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Clinical significance of granuloma in Crohn's disease

World journal of Gastroenterology 2005年第20期11卷 3118-3121页

作者： Tamás Molnár László Tiszlavicz Csaba Gyulai Ferenc Nagy jános lonovics First Department of Medicine Faculty of Medicine University of Szeged H-6720 Szeged Korányi fasor 8. Hungary Department of Pathology Faculty of Medicine University of Szeged H-6720 Szeged Korányi fasor 8. Hungary Department of Radiology Faculty of Medicine University of Szeged H-6720 Szeged Korányi fasor 8. Hungary

AIM: Granuloma is considered the hallmark of microscopic diagnosis in Crohn's disease (CD), but granulomas can be detected in only 21-60% of CD patients. The aim of this study was to evaluate the frequency of granulomas by multiple endoscopic biopsies in patients with CD and to examine whether group of patients with or without granuloma exhibit a different clinical course. METHODS: Fifty-six patients with newly diagnosed CD were included in the study. jejunoscopy, enteroclysis and ileo-colonoscopy were performed in all patients. At least two biopsy specimens from each examined gastrointestinal segment were examined microscopically searching granuloma. The clinical course was followed in all patients, and extraintestinal manifestations as well as details of any immunosuppressive therapy and surgical intervention were noted. RESULTS: Granuloma was found in 44.6% of the cases (25 patients). Patients with granuloma had higher activity parameters at the time of the biopsies. Extraintestinal manifestations were observed and surgical interventions were performed more often in the granuloma group. The need of immunosuppressive therapy was significantly more frequent in the patients with granuloma. Granuloma formation is mote often seen in younger patients, and mainly in the severe, active penetrating disease. CONCLUSION: The significantly higher frequency of surgical interventions and immunosuppressive therapy suggests that granuloma formation is associated with a more severe disease course during the first years of CD.

关键词： Crohn's disease Granuloma Activity Complication

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Autoimmune pancreatitis: Functional and morphological recovery after steroid therapy

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World journal of Gastroenterology 2006年第11期12卷 1810-1812页

作者： László Czakó (E|')va Hegyk(o|¨)zi Attila Pálinkás jános lonovics First Department of Medicine University of Szeged SzegedHungary Elizabeth Hospital Hódmez(o|″)vásárhely Hungary

Autoimmune pancreatitis, a recently recognized type of chronic pancreatitis, is not rare in japan, but reports of it elsewhere are relatively uncommon. We report the first preoperatively diagnosed case of autoimmune pancreatitis in Hungary, which responded well to steroid treatment and provided radiographic and functional evidence of this improvement. A 62-year-old female presented with a 4-month history of recurrent epigastric pain and a 5-kg weight loss. The oral glucose tolerance test （OGTT） indicated diabetes mellitus and the result of the fecal elastase test was abnormal. Ultrasonography （US） and the CT scan demonstrated a diffusely enlarged pancreas, and endoscopic retrograde cholangiopancreatography （ERCP） an irregular main pancreatic duct with long strictures in the head and tail. Autoimmune pancreatitis was diagnosed. The patient was started on 32 mg prednisolone daily, After 4 wk, the OGTT and faecal elastase test results had normalized. The repeated US and CT scan revealed a marked improvement of the diffuse pancreatic swelling, while on repeated ERCP, the main pancreatic duct narrowing was seen to be ameliorated. It is important to be aware of this disease and its diagnosis, because AIP can clinically resemble pancreatobiliary malignancies, or chronic or acute pancreatitis, However, in contrast with chronic pancreatitis, its symptoms and morphologic and laboratory alterations are completely reversed by oral steroid therapy.

