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J Fritsch

Publications and source records attributed to J Fritsch.

At least 37 records · Page 2Linked to original sources

Properties of chloride-conductive pathways in rat kidney cortical and outer-medulla brush-border membranes--inhibition by anti-(cystic fibrosis transmembrane regulator) mAbs.

The activity of the Cl(-)-conductive pathways, their regulation by protein kinase A (PKA) and their relationship to the cystic fibrosis transmembrane regulator (CFTR) protein were assessed in rat kidney cortical brush-border-membrane vesicles (cBBMV) and outer medullary vesicles (OMV) by measuring the rate of valinomycin-induced microsomal swelling by light scattering in the presence of an inward Cl- gradient. Valinomycin increased the rate of swelling of cBBMV and OMV, which is consistent with the presence of a Cl(-)-conductive pathway. PKA further increased these rates. This effect was blocked by the inhibitor of protein kinase A, suggesting that phosphorylation by PKA activates these pathways. Four anion-transport inhibitors were tested ¿N-phenylanthranilic acid (PhNHPhCOOH), 5-nitro-2-(3-phenylpropylamino)benzoic acid [N(PhPrNH2)BzOH], glybenclamide and 4-acetamido-4'-isothiocyanato-stilbene-2,2'-disulfonic acid¿. Ph2COOH and 4-acetamido-4'-isothiocyanato-stilbene-2,2'-disulfonic acid inhibited the basal Cl(-)-conductive pathways, while PKA-treated microsomes were sensitive also to N(PhPrNH2)BzOH and glybenclamide, suggesting that additional Cl- pathways were activated by phosphorylation. The pharmacological properties of these pathways were similar to those of the CFTR Cl- channel. Two anti-CFTR mAbs inhibited PKA-activated valinomycin-induced swelling in cBBMV and OMV, while immunoblot analysis of the corresponding proteins with the same antibodies indicated the presence of a 170-kDa protein. The results thus indicate the presence of a PKA-activated Cl(-)-conductive pathway in cBBMV and OMV, and suggest that CFTR protein is involved in PKA-activated Cl- fluxes in these vesicles.

Animals↗

Endoscopic sphincteroclasy: a useful therapeutic tool for biliary endoscopy in Billroth II gastrectomy patients.

BACKGROUND AND STUDY AIMS: Endoscopic exploration of the common bile duct is generally more difficult and hazardous in patients with a Billroth II gastrectomy than in patients with normal anatomy. Hydrostatic dilation of the papilla, which we term "endoscopic sphincteroclasy", provides a useful alternative to sphincterotomy in such patients. PATIENTS AND METHODS: Endoscopic sphincteroclasy was carried out in five patients with a Billroth II anastomosis. There were four men and one woman, aged 58 to 90 years. One patients was cirrhotic, with impaired coagulation. Four presented with typical cholangitis, and one had pain and jaundice. The common bile duct was dilated in all five patients. Four had choledocholithiasis and one had a cholangiocarcinoma. RESULTS: Sphincteroclasy was carried out with balloon dilators mounted on 0.035-inch guide wires. Immediate extraction of stones was achieved in three of the four patients with choledocholithiasis. In one case, a control endoscopic retrograde cholangiopancreatography was necessary to remove residual stones, without additional dilation. Insertion of the endoprosthesis was possible without difficulty in the patient with a malignant stricture. None of the patients required a sphincterotomy. No complications were observed up to six months after the sphincteroclasy. CONCLUSIONS: We recommend the use of endoscopic sphincteroclasy in patients with a Billroth II gastrectomy who require endoscopic therapy, as well as in patients in need of emergency bile duct decompression who have impaired coagulation.

Aged↗

What role can endoscopy play in the management of biliary complications after laparoscopic cholecystectomy?

BACKGROUND AND STUDY AIMS: This study was carried out to establish the indications for biliary endoscopy due to biliary complications after laparoscopic cholecystectomy (LC). PATIENTS AND METHODS: One hundred nineteen patients (36 men, 86 women; median age 59, range 16-93) were referred for endoscopic retrograde cholangiopancreatography (ERCP) to five centers between 1990 and 1994, and included in the study. The delay between LC and ERCP was 105 +/- 21 days. RESULTS: Four types of complications were observed. a) Fifty-seven patients had residual stones or clip migration into the common bile duct (CBD); all were successfully treated with endoscopic sphincterotomy (ES). b) Twelve major injuries to the CBD were diagnosed by ERCP; successful surgical repair was carried out in most of these cases. c) Twenty patients had a partial biliary stricture; endoscopic stenting was attempted as a primary procedure in eight patients, with a satisfactory outcome in five (63%). d) Thirty patients had a bile leak; endoscopic therapy (26 patients) led to recovery in 18 (69%). The benefit of endoscopic treatment was less clear in five (19%); ES failed to bring about improvement in three patients (12%). CONCLUSIONS: ERCP is indicated when a biliary complication is suspected after laparoscopic cholecystectomy. Endoscopic sphincterotomy is effective for the treatment of retained stones, clip migration, and bile leakage. Endoscopic stenting may be offered as a primary option in partial CBD strictures.

Adolescent↗

Osmosensitivity of the hyperpolarization-activated chloride current in human intestinal T84 cells.

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).

Cells, Cultured↗

[Intra-corporeal shockwave lithotripsy in the treatment of complex lithiasis of the bile ducts. Comparison of endoscopic techniques and long-term results].

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.

Aged↗

Properties of a Cl(-)-conductive pathway(s) in microsomes from rat kidney inner medulla. Involvement of cystic fibrosis transmembrane regulator protein.

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.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Prospective controlled study of endoscopic ultrasonography and endoscopic retrograde cholangiography in patients with suspected common-bileduct lithiasis.

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.

Adult↗

Modulation of the hyperpolarization-activated Cl- current in human intestinal T84 epithelial cells by phosphorylation.

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.

Adenosine Triphosphate↗

Endoscopic sphincterotomy in patients with liver cirrhosis.

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.

Adult↗

Biliary obstruction caused by portal cavernoma: a study of 8 cases.

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.

Abdomen↗

Biliary symptoms and complications more than 8 years after endoscopic sphincterotomy for choledocholithiasis.

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.

Adult↗

Bile levels of carcino-embryonic antigen in patients with hepatopancreatobiliary disease.

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.

Adult↗

Partial purification of the pig kidney cystic fibrosis transmembrane regulator protein.

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.

Animals↗