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Biomedical subjects

K J Hengels

Publications and source records attributed to K J Hengels.

At least 19 recordsLinked to original sources

Influence of lansoprazole on intragastric 24-hour pH, meal-stimulated gastric acid secretion, and concentrations of gastrointestinal hormones and enzymes in serum and gastric juice in healthy volunteers.

Twelve healthy volunteers (6 females, 6 males) between 26 and 36 years of age were enroled in this double-blind, randomized, placebo-controlled, three-way cross-over study. The objective was to determine the influence of lansoprazole (Agopton, Takeda Pharma GmbH, Aachen), a novel proton pump inhibitor, in doses of 30 and 60 mg, on the intragastric pH, on meal-stimulated gastric acid secretion and on the concentration of gastrointestinal hormones and enzymes in serum and gastric juice. Active drug or placebo had to be taken as single daily morning doses on an empty stomach for 7 days. Each wash-out period between drug application periods was 2 weeks long. Lansoprazole induced a dose-related increase in intragastric pH as well as a relevant reduction of basal acid output, meal-stimulated acid output and meal-stimulated secretion volume. 60 mg lansoprazole was significantly superior to 30 mg in increasing intragastric pH. The basal secretion volume in volunteers on 30 and 60 mg lansoprazole were lower than in volunteers on placebo. Serum gastrin and serum pepsinogen concentrations increased in a dose-dependent manner. Pepsin output and pepsin activity in gastric juice were slightly decreased in volunteers on 30 mg lansoprazole and markedly suppressed in volunteers on 60 mg lansoprazole 2 h after meal stimulation. Intrinsic factor concentration increased in volunteers on lansoprazole with a clear dose relationship. The evaluation of laboratory data and reported nonserious adverse events proved the relative safety of this new antiulcer agent.

2-Pyridinylmethylsulfinylbenzimidazoles

The epidemiology of low serum pepsinogen A levels and an international association with gastric cancer rates. EUROGAST Study Group.

BACKGROUND/AIMS: Low serum levels of pepsinogen A are indicative of chronic atrophy, a risk factor for gastric cancer. This study investigated the relationships between low pepsinogen A levels, Helicobacter pylori seropositivity, and gastric cancer rates in 17 populations worldwide. METHODS: In each center, about 200 randomly selected subjects (50 male and 50 female, aged 25-34 and 55-64 years) provided serum samples for pepsinogen analysis and H. pylori serology. RESULTS: Cumulative gastric cancer rates were associated with the prevalence of low pepsinogen A levels in men (coefficient, 0.15 [P = 0.06] for mortality; coefficient, 0.36 [P = 0.01] for incidence) but not women. The prevalence of low pepsinogen A levels was also correlated with H. pylori seropositivity in the older age group (r = 0.55; P = 0.02). Low pepsinogen A levels were significantly more common in the older group (7.5% vs. 2.1% in the younger group; P < 0.001), among women (5.5% vs. 4.1% in men; P = 0.04), and among nonsmokers (5.8% vs. 2.9% in current smokers; P = 0.001). CONCLUSIONS: Low pepsinogen A levels are more common in areas with a high seroprevalence of H. pylori and in men in areas with high rates of gastric cancer. The prevalence of low pepsinogen A levels increases with age, but the excess in women and nonsmokers could reflect factors other than gastric pathology.

Adult

Effects of Helicobacter pylori on histamine and carbachol stimulated acid secretion by human parietal cells.

Helicobacter pylori (H pylori) infection is associated with hypo, normal, and hypersecretory disorders of the gastric mucosa. Pathophysiological pathways by which H pylori interacts with acid secretion are still unclear. The effects of H pylori on (14C) aminopyrine uptake by human parietal cells were examined as an indirect assay for acid secretion. Isolated oxyntic glands were stimulated with submaximal concentrations of histamine or carbachol and incubated with sonicates of different H pylori strains. Omeprazole and sonicates of Campylobacter jejuni served as positive and negative controls, respectively. Two of four H pylori strains reduced hydrochloric acid sequestration within the parietal cells significantly and in a dose dependent manner in up to 80%. Interaction with acid secretion may therefore constitute a factor contributing to a distinct pathogenicity of H pylori strains.

Aminopyrine

Effect of Helicobacter pylori on dbc-AMP stimulated acid secretion by human parietal cells.

