Acute pancreatitis revealing diffuse infiltration of the pancreas by melanoma.
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Biomedical subjects
Publications and source records attributed to J Fritsch.
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The osmosensitivity of the hyperpolarization-activated chloride current (I(Clhyp)) in T84 cells was studied using the whole cell patch-clamp recording configuration. Hypotonicity is known to activate an outwardly rectifying chloride current (HIORC) distinct from I(Clhyp) in these cells. The differing sensitivities of HIORC and I(Clhyp) toward inhibitors (1,9-dideoxyforskolin blocked HIORC but not I(Clhyp), and Cd2+ inhibited I(Clhyp) but not HIORC) allowed us to investigate the osmoregulation of I(Clhyp). Hypotonicity induced an increase in I(Clhyp) amplitude. Protein phosphatase inhibitors prevented this effect, and hypotonic solutions became slightly inhibitory. Hypertonicity resulted in a transient increase in I(Clhyp) amplitude followed by a large decrease. The complex responses of I(Clhyp) to osmotic changes indicate that these signals affect the same channel via multiple transduction pathways. The responses of I(Clhyp) to hypotonicity have features in common with the responses of ClC-2 channels expressed in Xenopus oocytes (activation) and with hyperpolarization-activated chloride currents in other cell types, such as osteoblasts and mandibular duct cells (inhibition).
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OBJECTIVES: About 2% of common bile duct stones and most intra-hepatic stones cannot be removed by conventional endoscopy. Intra-corporeal lithotripsy is an alternative technique for these patients. Contact lithotripsy can be obtained by a pulsed dye laser or by electro-hydraulic shockwaves. We compared and assessed the results of these two methods. METHODS: Thirty-seven patients (79 +/- 9.8 years, 25 women and 12 men) underwent laser lithotripsy (n = 21), electro-hydraulic lithotripsy (n = 9) or both methods consecutively (n = 7) for common bile duct stones (n = 31), intra-hepatic stones (n = 3) or diffuse lithiasis (n = 3). The mean diameter of the largest stone was 23 +/- 12 mm. Lithotripsy was performed by a retrograde approach in 35 cases and a combined, retrograde and transhepatic approach in 2 cases. RESULTS: The mean number of lithotripsy sessions was 1.5 +/- 0.65. The overall success rate (free bile ducts with patent drainage) was 95%. In 2 patients, stones were not fully extracted: one underwent surgery, the other one was treated conservatively with antibiotics. The duration of the hospital stay was 9.3 +/- 4.5 days. Morbidity at 30 days was 27% and only one case of major morbidity (hemorrhage after sphincterotomy, 2.7%) was observed. There were no procedure-related mortality. Electro-hydraulic and laser groups did not differ significantly for success rate, morbidity and time spent at hospital. Follow-up information was obtained in 34 patients (91.8%) a median of 17 months after lithotripsy (range: 4.52 months). Ten patients died of non-biliary diseases. Two patients (5.8%) developed biliary symptoms 24 and 34 months after lithotripsy, one after unsuccessful lithotripsy. CONCLUSION: Intra-corporeal lithotripsy is a valuable tool for the most complex cases of duct stones, and with an acceptable morbidity. The results of the two techniques are similar. Late biliary complications after intra-corporeal lithotripsy appear to be rare.
The properties of a protein-kinase-A(PKA)-activated Cl(-)-conductive pathway(s) in alkaline phosphatase-enriched microsomes from the rat inner medulla (IMV) were investigated. Transcripts of cystic fibrosis transmembrane regulator (CFTR) were detected by reverse transcription/polymerase analysis of total RNA from the inner medulla, while immunoblot analysis using anti-CFTR antibodies detected a 170-kDa protein in the IMV. The PKA Cl(-)-conductive pathway(s) was studied by measuring the rate of valinomycin-induced microsomal swelling by light scattering. PKA increased the rate of valinomycin-induced swelling of vesicles consistent with the presence of Cl(-)-conductive pathway(s). The pharmacological properties and anion selectivity of the PKA-activated Cl(-)-conductive pathway(s) were similar to those of the CFTR Cl(-) channel. Our results show that a CFTR Cl(-) channel and possibly another cAMP-activated pathway(s) may participate in Cl(-) secretion in the rat inner medulla.
