Severe shock during upper GI endoscopy in a patient with systemic mastocytosis.
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Biopsy↗
Biomedical subjects
E G Hahn
Publications and source records attributed to E G Hahn.
KTP laser destruction of dysplasia and early cancer in columnar-lined Barrett's esophagus.
BACKGROUND: The rising incidence of esophageal adenocarcinoma in western countries requires a new strategy in the management of dysplasia in Barrett's esophagus. Esophagectomy, which has high morbidity and mortality rates, has been recommended to treat patients with severe dysplasia. Strictly superficial laser coagulation with tissue ablation therefore is a desirable option for the management of dysplasia in Barrett's esophagus because the tissue to be ablated is only about 2 mm thick. Potassium-titanyl-phosphate (KTP) laser light with a wavelength of 532 nm is preferentially absorbed by hemoglobin and therefore combines excellent coagulation with limited tissue penetration. We report first clinical results with KTP laser superficial vaporization of dysplasia and early cancer in Barrett's esophagus. METHODS: Eight men and 2 women 43 to 84 years of age with short segments of Barrett's esophagus or traditional Barrett's esophagus and histologically proved low-grade (n = 4) and high-grade (n = 4) dysplasia or early adenocarcinoma (n = 2) were selected for this pilot study. For all patients thermal endoscopic destruction was conducted with a frequency-doubled neodymium:yttrium-aluminum-garnet (Nd:YAG) KTP laser system. Laser therapy was performed by means of the free-beam method with coaxial insufflation of gas. An average of 2.4 sessions per patient were required for ablation of the Barrett's mucosa. RESULTS: Two to three days after laser treatment the response of the ablated mucosa was assessed with endoscopy and biopsy. Samples taken showed fibrinoid necrosis of the mucosal layer. A complete response was obtained for all 10 patients. Replacement by normal squamous cell epithelium was induced in combination with acid suppression therapy of up to 80 mg omeprazole daily. No complications occurred. In two patients biopsy showed specialized mucosa beneath the restored squamous cell epithelial layer. Follow-up times were as long as 15 months (mean value 10.6 months). CONCLUSIONS: KTP laser destruction of Barrett's esophagus induced mucosal regeneration with normal squamous cell epithelium in combination with acid suppression. Limitation of the depth of thermal destruction in Barrett's esophagus minimizes risk for perforation or stricture formation. KTP laser ablation of Barrett's esophagus seems to be feasible and safe in short segments of Barrett's esophagus with dysplasia or early cancer.
Adenocarcinoma↗
Impact of skill and experience of the endoscopist on the outcome of endoscopic sphincterotomy techniques.
BACKGROUND: Our aim was to assess the influence of the skill and experience of the endoscopist on the success and risk of endoscopic sphincterotomy techniques. METHODS: The outcome of all endoscopic sphincterotomies (n = 1335) carried out between 1988 and 1995 were retrospectively analyzed with respect to the endoscopist performing the procedure. Endoscopists were differentiated according to whether they had previous experience with endoscopic sphincterotomy techniques (n > 100) and the frequency of endoscopic sphincterotomy during the study period (>40, 26 to 40, 10 to 25, <10 per year). RESULTS: Indications for endoscopic sphincterotomy techniques and technical execution had only a minor influence on the results of endoscopic sphincterotomy and were comparable for the individual endoscopists. The overall success rate of endoscopic sphincterotomy was 94.4% and did not significantly differ among the endoscopists. The overall complication rate of endoscopic sphincterotomy was 7.3%. Endoscopists learning endoscopic sphincterotomy techniques with a case frequency of less than 10 procedures per year had a consistently high complication rate (10.5%). Those learning endoscopic sphincterotomy techniques with a case frequency of more than 25 procedures per year had an above-average complication rate for their first 40 endoscopic sphincterotomy procedures and a significant decrease in complication rate as the number of procedures increased. The complication rate for experienced endoscopists was 7.7%. There were distinct and, in one case, significant differences in complication rates between individual endoscopists (11.5% vs. 4.8%, p = 0.01). However, when corrected for multiple testing, there were no significant differences at the p < 0. 05 level. The endoscopic sphincterotomy frequency of the endoscopist was the only significant risk factor for complications. Endoscopists with a frequency of more than 40 procedures per year had a significantly lower complication rate (5.6%) than endoscopists with a lower case frequency (9.3%, p < 0.05). CONCLUSIONS: A low endoscopic sphincterotomy frequency is, even for endoscopists with previous experience with the procedure, a risk factor for complications after endoscopic sphincterotomy. The learning of endoscopic sphincterotomy techniques requires a minimum of 40 procedures, but also after 100 procedures a further decrease of the complication rate can be expected.