This study examines the effect of different H.p. strains (A-D) on dbc-AMP stimulated acid secretion by human parietal cells in vitro. H.p. strains A and D reduced acid secretion dose-dependently between 20 and 80%. In contrast, H.p. strains B and C had little or no effect. We conclude that H.p. strains vary in their ability to suppress acid secretion, and that the site of inhibition lies beyond the c-AMP level, possibly involving the K+H(+)-ATPase of the parietal cell. Interference with acid secretion may facilitate H.p. colonization of the stomach and may prove to be an important pathogenetic factor.

Aminopyrine

[Visceral leishmaniasis with gastrointestinal involvement in a 30-year-old HIV infected patient].

We report the case of a 30-years old HIV-infected woman who suffered from recurrent fever up to 41 degrees C, loss of appetite, loss of 8 kg body weight and swelling of the cervical and inguinal lymph nodes. The diagnostic work-up revealed infection with leishmania in gastric and duodenal biopsies. The parasites were also found in the inguinal lymph nodes and in the bone marrow of the patient. According to patient's history the infection was acquired on a holiday in southern spain. The patient was treated with pentavalent antimony in combination with interferon gamma. Visceral leishmaniosis in immuno-suppressed patients is discussed and therapeutic approaches are described.

AIDS-Related Opportunistic Infections

[Sclerosing cholangitis with papillary stenosis in an HIV-infected patients with Cryptosporidium infection].

We report the case of a 46-year old HIV-infected patient who suffered from severe recurrent diarrhoea for 18 months. In stool cultures cryptosporidiae were identified. The cryptosporidial enteritis was unresponsive to therapy. In the further course of cryptosporidial infection the patient developed HIV-associated cholangitis with increasing upper abdominal pain, progredient laboratory cholestasis and morphological changes indicating posthepatic cholestasis. Papillary stenosis with erosive papilitis caused by cryptosporidia was diagnosed. Sphincterotomy significantly improved the clinical status of the patient. Cholangitis with associated crytosporidial infection in a HIV-infected patient ist discussed and necessary diagnostic and differential therapeutic approaches are described.

AIDS-Related Opportunistic Infections

Hereditary hemorrhagic telangiectasia associated with multiple pulmonary arteriovenous malformations and juvenile polyposis.

A case with multiple telangiectases of the gastrointestinal tract that caused recurrent bleeding is reported. The hemorrhagic telangiectases were associated with multiple pulmonary arteriovenous malformations leading to significant right-to-left shunting and in combination with an atrial septal defect to progressive right heart failure and finally to the death of the patient. Juvenile polyps and tubulovillous adenomas of the colon were removed. Hemicolectomy had to be performed because of carcinomatous infiltration originating from adenomatous epithelium developing in a juvenile polyp. The pathogenesis of hemorrhagic telangiectases is unknown. It is an important source of intestinal hemorrhage and may be complicated by the additional finding of arteriovenous fistulas and the occurrence of recurrent juvenile, adenomatous epithelium containing colonic polyps eventually leading to carcinoma. The present case suggests an inherited association of hemorrhagic telangiectases and juvenile polyposis. It also highlights that rapidly progressive right-to-left shunting rather than hemorrhagic anemia my be the major determinant of the course of the disease.

Adenomatous Polyposis Coli

Histogenetical investigations on adenocarcinomas of the esophagogastric junction. An immunohistochemical study.

The presence of Pepsinogen II (PG II), gastral mucin (2B5), CA 19-9, BW 494 and Cytokeratin 20 (CK 20) was investigated in 69 adenocarcinomas of the esophagogastric junction (15 carcinomas in Barrett's esophagus, 9 distal esophageal carcinomas, 31 carcinomas of the cardia and 14 subcardial carcinomas). Evidence of gastric differentiation (expression of Pepsinogen II and/or gastric mucin) was found in more than 50% of the Barrett's carcinomas and the carcinomas of the cardia, but only in 20% of the subcardial carcinomas. High rates of antigen expression were found for the "intestinal" markers CA 19-9 (between 55.5% and 100%) and BW 494 (between 42.9 and 86.7%). CK-20 expression was detected to a significantly higher degree in Barrett's carcinomas (73.3%) than in the other groups (between 29% and 44.4%). These data indicate that the distribution of adenocarcinomas with gastric and/or intestinal differentiation at the esophagogastric junction forms a continuum without clear-cut borders.

Adenocarcinoma

Local gastric and serum amoxicillin concentrations after different oral application forms.

