HLA DQ2 and/or DQ8 is associated with celiac disease-specific autoantibodies to tissue transglutaminase in families with thyroid autoimmunity.
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Antibody Specificity↗
Biomedical subjects
E G Hahn
Publications and source records attributed to E G Hahn.
Endoscopic fluorescence spectroscopy in the upper GI tract for the detection of GI cancer: initial experience.
OBJECTIVE: The aim of this study was to investigate autofluorescence spectroscopy using violet-blue excitation light for the in vivo diagnosis of GI cancer during routine endoscopy. METHODS: Fluorescence spectra were obtained from normal mucosa and cancerous lesions of the esophagus and stomach. The spectroscopic system used comprised a special light source capable of delivering either white or violet-blue light to induce autofluorescence of tissue via the endoscope. Endogenous fluorescence spectra emitted by the tissue were recorded with a fiberoptic probe and analyzed with a spectrographic detector system consisting of a polychromator with a photodiode array and an optical multichannel analyzer. The data of each spectrum were sampled within the range of 450-700 nm and stored in a personal computer. RESULTS: Esophageal squamous cell cancer, adenocarcinoma of the esophagus, and adenocarcinoma of the stomach show specific differences in the emitted fluorescence spectra compared with normal mucosa. CONCLUSIONS: Light-induced fluorescence spectroscopy might be a useful tool for the endoscopic in vivo detection of dysplasia and early carcinoma in the upper GI tract. Further trials are needed to test the validity of this new optical detection system.
Adenocarcinoma↗
Reproducibility of a standardized titration procedure for the initiation of continuous positive airway pressure therapy in patients with obstructive sleep apnoea.
BACKGROUND: Manual titration of continuous positive airway pressure (CPAP) under polysomnographic control is the method most commonly employed to establish the minimal effective pressure (P(eff)) for the treatment of the obstructive sleep apnoea syndrome (OSA). To date, however, the reproducibility of P(eff) titrated in this way has not been investigated in any detail. OBJECTIVES: The present study aims to establish the reproducibility of P(eff) determined by manual titrations of CPAP under polysomnographic control in the sleep lab. METHODS: In a group of 50 patients (5 women), with a mean (SD) apnoea-hypopnoea index of 39.3 (21.8), apnoea index of 28.1 (20.9) and oxygen desaturation index of 39.3 (22.6), with newly diagnosed OSA, manual titration of CPAP was performed on two consecutive nights using the following standard titration protocol: starting at 4 mbar, CPAP was increased by steps of 1 mbar at intervals of at least 5 min, until no signs of airway obstruction could be seen, and arousals were no longer elicited. When no airway obstruction was detected over a period of 30 min, the pressure was lowered once during the night in steps of 1 mbar at intervals of at least 10 min, until obstructive events reappeared, whereupon the pressure was again increased as described above, until, once more, no signs of airway obstruction and no arousals occurred. The second titration was carried out in a blind manner, that is the lab technician did not know the results of the first pressure titration. RESULTS: The mean (SD) P(eff) for all titrations was 8.1 mbar (2.9). A high level of correlation was found between the P(eff) titrated on the first night and that titrated on the second night (Spearman correlation coefficient = 0.89). In a few individual cases, however, differences of up to 3 mbar were found between P(eff) on the first night and P(eff) on the second night. On average, the P(eff) measured on the second night was 0.5 mbar (SD = 1.3, range: -2.0 to 3.0 mbar) higher than that of the first night. CONCLUSIONS: With standardization of the manual titration of CPAP, P(eff) is readily reproducible. In individual cases, however, a difference of as much as 3.0 mbar between the two titrations is possible.
Adult↗
Evaluation of a portable recording device (Somnocheck) for use in patients with suspected obstructive sleep apnoea.
