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Biomedical subjects

A Gillessen

Publications and source records attributed to A Gillessen.

18 recordsLinked to original sources

Gastric cancer in pregnancy: do pregnancy, age or female sex alter the prognosis? Case reports and review.

The coincidence of gastric cancer and pregnancy is a rare event. By literature research of the last three decades only 31 cases from outside Japan were identified including two own patients. The analysis of these and another 61 cases from Japan revealed the same predominance of poorly differentiated diffuse carcinomas with peritoneal and lymphatic metastases as in other young patients (<40 years). The survival rate is not obviously affected by pregnancy, young age or female sex. Experimental and epidemiological data suggest a protective effect of oestrogen against the induction of (intestinal) gastric cancer, while the cancer growth itself seems to be enhanced. Oestrogen receptors (ER) are found in about 22% of gastric cancer cells, especially in the poorly differentiated type. In contrast to target organs like the breast, ER in gastric cancer seem to be a sign of tumour adaptation involving e.g. the pathway of the epidermal growth factor. The results of treatment with anti-oestrogen are controversial in experimental and clinical settings. Due to the very common epigastric complaints early diagnosis of gastric cancer is even more difficult in pregnancy, so that early gastroscopy is advisable in patients on risk. Main effort should be given, however, to primary prevention.

Adult

[Intramural pseudodiverticulosis of the esophagus. Diagnosis on second look].

HISTORY: Case 1. A 56-year-old man had experienced increasing dysphagia for 6 months, accompanied by a weight loss of 20 kg. A stenosing oesophageal carcinoma was suspected. Case 2. A 82-year-old man had been suffering intermittently from nausea for some years but had maintained his weight (80 kg; height 173 cm). Endoscopy 4 months before this admission had revealed a duodenal ulcer; its treatment briefly improved the symptoms. INVESTIGATIONS, DIAGNOSIS AND TREATMENT: Endoscopy in case 1 detected a severe oesophageal stenosis which could not be passed, and its cause could not be ascertained despite biopsy, barium swallow and computed tomography. After bougie dilatation an endoscope was finally passed and the typical picture of oesophageal pseudodiverticulosis (OPD) seen. In case 2, endoscopy at first indicated only marked Candida oesophagitis. But after antimycotic treatment a second endoscopy revealed OPD. No treatment is known nor necessary since OPD causes no clinical symptoms unless there are complications. CONCLUSIONS: OPD, a rare condition, presents in various ways, both in its symptoms and at endoscopy. In case of oesophageal stenosis of unknown cause or Candida oesophagitis repeat endoscopy my be necessary to establish the true diagnosis: OPD should be included in the differential diagnosis.

Aged

Vitamin supplementation during weight reduction--favourable effect on homocysteine metabolism.

Moderately elevated homocysteine concentrations, reflecting deficiency of some nutritional factors required for homocysteine metabolism (folate, vitamin B-6, vitamin B-12) and/or less severe genetic defects, are common in the general population. Several studies have indicated the role of homocysteine as an independent risk factor for vascular disease. A pilot study published recently suggested that plasma homocysteine levels increase during weight reduction in slightly overweight, otherwise healthy subjects (group A). We examined a comparable group of 13 overweight subjects (group B) using a standardised caloric intake and defined vitamin supplementation (Medyn: folate 0.2 mg/ vitamin B-68.0 mg/ vitamin B-120.010 mg three times the day orally) to determine the effect of weight reduction on serum homocysteine levels and to compare the results with those of the pilot study. Mean body weight declined from 87.0 +/- 20.2 to 84.2 +/- 20.1 kg (P < 0.05) in group A and 85.7 +/- 11.3 to 82.5 +/- 9.9 kg (P = 0.049) in group B. Serum homocysteine levels rose from 7.9 +/- 2.0 to 8.7 +/- 2.3 mumol/l (P < 0.0001) in group A and decreased from 8.19 +/- 1.73 to 7.35 +/- 0.88 mumol/l (P = 0.0022) in group B. No correlation was found between the changes in body weight and in homocysteine levels (r = 0.02 in group A, r = 0.18 in group B). Additionally, no correlation was found between serum folate levels and changes in homocysteine levels (r = 0.03 in group A, r = 0.09 in group B). The results suggest that an adequate oral vitamin-supplementation protects against increased homocysteine production during weight reduction.

