix structure. The presence of a 2-AP-C mismatch strongly reduces the stability of the duplexes in comparison with the natural double strand, indicated by a biphasic melting behaviour. SsoII restriction endonuclease recognizes and cleaves the modified substrate with a 2-AP-T mismatch in the centre of the recognition site, but it does not cleave the duplexes containing 2-aminopurine in place of inner and outer G, or both. EcoRII restriction endonuclease does not cleave duplexes containing 2-aminopurine at all. The two-substrate mechanism of EcoRII-DNA interaction, however, allows hydrolysis of the duplex containing 2-aminopurine in place of adenine in the presence of the canonical substrate.

2-Aminopurine↗

Impact of metabolic activity of beta cells on cytokine-induced damage and recovery of rat pancreatic islets.

The influence of beta cell activity on cytokine-induced functional and structural impairments as well as the ability of those damaged cells to recover were investigated. Rat islets cultured for 4 days in the presence of 5, 10, and 30 mmol/l glucose were exposed to interferon-gamma (IFN, 500 U/ml) and tumor necrosis factor-alpha (TNF, 250 U/ml) for the last 24 h. After cytokine removal islets were allowed to recover spontaneously in culture medium containing 10 mmol/l glucose for a further 7 days. Cytokines significantly inhibited insulin release into culture medium, insulin storage, glucose-stimulated insulin secretion, protein, and DNA synthesis. In the presence of cytokines there was a six- to eightfold increase in nitrite production by the islets. The functional impairments were more pronounced in metabolically stimulated beta cells. In addition, cytokines caused membrane alterations as indicated by increased spontaneous chromium-51 release. The cytokines specifically induced the synthesis of two proteins (72 and 88 kDa, respectively). By immunoblotting, the 72-kDa protein was identified as heat shock protein. After a 1-week recovery period, insulin storage and stimulated insulin secretion of cytokine-treated islets were still significantly diminished. However, protein and DNA synthesis of cytokine-exposed islets returned to pre-exposure levels. In conclusion, high beta cell activity increases islet susceptibility to TNF+IFN. Cytokine-induced, long-lasting, inhibitory effects are primarily directed to beta-cell-specific functions, while general vital cell functions clearly recover after cytokine removal. The induction of certain proteins and the increased protein synthesis and replication rate after cytokine removal might reflect activated repair processes.

Animals↗

Signs and symptoms of carbamazepine overdose.

Carbamazepine (CBZ) has been successfully employed in a variety of neurological and psychiatric disorders. The side-effects of CBZ treatment have been extensively studied. As little is known about the symptoms and prognosis of CBZ overdose, our objective was to identify the factors relevant to its prognosis. In a retrospective study of 427 cases, we analysed the distribution of age, sex, total CBZ dose, CBZ plasma level, frequency of symptoms and their association with outcome. In those patients who recovered, coma, somnolence, cerebellar syndrome and epileptic seizures were the most common manifestations of CBZ overdose. In fatal courses coma, epileptic seizures, respiratory depression and respiratory arrest ranked highest. Cardiac arrhythmias and other cardiovascular complications were rare. In 41 of 307 patients (13%) in whom outcome was reported, intoxication was fatal. The occurrence of seizures and CBZ doses exceeding 24 g proved to be important indicators of a fatal outcome. The course of intoxication seems to be more benign in patients aged below 15 years.

Adolescent↗

No association of converting enzyme insertion/deletion polymorphism with immunoglobulin A glomerulonephritis.

It has been recently reported that in type 1 diabetes the insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme gene is associated with the presence of diabetic nephropathy. Tissue angiotensin I-converting enzyme is determined by I/D polymorphism, and it has been speculated that in diabetes differences of local angiotensin II availability determine the risk of renal disease. Since angiotensin II is thought to play an important role in the evolution of renal disease in general, we tested whether genotype distribution of the I/D polymorphism is also different in patients with immunoglobulin A-glomerulonephritis (IgA-GN). Furthermore we compared IgA-GN patients with (1) stable renal function or (2) terminal renal failure to investigate a potential role of the I/D polymorphism in the renal prognosis. We examined 122 patients with biopsy-confirmed IgA-GN who had stable renal function and 82 dialysis-dependent or transplanted patients with biopsy-confirmed IgA-GN. Furthermore, in 134 healthy individuals used as controls we analyzed the DNA for normal distribution of genotypes and allele frequencies. The polymorphic region was amplified using polymerase chain reaction with specific primers. Alleles were detected on 2% agarose gels. Genotype distributions and allele frequencies were not significantly different between controls and patients with IgA-GN and stable renal function. Furthermore, no significant difference in genotype distribution was detected between patients with IgA-GN and stable renal function compared with patients with IgA-GN and end-stage renal failure, although a trend for a higher frequency of DD-homozygotes was noted in the latter group (P = 0.07).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

An unusual case of central nervous system cryptococcosis.

