PubMed HealthSearch

Biomedical subjects

T Günther

Publications and source records attributed to T Günther.

At least 19 recordsLinked to original sources

Characterization of Mg(2+) efflux from rat erythrocytes non-loaded with Mg(2+).

Non-Mg(2+)-loaded rat erythrocytes with a physiological level of Mg(2+)(i) exhibited Mg(2+) efflux when incubated in nominally Mg(2+)-free media. Two types of Mg(2+) efflux were shown: (1) An Na(+)-dependent Mg(2+) efflux in NaCl and Na gluconate medium, which was inhibited by amiloride and quinidine, as was Na(2+)/Mg(2+) antiport in Mg(2+)-loaded rat erythrocytes; and (2) an Na(+)-independent Mg(2+) efflux in sucrose medium and choline Cl medium, which may be differentiated into SITS-sensitive Mg(2+) efflux at low Cl(-)(o) (in sucrose) and into SITS-insensitive Mg(2+) efflux at high Cl(-)(o) (in 150 mmol/l choline Cl).

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo

Multimodal imaging of residual function and compensatory resource allocation in cortical atrophy: a case study of parietal lobe function in a patient with Huntington's disease.

In a case of Huntington's disease (HD) with dementia and pronounced parieto-frontal atrophy, the functional state of the affected regions was investigated using functional magnetic resonance imaging (fMRI) and fluorodeoxyglucose-positron emission tomography (FDG-PET). It was observed that although parietal areas showed extensive atrophy and reduced resting glucose metabolism, the patient performed with similar accuracy but with longer response time in a visuospatial task compared with healthy control subjects. At the same time, the blood oxygen level-dependent (BOLD) fMRI signal in these areas, which are involved in visuospatial processing, showed a similar task-dependent modulation as in control subjects. The signal amplitude (signal percent change) of the task-dependent activation was even higher for the HD patient than in the control group. This residual functionality of parietal areas involved in visuospatial processing could account for the patient's performance in the task concerned, which contrasted with his poor performance in other cognitive tasks. The increased percent-signal change suggests that a higher neuronal effort was necessary to reach a similar degree of accuracy as in control subjects, fitting well with the longer reaction time. We propose that fMRI should be considered as a tool for the assessment of functionality of morphologically abnormal cortex and for the investigation of compensatory resource allocation in neurodegenerative disorders.

Atrophy

[Gastrointestinal stromal tumors--problems in diagnosis and therapy].

Gastrointestinal stromal tumors (GIST), which form a rare group of neoplasias of the gastrointestinal tract, have not yet been fully investigated. Although good progress has been made in their diagnosis, classification of these lesions with regard to their histogenesis and biological behavior remains problematic. Between 1994 and 1998, 18 GIST patients underwere operation in the Department of Surgery. Twelve of these patients (67%) had stromal tumors in the stomach, and six (33%) had intestinal stromal tumors. The primary tumor could be removed in all patients with R0 resection. Six patients developed hematogenous liver metastasis, with the size of their primary tumor exceeding 10 cm. Extrahepatic distant metastases were not found in any case. Lymphadenectomy showed that lymph node metastases did not occur. Histological evaluation was made according to the guidelines of Lewin, Weinstein and Riddell. Currently established therapy is limited to complete surgical resection of the primary tumor and its metastases. Adjuvant or neoadjuvant chemotherapy approaches have failed.

Adult

Role of aging in the expression of Helicobacter pylori gastritis in the antrum, corpus, and cardia.