The high recolonization rate after monotherapy of Helicobacter pylori-positive gastritis may be due to insufficient local drug concentrations. To investigate the role of local diffusion, we measured levels of amoxicillin, a drug with good in vitro activity against H. pylori, in the mucosa and serum. One gram of amoxicillin was given to healthy volunteers as a tablet (n = 6) or as water-dissolved, fizzing "Tab" (n = 6). Gastroscopy with biopsies from the antrum, corpus, and fundus was performed at 30, 60, and 90 min. Concentrations in the mucosa were measured after homogenization with the agar diffusion method using Bacillus subtilis as the biological indicator. Serum samples, taken basally and every 15 min, were analyzed by high-pressure liquid chromatography. Drug levels in the fundus and corpus remained far below those in the antrum for both application forms. The highest concentrations were reached after 30 min, with bactericidal levels in the antrum in two of six subjects who took the tablet form and five of six subjects who used Tabs. At 60 and 90 min, almost all values were below the MBC for 90% of the strains tested. The concentrations in serum, however, rose continuously, to reach a maximum after 75 or 90 min. These results show that incomplete elimination may be due to subbactericidal concentrations of antibiotics with high in vitro efficiency at the desired site of action in vivo and that local diffusion in the mucosa is essential for therapeutic effectiveness against H. pylori.

Administration, Oral

Peptic ulcer bleeding: medical and surgical point of view. Results of a prospective interdisciplinary multicenter observational study. DUSUK Study Group.

Various treatment policies and clinical disciplines compete for the treatment of bleeding peptic ulcer. In a prospective multicenter and interdisciplinary study performed during a 1-year period at ten hospitals in Düsseldorf, all patients admitted for peptic ulcer bleeding were recorded. The characteristics of patients admitted to surgical and to medical departments, the distribution of endoscopic treatment, indications for surgery, type of surgical procedures, and outcome were investigated. In the study period 387 bleeding peptic ulcers were recorded. Of these patients 82% were primarily admitted to medical and 18% to surgical departments. No differences in terms of severity of ulcer disease or bleeding activity were noted between the groups of medical and surgical patients. However, accompanying or underlying diseases were detected more often in patients admitted to medical departments. Endoscopy treatment was performed in the majority of patients with arterial spurting bleeding (88%) or a visible vessel (80%). Injection therapy with epinephrine or polidocanol was mainly used (78%). In 16% of cases the patients underwent operation; 44% of the patients primarily admitted to a surgical department were operated (medical departments, 10%). About half of the operated patients underwent emergency surgery; in the majority of cases resections were performed (gastric ulcer, 76%; duodenal ulcer, 56%). Overall mortality was 11%, with no difference between surgical and medical patients. A high mortality was observed in the subgroup of patients with late recurrent bleeding (27%). It is concluded that for optimal treatment of peptic ulcer bleeding intensive cooperation between physicians and surgeons is necessary, and that agreed and evaluated treatment policies are needed.

Aged

Association of Crohn's disease and multiple sclerosis. Is there a common background?

Crohn's disease (CD) and multiple sclerosis (MS) share familial occurrence and similar epidemiological traits. Apart from one report of both diseases occurring among consanguineous relatives, only three cases of CD and MS in the same patient have thus far been described. We describe here a 29-year-old woman in whom MS developed in 1983 and CD in 1989. The MS may have been the result of a strongly HLA-associated genetic predisposition, while the additional development of CD may have been due either to genetic factors or perhaps simply to chance. Viewing this case in the context of epidemiological data, however, we suggest that the development of CD and MS is based on one or more common genetic factors acting in conjunction with other presumably exogenous factors and triggering HLA antigens to lead to one disease or the other.

Adult

DNA aneuploidy in Crohn's disease and ulcerative colitis: results of a comparative flow cytometric study.

DNA ploidy and S-phase fractions were assessed by flow cytometry in colonic biopsy specimens from 28 patients with ulcerative colitis and 51 with Crohn's disease. Whereas only diploid DNA histograms were found in Crohn's disease and control subjects, three patients with ulcerative colitis exhibited DNA aneuploidy. In one case, aneuploidy was associated with low grade dysplasia. S-phase fractions were higher in ulcerative colitis (mean (SD) 17.8 (7.7)%) than in Crohn's disease (13.1 (4.6)%) or control subjects (14.2 (4.6)%), but did not correlate with either disease activity or duration in any group. In this study, aneuploidy was associated exclusively with ulcerative colitis, even in the absence of dysplasia. In view of the epidemiological differences in malignant colonic transformation between ulcerative colitis and Crohn's disease, this study suggests that flow cytometry may help to identify individuals with an increased cancer risk in ulcerative colitis.