Opportunistic infections of the central nervous system (CNS) in immunocompromised patients often represent a diagnostic and therapeutic challenge due to the variety of possible infectious agents causing CNS disease. We report the case of a severely immunocompromised 43-year-old woman presenting with headache, confusion, abnormal CSF findings (cell count 237/mm3 with 50% eosinophils and elevated protein), multiple contrast enhancing lesions on CT and MRI in the basal ganglia, and serologic findings compatible with latent or reactivated toxoplasmosis with high IgA and IgG antibody titers against Toxoplasma gondii in whom a final diagnosis of CNS cryptococcosis was made. This case illustrates the considerable difficulties in the differential diagnosis of opportunistic CNS infection in the immunocompromised host. We conclude from our report that (1) the diagnosis of toxoplasma encephalitis should not be based on serological findings but rather be proven by either PCR, mouse inoculation or brain biopsy, (2) CNS cryptococcosis can be associated with marked CSF eosinophilia and multiple cryptococcomas, and (3) cryptococcomas can persist on CT and MRI despite successful antifungal treatment.

Adult↗

Association of ACE gene polymorphism and diabetic nephropathy? The Diabetic Nephropathy Study Group.

In patients with type 1 diabetes an association has been found between an insertion/deletion (I/D) polymorphism in the gene for angiotensin I converting enzyme and the presence of diabetic nephropathy. Our objective was (i) to assess this association in a large cohort of patients with type 1 diabetes and (ii) to examine whether this finding also applies to type 2 diabetes. We examined 247 patients with type 1 diabetes of more than 10 years duration (135 patients > or = 20 years): Nephropathy was present in 114 and absent in 133 patients. Furthermore we separately analyzed 455 patients with type 2 diabetes of more than 10 years duration (158 patients > or = 20 years). Nephropathy was present in 247 and absent in 208 patients. Nephropathy was defined by confirmed presence of albuminuria > 30 mg/day (or > 20 micrograms/min). The I/D polymorphism was analyzed with PCR technique and alleles were visualized on 2% agarose gels after ethidium staining. Allele frequencies in the overall diabetic population did not differ significantly from the normal population. Distribution of genotypes was not significantly different between type 1 patients with and without nephropathy (P = 0.377). Also, no significant difference in genotype distribution was found between type 2 diabetic patients with and without nephropathy (P = 0.948). We conclude that no significant association between I/D polymorphism and nephropathy was demonstrable in either type 1 or type 2 diabetes, despite considerable statistical power of the patient sample and adequate duration of diabetes for nephropathy to become manifest.

Adult↗

Inhibition of gap junctional communication by polyunsaturated fatty acids in WB cells: evidence that connexin 43 is not hyperphosphorylated.

Polyunsaturated fatty acids have attracted much interest due to their wide spectrum of biological activities which include the modulation of gap junctional communication (GJC). Since gap junctions play critical roles in maintaining the functional integrity of organs and tissues, and loss of intercellular communication is associated with a number of pathological conditions, we investigated the effects of the n-6 and n-3 series of polyunsaturated fatty acids and their derivatives on GJC in WB cells as determined by the ability of Lucifer Yellow-loaded cells to transfer the dye to neighbouring recipient cells. Studies were also conducted to investigate the possible mechanisms of action of the fatty acids. Treatment of cells with 10 microM arachidonic acid (20:4 n-6) resulted in a rapid and transient loss of communication competence. The response to 20 microM 20:4 (n-6) was prolonged (> 210 min) but was readily reversible by washing the cells with fatty acid-free bovine serum albumin. Cells which had regained their communication competence responded to further additions of 20:4 (n-6). The fatty acids, 18:3 (n-6), 20:5 (n-3), 22:6 (n-3) and the 15-hydroxy- and the 15-hydroperoxy-derivatives of 20:4 (n-6) were also powerful inhibitors of GJC, while 23:4 (n-6) was a relatively weak inhibitor. The saturated 20 carbon fatty acid, 20:0, and the methyl ester of 20:4 (n-6) were without effect. This illustrates the importance of unsaturation and the carboxyl group as structural requirements for activity. 20:4 (n-6)-induced inhibition of dye transfer was not attenuated by pretreating the cells with either phorbol-12-myristate-13-acetate (PMA) or indomethacin, suggesting that regulation of gap junctional permeability by 20:4 (n-6) in WB cells was neither dependent on PMA-responsive isozymes of protein kinase C nor required the metabolism of the fatty acids by cyclo-oxygenase. However, the effect of 20:4 (n-6) was antagonized by preincubating WB cells with either nordihydroguaiaretic acid or (+/-)-isoproterenol and isobutylmethyl-xanthine. Western blot analysis of connexin 43 (Cx43), the major gap junctional protein expressed in these cells, revealed no detectable changes to the electrophoretic mobility of Cx43 even after 60 min of incubation in the presence of 20:4 (n-6). As expected, other inhibitors of gap junctional permeability including epidermal growth factor, phorbol ester or lysophosphatidic acid induced a retardation in the mobility of Cx43, indicating an enhancement in the phosphorylation of Cx43 protein.(ABSTRACT TRUNCATED AT 400 WORDS)

1-Methyl-3-isobutylxanthine↗

Fluid mechanics of the stagnation point flow chamber and its platelet deposition.

The interaction of flow and thrombus generation often is a crucial question for the engineer working in the field of artificial organs. However, this interaction is only incompletely known, and quantitative data under well-defined experimental conditions are especially rare. These can be attained with the stagnation point flow chamber. This flow model applies platelet-rich plasma (PRP) as fluid. Its flow conditions are assessed with the help of computational fluid mechanics. In addition, the concept of the boundary layer is introduced, which permits assessment of the platelet flow along the wall. The results of the experiment indicate that platelets are deposited at a defined shear rate.

Animals↗