Adult

[Intraductal ultrasound in the pancreaticobiliary duct system].

BASIC PROBLEM AND OBJECTIVE OF STUDY: The power of resolution of conventional imaging methods is too low for the diagnosis of very small pancreaticobiliary tumours. High-frequency ultrasound transducers (20 MHz), adapted to the dimensions of the pancreaticobiliary systems (2 mm diameter), make intraductal ultrasound examination possible during endoscopic retrograde cholangiopancreatography (ERCP). In a prospective study the invasiveness and diagnostic value of intraductal ultrasound (IDUS) was compared with ERCP, endosonography (ES) and computed tomography (CT). PATIENTS AND METHODS: During ERCP in 51 consecutive patients an intraductal ultrasound transducer was introduced into the pancreaticobiliary duct system, the results being compared with those obtained with the other imaging modalities and histopathological findings, if available. RESULTS: IDUS of the pancreatic and bile duct systems is a rapid, simple and reliable method during ERCP and provides valuable additional information on periductal tissues. In the diagnosis of carcinoma of the pancreas its sensitivity was 75% (six of eight cases), that of ERCP 37% (3/8), ES 50% (4/8) and CT 37% (3/8). In the diagnosis of biliary tract tumour the sensitivity of the different modalities (in the above order) was 89% (8/9), 78% (7/9), 33% (3/9) and 33% (1/3). Specificity was 67% (2/3), 67% (2/3), 67% (2/3) and 33% (3/9); predictability 89%, 88%, 75% and 60%. CONCLUSIONS: The use of small ultrasound catheter transistor system in the biliary and pancreatic ducts, introduced during ERCP, is technically simple and has few complications. It is a valuable addition to ERCP in the precise diagnosis of small pancreaticobiliary lesions.

Adult

Simultaneous restitution of matrix and cells in gastric ulcer: use of a combined in-situ hybridization and immunohistochemistry technique applicable to paraffin-embedded tissue.

The restoration of gastric tissue after ulceration involves cellular and matrix components. Our aim was to investigate the kinetics of collagen expression and cellular proliferation in an animal model of gastric ulcer. To demonstrate the expression of type I and IV collagen mRNAs by proliferating cells, a method combining in-situ hybridization and immunohistochemistry was devised. In order to avoid the disadvantages of radioisotopes, digoxigenin-labeled RNA-riboprobes were utilized and combined with single-step immunohistochemistry. This method proved sensitive enough to detect type I and IV procollagen mRNA transcripts in the submucosal area beneath the ulcer crater or adjacent to the ulcer rim. In addition, a subset of cells transcribing either procollagen type I or IV RNA was concomitantly positive for proliferating cell nuclear antigen by immunohistochemistry. Focal proliferation of cells simultaneously expressing extracellular matrix components may therefore occur in the gastric submucosa after ulceration, starting as soon as 3 days after the insult and continuing for several weeks. The devised method of combined in-situ hybridization and immunohistochemistry can be used with standard paraffin-embedded tissues, yields results within 2 days, and avoids radioisotopes.

Acetic Acid

Gastric ulcer healing in the rat: kinetics and localisation of de novo procollagen synthesis.