Adult↗
A heated humidifier reduces upper airway dryness during continuous positive airway pressure therapy.
Upper airway dryness is a frequent side-effect of nasal continuous positive airway pressure (nCPAP) therapy in obstructive sleep apnoea (OSA). In this situation, heated humidification is often used. Alternatively, oily nose drops are frequently applied to relieve dryness. The present study aimed to investigate the efficacy of a heated humidifier in comparison with oily nose drops. Twenty-four OSA patients complaining of serious nCPAP-related upper airway dryness were randomized to 6 weeks of treatment either with heated humidification (HC 100, Fischer & Paykel, Inc., Auckland, New Zealand) or oily nose drops (Colda-Stop, Desitin, Inc., Germany). The patients completed questionnaires on the degree and frequency of upper airway dryness, compliance with nCPAP, intention to terminate nCPAP and comfort during the nCPAP therapy. All 12 patients treated with heated humidification improved in terms of the degree and frequency of upper airway dryness, and reported greater comfort when using the nCPAP device. All patients in the heated humidification group intending to terminate nCPAP therapy because of upper airway dryness persisted with nCPAP on addition of humidification. In contrast, only five out of 12 patients (42%) in the oily nose drops group reported their degree of upper airway dryness to be improved (P = 0.003), only three patients (25%) reported an improvement in the frequency of upper airway dryness (P < 0.001), and only five patients (42%) reported greater comfort when using the nCPAP device with oily nose drops (P < 0.001). In the group using oily nose drops none of the three patients who intended to terminate nCPAP therapy persisted with nCPAP. Heated humidification is highly effective and superior to oily nose drops in reducing the symptoms of upper airway dryness during nCPAP.
Aged↗
Hypersensitivity to 5-ASA suppositories.
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Anti-Inflammatory Agents, Non-Steroidal↗
Mouse model of Helicobacter pylori infection: studies of gastric function and ulcer healing.
BACKGROUND: Helicobacter pylori infection in humans is a major risk factor for peptic ulcer, but studies on the relation between H. pylori infection and gastric pathology are limited due to a deficiency of convenient animal models resembling this infection in humans. METHODS: We studied the effects of inoculation of conventional BALB/c mice with CagA and VacA positive (type I) H. pylori or CagA and VacA negative H. pylori (type II) strains on gastric secretion and healing of chronic acetic acid-induced ulcers in mouse stomachs. The ulcer area, gastric blood flow, plasma interleukin (IL)-1beta and IL-12, as well as plasma gastrin and gastric luminal somatostatin were determined. Gastric mucosal biopsy samples were also taken for assessment of the presence of viable H. pylori using a rapid urease test, H. pylori-culture and the RT-PCR analysis of the signal for H. pylori CagA. RESULTS: Gastric acid and pepsin secretion was reduced by over 50% immediately after H. pylori inoculation and accompanied by a significant increment in plasma gastrin and fall in gastric luminal somatostatin content observed over all test days, particularly in mice infected with type I H. pylori. The area of ulcers in vehicle-treated controls decreased significantly starting from day 2 after ulcer induction and then continued to decline for a further 14 days to heal almost completely after 28 days. In contrast, the ulcers were present until day 28 in all mice infected with type I or type II H. pylori strains, being significantly larger, especially with type I H. pylori infection. The gastric blood flow at the ulcer margin and ulcer crater in vehicle-treated mice gradually increased with decreasing ulcer size, after 14 and 28 days reaching a value which was not significantly different from that in vehicle-administered mice. In contrast, the gastric blood flow in type I H. pylori and, to a lesser extent, in type II H. pylori infected mice was significantly lower than in vehicle controls, both at the margin and at the crater of ulcers at all tested days. Histological changes such as oedema or congestion of surface epithelium were found after 7 days whereas mucosal inflammatory infiltration appeared after 14 days with a further increase after 28 days, especially in type I H. pylori and to a lesser extent in type II H. pylori infected mice. Plasma IL-1beta and IL-12 were significantly elevated at all tested days of ulcer healing and their increments were significantly higher in type I than in type II H. pylori infection. CONCLUSIONS: Conventional mice with gastric ulcers can be successfully infected by both toxigenic and nontoxigenic H. pylori strains, and this infection causes an immediate suppression of gastric secretion and markedly delays the healing of ulcers due to the fall in mucosal microcirculation in the ulcer region, cytokine release and an impairment in the gastrin-somatostatin link that appears to be independent of gastritis and more pronounced with infection of toxigenic than nontoxigenic strains.