BACKGROUND: Earlier studies identified a pylorocardial expansion of chronic gastritis. We investigated the age-dependent changes in grading and topography of Helicobacter pylori gastritis. METHODS: Antral, corpus, and cardial biopsy specimens from 216 H. pylori-positive patients with no peptic ulcer disease (PUD), malignancy, or Barrett's oesophagus were evaluated with haematoxylin and eosin and modified Giemsa. The patients were separated into four equal-sized age groups (1, < 46 years; II, 46-56 years; III, 57-68 years; IV, > 69 years). Sydney-system gradings of bacterial density and activity and degree of gastritis were used to calculate gastritis sum scores for age- and biopsy site-dependent comparisons. The prevalence of intestinal metaplasia (IM) and atrophy was also compared. RESULTS: Mean antral sum scores decreased slightly in group IV but were higher than those in the corpus or cardia in all groups (P < 0.05 each). In the corpus mean scores increased in groups II-IV versus group I (P < 0.05 each), and aging was associated with a significant increase in bacterial density and active inflammation. The cardia scores remained virtually constant in all groups and exceeded significantly that in the corpus in group I. IM and atrophy increased with age, occurring more frequently and earlier in the antrum and cardia than in the corpus. CONCLUSIONS: Progression of gastritis with age involves the corpus but not the cardia. Antral inflammation decreases slightly in patients of advanced age.

Adult

Multimodal treatment of neuroendocrine tumors of the pancreas and the ampulla of Vater.

Neuroendocrine tumors are not seen frequently. They are most commonly located in the small bowel including the vermiform appendix. Neuroendocrine tumors of pancreatic origin are extremely rare. Symptoms caused by excessive hormone production by large liver metastases often lead to their diagnosis. Preoperative diagnostics include analysis of specific hormones in serum and urine, ultrasound, CT and somatostatin receptor scintigraphy. Liver metastases of neuroendocrine tumors of the pancreas are common at the time of diagnosis. Curative resection should be performed whenever possible, although patients often benefit from debulking procedures, too. Liver metastases can be subjected to surgical resection, embolization, regional chemotherapy or local procedures such as alcohol injection or cryoablation. As an exception, liver transplantation can be considered in selected cases where radical surgery for the primary tumor could be performed and extrahepatic metastases are not present. Supplementary or alternative options include octreotide and/or interferon-alpha administration. In this article, we report on 6 patients suffering from primary neuroendocrine tumors of the pancreas or the ampulla of Vater who were treated at our department over the past 5 years. In addition, we discuss our own experience with this rare condition in the light of the recent literature.

Adult

Multimodal imaging of residual function and compensatory resource allocation in cortical atrophy: a case study of parietal lobe function in a patient with Huntington's disease.

In a case of Huntington's disease (HD) with dementia and pronounced parieto-frontal atrophy, the functional state of the affected regions was investigated using functional magnetic resonance imaging (fMRI) and fluorodeoxyglucose-positron emission tomography (FDG-PET). It was observed that although parietal areas showed extensive atrophy and reduced resting glucose metabolism, the patient performed with similar accuracy but with longer response time in a visuospatial task compared with healthy control subjects. At the same time, the blood oxygen level-dependent (BOLD) fMRI signal in these areas, which are involved in visuospatial processing, showed a similar task-dependent modulation as in control subjects. The signal amplitude (signal percent change) of the task-dependent activation was even higher for the HD patient than in the control group. This residual functionality of parietal areas involved in visuospatial processing could account for the patient's performance in the task concerned, which contrasted with his poor performance in other cognitive tasks. The increased percent-signal change suggests that a higher neuronal effort was necessary to reach a similar degree of accuracy as in control subjects, fitting well with the longer reaction time. We propose that fMRI should be considered as a tool for the assessment of functionality of morphologically abnormal cortex and for the investigation of compensatory resource allocation in neurodegenerative disorders.

Adult

Long-term results after repair of complete atrioventricular septal defects: analysis of risk factors.