BACKGROUND AND AIMS: To gain further insight into the role of the extracellular matrix during healing of peptic ulcers, sequential changes of procollagen expression were studied over 30 days of ulcer healing. MATERIALS AND METHODS: Procollagens alpha 1 (I), alpha 1 (III), and alpha 1 (IV) RNA and their polypeptides were assessed in acetic acid induced rat gastric ulcers by in situ hybridisation and immunohistochemistry. RESULTS: Three days after ulcer induction, intense hybridisation signals were obtained with all probes, with procollagen alpha 1 (I) showing the highest transcript levels. Procollagen gene expression remained elevated up to day 15, but was reduced to initial low levels on day 30. Immunohistochemical staining documented increased deposition of the three procollagen types parallel to their respective transcript levels, again with type I showing the earliest and the most prominent deposits. The highest procollagen transcript levels were found in the intact submucosa surrounding the ulcer margins, followed by the muscularis propria and the serosa, with the lamina propria exhibiting the lowest transcript levels. CONCLUSION: The procollagens studied are regulated differentially at the transcriptional and post-transcriptional levels. The early onset and long duration of procollagen expression as well as the involvement of all layers of the gastric wall points to their central structural and functional role in gastric ulcer healing.

Acetic Acid

Expression of type I and IV collagen mRNAs in healing gastric ulcers--a comparative analysis using isotopic and non-radioactive in situ hybridization.

The sensitivity and practicability of in situ hybridization methods utilizing isotopic or non-radioactive labeling were compared. The aim of this study was to determine whether digoxigenin-labeled riboprobes are as sensitive as 35S-labeled probes to detect changes in type I and IV procollagen expression in an animal model of rat gastric ulcer. Both labeling and detection methods yielded similar results, with a superimposable signal distribution in the specimens. High levels of procollagen type I and IV transcripts were observed in spindle-shaped cells, presumably fibroblasts or myofibroblasts, localized in the ulcer base and rim. The increased expression of these collagen types suggests a remarkable upregulation of collagen expression during the healing of gastric ulcers. Liver tissue adhering to perforated ulcers displayed signals related to non-parenchymal cells, with hepatocytes demonstrating no detectable transcripts of type I or IV collagen genes. Due to the identical pattern of signal distribution by both hybridization techniques it is concluded that non-radioactive in situ hybridization is of value in monitoring highly expressed genes and yields results similar to those achieved with radioactive probes. In these cases, non-radioactive techniques are preferable because they are performed more rapidly and do not require handling of isotopes.

Animals

Eradication of Helicobacter pylori restores the inhibitory effect of cholecystokinin on postprandial gastrin release in duodenal ulcer patients.

Helicobacter pylori infection may be associated with duodenal ulcer (DU) and accompanied by enhanced gastrin release but the mechanism of this H pylori related hypergastrinaemia in DU patients is unclear. Cholecystokinin (CCK) has been implicated in the feedback control of gastrin release and gastric acid secretion in healthy subjects. This study therefore investigated if CCK participates in the impairment of postprandial gastrin release and gastric secretion in six DU patients. Tests were undertaken with and without elimination of endogenous CCK by loxiglumide, a selective CCK-A receptors antagonist, before and after eradication of H pylori with triple therapy (omeprazole, amoxicyllin, bismuth). In H pylori positive DU patients, the post-prandial decline in pH (with median pH 3.5) was accompanied by a pronounced increment in plasma gastrin but the administration of loxiglumide did not affect significantly this postprandial rise in plasma gastrin and gastric pH profile. After eradication of H pylori, the plasma gastrin concentration was reduced while the median postprandial pH was significantly increased (median pH 4.3). The administration of loxiglumide resulted in significantly greater increase in postprandial plasma gastrin and greater decrease in pH (median pH 3.1) in these patients. This study shows that (a) infection with H pylori is accompanied by an enhanced gastrin release and gastric acidity in DU patients, (b) the failure of loxiglumide to affect plasma gastrin or gastric acid secretion in H pylori infected DU patients could be attributed, at least in part, to the failure of endogenous CCK to control gastrin release and gastric secretion by releasing somatostatin, and (c) the test with loxiglumide may be useful in the identification of patients with impaired feedback control of gastrin release and gastric secretion resulting from infection with H pylori.