Animals↗
Antibiotic prophylaxis in percutaneous endoscopic gastrostomy (PEG): a prospective randomized clinical trial.
BACKGROUND AND STUDY AIMS: The most frequent complication reported for percutaneous endoscopic gastrostomy (PEG) is peristomal wound infection which occurs in as many as 30 % of patients. In the studies published so far, the question of whether antibiotic prophylaxis reduces the incidence of peristomal wound infection has remained controversial. We therefore conducted a prospective, randomized trial to determine whether antibiotic prophylaxis can reduce the incidence of peristomal wound infection associated with PEG. PATIENTS AND METHODS: During a 2-year-period a total of 347 patients (251 men, 96 women; mean age 60.2+/-5) were included in our study. In all cases, a 9-French gauge Freka gastrostomy tube was inserted using the "pull" technique. The patients were randomly assigned to three different treatment groups (group 1, antibiotic prophylaxis with 2 g cefotaxime; group 2, antibiotic prophylaxis with 4g piperacillin plus 0.5g tazobactam; group 3, no antibiotic prophylaxis). For a period of one week after gastrostomy, the peristomal area was evaluated using a wound score. According to the score, peristomal infections were classified as being of degree I-IV. Infections of up to degree III were regarded as minor, while an infection of degree IV was defined as a severe complication. RESULTS: PEG tubes were successfully placed in 336/347 patients (97 %). Of the 336 patients, 29 were excluded because of incomplete follow up (dropout rate 9%). Cases included were: in group 1, n = 101; in group 2, n = 100, and in group 3, n = 106. There was no mortality related to PEG insertion. There were five instances of severe complications (1.6%). Patients who received antibiotic prophylaxis had mean daily combined wound scores that were significantly lower than those of patients without antibiotic prophylaxis (P < 0.01). The control group (no antibiotic prophylaxis) exhibited significantly more peristomal wound infections of degree III (n = 8) than antibiotic prophylaxis group 1 (n = 0, P < 0.001) or antibiotic prophylaxis group 2 (n = 1, P < 0.012). Three patients in group 3 (no antibiotic prophylaxis) and one patient in group 2 developed peritonitis. CONCLUSIONS: Severe wound infections requiring medical or endoscopic intervention are very rare events after PEG insertion. Antibiotic prophylaxis significantly reduces the risk of peristomal wound infection associated with PEG insertion. Antibiotic prophylaxis, therefore, is to be recommended as a general measure in percutaneous endoscopic gastrostomy.
Antibiotic Prophylaxis↗
[Color doppler ultrasonographic detection of focal thyroid nodules].
AIM: To determine if colour Doppler sonography is a sensitive tool to detect solitary hot thyroid nodules. METHODS: All patients evaluated in our ultrasound laboratory during study period also underwent thyroid sonography. If one or more nodules with a diameter of at least 8 mm were present, thyroid scientigraphy was performed. Hyperperfusion within the nodule compared to the surrounding tissue indicated autonomy according to the study protocol. RESULTS: 1010 patients were screened. 385 had one or more nodules, 309 of them with a diameter of more than 8 mm. Among these patients a hot nodule was proved with scintigraphy in 120 cases. 116 of these 120 patients were correctly identified with colour Doppler sonography. CONCLUSION: Colour Doppler sonography is a reliable method to detect solitary hot or hyperperfused thyroid nodules and to identify a risk group of patients prior to the administration of x-ray contrast media.
Adult↗
Esophageal achalasia: intrasphincteric injection of botulinum toxin A versus balloon dilation.
