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Biomedical subjects

F Schulte

Publications and source records attributed to F Schulte.

At least 19 recordsLinked to original sources

The relationship between binge eating disorder and non-purging bulimia nervosa.

AIMS: To further investigate the differentiation between non-purging bulimia nervosa (BN-NP) and binge eating disorder (BED), particularly as concerns weight-shape overconcern affecting self-esteem, a core belief to both anorexia and bulimia nervosa. METHODS: Twenty-five female subjects with BN-NP and 25 female subjects with BED, consecutively referred to the Eating Disorder Unit of the DPPhNB, were administered the BEDCI, the EDI-2 and the BUT. RESULTS: BED patients had a higher BMI (35.5 vs. 23.8 kg/m2, p<0.0001) and were slightly older than BN-NP ones. Weight-shape concerns as one of the main/the most important things influencing self-esteem were reported by 68% of BN-NP patients and 62.5% of BED ones. Age at onset of binge-eating, weight-cycling, overall impairment due to the eating behavior, sexual harassment, depressive and substance abuse comorbidity were equally represented in the two groups of patients. BN-NP patients scored higher than BED ones as regards EDI drive for thinness (p<0.05) and BUT weight phobia (p<0.05), with these scores significantly related to differences in BMI (p<0.0005 and p=0.012). Weight-shape overconcern influencing self-esteem was predictive of an earlier onset of binge-eating (p<0.05) and higher scores at the BUT weight phobia, and body image concerns (p<0.05). CONCLUSIONS: Differences between BED and BN-NP seem to be more of degree than type and there seems little value in the separation between BED and BN-NP based on weight-shape concerns that substantially impair self-esteem. This construct seems core to both disorders and plays a substantial role in triggering and maintaining the binge-eating cycle.

Age of Onset↗

Second-line treatment of advanced colorectal cancer with a weekly simultaneous 24-hour infusion of 5-fluorouracil and sodium-folinate: a multicentre phase II trial.

BACKGROUND: A weekly continuous 24-h infusion therapy with 5-fluorouracil (5-FU) preceded by a 2-h infusion of calcium folinate (CA-FA) was shown to be an effective first- and secondline treatment in advanced metastatic colorectal cancer. Substitution of CA-FA by the new formulation sodium folinate (S-FA) allows the simultaneous i.v. administration of folinic acid with 5-FU in one pump. PATIENTS AND METHODS: From 1999 to 2001, 42 patients with metastatic colorectal cancer after pre-treatment with a 5-FU bolus regimen were recruited in 5 centres to receive weekly 24-h infusions of 5-FU (2,600 mg/m2) and S-FA (500 mg/m2) dissolved in one pump for 6 weeks as second-line treatment. The treatment cycle was repeated after a 2-week rest period. RESULTS: 106 6-week cycles (median 2, range 1-6 per patient) were administered during the study. The median followup was 22 months. Out of 42 patients, 1 (2%) achieved complete remission, 3 (7%) partial remission, and 31 (74%) no change. Median time to tumour progression was 5.7 months (95% CI: 4.1-6.5). The median survival was reached at 14.7 months (95% CI: 11.0-22.0). Among major toxicities, NCI-CTC grade III/IV diarrhoea occurred in 8/42 (19%), grade III hand-foot-syndrome in 5/42 (12%) and grade III/IV stomatitis in 3/42 (7%) patients. CONCLUSION: Similar to conventional 24-h 5-FU + CA-FA treatment, the combination with S-FA in second-line therapy induced 9% objective responses and stopped tumour progression in 74%. The simultaneous administration of both, S-FA and 5-FU over 24 h dissolved in one pump is convenient, safe and effective as second-line treatment for patients with colorectal cancer.

Adult↗

Contribution of lymphatic drainage system in corneal allograft rejection in mice.