关键词： Autoimmune pancreatitis Steroid therapy Chronic pancreatitis Pancreatic endocrine function Pancreatic exocrine function

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Diagnostic role of secretin-enhanced MRCP in patients with unsuccessful ERCP

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World journal of Gastroenterology 2004年第20期10卷 3034-3038页

作者： László Czakó Tamás Takács Zita Morvay László Csernay jános lonovics First Department of Medicine University of SzegedSzegedHungary International Medical Center SzegedHungary

AIM:To evaluate the value of MR cholangiopancreatography (MRCP)in patients in whom endoscopic retrograde cholangiopancreatography(ERCP)was unsuccessfully performed by experts in a tertiary center. METHODS:From january 2000 to june 2003,22 patients fulfilled the inclusion *** indications for ERCP were obstructive jaundice(n=9),abnormal liver enzymes(n=8), suspected chronic pancreatitis(n=2),recurrent acute pancreatitis(n=2),or suspected pancreatic cancer(n=1). The reasons for the ERCP failure were the postsurgical anatomy(n=7),duodenal stenosis(n=3),duodenal diverticulum(n=2),and technical failure(n=10).MRCP images were evaluated before and 5 and 10 rain after i.v. administration of 0.5 IU/kg secretin. RESULTS:The MRCP images were diagnosed in all 21 *** patients gave normal MR findings and required no further *** revealed abnormalities(primary sclerosing cholangitis,chronic pancreatitis,cholangitis,cholecystolithiasis or common bile duct dilation)in 20 patients,who were followed up *** patients subsequently underwent laparotomy(hepaticojejunostomy in consequence of common bile duct stenosis caused by unresectable pancreatic cancer;hepaticotomy+Kehr drainage because of insufficient biliary-enteric anastomosis;choledochoj- ejunostomy,gastrojejunostomy and cysto-Wirsungo gastrostomy because of chronic pancreatitis,or choledochojejunostomy because of common bile duct stenosis caused by chronic pancreatitis).Three patients participated in therapeutic percutaneous transhepatic *** indications were choledocholithiasis with choledochojejunostomy,insufficient biliary-enteric anastomosis,or cholangiocarcinoma. CONCLUSION:MRCP can assist the diagnosis and management of patients in whom ERCP is not possible.

关键词： Adult Aged Aged, 80 and over Biliary Tract Diseases Cholangiography Cholangiopancreatography, Endoscopic Retrograde Diagnosis, Differential Female Humans jaundice, Obstructive Magnetic Resonance Imaging Male Middle Aged Pancreatitis Prospective Studies Research Support, Non-U.S. Gov't Secretin Sensitivity and Specificity

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Efficacy of 6-mercaptopurine treatment after azathioprine hypersensitivity in inflammatory bowel disease

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World journal of Gastroenterology 2008年第27期14卷 4342-4346页

作者： Ferenc Nagy Tamás Molnár Zoltán Szepes Klaudia Farkas Tibor Nyári jános lonovics First Department of Medicine University of Szeged Faculty of Medicine Institute of Medical Informatics University of Szeged Faculty of Medicine

AIM:To investigate the efficacy of 6-mercaptopurine (6-MP) in cases of azathioprine (AZA) hypersensitivity in patients with inflammatory bowel disease. METHODS: Twenty nine previously confirmed Crohn’s disease (CD) (n = 14) and ulcerative colitis (UC) (n = 15) patients with a known previous (AZA) hypersensitivity reaction were studied prospectively. The 6-MP doses were gradually increased from 0.5 up to 1.0-1.5 mg/kg per day. Clinical activity indicies (CDAI/CAI), laboratory variables and daily doses of oral 5-ASA, corticosteroids, and 6-MP were assessed before and in the first, sixth and twelfth months of treatment. RESULTS: In 9 patients, 6-MP was withdrawn in the first 2 wk due to an early hypersensitivity reaction. Medication was ineffective within 6 mo in 6 CD patients, and myelotoxic reaction was observed in two. Data were evaluated at the end of the sixth month in 12 (8 UC, 4 CD) patients, and after the first year in 9 (6 UC, 3 CD) patients. CDAI decreased transiently at the end of the sixth month, but no significant changes were observed in the CDAI or the CAI values at the end of the year. Leukocyte counts (P = 0.01), CRP (P = 0.02), and serum iron (P = 0.05) values indicated decreased inflammatory reactions, especially in the UC patients at the end of the year, making the possibility to taper oral steroid doses. CONCLUSION: About one-third of the previously AZA- intolerant patients showed adverse effects on taking 6MP. In our series, 20 patients tolerated 6MP, but it was ineffective in 8 CD cases, and valuable mainly in ulcerative colitis patients.