BACKGROUND AND STUDY AIMS: In patients with esophageal achalasia, pneumatic dilation is the treatment of choice, but it bears the risk of perforation in about 4% of cases. A new nonsurgical method, intrasphincteric injection of botulinum toxin A, has shown promising initial results, and we thus undertook this study to compare the long-term outcome of these two methods. PATIENTS AND METHODS: In a prospective randomized study, 24 patients with definitive esophageal achalasia were divided into two equal groups and underwent either balloon dilation or injection of botulinum toxin (20 U injected into each of the four quadrants in the lower esophageal sphincter). The outcome was assessed on the basis of a symptom score documented before treatment and at regular intervals for two and a half years thereafter. Complications associated with the two techniques were also documented. RESULTS: No relevant complication occurred in either of the treatment groups. Initially, dilation was successful in 10 of 12 patients (83%), and botulinum toxin injection in 9 of 12 patients (75%). The symptom scores showed no significant differences between the two groups before and one month after treatment. Over the two and a half year follow-up, however, all nine successfully treated patients in the botulinum toxin group experienced recurrence of symptoms, but only four of the ten patients (40%) in the dilation group. CONCLUSIONS: The two treatment methods initially had equal success rates, but in the long term the effect of the botulinum toxin injection was statistically significantly shorter than that of balloon dilation. As fewer risks are associated with the injection treatment, studies should be undertaken either to identify patient subgroups in whom botulinum toxin can be effective long-term or to test substances with longer-lasting effects.
Adolescent↗
Effect of substance P on histamine secretion from gut mucosa in inflammatory bowel disease.
BACKGROUND: Mast cell hyperplasia in the gut is a feature of inflammatory bowel disease (IBD), but the role of mast cells in this disease is still unclear. Since mast cell-nerve interactions might have some impact on intestinal inflammation, the present study investigated whether the neuropeptide substance P causes histamine secretion from human gut mucosal mast cells. METHODS: Four hundred and eighteen colorectal endoscopic samples from 20 patients with IBD and 10 controls were studied. Colorectal biopsy samples were cultured in an oxygenated medium for spontaneous histamine release or were stimulated with substance P, anti-human immunoglobulin E, and a combination of substance P and anti-human immunoglobulin E. Histamine release was measured using a highly sensitive and specific radioimmunoassay. RESULTS: Substance P failed to induce mast cell activation in histologically normal mucosa from controls. In contrast, mucosal specimens taken from inflamed IBD tissue or from uninvolved Crohn disease tissue showed a considerably enhanced rate of histamine secretion towards substance P, alone or in combination with anti-IgE. Unaffected mucosa with ulcerative colitis appeared insensitive towards substance P. CONCLUSIONS: The neuropeptide substance P was shown to preferentially enhance mucosal mast cell mediator secretion in active IBD. Thus, it appears likely that mast cell-nerve interactions are involved in as yet uninvestigated neurovegetative histamine-releasing processes of the gut in IBD.
Adult↗
Helicobacter pylori induces apoptosis in gastric mucosa through an upregulation of Bax expression in humans.
BACKGROUND: Maintenance of gastric mucosal integrity depends on the balance between cell loss due to apoptosis and cell proliferation. Helicobacter pylori induces apoptosis in gastric epithelial cells, but the regulation of this process has been little studied. The Bcl-2 proteins are the best-studied family of proteins involved in the mechanism of apoptotic death. Some members of this family, such as Bcl-2, inhibit apoptosis, whereas others, such as Bax, induce it. The present study was performed to determine the apoptosis rate and mRNA and protein expression for Bax and Bcl-2 in the gastric mucosa of duodenal ulcer (DU) patients with H. pylori infection before and after H. pylori eradication. We recruited 8 H. pylori-negative control subjects and 20 DU patients (H. pylori-positive) given a 1-week triple therapy to eradicate H. pylori. The apoptosis was analyzed by means of terminal deoxyribonucleotide transferase-mediated digoxigenin-11-deoxyuridine triphosphate biotin nick-end labeling (TUNEL) staining, and the expression of mRNA for Bax and Bcl-2 by reverse transcription polymerase chain reaction (RT-PCR) and Southern blot. In all patients gastritis was assessed histologically on the basis of the Sydney classification, the presence of H. pylori, and analysis of cagA status. RESULTS: All 20 DU patients were H. pylori-positive, and 18 (90%) were CagA-positive. The apoptotic cells were infrequently identified in gastric surface epithelium by TUNEL histochemistry in H. pylori-negative controls. In DU patients infected with H. pylori, apoptotic cells were more numerous and seen deep in the gastric glands. The infection was associated with significantly upregulated expression of mRNA and protein for Bax and suppressed mRNA and protein expression for Bcl-2, as determined using RT-PCR and Western blot analysis. The Bax overexpression was significantly stronger in the antrum than in the corpus of H. pylori-infected patients. Four weeks after the eradication a marked decrease of neutrophil infiltration, an improvement of the grade of gastritis (mononuclear infiltration), and significant reduction in apoptosis rate were observed. After eradication the Bax mRNA expression was still at an increased level, whereas the Bcl-2 mRNA expression remained suppressed. CONCLUSIONS: 1) H. pylori induces apoptosis in the gastric epithelium, at least in part, due to an upregulation of proapoptotic Bax and downregulation of antiapoptotic Bcl-2, and 2) Bax mRNA and protein expression was higher in the antrum than in the corpus, and this was probably due to greater inflammatory changes observed in the antrum than in the corpus.