BACKGROUND: Portable recording devices for the diagnosis of obstructive sleep apnoea (OSA) should be carefully evaluated before being used on a routine basis in out-patients. OBJECTIVE: This study was designed to evaluate the diagnostic accuracy of the new portable recording device, Somnocheck (SC). METHODS: Nocturnal polysomnographies (PSG) and SC recordings were performed simultaneously in the sleep laboratory in 51 patients with suspected OSA, and were analysed manually by a blinded investigator. RESULTS: The apnoea/hypopnoea index (AHI) obtained by manual SC analysis correlated closely with that obtained by PSG (r = 0.98), but the correlation with AHI obtained by automatic SC analysis was markedly lower (r = 0.83). When an AHI > or =10 was defined as indicative of OSA, the sensitivity of manual SC analysis was 0.97 and its specificity 1.00. The sensitivity of automatic analysis was 0.83 and its specificity 0.95. CONCLUSIONS: In this experimental setting, the SC showed a very high diagnostic accuracy for the diagnosis of OSA and was able to define its severity precisely. The diagnostic accuracy of manual analysis was found to be superior to that of automatic analysis. Considering the results of this technical evaluation, the SC may also be expected to work reliably when it is used in an ambulatory setting.
Adult↗
Celiac disease and its link to type 1 diabetes mellitus.
Celiac disease (CD) is a small intestinal disorder with overt malabsorption in the minority and with subclinical or atypical symptoms in the majority of patients. It is triggered by gluten and related cereal proteins in a unique genetic background (HLA-DQ2 or DQ8 and other unmapped genes). CD is characterized by a highly specific mucosal autoantibody response to tissue transglutaminase. In the intestine this enzyme creates antigenic neoepitopes in gluten peptides which are more efficiently presented to the immune system in the context of HLA-DQ2 or DQ8. Between 3% and 6% of patients with type 1 diabetes mellitus (DM) have (atypical) CD, and the prevalence of a variety of autoimmune diseases in patients with CD correlates with the time of gluten exposure, reaching 35% after 20 years. It is still unknown whether oligosymptomatic CD favors the development of type 1 DM and whether a gluten-free diet modifies the progression of DM in general. Apart from shared or adjacent HLA loci in both diseases, post-translational modification of potential autoantigens by enzymes such as tissue transglutaminase could play a role in the autoimmunity of type 1 DM.
Autoantigens↗
Detection of liver metastases: comparison of contrast-enhanced wide-band harmonic imaging with conventional ultrasonography.
OBJECTIVE: To compare the detection rate of conventional ultrasonography and contrast-enhanced wide-band harmonic ultrasonographic imaging in the detection of small liver metastases. METHODS: Consecutive patients with histologically proved gastrointestinal carcinoma liver metastases were studied. Biphasic helical computed tomography, conventional ultrasonography, and contrast-enhanced wide-band harmonic imaging were performed on all patients within a 5-day period. The biphasic helical computed tomographic scans were reviewed and interpreted by a skilled radiologist. The number of lesions and their descriptive characteristics were recorded for analysis. In addition, videotape recordings of the conventional ultrasonography and contrast-enhanced wide-band harmonic imaging were blindly reviewed, after which the number of detected lesions and their characteristics were then compared with those detected on biphasic helical computed tomography, considered the standard of reference. RESULTS: Twenty-eight patients (10 female and 18 male; age range, 45-72 years) were studied. Conventional ultrasonography detected 37 (59%) of all lesions visualized by biphasic helical computed tomography. The detection rate for contrast-enhanced wide-band harmonic imaging was significantly higher (61 [97%] of 63). In our series, two 10-mm lesions near the diaphragm were not visualized by wide-band harmonic imaging. CONCLUSIONS: The use of contrast-enhanced imaging techniques significantly improves the ultrasonographic detection of liver metastases. Our results achieved the sensitivity of biphasic helical computed tomography.
Aged↗
Heat shock protein 70 (HSP70) in gastric adaptation to aspirin in Helicobacter pylori infection.