BACKGROUND: We analyzed data from 320 patients to evaluate the impact of different preoperative, operative, and postoperative factors on the outcome after repair of complete atrioventricular septal defect. METHODS: Between October 1974 and December 1995, 320 patients with complete atrioventricular septal defect not associated with major cardiac anomalies were operated on. Two hundred seventy-four patients underwent total repair. Sixty-three patients (23%) were less than 6 months old. One hundred ninety-eight (72.2%) underwent primary repair. Seventy-six patients (27.7%) had a previous palliative operation. RESULTS: Operative mortality in patients who underwent primary repair decreased from 17.6% (1974 to 1979) to 5.0% (1990 to 1995) despite an increase in the number of patients younger than 6 months. In patients undergoing a two-stage procedure operative mortality was 3.9% (late mortality, 7.9%). Young age (<6 months) was an incremental risk factor (p = 0.008) for operative mortality in the early study period. Coarctation of the aorta (p = 0.02) and severe dysplastic left atrioventricular valve (p = 0.001) were associated with a higher risk for operative mortality. Freedom from reoperation at 10 years was 82.5% +/- 3.8%. CONCLUSIONS: In patients with complete atrioventricular septal defect, primary repair is the treatment of choice and can be accomplished with good results. In our experience over a period of more than 20 years, earlier date of operation, young age (<6 months), dysplastic left atrioventricular valve, and coexisting coarctation were incremental risk factors for hospital death. The presence of a previously placed pulmonary artery band did not alter the outcome of repair. The reconstructed atrioventricular valve shows a good and long-lasting performance.

Age Factors

Somatic DNA alterations in breast carcinomas of different lymph-node status by DNA fingerprint analyses.

The purpose of this study was to screen for somatic changes in invasive breast tumors by multilocus DNA fingerprints comparing normal (blood) and malignant tissue samples from 34 patients. The comparison of lymph node-positive and node-negative breast carcinomas was of primary interest. After restriction enzyme digestion with HinfI and HaeIII, altered banding patterns were detected by using the oligonucleotide probe (GTG)5 in 7 of 34 (20.5%) and in 3 of 34 (8.8%) tumors after hybridization with (GACA)4. The overall frequency of changes thus amounted to 29.4%. Because long (GACA)n repeat motifs, generating predominant DNA fingerprint bands, are localized on the short arms of the human acrocentric chromosomes, sequences that are important in breast carcinogenesis may be present in these regions. The overall methylation status of the DNA does not appear to be responsible for DNA fingerprint differences, as can be demonstrated with the restriction endonuclease HaeIII. DNA fingerprint differences did not correlate with tumor grade, stage, and hormone receptor status. Tumors with lymph-node metastases expressed DNA fingerprint differences more frequently.

Aged

The pS2 protein in colorectal carcinomas and metastases.

Expression of pS2 protein in 50 primary tumors, metastases and recurrent tumors of colorectal carcinomas has been analyzed by immunohistochemistry. Sixty percent of the primary tumors were at least focally positive for the antigen. There was no correlation between pS2 expression and histologic grade of the lesions. In contrast, pS2 expression in T4 and T3 tumors was significantly higher than in T2 carcinomas. Immunoreactions in carcinomas with distant metastases (MI) were stronger than in M0 cases. However, this difference did not reach statistical significance. The presence of lymph node metastases did not correlate with pS2 expression. High expression of pS2 in T4 and T3 carcinomas together with the finding of pronounced expression of the antigen at invasion fronts in single cases could be interpreted as a function in tumor cell invasion and motility. However, in metastases and recurrent tumors, pS2 expression did not differ from primary lesions (53% positive lesions). All in all, under consideration of the latter finding in particular and together with the randomly distributed immunopositive tumor cells and cell clusters in the majority of cases, it is more likely that the expression pattern of pS2 in colorectal carcinomas is a result of overall tumor cell heterogeneity.

Carcinoma

Alterations of the p16/MTS1-tumor suppressor gene in gastric cancer.