Adult↗
Gastric involvement in progressive systemic sclerosis: electrogastrographic and sonographic findings.
OBJECTIVE: To determine whether electrogastrography (EGG) can discern sonographically demonstrated motility disorders in patients with progressive systemic sclerosis (SSc) and to evaluate EGG as a possible diagnostic tool. DESIGN: Prospective study with control group and testing for reliability. SUBJECTS: 15 SSc patients [women aged 33-70 years (mean 53.3 years)] and 15 healthy volunteers. METHODS: Bipolar cutaneous EGG was recorded to obtain the following parameters: period dominant frequency (PDF), percentage of gastric dysrhythmia and normogastria (defined as 2-4/min), period dominant power (PDP) and its change after a standardized meal of 500 kcal (2093 kJ), and instability coefficients of dominant frequency and power (DFIC, DPIC). Simultaneously, real-time sonography was performed in the aortomesenteric plane (3.5-MHz curved-array probe). In 10 patients and 13 control subjects, the distance from the anterior wall of the gastric antrum to the abdominal skin was measured. RESULTS: Three patients (20%) showed hypomotility of the gastric antrum sonographically. The percentage of bradygastria was significantly lower in these patients, but the PDF, DFIC and DPIC values were not significantly different. The distance between the cutaneous electrodes and the antrum bore a greater relationship to the PDP values than did the sonographically demonstrated number of gastric contractions. CONCLUSIONS: Although cutaneous EGG can be performed in SSc patients without apparent derangement in frequency and stability of the signal, it offers no advantage over sonography in diagnosis and follow-up.
Adult↗
Gastroprotection and control of food intake by leptin. Comparison with cholecystokinin and prostaglandins.
Circulating peptide leptin which is the product of the ob gene is known to provide feedback information on the size of fat stores to central OB-receptors that control food intake. Recently, leptin messenger RNA and leptin protein have been detected in gastric epithelium and leptin was found to be released by CCK into circulation but the physiological role of this gastric leptin remains unknown. As CCK has been reported to protect gastric mucosa against various noxious agents, we designed the study to determine the influence of leptin and CCK on the gastroprotection and the control of food intake and to compare them with classic gastroprotective substance, prostaglandin E2, in rats with acute gastric mucosal lesions induced by topical application of 75% ethanol. Four series of Wistar rats (A, B, C and D) were used to determine; A) the effects of various doses of leptin (0.1-10 microg/kg) given intraperitoneally (i.p.) on ethanol-induced gastric lesions, gastric blood flow (GBF) and plasma levels of immunoreactive leptin; B) the effects of various doses of CCK-8 (0.1-10 microg/kg i.p.) on ethanol-induced gastric lesions, GBF and plasma levels of leptin; C) the effects of various doses of PGE2 (12.5--100 microg/kg) given intragastrically (i.g.) on ethanol-induced gastric lesions and GBF and D) the influence of leptin, CCK and PGE2 on the intake of liquid meal in rats. Rats were anesthetized with ether 1 h after i.g. administration of 75% ethanol to measure the GBF using H2-gas clearance technique and blood samples were withdrawn for the measurement of plasma leptin levels by radioimmunoassay (RIA). Food intake was assessed in separate group of rats fasted 18 h and then fed with liquid caloric meal. Leptin, CCK and PGE2 reduced dose-dependently gastric lesions induced by 75% ethanol, the dose reducing these lesions by 50% (ED50) being, respectively, 1 microg/kg, 5 microg/kg and 20 microg/kg. The protective effects of leptin, CCK-8 and PGE2 were accompanied by significant attenuation of the fall of the GBF caused by ethanol. Leptin and CCK reduced also dose-dependently the food intake while PGE2 was not effective. Leptin and CCK resulted a dose-dependent increment in the plasma leptin levels. We conclude that: 1) exogenous leptin and CCK, causing similar increments in plasma immunoreactive leptin levels, protect dose-dependently gastric mucosa against the damage provoked by 75% ethanol; 2) Leptin and CCK afford similar gastroprotective activity to that attained with PGE2 but unlike PGE2 were highly effective in the reduction in food intake and 3) the protective effects of leptin, CCK and PGE2 were accompanied by significant increase of GBF suggesting that the protection afforded by these substances are mediated, at least in part, by gastric hyperemia.