Aneuploidy

Incidence and pattern of peptic ulcer bleeding in a defined geographical area. DUSUK Study Group.

Despite the introduction of effective medical treatment for peptic ulcer disease, no decrease in the incidence of bleeding has been observed. Unfortunately, most incidence studies rely on a questionable case ascertainment and poor data. We therefore conducted a prospective study, to achieve an unbiased estimate of incidence and pattern of peptic ulcer bleeding in Düsseldorf (Germany). In a 1-year period all patients with endoscopically verified peptic ulcer bleeding who were admitted to the departments of internal medicine or surgery in nine hospitals or seen by nine general practitioners offering endoscopic service were included in the study. Incidence rates were calculated in accordance with sociodemographic variables and expressed per 100,000 person-years of observation. The overall incidence of peptic ulcer bleeding was 51.4, with almost even rates for gastric (26.5) and duodenal (24.9) ulcer. Age was associated with an increased likelihood of bleeding in gastric ulcer patients of 19 per decade from about 40 years onwards (duodenal ulcer, 15). The incidence was about twice as high in men as in women (relative risk = 1.9). The pattern of peptic ulcer bleeding was similar in gastric and duodenal ulcers with regard to ulcer size, multiple lesions, and bleeding activity at endoscopy. However, patients with gastric ulcer bleeding had significantly more often accompanying or underlying diseases. No significant differences were observed between gastric and duodenal ulcer bleeding with regard to nonsteroidal antiinflammatory drug intake and ulcer history. The incidence rates in our study are in the upper range of the literature and comparable to rates from the USA and UK both before and after the introduction of H2 blockers. We hypothesize that the persistently high incidence rate is a superposition of two trends: higher incidences due to a more elderly and diseased population and more NSAID intake, and lower incidences due to effective medical treatment.

Adult

[DNA ploidy and dysplasia in ulcerative colitis--interim analysis of a prospective study].

DNA ploidy and cell cycle phases were evaluated by flow cytometry in colonic biopsy specimens from 107 patients with ulcerative colitis in order to analyse the prevalence of DNA aneuploidy as an indicator of numerical chromosomal aberrations and the cell proliferation in all forms of ulcerative colitis. Whereas G2/M-phase fractions in ulcerative colitis and in controls were comparable (2.7 +/- 1.1% vs. 2.8 +/- 1.1%), S-phase fractions in ulcerative colitis exceeded those of controls (7.5 +/- 3.2% vs. 6.5 +/- 2.3%; p < 0.01). In 28 control patients, only diploid DNA histograms existed. Single or multiple aneuploid stem lines were detected in 10 patients with ulcerative colitis (9.3%). Aneuploidy was nearly exclusively associated with pancolitis. Dysplasia was present in 13 patients (indefinite: 8; low-grade: 5), of whom 5 patients also showed DNA aneuploidy. 5 patients with non-dysplastic mucosa exhibited DNA aneuploidy. Because dysplasia and DNA aneuploidy can be discordant and might therefore identify different subgroups at risk, flow cytometry might play a role as a valuable complement to histological examination in surveillance programs of ulcerative colitis.

Adult

Assessment of proliferative activity in carcinomas of the human alimentary tract by Ki-67 immunostaining.

The monoclonal antibody (MAb) Ki-67, which is directed against a proliferation-associated nuclear antigen, was used to measure tumor proliferation in 165 carcinomas of the esophagus, stomach, colon and rectum with an indirect immunoperoxidase technique. The percentage of Ki-67-positive tumor cells (Ki-67 index) was evaluated with the point-counting method. The Ki-67 index in gastric cancers (mean, 24.8%; standard deviation, 11.1%) was significantly lower than in tumors of the esophagus (35.7 +/- 12.6%), colon (37.6 +/- 15.2%), and rectum (34.3 +/- 16.4%). A wide range of the Ki-67 index (5.9-75.3%) could be observed within the various tumor types. In recurrent colorectal carcinomas, the Ki-67 index significantly increased to 51.9%. The Ki-67 index was independent of pathologic (e.g., TNM-stage, grading, tumor volume, tumor site) and clinical variables (age and gender of the patients). A marked heterogeneity of Ki-67 expression within different tumor stages was noted. Statistically significant regional variations in tumor proliferation existed between different areas within the same tumor.

Adult