PURPOSE: To modulate aqueous outflow via the uveoscleral pathway and to determine its influence on corneal graft survival in mice. METHODS: BALB/c mice received corneal transplants from C3H mice and were placed randomly in three treatment groups: saline, pilocarpine or latanoprost. Three further groups received adjuvant systemic and topical corticosteroids. The kinetics of infiltrating lymphocytes, neutrophils and macrophages in the transplants was investigated in an additional 96 animals. Cytokine expression in the submandibular lymph nodes and spleen was investigated using in-situ hybridization and RNAse protection assay. Tracer experiments were conducted using 99mTC colloidal albumin Nanocoll; count rates were determined in the submandibular lymph nodes, spleen and blood following both subconjunctival and intracameral injection. RESULTS: Neither pilocarpine nor latanoprost had any influence on aqueous outflow or allograft survival in mice. Neutrophils and macrophages dominated the infiltrating cells 11 days postoperative in both treated and untreated grafts. On postoperative day 13, a greater increase in lymphocytes than in other cell groups was observed in allogeneic grafts. Following allogeneic transplantation, 1% of lymphocytes in ipsilateral submandibular lymph nodes were positive for IFN-gamma. Tracer studies revealed a 16% aqueous outflow via the uveoscleral routes following intracameral injection of Nanocoll; this was increased by 97% with subconjunctival injection. CONCLUSION: Our data confirm the existence of functional lymphatic drainage via the uveoscleral pathway and conjunctiva in the mouse. Cells within the ipsilateral submandibular lymph node respond to stimuli upstream. This reaction could potentially be manipulated to improve graft survival.

Animals↗

The effect of corticosteroid and cyclosporin A on murine corneal allograft rejection.

BACKGROUND: The immunomodulatory T-helper type 1 (Th1) cytokine interferon-gamma (IFN-gamma) was measured in serum and cornea to ascertain its general contribution to corneal graft rejection and to establish a rational basis for the decision for or against systemic therapy. METHODS: Eight groups of differently treated BALB/c (H-2d) mice received a C3H (H-2 k) corneal graft. There was one saline-treated control group and two groups that received intramuscular cyclosporin A (CsA) for 14 or 40. Three groups received systemic or topical, systemic plus topical corticosteroid treatment, which was combined with CsA in two further groups. To measure the IFN-gamma level by enzyme-linked immunosorbent assay (ELISA), blood was taken by heart puncture and corneae were excised at the limbus. RESULTS: Five days of systemic corticosteroid and 14 days of CsA had no significant effect on graft survival. A 40-day CsA treatment and a 40-day combined corticosteroid treatment significantly prolonged graft survival. An 80-day topical corticosteroid treatment produced additional prolongation. IFN-gamma could not be detected (limit of detection 25 pg/ml) in any of the serum samples, while significantly increased amounts of IFN-gamma were detected in the supernatants of the corneal tissue 13 or 14 days after allogeneic but not syngeneic corneal graft, corresponding to 9.5 pg, 5.1 pg and 1.8 pg per cornea. CONCLUSION: The detection of Th1 cytokines in the cornea but not the serum of mice at the time of allograft rejection is in accordance with the finding of long-lasting dose-dependent immunosuppression of topical steroids and the inefficacy of short-term systemic CsA and corticosteroids.

Animals↗

The HTR1 gene is a dominant negative mutant allele of MTH1 and blocks Snf3- and Rgt2-dependent glucose signaling in yeast.

Saccharomyces cerevisiae HTR1 mutants are severely impaired in the uptake of glucose. We have cloned dominant HTR1 mutant alleles and show that they encode mutant forms of the Mth1 protein. Mth1 is shown to be involved in carbon source-dependent regulation of its own, invertase and hexose transporter gene expression. The mutant forms block the transduction of the Snf3- and Rgt2-mediated glucose signals upstream of the Rgt1 transcriptional regulator.

Adaptor Proteins, Signal Transducing↗

Characterization of a glucose-repressed pyruvate kinase (Pyk2p) in Saccharomyces cerevisiae that is catalytically insensitive to fructose-1,6-bisphosphate.

We have characterized the gene YOR347c of Saccharomyces cerevisiae and shown that it encodes a second functional pyruvate kinase isoenzyme, Pyk2p. Overexpression of the YOR347c/PYK2 gene on a multicopy vector restored growth on glucose of a yeast pyruvate kinase 1 (pyk1) mutant strain and could completely substitute for the PYK1-encoded enzymatic activity. PYK2 gene expression is subject to glucose repression. A pyk2 deletion mutant had no obvious growth phenotypes under various conditions, but the growth defects of a pyk1 pyk2 double-deletion strain were even more pronounced than those of a pyk1 single-mutation strain. Pyk2p is active without fructose-1,6-bisphosphate. However, overexpression of PYK2 during growth on ethanol did not cause any of the deleterious effects expected from a futile cycling between pyruvate and phosphoenolpyruvate. The results indicate that the PYK2-encoded pyruvate kinase may be used under conditions of very low glycolytic flux.

Allosteric Regulation↗

Glucose uptake and metabolism in grr1/cat80 mutants of Saccharomyces cerevisiae.