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BACKGROUND: Endoscopic sphincterotomy is sometimes done unnecessarily in patients with suspected choledocholithiasis. Our aims were to assess the diagnostic accuracy of endoscopic ultrasonography and endoscopic retrograde cholangiography (ERC) and to find out whether endoscopic ultrasonography may help to prevent unnecessary sphincterotomy or surgical explorations. METHODS: We recruited 119 patients aged 70.4 (SD 16.1) years with strongly suspected choledocholithiasis who presented to our endoscopy unit between January, 1994, and January, 1995. During the same spell of sedation or within 2 h of each other, endoscopic ultrasonography and ERC were carried out by investigators unaware of the patient's history. Endoscopic sphincterotomy with instrumental exploration was then done as the gold standard for the presence or the absence of stones. FINDINGS: 78 (66%) patients had choledocholithiasis; 17 (14%) had other bileduct diseases; 24 (20%) had a clear bileduct or did not require an invasive endoscopic procedure. The sensitivity of endoscopic ultrasonography was 93%, specificity 97%, positive predictive value 98%, and negative predictive value 88%. The corresponding values for ERC were 89%, 100%, 100%, and 83%. There were five false-negative cases by endoscopic ultrasonography (of which three were also negative with ERC) and one false-positive. The morbidity rate was 4.1%. INTERPRETATION: We conclude that endoscopic ultrasonography is at least as sensitive as ERC. Endoscopic ultrasonography may prevent inappropriate invasive explorations of the common bileduct.
1. Hyperpolarization-activated Cl- currents (ICl,hyp) were investigated in the T84 human adenocarcinoma cell line, using the patch-clamp whole-cell configuration. 2. During whole-cell recording with high-chloride and ATP-containing internal solutions, hyperpolarizing jumps from a holding potential of 0 mV elicited slow inward current relaxations, carried by Cl- and detected at membrane potentials more negative than -40 mV. Analysis of the relative permeabilities to monovalent anions gave the following sequence: Cl- > Br- > I- > glutamate. 3. ICl,hyp was partially inhibited by 1 mM diphenylamine-2-carboxylic acid or 0.1 mM 5-nitro-2-(3-phenylpropylamino)-benzoate, and was completely blocked by Cd2+ (> 300 microM). It was insensitive to 1 mM external 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid or 1 mM Ba2+. 4. ICl,hyp was inhibited by external application of 500 microM cptcAMP (8-(4-chlorophenylthio)-adenosine 3':5'-cyclic monophosphate) or 500 nM of the protein kinase C activator, phorbol 12-myristate, 13-acetate. 5. (i) Omission of ATP from the pipette solution, (ii) ATP replacement by the non-hydrolysable ATP analogue 5'-adenylylimidodiphosphate, and (iii) inhibition of protein kinase C by staurosporine or calphostin C accelerated the activation kinetics of the current and increased its amplitude, but did not alter its pharmacological properties. 6. We conclude that hyperpolarization-activated Cl- channels similar to those of ClC-2 channels (mammalian homologue of Torpedo chloride channel ClC-0) are present in T84 cells, and that their gating properties are modulated by phosphorylation.