Adult

Evidence of de novo collagen synthesis in healing human gastric ulcers.

BACKGROUND: The fibrillar collagens, types I and III, have been demonstrated in healthy human gastric mucosa as well as in the submucosa of gastric ulcer edges, where they are remarkably increased. METHODS: To verify the occurrence and activity of de novo collagen synthesis, we examined gastric biopsy specimens from six patients with antral ulcers and six normal controls. By means of in situ hybridization, using a 35S-labeled RNA probe, we could localize the specific procollagen mRNA for type-I collagen. RESULTS: In normal gastric mucosa this mRNA was expressed by only a very limited number of cells, whereas at the ulcer edges the specific signal could be demonstrated in a large number of submucosal cells. CONCLUSION: These results suggest a substantial role of fibroneogenesis in the process of gastric ulcer healing.

Adult

Diffuse esophageal spasm: a malfunction that involves nitric oxide?

OBJECTIVE: As recently suggested, nitric oxide (NO) may play an important role in the regulation of esophageal motility, being partly responsible for the latency period and latency gradient between the onset of a swallow and contractions of esophageal circular smooth muscles. Diffuse esophageal spasm appears to be a classical example in which the mechanisms normally responsible for the physiologic timing of the contractions occurring in the esophageal body after swallowing are disturbed. METHODS: Five patients (one male and four female; age, 18-48 years) with symptomatic esophageal spasm were give glyceryl trinitrate (GTN) intravenously in gradually increasing doses or L-arginine on two separate occasions and underwent manometric measurements of esophageal motility after wet swallows, using a multilumen perfused catheter system (Synetics Medical, Stockholm, Sweden). The amplitude, duration, and propagation of the contractions and the latency period were analyzed, using specially designed software. Additionally, during the GTN infusion period arterial blood pressure was measured every 5 min, RESULTS: GTN infusion given at a dose of 100 to 200 micrograms/kg-h intravenously caused the occurrence of and a dose-dependent elongation of the latency period after swallowing. The mean amplitude of the contractions did not show any significant alterations, whereas the mean duration of the contractions decreased significantly, from 11.2 +/- 4.8 sec to 5.4 +/- 0.8 sec. These effects were accompanied by significant alleviation of symptoms during swallowing. Interestingly, no adverse side effects such as headache or flush were observed at any dose of GTN. The blood pressure did not show any changes during the studies in any of the five patients. Administration of L-arginine (300 mg/kg-h intravenously) did not cause any significant alterations of motility pattern or alleviation of dysphagia. CONCLUSIONS: 1) NO may play an important role in the control of human esophageal motility, being involved in the mechanisms responsible for the timing of propulsive contractions in the body after swallowing; 2) GTN may to be of benefit in the treatment of diffuse esophageal spasm in symptomatic patients; and 3) patients with diffuse esophageal spasm may have a malfunction in endogenous NO synthesis and/or degradation.

Adolescent

Collagen mRNA and fibronectin are increased in healing gastric ulcers in man.

The fibrillar collagens, types I and III, have been demonstrated in healthy human gastric mucosa as well as in the submucosa of gastric ulcer edges, where they were found to be remarkably increased. In order to verify the occurrence and activity of de novo collagen synthesis, we examined gastric biopsy specimens from six patients with antral ulcers and six normal controls. By means of in situ hybridization, using a 35-S-labelled RNA probe, we could identify the specific procollagen mRNA for type I collagen. Fibronectin was stained immunohistochemically employing specific polyclonal antibodies. In normal gastric mucosa, procollagen type I mRNA was expressed by only a very limited number of cells while at the ulcer edges the specific signal could be demonstrated in a large number of submucosal cells. Fibronectin as marker of newly built connective tissue was found to be markedly increased in the submucosa of healing gastric ulcers as compared to normal controls. These results suggest a substantial role of fibroneogenesis in the process of gastric ulcer healing.