Glucose repression in the yeast Saccharomyces cerevisiae designates a global regulatory system controlling the expression of various sets of genes required for the utilization of alternate carbon sources. In a screen, designed for the selection of mutants with reduced glycolytic flux we obtained isolates which were shown by complementation of the cloned wild-type gene to be allelic to the glucose repression mutants grr1/cat80/cot2 previously described. We demonstrate that the grr1 lesion lead to a concentration-dependent decrease in glycolytic flux on glucose. It is very likely that this is caused by a significant decrease in the expression of various genes encoding hexose transporters (HXT1,3) leading to a reduced glucose-uptake rate. In contrast, expression of the maltose permease gene (MAL11) and maltose utilization is normal. There is indirect evidence that grr1 affects the uptake of amino acids, and others have shown that the sugar-induced transport of divalent cations is impaired. These effects are not glucose-specific. We suggest that Grr1, a putative cytoplasmic protein, has a central function in the sensing of nutritional conditions for a variety of unrelated substances, and that relief from glucose repression may be a corollary of this defect in sensing.

Biological Transport↗

Endoscopic and bioptic diagnosis of malignant non-Hodgkin's lymphoma of the stomach.

Experience in the endoscopic and bioptic diagnosis of malignant non-Hodgkin's lymphomas of the stomach in 66 patients is reported all of which were B cell lymphomas originating in the mucosa associated lymphoid tissue (MALT) type. Two types of tumor could be differentiated by their appearance on endoscopy (two patients had both types). An exophytic type (n = 24) was easily recognized as malignancy on endoscopy and the diagnosis confirmed by endoscopic biopsy (mean of 1.2 endoscopic-bioptic examinations). It could be classified according to the Palmer classification; 50% were low-grade malignancies and 50% high-grade malignancies. Resection (n = 17) showed wall penetration beyond the muscularis propria in 70%. An infiltrative type (n = 44) was difficult to diagnose by means of endoscopy and biopsy (mean of 2.9 endoscopic-bioptic examinations); in one case a histological diagnosis could only be established on surgery. A classification system is suggested for this type (I--elevated, II--flat, III--cavitated). Most of these lymphomas were low-grade malignancies (77%), and limited to the mucosa and submucosa (79% of 34 resected cases). It is concluded that attention should be paid especially to the infiltrative type of gastric lymphoma which is difficult to diagnose and to differentiate from other gastric conditions such as ulcers and erosions, but which is most often found at an early stage and has a better prognosis. Complete tumor resection (R0) was achieved in 49 of 51 patients undergoing surgery (96%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Long-term results of treatment of malignant non-Hodgkin's lymphoma of the stomach.

Our experience with 66 endoscopic-bioptic diagnosed malignant non-Hodgkin's lymphomas (NHL) showed that in most of them (57 of 66 patients) a tumor stage IE or IIE was present. All 57 primary gastric lymphomas were B-cell-lymphomas arising from the mucosa-associated lymphoid tissue (MALT). After curative primary gastric resection in stage IE and IIE the 5-year survival rate was 81%, and the 5-years lymphoma-related survival rate was 88%. These results are superior to those reported in the literature. The following two points are probably of importance for improving the prognosis: early diagnosis made possible by better knowledge of the infiltrative-flat type of tumor growth (38 out of 57 patients, including 23 cases in which infiltration was limited to mucosa and submucosa = "early lymphoma"), and extensive preoperative staging. The infiltrative-flat type, which is difficult to diagnose endoscopically, usually shows low-grade malignancy on histology (76%; in early lymphoma 83%) and has an excellent prognosis when submitted to surgery. In our experience the question as to whether additional treatment by chemotherapy and/or radiotherapy improves the prognosis of NHL of the stomach remains unanswered and further studies are needed.

Combined Modality Therapy↗

Adenoma and carcinoma of the duodenum and papilla of Vater: a clinicopathologic study.

In a retrospective study (1982-1990), 12 adenomas, 35 carcinomas of the papilla of Vater, and 21 duodenal adenomas were examined. All patients had endoscopicbioptic examinations (5-10 forceps biopsies, snare biopsy or forceps-biopsies after endoscopic sphincterotomy). Special attention was paid to malignant transformation of adenomas and of residual adenomatous tissue in surgical resected cancer. Follow-up data were gained by reexamination or questionnaires. In papillary adenomas, an adenocarcinoma was found in 30% at operation or by follow-up. In 41.2% of the operated cases, residual adenomatous tissue was found, more often in well-differentiated adenocarcinomas than in other histological types. A transformation from duodenal adenomas to adenocarcinomas was seen less frequently (9.5%). Therefore, the risk of malignancy in ampullary adenomas is greater than elsewhere in the duodenum. In eight of 11 patients (72.7%) with duodenal adenomas, one or more simultaneously developed colonic adenomas were found (in four cases a Gardner syndrome not known before). We conclude that there is strong evidence that most ampullary and duodenal carcinomas develop in preexisting adenomas, with an adenoma-cancer sequence similar to that accepted for colorectal carcinoma. This has to be kept in mind for diagnostic as well as therapeutic reasons. When either an adenoma of the ampulla or duodenum is diagnosed, colonoscopy is mandatory to find or exclude colonic adenomas. In patients with familiar adenomatosis, the duodenum and the papilla of Vater have to be examined endoscopically.