We have recently shown that adaptation of gastric mucosa to aspirin (ASA) is disturbed in Helicobacter pylori (H. pylori)-infected human stomach, but can be restored by eradication of the bacterium. The aim of this study was 1) to evaluate the influence of H. pylori on expression of heat shock protein 70 (HSP70) during ASA ingestion in these subjects and in mice model and 2) to evaluate, whether altered HSP70 expression might be associated with different adaptation to ASA in H. pylori-positive and eradicated subjects. The gastric mucosal HSP 70 gene expression was determined by quantitative RT-PCR and Western blot and immunohistochemistry during 14 days of ASA ingestion (1 g bid) in the same 8 subjects before and 3 months after successful eradication of H. pylori. In addition, HSP70 mRNA and protein expression were examined in 30 mice without and with H. pylori infection and eradication. During 14 days of ASA treatment, human H. pylori-infected mucosa revealed a decrease of HSP70 expression, while after eradication a higher expression and further increase of HSP70 expression during ASA ingestion were observed. Mice inoculated with H. pylori also exhibited decreased gastric mucosal HSP70 mRNA expression that was restored after eradication therapy. Decreased basal and ASA-induced expression of HSP70 may partly be responsible for impaired gastric adaptation to ASA in H. pylori-positive subjects. We conclude that 1. The HSP70 gene and protein expression is reduced during infection with H. pylori in men and mice and that gastric adaptation to ASA in H. pylori eradicated subjects is accompanied by increased HSP70 expression; 2. It is reasonable to assume that decreased HSP70 expression might contribute to disturbed gastric adaptation in H. pylori infection in humans and 3. The expression of HSP70 plays an important role in the mechanism of gastric adaptation to ASA and that H. pylori infection interferes with this adaptation due to decrease of HSP70 expression in gastric mucosal cells.
Adaptation, Physiological↗
Effect of local injection with basic fibroblast growth factor (BFGF) and neutralizing antibody to BFGF on gastric ulcer healing, gastric secretion, angiogenesis and gastric blood flow.
Exogenous administration of bFGF was shown to accelerate tissue repair predominantly due to an increase in the formation of new microvessels (angiogenesis) suggesting that bFGF plays an important role in healing of gastric ulcer. This study was designed: 1) to examine the effect of local application of bFGF with or without neutralizing antibody (NA) to bFGF and 2) to determine the role of gastric secretion, gastric blood flow (GBF) at the ulcer margin and angiogenesis during gastric ulcer healing with or without local application of NA, bFGF or the combination of NA and bFGF. Chronic gastric ulcers were induced in Wistar rats by subserosal application of acetic acid (ulcer area 28 mm2) and gastric secretion during ulcer healing was assessed using animals additionally equipped with chronic gastric fistulas. The bFGF without or with NA to bFGF (10 ng/100 microl]), irrelevant antibodies (rabbit IgG; 10 microg/100 microl) or vehicle (saline) were locally injected into the subserosa immediately upon ulcer induction (day 0) and at day 2. Rats with acetic acid ulcers without subserosal injections served as controls. At day 11, all animals were anaesthetized and GBF was determined at the ulcer base, ulcer margin as well as in intact mucosa using the H2-gas clearance technique and the area of gastric ulcers was measured by planimetry. Gastric mucosa with ulcer was excised and the percentage of area covered with blood vessels, the number of fibroblasts and the percentage of connective tissue at the ulcer edge was assessed by histology. The gastric ulcers were healed spontaneously in control vehicle-treated rats at day 11 and this was accompanied by the significant increase in the GBF and number of microvessels in the ulcer area. The gastric secretion was suppressed immediately after ulcer induction and increased significantly at day 2 and day 11 but failed to return to that recorded in intact animals. In contrast, local application of bFGF inhibited gastric acid and pepsin outputs at each study time intervals tested and this effect was reversed by addition of NA to bFGF. Locally applied bFGF accelerated significantly ulcer healing and this was accompanied by the greater rise in the GBF of ulcer margin and more marked increase in number of microvessels as compared to those in vehicle-treated rats. Subserosal application of NA to bFGF prolonged significantly the ulcer healing and this effect was accompanied by a significant fall in the GBF at the ulcer margin and a decrease in number of capillaries in ulcer bed without significant alteration in gastric acid and pepsin outputs. The ulcer healing effect of bFGF and accompanying increase in the GBF at ulcer margin and in thenumber of microvessels as well as inhibition of gastric acid secretion evoked by bFGF were significantly attenuated by the addition of NA to bFGF. The number of fibroblasts and the distribution of connective tissue did not differ between groups studied. We conclude that; 1) depletion of endogenous bFGF at the ulcer area by specific NA to bFGF delays healing of gastric ulcers, reduces angiogenesis of ulcer bed and impairs the microcirculatory effect of this growth factor at the ulcer margin indicating that the availability of bFGF in the ulcer area plays a crucial role in the ulcer healing through induction of angiogenesis; 2) this prominent antiulcer effect of locally applied bFGF depends, at least in part, upon the inhibition of acid secretion by this peptide.