Deletions, mutations and the functional inactivation of tumor suppressor gene p16 are involved in the genesis of different neoplasias. Little is known about the role of p16 gene alterations in the genesis of gastric carcinomas. This study aimed to detect genetic alterations of the p16 gene in gastric carcinomas. We analyzed p16 gene mutations and the frequency of loss of heterozygosity (LOH) at the p16 locus in 43 gastric carcinomas. PCR-SSCP analysis of exons 1 and 2 revealed only one gene mutation in a carcinoma of the diffuse type. Besides carcinomas of the diffuse, intestinal and the mixed type, we also investigated a small-cell primary gastric carcinoma, which was the only one to show a deletion in the p16 gene. LOH analysis was performed using two polymorphic markers located near the p16 gene (D9S171, D9S162) and a sequence-tagged-site marker (c5.1). Allelic loss was noted in two carcinomas of the diffuse type and in one carcinoma of the intestinal type. Allelic instabilities were found in one tumor of the intestinal type and diffuse type each. Although only five of 43 (11.6%) gastric carcinomas had p16 alterations, tumors of the diffuse type tend to show a higher number of genetic alterations near the p16 locus.

Adenocarcinoma

Specific expression in mouse mesoderm- and neural crest-derived tissues of a human PDGFRA promoter/lacZ transgene.

The platelet-derived growth factor alpha-receptor (PDGFR-alpha) displays a lineage-specific expression pattern in the mouse embryo and is required for normal development of mesoderm and cephalic neural crest derivatives. The purpose of the present study was to demonstrate the in vivo promoter function of genomic DNA fragments representing the 5'-flanking part of the human PDGFRA gene. 2.2, 0.9 and 0.4 kb PDGFRA promoter fragments, ligated to a lacZ reporter gene, were microinjected into fertilized mouse eggs and transgenic mouse lines were established. The expression patterns were basically similar in the 2.2 and 0.9 kb lines and overlapped grossly the endogenous Pdgfra gene expression pattern. The transgenic line with the highest expression level was chosen for detailed analysis. Expression was, as expected, mainly confined to tissues of mesodermal and neural crest origin. No expression was found in epithelial tissues of endo- or ectodermal origin. The promoter fragments were also active in neuroepithelium and in certain neuronal cell types that did not faithfully express PDGFR-alpha mRNA, while they failed to specify reporter expression in PDGFR-alpha expressing O-2A progenitor cells and other glial elements of the central nervous system. Thus, the isolated human PDGFRA promoter contains most but not all of the regulatory elements that are necessary to establish tissue specific gene expression during development.

Animals

Performance of a rapid whole blood test for Helicobacter pylori in primary care: a German multicenter study.

BACKGROUND: Serological rapid whole-blood tests for the detection of H. pylori are presently being promoted for use in primary care. We conducted a multi-center study to investigate the diagnostic accuracy of the Boehringer Mannheim Helicobacter pylori test (BM test), which is identical with the Cortecs Helisal test. PATIENTS AND METHODS: A previous diagnosis of H. pylori, a history of peptic ulcer diseases, or proton-pump inhibitor, bismuth or antibiotic use during the preceding month were exclusion criteria. The BM test was performed prior to endoscopy by 7 primary care physicians, 5 practicing gastroenterologists, or a single physician in the university hospital outpatient service. During endoscopy, antral and corpus biopsies were obtained for histology and rapid urease testing (RUT). H. pylori positivity was defined by histology and/or RUT as reference methods. H. pylori IgG-ELISA was performed additionally. RESULTS: Of the 203 patients included, 151 were H. pylori-positive by reference methods (74.4%). The overall accuracy of the BM test was 77.3%. Eight BM tests were indeterminate, and in the other 195 patients the test performed as follows: sensitivity 80.3%, specificity 81.3%, positive predictive value 92.9%, negative predictive value 57.4%. Using IgG-ELISA as reference, the BM test performance was similar. It also did not differ substantially among the three groups of physicians involved. CONCLUSIONS: We found the performance of the BM test to be insufficiently accurate, as both over- and underdiagnosis of H. pylori infection were not infrequent. This test needs to be improved before its use in primary care can be recommended.