关键词： Inflammatory bowel disease Azathioprine 6-mercaptopurine Side effects Efficacy

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Characterization of functional biliary pain and dyspeptic symptoms in patients with sphincter of Oddi dysfunction:Effect of papillotomy

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World journal of Gastroenterology 2006年第42期12卷 6850-6856页

作者： László Madácsy Roland Fejes Gábor Kurucsai Ildikó joó András Székely Viktória Bertalan Attila Szepes jános lonovics Department of Operative Gastroenterology and Endoscopy Fejér Megyei Szent-Gyrgy Hospital Székesfehérvár Hungary First Department of Internal Medicine University of Szeged Hungary

AIM： To characterize functional biliary pain and other gastrointestinal （GI） symptoms in postcholecystectomy syndrome （PCS） patients with and without sphincter of Oddi dysfunction （SOD） proved by endoscopic sphincter of Oddi manometry （ESOM）, and to assess the postendoscopic sphincterotomy （EST） outcome. METHODS： We prospectively investigated 85 cholecystectomized patients referred for ERCP because of PCS and suspected SOD. On admission, all patients completed our questionnaire. Physical examination, laboratory tests, abdominal ultrasound, quantitative hepatobiliary scintigraphy （QHBS）, and ERCP were performed in all patients. Based on clinical and ERCP findings 15 patients had unexpected bile duct stone disease and 15 patients had SOD biliary type Ⅰ. ESOM demonstrated an elevated basal pressure in 25 patients with SOD biliary-type Ⅲ. In the remaining 30 cholecystectomized patients without SOD, the liver function tests, ERCP, QHBS and ESOM were all normal. As a control group, 30 ‘asymptomatic＇ cholecystectomized volunteers （attended to our hospital for general cardiovascular screening） completed our questionnaire, which is consisted of 50 separate questions on GI symptoms and abdominal pain characteristics. Severity of the abdominal pain （frequency and intensity） was assessed with a visual analogue scale （VAS）. In 40 of 80 patients having definite SOD （i.e. patients with SOD biliary type Ⅰ and those with elevated SO basal pressure on ESOM）, an EST was performed just afl：er ERCP. In these patients repeated questionnaires were filled at each follow-up visit （at 3 and 6 too） and a second look QHBS was performed 3 mo after the EST to assess the functional response to EST. RESULTS： The analysis of characteristics of the abdominal pain demonstrated that patients with common bile duct stone and definite SOD had a significantly higher score of symptomatic agreement with previously determined biliary-like pain features than patient groups of PCS without SOD and controls. In

关键词： Postcholecystectomy pain Sphincter of Oddi dysfunction Functional biliary-pain Dyspeptic symptoms Endoscopic sphincterotomy Follow-up

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Interplay between nitric oxide and VIP in CCK-8-induced phasic contractile activity in the rabbit sphincter of Oddi

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World journal of Gastroenterology 2005年第21期11卷 3264-3266页

作者： Attila Pálv(o|¨)lgyi Réka Sári józsef Németh Annamária Szabolcs István Nagy Péter Hegyi jános lonovics Zoltán Szilvássy First Department of Medicine Faculty of Medicine University of SzegedH-6720 SzegedKorányi fasor 8-10 Hungary Department of Pharmacology Medical University of Pécs H-7643 Pécs Szigeti u. 12 Hungary First Department of Medicine Faculty of Medicine University of Szeged H-6720 Szeged Korányi fasor 8-10 Hungary Department of Pharmacology Medical University of Debrecen H-4032 DebrecenNagyerdei krt.98Hungary