Adult

[Acute sigmoid diverticulitis--current diagnosis].

Acute sigmoid diverticulitis may present in different forms. Firstly, symptomatic diverticulosis and acute diverticulitis have to be differentiated to allow for the proper selection of treatment. In the initial phase of diagnostic procedures in addition to clinical features a few laboratory data, plain X-ray films of the abdomen and abdominal ultrasound are helpful to obtain information about the potential presence of perforation, abscess, tumor masses and the structure of the colonic wall. Computed tomography is capable to answer most of the questions in the diagnostic work-up of acute diverticulitis. On the other hand, contrast barium enema provides little additional information and should be considered as contraindicated in acute diverticulitis. If at all, water-soluble contrast media should be employed. Endoscopy has its place in the differential diagnostic evaluation of severe bleeding and suspected tumor, but should be reserved for these limited indications.

Acute Disease

[The significance of cytokines and extracellular matrix for stomach ulcer healing].

The healing process of gastric ulcers is regulated by many factors. Cytokines play a central role in the different stages of healing. In the early stage of inflammation, TNF-alpha and interleukins regulate cell-migration and -proliferation. In the ulcer's base revascularisation is stimulated by b-FGF, collagen synthesis by TGF-beta. The reepithelialization is mediated by EGF, which accelerates ulcer healing in animal models, while TGF-alpha is involved in mucosal protection. The extracellular matrix (ECM) is important for the stability and quality of the ulcer scar, as known from dermatological experiments. An increase of collagen types I and III in healing gastric ulcers was demonstrated recently, which might illuminate the particular role of ECM proteins for the gastric ulcer healing process.

Animals

Myofibroblast-like cells produce mRNA for type I and III procollagens in chronic active hepatitis.

In chronic active hepatitis the rate of collagen biosynthesis is largely determined by intracellular mRNA concentrations. To localize procollagen mRNA-producing cells, we investigated biopsy specimens from five patients with hepatitis B surface antigen-positive chronic active hepatitis and five patients without liver disease by in situ hybridization. We used type I and III procollagen cDNAs for transcription to (35S)-labeled probes. Parallel sections were stained with anti-actin monoclonal antibodies. Our results show that cells in which collagen synthesis is ostensibly enhanced can be localized by in situ hybridization of procollagen mRNAs. These cells were also anti-actin-positive in parallel sections and were localized in areas of inflammatory cell infiltration and necrosis. We conclude that myofibroblast-like cells may express procollagen mRNAs in chronic active hepatitis. Moreover, in situ hybridization may be a valuable diagnostic tool for providing additional morphologic information on the degree of fibrogenesis activity.

Actins

Distribution of collagen types I, III, and IV in peptic ulcer and normal gastric mucosa in man.

The quality of peptic ulcer healing does not only mean complete epithelial restitution of the mucosal surface but also adequate repair of the underlying connective tissue. To obtain more information about the metabolism of extracellular matrix proteins in gastric mucosa and submucosa, we investigated biopsy specimens from six patients with antral peptic ulcers and six normal controls by staining of collagen types I, III, and IV with an immunofluorescence technique. In normal mucosa we found a certain amount of collagen types I and III in equal distribution and almost no collagen type IV. In contrast, there was a remarkable increase of collagen types I and III in peptic ulcers predominantly located at the ulcer edges. These results are compatible with the view that extracellular matrix proteins play some part in the ulcer healing process.

Collagen

[Identification of procollagen mRNA in chronic active hepatitis B].

In situ hybridization is a tool for staining intracellular procollagen mRNAs with specific probes. Our study shows the amounts of procollagen mRNAs of types I and III to be increased in liver biopsies of five patients with chronic active hepatitis B as compared with five healthy controls. Parallel staining employing anti-smooth-muscle-actin antibodies was able to identify myofibroblast-like cells at the same localization where procollagen mRNAs were found. Consequently, these transformed Ito-cells might be the procollagen-producing cells.

Actins