Adolescent

Differing patterns of Helicobacter pylori gastritis in patients with duodenal, prepyloric, and gastric ulcer disease.

BACKGROUND: We investigated the risk relationship between histotopographic patterns of Helicobacter pylori gastritis and peptic ulcer site. METHODS: Three hundred and eighty-three infected patients were classified as having duodenal ulcer (n = 79), prepyloric ulcer (n = 39), gastric (angular) ulcer (n = 28), and no ulcer (n = 237). Antral and corpus biopsy specimens were taken. Sydney system-based scores for bacterial density and activity and degree of gastritis were added to antral and corpus sum scores (SS) (range, 0-9). These were used to categorize the phenotype of gastritis. In addition, the presence or absence of mucosal atrophy was taken into account. The relative risk for ulcer association with these conditions was calculated. RESULTS: High-grade antral (SS > 5) associated with mild to moderate corpus (SS > 5) gastritis increased duodenal (RR = 4.9; confidence interval (CI), 2.8-8.5) and prepyloric ulcer risk (RR = 2.99; CI, 1.4-6.2). High-grade gastritis in the antrum (SS > 5) and corpus (SS > 5) increased gastric ulcer risk (RR = 3.7; CI, 1.6-8.3). Antral atrophy and/or intestinal metaplasia is associated with an increased gastric ulcer risk (RR = 3.3; CI, 1.4-7.8). CONCLUSION: The pattern of H. pylori gastritis may define a risk for peptic ulcer at various sites, but additional factors, not reflected in histology, also contribute to this risk.

Atrophy

The prevalence of Helicobacter pylori gastritis in patients with reflux oesophagitis: a case-control study.

OBJECTIVES: To investigate the prevalence of Helicobacter pylori in patients with erosive oesophagitis in comparison with asymptomatic subjects. DESIGN: Hospital based case-control study. METHODS: Two hundred and nineteen consecutive patients with erosive oesophagitis diagnosed over 2 years were studied. Patients with secondary gastro-oesophageal reflux disease, prior H. pylori eradication therapy, PPI or antibiotics were excluded and two case groups were formed: (1) patients with oesophagitis alone (OEA), and (2) patients with oesophagitis and concomitant peptic ulcer disease (OE&PUD). H. pylori was assessed by antral and corpus mucosa histology and the rapid urease test. Age- and sex-matched controls, who underwent voluntary screening for H. pylori by the 13C-urea breath test, had neither symptoms nor a history of upper gastrointestinal disease. RESULTS: The 130 patients in the OEA group had a prevalence of H. pylori of 38.5% compared with 75.6% in the 41 patients in the OE&PUD group and 88.5% in a subgroup of the latter with duodenal ulcer (26 patients). Infected and non-infected cases showed no significant differences in terms of grade of oesophagitis and incidence of Barrett's oesophagus. The prevalence of H. pylori infection in OEA was similar to that found in matched controls. In OE&PUD the relative risk of H. pylori infection was 3.6-fold higher than in controls [P = 0.0069, 95% confidence interval (CI), 1.401-9.195]. CONCLUSION: The prevalence of H. pylori in oesophagitis without PUD is similar to that of the asymptomatic population with no history of upper gastrointestinal disease. When oesophagitis and PUD occur together, the infection rate is within the range found in PUD alone.

Adult

Intestinal metaplasia at the gastro-oesophageal junction: Helicobacter pylori gastritis or gastro-oesophageal reflux disease?