Animals↗
Brain-gut axis in gastroprotection by leptin and cholecystokinin against ischemia-reperfusion induced gastric lesions.
Leptin, a product of ob gene controlling food intake, has recently been detected in the stomach and shown to be released by CCK and implicated in gastroprotection against various noxious agents but it is unknown whether centrally applied leptin influences ischemia-reperfusion (I/R)-induced gastric erosions that progress into deeper gastric ulcerations. In this study we compared the effects of leptin and CCK-8 applied intracerebroventricularly (i.c.v.) or intraperitoneally (i.p.) on gastric mucosal lesions induced by I/R and topical application of 75% ethanol. Several major series of Wistar rats were used to examine the effects of leptin and CCK applied centrally on gastroprotection against I/R and ethanol in rats with A) vagotomy by cutting of vagal nerves, B) suppression of NO-synthase with L-NNA (20 mg/kg i.p.), C) inactivation of sensory nerves by capsaicin (125 mg/kg s.c.) and D) inhibition of CGRP receptors with CGR(8-37) (100 microg/kg i.p.) applied with or without the i.c.v. pretreatment with leptin or CCK-8. Rats were anesthetized 1 h after ethanol administration or at 3 h and 3 days upon the end of ischemia to measure the gastric blood flow (GBF) and then to determine the area of gastric lesions by planimetry. Blood was withdrawn for the measurement of plasma leptin and gastrin levels by radioimmunoassay (RIA). Leptin (0.1-20 microg/kg i.p.) dose-dependently attenuated gastric lesions induced by 75% ethanol and I/R; the dose reducing these lesions by 50% (ED50) was 8 microg/kg and 6 microg/kg, respectively and this protective effect was similar to that obtained with CCK-8 applied in a standard dose of 10 microg/kg i.p. This protective effect of leptin was accompanied by a significant increase in GBF and plasma gastrin levels whereas CCK-8 increased plasma leptin levels but failed to affect plasma gastrin levels. Leptin and CCK-8 applied i.c.v. in a dose of 625 ng/rat reduced significantly the area of I/R induced gastric lesions and raised the GBF and plasma leptin levels with the extent similar to those achieved with peripheral administration of leptin or CCK-8 (10 microg/kg i.p.). The protective and hyperemic effects of centrally administered leptin or CCK-8 (625 ng/rat i.c.v.) were completely abolished by vagotomy and significantly attenuated by sensory denervation with capsaicin or by CGRP antagonist, CGRP(8-37). The pretreatment with L-NNA to inhibit NO-synthase activity attenuated significantly the protective and hyperemic effects of CCK but not those of leptin while capsaicin denervation counteracted leptin-induced protection and rise in the GBF but attenuated significantly those of CCK. We conclude that: 1) central leptin exerts a potent gastroprotective activity against I/R-induced gastric erosions that progress into deeper gastric lesions and this protection depends upon vagal activity and sensory nerves and involves hyperemia probably mediated by NO and 2) leptin mimics the gastroprotective effect of CCK and may be implicated in the protective and hyperemic actions of this peptide against mucosal damage evoked by I/R.
Animals↗
Central and peripheral neural aspects of gastroprotective and ulcer healing effects of lipopolysaccharides.