BACKGROUND: Nonsurgical alternatives in biliary diseases have not been studied in large series of patients with cirrhosis. Our aim was to determine the indications and results of endoscopic treatment in this subset of patients. METHODS: Fifty-two patients (36 men, 16 women-Child-Pugh Class A, 18; B, 22; C, 12) aged 63 +/- 18 years underwent endoscopic sphincterotomy (ES) between 1988 and 1993. Antibiotic prophylaxis was routinely carried out and coagulopathy was corrected before ES when required. The data were collected retrospectively up to 30 days after ES. RESULTS: ES succeeded in 98% of the patients (12 cases of needle-knife papillotomy). Twenty-nine patients (55.7%) had choledocholithiasis, 18 had biliary strictures (12 malignant), and 5 had pancreatic or other biliary diseases. Five days after ES, morbidity was 13.5% and mortality was 7.7%. At 1 month, morbidity was 22.9% and mortality 12.5%. Only endoscopic procedures and Ineffective drainage were seen to be significant risk factors or morbidity. The results of the subgroup of cirrhotic patients with choledocholithiasis (n = 29) were compared with those of matched noncirrhotic patients (n = 58). The cirrhotic and noncirrhotic patients treated for choledocholithiasis showed similar results for stone clearance, morbidity, and mortality. CONCLUSION: ES is a safe and effective procedure for treating choledocholithiasis in cirrhotic patients. ES can therefore be considered as an alternative to surgery in Child class A and B patients and must be preferred for Child class C patients with life-threatening biliary complications.
BACKGROUND/AIMS: Biliary obstruction secondary to portal cavernoma is a rare and little-known entity. From 1985 to 1994, we observed eight cases of portal cavernoma compressing the biliary tract. We report here the features of biliary involvement in these cases of portal cavernoma including the circumstances of diagnosis, biliary tract morphology, liver pathology and the efficiency of various treatments. METHODS AND RESULTS: The causes of portal vein obstruction were portal vein thrombosis in one case, peritonitis in another, omphalitis in two cases, portal vein catheterization in one case and unknown in two cases. The portal cavernoma was revealed through esophageal varices ruptures in four patients. The mean time from portal cavernoma diagnosis to biliary involvement was 8 years (range 0-21). Six patients had acute cholangitis, one of whom revealed portal vein obstruction. All the patients had abnormal liver function tests. Imaging techniques (transparietal abdominal ultrasonography and abdominal computed tomography scan [n = 8], endosonography [n = 5] and endoscopic retrograde cholangiography [n = 7]) showed in all cases an extraluminal obstacle, laminating the common bile duct. Pathologic examination of the liver showed secondary biliary cirrhosis in one patient, periportal and perisinusoidal fibrosis in another and no abnormalities in three other cases. Three patients were treated by endoscopic sphincterotomy but cholangitis persisted in two cases, leading to death in one. One patient who underwent a splenorenal shunt was symptom-free 60 months after surgery. Balloon endoscopic dilatation of the common bile duct, performed in one case, led to normalization of liver biological tests. The patients with abnormal liver pathology were treated by propranolol and ursodesoxycholic acid. No complication had occurred after 6 and 24 months of follow-up. CONCLUSIONS: In conclusion, eliminating biliary obstruction seems to be essential in providing the best change of survival for patients when biliary obstruction becomes symptomatic. In cases of abnormal liver pathology, associating propranolol with ursodesoxycholic acid would seem to be useful.
BACKGROUND & AIMS: Although long-term results of endoscopic sphincterotomy (ES) have been poorly estimated, extended indications of ES have been proposed, especially in young patients. The aim of this study was to assess late biliary complications of ES. METHODS: Between 1981 and 1986, 169 patients younger than age 70 (55+/-11.8 years; range, 24-70 years; male-female sex ration, 0.55) underwent ES for choledocholithiasis. One hundred fifteen patients (68%) underwent cholecystectomy. Long-term data were obtained retrospectively from the patients and general practitioners. RESULTS: Information was obtained for 156 patients, 2 of whom died within 1 month (one ES-related death). The mean follow-up for 154 patients was 9.6+/-3.3 years (range 8-13 years); 138 patients had no biliary symptoms. During follow-up, 16 patients experienced biliary symptoms; 2 of these patients underwent elective cholecystectomy, 3 had malignant strictures, 1 had a complicated cirrhosis, and 1 had a benign stricture related to the previous cholecystectomy. Nine patients developed potentially ES-related biliary symptoms. Second endoscopic exploration showed papillary stenosis in 3 patients (with stones in 2 patients) and recurrent bile duct stones in 3 others. Two patients had sine materia cholangitis, and 1 patient developed liver abscesses. CONCLUSIONS: Long-term ES-related complications seem to be rare, ES could reasonably be included in management strategies of choledocholithiasis, even in young patients.