Adenocarcinoma↗

[Quo vadis endoscopic sphincterotomy?].

The results of a study from 25 centers (= Series I: 1974-1980) covering 9041 endoscopic sphincterotomies (EST) were compared with those of a second study from 20 centers (= Series II: 1981-1986) covering 10177 cases. A change was seen in the indications during the past 5 years: While choledocholithiasis after cholecystectomy remained the main indication, EST is performed with increasing frequency in patients with common bile duct stones having their gallbladder in situ as a definitive method with low complications (only 0.61% emergency cholecystectomies): Circumscript papillary stenosis became quite a rare indication. The success rate of EST because of choledocholithiasis was not improved in spite of new techniques (stone-free common bile ducts in I: 84.06%, in II: 83.97%). The complication rate decreased from 7.55% to 5.04%. Types of complications did not change. Only perforations decreased, the rates of bleeding, cholangitis and pancreatitis remained the same. The mortality diminished from 1.12% to 0.60% (the figures remained twice as high in papillary stenosis than in choledocholithiasis). There was no change in the results of EST during the past 5 years. Follow-up studies using radiological methods show worse results (recurrent stones in II: 21.2%, in I: 5.8%, stenosis of EST in II: 6.1%, in I: 3.1%): Late results of EST because of papillary stenosis are still worse compared to those of choledocholithiasis. Therefore, in spite of increasing experience and introduction of new techniques the method became safer, but the therapeutic results did not appreciably improve.

Ampulla of Vater↗

[Endoscopic biopsy diagnosis of malignant lymphoma of the stomach and early stomach lymphoma].

From 1978 to 1988 a malignant lymphoma of the stomach was diagnosed endoscopic-bioptically in 47 patients. In 41 patients it was a primary gastric lymphoma, in 6 a generalized lymphoma. In 20 cases an advanced gastric lymphoma was present which was diagnosed endoscopic-bioptically without problems. In 27 cases, however, lymphomas showed polymorphous lesions which did not look tumorous. In such cases the lymphomas were found in an early stage and bioptic verification was difficult. On an average three bioptic series were needed for histological proof. In 16 lymphomas of this group the malignant infiltration was limited to mucosa/submucosa on operative resection specimens ("early gastric lymphomas") The endoscopic appearance of these early lymphomas was: thickening mucosa-folds (2 cases), extended areas of "regenerative mucosa" and granular pattern (6 cases), mainly multiple irregular ulcerations (8 cases). The above mentioned endoscopic findings are strongly suspected for an early gastric lymphoma and should be clarified by, if needed repeated, bioptic series.

Adult↗

[The prognosis of carcinoid tumors of the stomach].

Follow-up examinations were carried out in 55 patients with small carcinoid tumours in the stomach (diameter 0.5-1.7 cm). For the most part, the tumours were located within the body and fundus of the stomach, with only 3 being found in the antrum. Thirty-five of the 55 patients (63.6%) had multiple gastric carcinoids, while in 46 patients (83.6%) concomitant chronic atrophic gastritis was also present. Eight patients were treated surgically, while 47 patients were merely kept under endoscopic/bioptic surveillance. In 34 out of 40 patients in whom the diagnosis had been established more than 6 months previously (longest observation period 13 years), follow-up findings were available (7 surgical patients, 27 non-operated patients). The patients submitted to surgery (average follow-up period 3.5 years) are alive and free of complaints between 1 and 9 years post-op; no metastases have occurred, but a recurrent tumour has developed in a single patient. Among the 27 non-operated patients (average follow-up period 3.6 years), 3 have died of diseases unrelated to the carcinoid tumours, in none of the other patients has there been any change in the findings. On the basis of these results it is concluded that, in carcinoid tumours of the stomach with a diameter of less than 1.0 cm, surgical treatment is not absolutely necessary, and that, in comparison with the risks represented by surgical mortality and post operative morbidity, regular endoscopic/bioptic follow-up can be considered to be adequate.

Adult↗