AIM: The sphincter of Oddi (SO) plays an important role in delivery of bile into the duodenum. To establish whether vasoactive intestinal polypeptide (VIP) and nitric oxide (NO) were involved in phasic contractile activity of the rabbit SO stimulated by cholecystokinin-octapeptide (CCK-8). METHODS: Isolated SO muscle rings were cleaned of fat and mounted horizontally on two small L-shaped hooks one of which was connected to a force transducer for the measurement of isometric *** experiments were carried out in a thermostatically controlled (37±0.2℃) organ bath (5 mL) containing Krebs *** organ fluid was gassed with 95% O2 and 50 mL/L CO2 to keep the pH at 7.40±0.05. Contractile responses to CCK-8 (1 μmol/L) were evaluated in the presence and absence of NG-nitro-L-arginine (LNNA), an inhibitor of NO synthase (100 μmol/L), and (p-chloro-D-Phe6-Leu17)-VIP (VlPa, 30 μmol/L), a VIP receptor antagonist. RESULTS: CCK-8 stimulated the phasic activity of the SO. NO synthase inhibition increased the frequency and amplitude of contractions with a slight increase in developed tension. Pre-incubation with VlPa also attenuated this CCK-8 effect. The combined application of LNNA and VlPa abolished the phasic activity of the muscle rings with a marked increase in tension in response to CCK-8. CONCLUSION: VIP and NO together contribute to an increase in phasic activity of SO.

关键词： Sphincter of Oddi CCK VIP NO LNNA

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Insulin is necessary for the hypertrophic effect of cholecystokinin-octapeptide following acute necrotizing experimental pancreatitis

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World journal of Gastroenterology 2004年第15期10卷 2275-2277页

作者： Péter Hegyi Zoltán Rakonczayjr Réka Sári László Czakó Norbert Farkas Csaba Góg józsef Németh jános lonovics Tamás Takács First Department of Medicine Faculty of MedicineUniversity of Szeged Szeged H6722Hungary School of Cell and Molecular BiosciencesMedical SchoolUniversity of NewcastleNewcastle upon TyneNE2 4HHUnited Kingdom First Department of Medicine Faculty of MedicineUniversity of Szeged Szeged H6722Hungary Jr.School of Cell and Molecular BiosciencesMedical SchoolUniversity of NewcastleNewcastle upon TyneNE2 4HHUnited Kingdom First Department of Medicine Faculty of MedicineUniversity of Szeged Szeged H6722Hungary

AIM:In previous experiments we have demonstrated that by administering low doses of cholecystokinin-octapeptide (CCK-8),the process of regeneration following L-arginine (Arg)-induced pancreatitis is *** rats that were also diabetic(induced by streptozotocin,STZ),pancreatic regeneration was not *** aim of this study was to deduce whether the administration of exogenous insulin could in fact restore the hypertrophic effect of CCK-8 in diabetic-pancreatitic rats. METHODS:Male Wistar rats were used for the experiments. Diabetes mellitus was induced by administering 60mg/kg body mass of STZ intraperitoneally(i.p.),then,on d 8, pancreatitis was induced by 200mg/100 g body mass Arg *** at an interval of 1 *** animals were injected subcutaneously twice daily(at 7 *** 7 p.m.)with 1 μg/kg of CCK-8 and/or 2 IU mixed insulin(300g/L short- action and 700g/L intermediate-action insulin) for 14 d after pancreatitis *** this the animals were killed and the serum amylase,glucose and insulin levels as well as the plasma glucagon levels,the pancreatic mass/body mass ratio(pm/bm),the pancreatic contents of DNA,protein,amylase,lipase and trypsinogen were *** tissue samples were examined by light microscopy on paraffin-embedded sections. RESULTS:In the diabetic-pancreatitic rats treatment with insulin and CCK-8 significantly elevated pw/bm and the pancreatic contents of protein,amylase and lipase vs the rats receiving only CCK-8 ***-8 administered in combination with insulin also elevated the number of acinar cells with mitotic activities,whereas CCK-8 alone had no effect on laboratory parameters or the mitotic activities in diabetic-pancreatitic rats. CONCLUSION:Despite the hypertrophic effect of CCK-8 being absent following acute pancreatitis in diabetic-rats, the simultaneous administration of exogenous insulin restored this *** results clearly demonstrate that insulin is necessary for the hypertrophic ef