Adipose Tissue↗
Successful treatment of Bouveret's syndrome by endoscopic laserlithotripsy.
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Cholelithiasis↗
[Optimized extracorporeal shockwave lithotripsy of gallbladder calculi: a prospective randomized therapy comparison].
UNLABELLED: Is "pulverization" or "fragmentation" the best endpoint of extracorporeal shock wave application in ESWL of gallbladder stones? Has gallbladder motility a potential for the prevention of stone recurrence? METHODS: Prospective, monocentric study with randomization between the conventional treatment strategy (endpoint of shock wave application: fragments < or = 4 mm, concomitant oral chemolitholysis) and an intensified treatment strategy (endpoint of shock wave application: Pulverization, no chemolitholysis). Prevention of stone recurrence: At least once per month for one hour after a meal standardized position (back position, lowered chest). RESULTS: 34 patients, age 46 +/- 14 years (27 women, seven men) were included (F-ESWL: n = 18; P-ESWL: n = 16). Gallbladder motility, number, size and CT-measured calcifications of stones were comparable for both groups. P-ESWL patients received more shock wave pulses than F-ESWL patients and more treatment sessions. P-ESWL resulted in a better fragmentation and pulverization of stones was reached significantly more often (p < 0.05). The time period for stone clearance was significantly depending on the fragmentation result (pulverization: 0.7 months vs. fragments < or = 4 mm: 6.6 months vs. fragments > or = 4 mm: 8.0 months; p < 0.01). The stone free rate after twelve months was 87.5% for P-ESWL and 72.2% for F-ESWL (n.s.) and correlated significantly with the fragmentation result (p < 0.01). Pain sensations during stone clearance were significantly reduced by P-ESWL. Stonefree patients were followed up for 30 +/- 13 months, the total recurrence rate was 7.1%. CONCLUSIONS: Aiming for pulverization of gallbladder stones by means of intensified extracorporeal shock wave application is at least equal or in tendency superior compared to disintegration to fragements < or = 4 mm. Gallbladder motility might be useful to prevent gallstone recurrence after successful ESWL.
Adult↗
[Augmentation of the immune response to islet cell antigens with development of diabetes mellitus caused by interferon-alpha therapy in chronic hepatitis C].
We report on a 36-year-old patient suffering from chronic hepatitis C. Because of elevated liver enzymes and histology showing chronic inflammation and periportal fibrosis, interferon-alpha (IFN) therapy was started with a dosage of 5 Mio units three times a week. Four months later the patient hat to be hospitalized due to the typical clinical features of a recent onset type 1 diabetes (BG > 300 mg/dl, HbA1c 9.6%, ketonuria). In serum samples prior to and following interferon therapy, we analyzed titers of diabetes-related autoantibodies responding to GAD65 (glutamic acid decarboxylase), IA2c (tyrosine phosphatase) and ICA (islet cell autoantibodies). While ICA were negative before starting therapy, IA2c-antibodies were highly elevated. In contrast. GAD65-antibodies were elevated only slightly over the cut-off of the assay before therapy (controlled by a second different RIA assay) and increased 100 fold during IFN-alpha treatment. Additionally thyroid antibodies appeared. After the end of the IFN therapy, GAD65- and IA2c antibodies remained on high levels and also ICA could now be found. The patient was positive for HLA-DR4. This case supports the hypothesis that IFN-alpha therapy may lead to an augmented autoimmune reaction against islet cell antigens resulting in the development of diabetes mellitus type 1, especially if there are other predisposing factors before IFN treatment. We further discuss the possible involvement of interferon-alpha in the pathogenesis of autoimmune diabetes with reference to recent studies.
Adult↗
Apoptosis in gastric mucosa with stress-induced gastric ulcers.