OBJECTIVE: To evaluate the value of biliary carcino-embryonic antigen (CEA) in the differential diagnosis of malignant and benign hepatopancreatobiliary disease. PATIENTS: One hundred patients were prospectively studied. Benign diseases were present in 39% of the patients while 61% had malignant diseases. METHODS: Samples of serum were taken from all patients just before endoscopic retrograde cholangiopancreatography (ERCP) and samples of biliary CEA were obtained during ERCP. RESULTS: The sensitivity of serum CEA and carbohydrate antigen 19-9 (CA 19-9) in detecting malignancy were 50% and 92%, respectively, while the respective specificities were 95% and 72%. The mean biliary CEA level of the benign group was significantly different from that of the malignant group (35.7 +/- 8.7 ng/ml vs 268 +/- 85.5 ng/ml), but there was considerable overlap between the two groups. With a cut-off level of 20 ng/ml, the sensitivity and specificity were 84% and 64% respectively. The mean bilirubinaemia value was significantly higher in malignant disease than in benign disease (57.4 +/- 13.9 mumol/l vs 235 +/- 19.8 mumol/l). Multidimensional analysis indicated that only bilirubinaemia (P < 109-3)) was independently predictive of malignant disease. CONCLUSION: Biliary CEA assessment seems useless in distinguished between benign and malignant causes of cholestasis.
The cystic fibrosis transmembrane conductance regulator (CFTR) is a transmembrane protein that is expressed in several epithelia, including kidney tubules. Mutations in CFTR (a PKA-chloride channel and/or regulator of other epithelial channels) give rise to the clinical manifestation of cystic fibrosis, and result in the synthesis of mutated proteins responsible for altering ion transport across secretory epithelia. The low abundance of endogenous CFTR makes a difficult to purify enough of the native protein to prepare anti-CFTR antibodies. We have used differential centrifugation to prepare cortical brush border membrane vesicles from pig kidney, cBBMV, and developed a method for the partial purification of CFTR. This is the first step in the isolation of native CFTR. The results show that CFTR is present in cBBMV. The purified protein will provide a clearer picture of the biophysical and biochemical properties of native CFTR.
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The cholangiographic features of intrahepatic bile ducts associated with cirrhosis or fibrosis are not well known. In order to achieve a radiological-pathological correlation, we studied nine livers with fibrosis or cirrhosis excised at autopsy. Cholangiograms were obtained within 24 hr after death from the nonfixed liver and multiple tissues samples were taken for histologic examination. Radiological data were interpreted by two independent investigators blinded to the clinical and histological findings. Cirrhosis (alcoholic in 4, posthepatitis in two) was observed in six livers, fibrosis (alcoholic in 2, posthepatitis in one) in three. No liver with fibrosis had cholangiographic abnormalities. In contrast, cholangiography of all livers with cirrhosis was abnormal. Abnormalities were a diminished arborization, a decrease of the distal opacification, an irregularity of caliber, and a tortuous course of the bile ducts. Histological study showed that the irregular and tortuous course were due to compression of the bile ducts by regenerative nodules. Furthermore, a thick fibrosis was organized around the bile ducts. In conclusion, fibrosis alone was not associated with cholangiographic abnormalities. In cirrhotic livers, intrahepatic bile ducts showed an irregular and tortuous course, a diminished arborization and a decrease of the distal opacification. These abnormalities were secondary to the presence of regenerative nodules and fibrosis organized around the bile ducts.