关键词： Animals Diabetes Mellitus, Experimental Hypoglycemic Agents Insulin Male Pancreatitis, Acute Necrotizing Rats Rats, Wistar Regeneration Research Support, Non-U.S. Gov't Sincalide

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Ethanol inhibits the motility of rabbit sphincter of Oddi in vitro

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World journal of Gastroenterology 2004年第23期10卷 3470-3474页

作者： Réka Sári Attila Pálv lgyi Zoltán Rakonczay jr Tamás Takács jános lonovics László Czakó Péter Hegyi Zoltán Szilvássy First Department of Medicine Faculty of MedicineUniversity of Szeged H-6720Koranyi fasor 10Hungary Department of Pharmacology Medical University of Debrecen H-4032Nagyerdei krt98Hungary

AIM:The rote of the sphincter of Oddi(SO)in ethanol (ETOH)-induced pancreatitis is *** aim was to characterise the effect of E-I-OH on basal and stimulated SO motility. METHODS:SOs removed from white rabbits were placed in an organ bath(Krebs solution,pH7.4,37℃).The effects of 2 mL/L,4 mL/L,6 mL/L and 8 mL/L of ETOH on the contractile responses of the sphincter were determined. SOs were stimulated with either 0.1 μmol/L carbachol,1 μmol/L erythromycin or 0.1 μmol/L cholecystokinin(CCK). RESULTS:ETOH at a dose of 4 mL/L significantly decreased the baseline contractile amplitude from 11.98±0.05 mN to 11.19±0.07 ***,no significant changes in the contractile frequency were ***(0.6%) significantly decreased both the baseline amplitude and the frequency compared to the control group(10.50±0.01 mN, 12.13±0.10 mN and 3.53±0.13 c/min,5.5±0.13 cycles(c)/min, respectively).Moreover,0.8% of ETOH resulted in complete relaxation of the ***(0.1 μmol/L)or erythromycin (1 μmol/L)stimulated the baseline amplitudes(by 82% and 75%,respectively)and the contractile frequencies (by 150% and 106%,respectively).In the carbachol or erythromydn-stimulated groups 2-6 mL/L of E-IOH significantly inhibited both the amplitude and the ***, a 4-5 min administration of 6 mL/L ETOH suddenly and completely relaxed the ***(0.1 μmol/L)stimulated the baseline amplitude from 12.37±0.05 mN to 27.40±1.82 mN within 1.60±0.24 *** this peak,the amplitude decreased to 17.17±0.22 mN and remained constant during the *** frequency peaked at 12.8±0.2 c/min, after which the constant frequency was 9.43±0.24 c/min throughout the rest of the *** at a dose of 4 mL/L significantly decreased the amplitude from 16.13±0.23 mN to 14.93±0.19 ***,no significant changes in the contractile frequency were *** at a dose of 6 mL/L inhibited both the amplitudes and the frequencies in the CCK-stimulated group,while 8 mL/L of E

关键词： Animals Carbachol Central Nervous System Depressants Cholecystokinin Cholinergic Agonists Erythromycin Ethanol Gastrointestinal Agents Gastrointestinal Motility In Vitro Male Rabbits Research Support, Non-U.S. Gov't Sphincter of Oddi

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Effect of herpesvirus infection on pancreatic duct cell secretion

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World journal of Gastroenterology 2005年第38期11卷 5997-6002页