The maintenance of gastric mucosal integrity depends upon the interplay between epithelial cell proliferation and apoptosis (programmed cell death). The Bcl-2 family of proteins plays a central role in the regulation of apoptotic cell death by suppressing the apoptosis while some others such as Bax proteins promote this process. Stress-induced gastric ulcerations are accompanied by the fall in gastric mucosal cell proliferation but little is known about the influence of the stress on the apoptosis in gastric mucosa. In the present study, the gastric epithelial apoptosis was determined by means of expression of Bax and Bcl-2 mRNA in the gastric mucosa following acute stress. Wistar rats were exposed to mild water immersion and restraint stress (WRS) for 3.5 h and then sacrificed at 0, 2, 4, 6, 12 and 24 h after the termination of WRS. At each time interval after WRS, the gastric blood flow (GBF) and the proliferating cell nuclear antigen (PCNA) labeling were determined. The apoptosis rate in the gastric mucosa was determined by the terminal deoxynucleotidyl transferase (TDT) mediated 2-deoxyuridine 5-triphosphate (dUTP)-biotin nick end-labeling (TUNEL) staining method and the expression of Bax and Bcl-2 mRNA was analyzed by RT-PCR and southern blot hybridization. WRS produced multiple erosions accompanied by the fall in GBF and PCNA index and by a dramatic enhancement in gastric epithelial apoptosis rate reaching maximum at 4 h after exposure to WRS. Following 6 and 12 h after the end of WRS the apoptotis declined but even 24 h after WRS it failed to reach the value recorded in intact gastric mucosa. The PCNA index was still significantly inhibited at 2 h after WRS but then showed significant rise at 6 and 12 h to reach at 24 h after WRS, the level similar to that measured in intact gastric mucosa. The expression of Bax mRNA was detected in intact gastric mucosa and gradually increased in first 4 h after WRS to decline at 24 h to the level not significantly different from that observed in the intact mucosa. In contrast, the expression of Bcl-2 mRNA was almost undetectable during first 4 h but showed strong signal at 6 and 12 h to decline to the control level 24 h after WRS. We conclude that: 1. Healing of WRS lesions involves an increase in GBF and mucosal cell proliferation and 2. The enhancement in gastric epithelial apoptosis accompanies the mucosal damage induced by stress and this appears to be triggered by the shift from the cell death effector Bax to the cell death repressor Bcl-2 protein.
Animals↗
Enhanced expression of leptin following acute gastric injury in rat.
Leptin, a product of ob-gene plays an important role in the regulation of food intake. Recently, leptin expression has been detected in gastric epithelium, but the physiologic role of gastric leptin remains unknown. The purpose of this study was: 1) to determine the effect of gastric injury by ethanol and aspirin on the expression of leptin in gastric mucosa and 2) to investigate whether exogenous leptin affects the integrity of gastric mucosa exposed to noxious agents such as ethanol or aspirin. In Wistar rats the acute gastric lesions were induced by intragastric application of 1.5 ml of 75% ethanol or acidified aspirin (100 mg/kg in 0.2 N HCl). Rats were divided into two groups and pretreated either with leptin (1-10 microg/kg i.p.) or vehicle (saline). Rats were anesthetized 1 h after i.g. induction of acute gastric lesions and the gastric blood flow (GBF) was measured by H2 gas clearance method. Then the rats were sacrificed, the stomach was excised and the mean lesions area was assessed by planimetry. In addition, mRNA and protein expression for leptin was analyzed in the gastric mucosa by reverse transcription polymerase chain reaction (RT-PCR) and Western blot, respectively. Both ethanol and acidified aspirin induced acute gastric lesions and led to significant reduction in GBF. In the intact gastric mucosa, the mRNA and protein expression for leptin was small but detectable. The exposure of gastric mucosa to noxious agents such as ethanol and aspirin was associated with markedly increased expression for gastric leptin at mRNA and protein level. Application of 75% ethanol or acidified aspirin caused wide-spread mucosal lesions. The pretreatment with exogenous leptin reduced dose-dependently these ethanol or aspirin-induced gastric lesions. The protective effects of exogenous leptin were accompanied by a significant attenuation of the fall of GBF. We conclude that: 1) Exogenous leptin exerts potent gastroprotective and hyperemic actions on gastric mucosa, and 2) Acute injury of gastric mucosa is associated with increased expression of leptin suggesting a possible role of this peptide in mediating of repair process in injured gastric mucosa.
Animals↗