Lipopolysaccharides (LPS) are major components of the outer membrane of gram-negative bacteria playing a central role as potent endotoxins in the pathogenesis of endotoxic shock. Although large amounts of endotoxin may produce hemorrhagic lesions in the stomach, the possible gastroprotective effect of central or peripheral LPS against the acute gastric lesions has not been extensively studied. The aim of the present study was to compare the effect of intracerebroventricular (i.c.v.) and parenteral (i.p.) injection of LPS against gastric lesions induced by 100% ethanol. Male Wistar rats were treated either with a) vehicle (control); b) E-coli-LPS in various concentrations (1-10 microg/kg i.c.v or 0.1-40 mg/kg i.p.) followed 30 min later by 100% ethanol. The effects of pretreatment with nonselective inhibitor of nitric oxide synthase (L-NAME, 20 mg/kg i.g.) or selective inhibitor of inducible nitric oxide synthase, L-NIL (30 mg/kg i.g.) on the gastroprotection induced by LPS was investigated. One hour after ethanol application, the gastric blood flow (GBF) and the area of gastric lesions were determined. In addition, the mucosal expression of iNOS, cNOS and leptin was assessed using RT-PCR. LPS applied i.c.v. or i.p. dose dependently reduced gastric lesions induced by ethanol and this effect was similar to that observed after the administration of NO donor (SNAP). LPS-induced protection was significantly abolished by L-NAME and significantly attenuated by the selective inhibitor of iNOS (L-NIL). The expression of cNOS was detected in vehicle treated gastric mucosa and did not change after LPS administration. iNOS was not detectable in intact mucosa but its expression dose-dependently increased after the LPS administration. The i.c.v. administration of LPS did not upregulate further the iNOS expression, and dose-dependently inhibited the leptin mRNA expression in gastric mucosa. We conclude that LPS applied centrally or peripherally protects gastric mucosa against ethanol-induced damage through an increase in gastric microcirculation mediated by NO due to overexpression of iNOS. Transcriptional downregulation of leptin in gastric mucosa is probably due to the increased leptin release induced by the intracerebroventricular application lipopolysaccharide.
Animals↗
Effect of central and peripheral actions of histamine and its metabolite N-alpha methyl histamine on gastric secretion and acute gastric lesions.
N alpha-methylhistamine (N alpha-MH) is one of unusual metabolite of histamine that was found in Helicobacter pylori-infected stomach and is believed to interact with specific histamine H1, H2 and H3-receptors to stimulate gastric acid secretion and gastrin release from isolated G-cells but the effects of N alpha-MH on gastric mucosal integrity have been little studied. This study was designed; 1) to compare the effect of intraperitoneal (i.p.), intracerebroventricular (i.c.v.) and gastric topical (intragastric i.g.) application of exogenous N alpha-MH with that of standard histamine on gastric secretion in rats equipped with gastric fistula (series A) and 2) to compare the effect of i.c.v. administration of histamine and N alpha-MH with that of peripheral (i.p. and i.g.) application of these amines on gastric lesions induced by 100% ethanol (series B) in rats with or without capsaicin-induced deactivation of sensory nerves. The area of gastric lesions was determined planimetrically, gastric blood flow (GBF) was assessed by H2-gas clearance method and venous blood was collected for determination of plasma gastrin levels by RIA. N alpha-MH and histamine (0.1-10 mg/kg i.p. or i.g.) dose-dependently increased gastric acid output (series A); whereas i.c.v. administration of histamine or N alpha-MH inhibited dose-dependently this secretion; the dose attenuating gastric acid output by 50% (ED50) being 4 and 6 microg/kg i.c.v. Both, N alpha-MH and histamine (2 mg/kg i.p. and i.g.) attenuated significantly the area of gastric lesions induced by 100% ethanol (series B) while producing significant rise in the GBF and plasma immunoreactive gastrin increments. Central application of N alpha-MH and histamine (0.01-5 microg/kg i.c.v.) inhibited ethanol-induced gastric damage whereas higher doses ranging from 10-100 microg/kg of histamine and N alpha-MH were significantly less effective. Capsaicin-induced deactivation of sensory nerves by itself augmented significantly ethanol damage and attenuated significantly the protective and hyperemic effects of histamine and its methylated analog applied i.p. but failed to affect significantly those caused by i.c.v. administration of these amines. We concluded that: 1) central histamine and N alpha-MH inhibits gastric acid secretion and exhibits gastroprotective activity against ethanol in similar manner to that afforded by parenteral and topical histamine and N-alphaMH, 2) central N-alphaMH- and histamine-induced protection involve the enhancement in gastric microcirculation unrelated to neuropeptides released from capsaicin-sensitive afferent nerves, and 3) the major difference between central and peripheral histamine and its methylated analog is the influence on gastric acid secretion which does not appear to play any major role in gastroprotective activity of these agents.
Animals↗
[Abscesses, endophthalmitis and retinopathy as "initial manifestations" of type 2 diabetes].