作者： Péter Hegyi Balázs rdg Zoltán Rakonczai jr Tamás Takács jános lonovics Annamária Szabolcs Réka Sári András Tóth julius G Papp András Varró Mária K Kovács Mike A Gray Barry E Argent Zsolt Boldogki First Department of Medicine Department of Biology Division of Cardiovascular Pharmacology School of Cell and Molecular Biosciences

AIM： To examine the effect of acute infection caused by herpesvirus （pseudorabies virus, PRV） on pancreatic ductal secretion. METHODS： The virulent Ba-DupGreen （BDG） and non- virulent Ka-RREp01acgfp （KEG） genetically modified strains of PRV were used in this study and both of them contain the gene for green fluorescent protein （GFP）. Small intra/ interlobular ducts were infected with BDG virus （10^7 PFU/mL for 6 h） or with KEG virus （10^10 PFU/mL for 6 h）, while non-infected ducts were incubated only with the culture media. The ducts were then cultured for a further 18 h. The rate of HCO3 secretion [base efflux -λ（B）] was determined from the buffering capacity of the cells and the initial rate of intracellular acidification （1） after sudden blockage of basolateral base loaders with dihydro-4,4,- diisothiocyanatostilbene-2,2,-disulfonic acid （500 μmol/L） and amiloride （200 μmol/L）, and （2） after alkali loading the ducts by exposure to NH4Cl. All the experiments were performed in HCO3-buffered Ringer solution at 37 ℃ （n = 5 ducts for each experimental condition）. Viral structural proteins were visualized by immunohistochemistry. Virallyencoded GFP and immunofluorescence signals were recorded by a confocal laser scanning microscope.RESULTS： The BDG virus infected the majority of accessible cells of the duct as judged by the appearance of GFP and viral anUgens in the ductal cells. KEG virus caused a similarly high efficiency of infection. After blockage of basolateral base loaders, BDG infection significantly elevated -λB-） 24 h after the infection, compared to the non-infected group. However, KEG infection did not modify -λB-）. After alkali loading the ducts, -λB-） was significantly elevated in the BDG group compared to the control group 24 h after the infection. As we found with the inhibitor stop method, no change was observed in the group KEG compared to the non-infected group. CONCLUSION： Incubation with the BDG or KEG strains of PRV results in an effective i

关键词： Pancreas Hypersecretion Ductal cells Infection Pseudorabies virus

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A case of interstitial pneumonitis in a patient with ulcerative colitis treated with azathioprine

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World journal of Gastroenterology 2007年第2期13卷 316-319页

作者： Ferenc Nagy Tamas Molnar Eva Makula Ildiko Kiss Peter Milassin Eva Zollei Laszlo Tiszlavicz janos lonovics First Department of Medicine University of Szeged Faculty of Medicine Szeged Hungary Department of Radiology University of Szeged Faculty of Medicine Szeged Hungary Medical Intensive Care Unit University of Szeged Faculty of Medicine Szeged Hungary Institute of Pathology University of Szeged Faculty of Medicine Szeged Hungary

The early hypersensitivity reaction and late bone marrow depression are well-known side-effects of azathioprine, whereas interstitial pneumonia is a rare complication. A 40-year old male patient had been treated with azathioprine in consequence of extensive ulcerative colitis for 10 years. He then complained of 7 d of fever, cough and catarrhal signs, without symptoms of active colitis. Opportunistic infections were ruled out. The chest X-ray, CT and lung biopsy demonstrated the presence of interstitial inflammation. Azathioprine therapy was discontinued as a potential source of the pulmonary infiltrate. In response to steroid therapy, and intensive care, the pulmonary infiltrate gradually decreased within 4 wk. Three months later, his ulcerative colitis relapsed, and ileo-anal pouch surgery was performed. In cases of atypical pneumonia, without a proven infection, azathioprine-associated interstitial pneumonitis may be present, which heals after withdrawal of the drug.

关键词： Inflammatory bowel disease Ulcerative colitis Azathioprine Interstitial pneumonitis

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