OBJECTIVE: To determine more precisely the clinical and biological characteristics of AIDS-related cholangitis, and to investigate prognostic variables of this disease. DESIGN: Retrospective clinical and prognostic study. SETTING: Biliary unit, Bicêtre Hospital, France. PATIENTS: HIV-positive patients (n = 52) referred to the unit between December 1986 and June 1993 for biliary symptoms leading to the suspicion of AIDS-related cholangitis, (42 men; 10 women; mean age, 37 +/- 8 years). INTERVENTION: Endoscopic retrograde cholangiopancreatography (ERCP) was performed in order to determine the cause of the biliary symptoms. MAIN OUTCOME MEASURE: Clinical features and evolution of the cholangitis. RESULTS: Among the 52 patients, 45 met the ERCP criteria of AIDS-related cholangitis (36 men; nine women). The diagnosis of cholangitis was strongly suggested by abdominal ultrasonography in 47% of the cases. ERCP showed papillary stenosis, diffuse cholangitis, extrahepatic cholangitis alone, and intrahepatic cholangitis alone in 60, 67, 7 and 27%, respectively. Endoscopic sphincterotomy was performed in 28 patients. Pain was relieved by sphincterotomy in nine patients, but the other clinical or biological features were not influenced. One-year and 2-year survival rates were 41 +/- 7% and 8 +/- 4%, respectively. Multidimensional analysis using a Cox model showed that a lymphocyte count > 500 x 10(6)/l was the only independent predictive factor of better survival. CONCLUSION: AIDS-related cholangitis is a disease which leads preferentially to papillary stenosis or diffuse abnormalities of the biliary tract. Prognostic factors depend on the stage of the HIV infection. Another diagnosis of cholestasis was found in approximately 15% of the patients who showed biliary symptoms.
We have identified an mRNA element that is involved in the initial cleavage of the pufBALMX mRNA species in Rhodobacter capsulatus. This endoribonuclease recognition site, the first to be identified in a bacterial species other than Escherichia coli, shows strong similarities to mRNA sequences cleaved by the endoribonuclease E in E. coli. The presence of an RNase E-like enzyme in R. capsulatus is further supported by in vitro cleavage of E. coli transcripts by R. capsulatus extracts at sites attributed to RNase E and by the cross-reaction of a polypeptide from R. capsulatus with antisera against E. coli RNase E. Our data provide evidence that mRNAs are degraded in different bacterial species by enzymes with similar recognition sequences and activities. We present a model that attributes the segmental differences in stability of the polycistronic puf transcript to a specific distribution of mRNA decay-promoting and mRNA decay-impeding elements.
OBJECTIVE: To characterize a subgroup of patients treated with endoscopic sphincterotomy (ES) for a suspected common bile duct lithiasis (CBDL) that was not confirmed and to compare it with the subgroup with confirmed CBDL. METHODS AND RESULTS: Over 18 months, ES was successful in 245 consecutive patients (age 23-97, mean 75 yr, SE 17 yr) with suspected CBDL; 159 patients had CBDL (group 1), and 86 did not (group 2), as confirmed by CBD exploration. Fifty-nine percent of the patients in group 1 and 76.7% of the patients in group 2 had gallbladder in situ. Both groups were different for age (p < 0.001), prevalence of chronic alcoholism (p < 0.001), gallbladder in situ (p < 0.01), and gallbladder stones (p < 0.05). Patients from group 1 had two or more presenting symptoms suggestive of CBDL more often than patients from group 2 (p < 0.05), and pancreatitis was a more frequent presenting manifestation in group 2 (p < 0.0001). Overall morbidity and mortality were not different between groups, but acute cholecystitis developed in six patients from group 2 and in one patient from group 1 (p < 0.01). In a univariate analysis, only elevated alkaline phosphatase and a dilated common bile duct were positively discriminant for the diagnosis of CBDL; chronic alcoholism was negatively discriminant for the diagnosis of CBDL. In a multivariate analysis, only chronic alcoholism and a dilated bile duct were found to be independently discriminant. CONCLUSION: The risk of ES-related complications in the group without CBDL suggests that the selection of patients should be improved by a better use of preoperative criteria.