The case of a 42 year old female patient is described, who presented with abscesses in the lung, the left kidney, the perspiratory glands of the axillae and endophthalmitis as well. Staphylococcus aureus could be isolated from sputum, urine, bronchoalveolar lavage and excisates of the abscesses in the right axilla. After long-term antibiotic and antimycotic treatment, restitutio ad integrum could be achieved. Since the further course excluded underlying malignancy, the septic course of Staphylococcus aureus infection must be regarded as an effect of immunosuppression in long-standing and untreated diabetes mellitus.
Abscess↗
[Isolated ACTH deficiency as a rare cause of recurrent syncope and hypoglycemia].
HISTORY AND CLINICAL FINDINGS: A 63-year-old man was assigned into emergency room presenting with an acute syncope associated with hypoglycemia and hypotension. Clinical findings showed a pale, waxing-colored skin and a disorder of impulse. During the clinical stay the patient's behavior was slowed down and adynamic. INVESTIGATIONS: After exclusion of cardiovascular and neurologic disorders as reason for the repeated syncopes a detailed endocrine diagnostic screening was performed, which revealed a deficiency of cortisol with missing increase of cortisol in the ACTH stimulation test. The ACTH-GnRH-TRH test showed an isolated deficiency of corticotropic hormones. Stimulation with CRH revealed no increase of ACTH or cortisol. Insulin tolerance test revealed an isolated ACTH insufficiency with consecutive deficit of cortisol. A tumor of the adrenal gland was excluded by abdominal scan. Cerebral CT was inconspicuous. Cerebral NMR was suspicious of volume deficiency of the hypophysis. TREATMENT AND COURSE: Under therapy with hydrocortisone 20 mg and fludrocortisone 0.05 mg orally the clinical symptoms of the patient improved impressively. The patient became efficient and dynamic. Systolic blood pressure increased in mean over 120 mm Hg. There were no more hypoglycemic episodes. CONCLUSION: Secondary insufficiency of the adrenal gland should be considered as a rare cause of hypoglycemia if combined with hypotensive circulatory disturbance and missing pigmentation of the skin.
Adrenal Insufficiency↗
Helicobacter pylori infection and gastrin and cyclooxygenase expression in gastric and colorectal malignancies.
Helicobacter pylori, infecting more than 50% of the world population, results in gastritis, usually located in the antral portion of the stomach, accompanied by hypergastrinemia, the key factor in gastric and colorectal carcinogenesis. Excessive mucosal cell proliferation for many years may eventually result in gastric atrophy, cell mutation and transformation of gastric mucosal cells into gastrin-producing cells, which also express gastrin receptors serving to stimulate cell proliferation and tumor growth. These processes may be completed by the expression of cyclooxygenase-2 (COX-2) as an inflammation enzyme to release excessive amounts of PGE(2), leading to further proliferation, reduction in apoptosis, angiogenesis and tumor growth. H. pylori eradication results in complete regression of MALT lymphoma and subsequent normalisation of excessive gastrin release and COX-2 expression. Reduction of gastrin by active immunisation (gastrimmune), blocking of gastrin receptors with specific blockers and suppression of COX-2 might be helpful in inhibiting tumor growth and invasion.
Animals↗
[Adverse drug effects. Prevention, detection and early intervention by a computer-assisted early warning system].
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Adverse Drug Reaction Reporting Systems↗
["Trapped" ascites; massive hernia formation in nephrectomy scar of a patient with liver cirrhosis].
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Ascites↗
[New trends in therapy of diabetes. More freedom, fewer risks, comfortable insulin administration].
The incidence of diabetes mellitus is increasing worldwide. Strict metabolic control can prevent late sequelae of this disease. For this purpose, not only more potent drugs with fewer side effects are needed, but also user-friendly techniques and devices for self-monitoring of blood glucose and the less painful application of insulin (jet application, inhalable insulin). More user-friendly insulins are the rapid- and short-acting human insulin analogues, which do away with the bothersome injection/meal interval, and improve the postprandial glycemic response. New long-acting insulins reduce the frequency of injections and the occurrence of nocturnal hypoglycemia. Type 2 diabetics will presumable benefit from the use of the rapid, short-acting glinides, for example, by enabling a greater measure of eating freedom during the course of the day. The thiazolidinediones, a group of agents that enhance the effects of insulin in target tissue, reduce insulin resistance and improve insulin sensitivity.
Diabetes Mellitus↗