BACKGROUND: Intestinal metaplasia, whether in the cardia or the distal oesophagus, has been uniformly defined as specialised columnar epithelium, suggesting a relation with Barrett's oesophagus. It is, however, not clear whether the risk factors associated with intestinal metaplasia are identical at both sites. AIMS: To investigate biopsy specimens obtained below the squamocolumnar junction (SCJ) in relation to endoscopic aspect, gastric histology, and clinical presentation. PATIENTS AND METHODS: In 423 patients investigated the endoscopic aspect of the SCJ was classified as unremarkable (group I, n = 315) or suggestive of Barrett's oesophagus (group II, n = 108). Standardised biopsy specimens from the antrum, corpus, and directly below the SCJ were investigated. RESULTS: Intestinal metaplasia was detected at the SCJ in 13.4% of group I patients, where it was significantly associated with gastric intestinal metaplasia (odds ratio (OR) 6.96; confidence interval (CI) 2.48 to 19.54) and H pylori (OR 7.85; CI 2.82 to 21.85), and in 34.3% of group II patients where it was significantly associated with reflux symptoms (OR 19.98; CI 6.12 to 65.19), erosive oesophagitis (OR 12.16; CI 3.86 to 38.24), and male sex (OR 6.25, CI 2.16 to 18.14), but not with H pylori or gastric intestinal metaplasia. CONCLUSION: This study suggests that the pathogenesis of intestinal metaplasia at the SCJ is not uniform: at an endoscopically unremarkable SCJ it is a sequela of H pylori gastritis, but coexisting with endoscopic features of Barrett's oesophagus it is associated with male sex and gastro-oesophageal reflux disease.

Barrett Esophagus

Age and Helicobacter pylori decrease gastric mucosal surface hydrophobicity independently.

BACKGROUND: Gastric mucosal surface hydrophobicity (GMSH) is an essential component of the mucosal defence system that is decreased by Helicobacter pylori and non-steroidal anti-inflammatory drugs (NSAIDs). Gastric ulcers occur predominantly in elderly subjects, and may thus reflect diminished mucosal resistance. AIMS: To investigate whether aging decreases GMSH. PATIENTS: One hundred and twenty patients without peptic ulcer disease were divided into three age groups: I (41 years or below); II (41-64 years); and III (65 years or above). METHODS: Biopsy specimens were taken from the antrum, corpus, and cardia for histology (Sydney system), urease testing for H pylori, and for contact angle measurement of GMSH with a goniometer. The presence of specific H pylori antibodies was checked by immunoblotting. RESULTS: Fifty two patients (43%) were infected, and 68 were uninfected with H pylori. GMSH at all biopsy sites was lower in H pylori infected subjects (p=0.0001), but also decreased with age independently of infection status (p=0.0001). The most notable decrease in GMSH occurred between age groups I and II in those with, and between age groups II and III in those without, H pylori infection. GMSH was greater in antral than in corpus mucosa in both infected (p=0.0001) and uninfected patients (p=0.0003). CONCLUSIONS: A physiological decrease in GMSH with aging may contribute to the risk of ulcer development in the elderly, and may act synergistically with H pylori and/or NSAIDs on gastric mucosal defence.

Adult

Expression of mdm2 and p53 in epithelial neoplasms of the colorectum.

AIMS: To evaluate the respective roles of mdm2 (murine double minute 2) and p53 in the development of colorectal carcinoma. METHODS: Formalin fixed, paraffin wax embedded tissues from 72 sporadic adenomas and 55 carcinomas were investigated by means of immunohistochemistry for mdm2 and p53. RESULTS: mdm2 was expressed weakly in 17 of 72 (23.6%) adenomas and in 14 of 55 (25.4%) carcinomas. p53 was expressed in 19 of 72 (26.4%) adenomas and in 23 of 55 (41.8%) carcinomas. Four adenomas and five carcinomas showed positive staining for both proteins. Overexpression of p53 in adenomas was associated with moderate and severe dysplasia but not with tumour size. No associations were found between the expression of mdm2 and either the degree of dysplasia or tumour size. In carcinomas, neither the expression of p53 nor mdm2 correlated with Dukes's stage, metastasis, or differentiation. No associations were found between the expression of p53 and mdm2 in either adenomas or carcinomas. CONCLUSIONS: Although mdm2 has been reported to be an oncogene, it does not appear to play a major role in the development of colorectal carcinoma.

Adenocarcinoma