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At least 541 records · Page 30Linked to original sources
PubMed1994

Restoration of exocrine pancreatic function following pancreas-liver-kidney transplantation in a cystic fibrosis patient.

Pancreatic transplantation for endocrine replacement is well-established for insulin-dependent diabetes mellitus. Exocrine pancreatic function after pancreas transplantation has been maintained after orthotopic cluster transplants for malignancy, and restoration of adequate exocrine function in a previously deficient patient has been reported in a patient with chronic pancreatitis who developed labile diabetes and steatorrhea after pancreatectomy. We performed a triple organ transplant (pancreas, liver and kidney) in a patient with exocrine pancreatic insufficiency and insulin-dependent diabetes related to cystic fibrosis (CF) after he developed hepatic and renal failure. Pancreatic exocrine secretions were drained enterically to the jejunum. At 24-month follow-up, malabsorption is absent. The 3-day stool fat, stool trypsin and chymotrypsin are normal. Serum carotene is within the normal range. Exocrine pancreatic insufficiency in CF patients can be corrected by pancreas transplantation. However, routine use in CF is precluded by the risks of surgery and immunosuppression. For diabetic patients with pancreatic exocrine insufficiency who require another organ transplant (e.g., lung, liver, or kidney), simultaneous pancreas transplantation with the exocrine secretions directed into the upper gastrointestinal tract should be considered.

Adult↗
PubMed1994

A 32-bp deletion (2991del32) in the cystic fibrosis gene associated with CFTR mRNA reduction.

Cystic fibrosis, a common recessive disorder of exocrine glands, is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. We describe the identification of a 32-bp deletion within the coding region of CFTR that involves the nucleotides 2991-3022 in exon 15 (2991del32). This unusual frameshift mutation was confirmed in three unrelated German families, accounting for a frequency of 0.3% in 1,028 CF chromosomes. All identified patients are compound heterozygotes for 2991del32 and for the most frequent cystic fibrosis mutation, delta F508. The evaluation of clinical data revealed typical symptoms of cystic fibrosis, including pancreatic insufficiency, in all three index cases. To characterize further the mutation in the CFTR transcript, we analysed RNA from lymphocytes by reverse transcription and PCR amplification. 2991del32 transcripts were detectable neither in the RNA sample from a patient compound heterozygous delta F508/2991del32 nor in the parental sample heterozygous wild-type/2991del32. These data indicate that the 32-bp deletion causes a pancreas insufficient cystic fibrosis phenotype by a severe reduction of CFTR mRNA.

Adolescent↗
PubMed2005

Mucinous cystadenocarcinoma of the pancreas in an adolescent with cystic fibrosis.

Epidemiologic studies indicate that the overall risk of malignancy among patients with cystic fibrosis (CF) is similar to that of the general population. However, these studies and a number of case reports suggest that patients with CF may be at increased risk for the development of specific gastrointestinal cancers. Tumors of the esophagus, stomach, small and large bowels, liver and biliary tracts, and pancreas have been described. Previous reports of pancreatic cancers among patients with CF have included only adenocarcinoma in adults. This is the first description of a mucinous cystadenocarcinoma of the pancreas in an adolescent with CF. The tumor developed within a pancreatic cyst that had been initially identified 13 years before resection. Our report highlights the increased risk of pancreatic malignancy among patients who have CF and illustrates the premalignant potential of pancreatic cysts in this at-risk population. Further, it reinforces the need for careful surveillance and suggests a role for more aggressive diagnostic and therapeutic interventions for patients with atypical findings on pancreatic imaging studies.

Adolescent↗
PubMed1993

Improvement of fecal fat excretion after addition of omeprazole to pancrease in cystic fibrosis is related to residual exocrine function of the pancreas.

Pancreatic function tests were performed in 11 adult cystic fibrosis (CF) patients with a fecal fat excretion of more than 10% during treatment with pancrease 2 capsules three times a day. These tests included urinary p-aminobenzoic acid (PABA) excretion, fasting serum trypsin and pancreatic polypeptide (PP), and glucose and insulin in fasting and postprandial serum. Subsequently, the patients entered a double-blind placebo-controlled crossover study to assess the effect of gastric acid inhibition by 20 mg omeprazole on fecal fat excretion. Adjunct therapy with omeprazole resulted in a reduction of fecal fat excretion in patients with residual pancreatic function. This improvement showed significant positive correlations with urinary PABA excretion and the increase in serum PP after the meal (P < 0.02 and P < 0.05), but not with the other parameters studied. Therefore, the addition of omeprazole to pancrease is most successful in CF patients with residual pancreatic function, determined by urinary PABA excretion or incremental PP.

Adult↗
PubMed1998

Acinar lumen pH regulates endocytosis, but not exocytosis, at the apical plasma membrane of pancreatic acinar cells.

A two-step exocytosis/endocytosis protocol was used in rat pancreatic acini to study membrane trafficking events at the apical plasma membrane (APM) as a function of extracellular pH. Exocytosis, as measured by cholecystokinin (CCK)-8-induced release of amylase into the incubation medium, was relatively insensitive to changes in extracellular pH from 5.5 to 9.0. In contrast, endocytosis, as measured by temperature-dependent uptake of horseradish peroxidase (HRP), was robust at pH values between 6.5 and 8.3 but abolished at acidic pH values of 5.5 to 6.0. Energy metabolism and cell viability were maintained during pH 6-induced cessation of HRP uptake, and the vesicular block could be reversed upon raising the luminal pH to 7.4. Histochemical and morphometric studies of HRP uptake examined by electron microscopy indicated that extracellular pH regulates endocytosis at the apical plasma membrane. At pH 6.0 in prestimulated cells, HRP uptake at the APM was abolished, and acinar lumen membranes remained markedly dilated with decreased density of microvilli and "arrested" exocytic images. At pH 7.4, HRP was taken up into endolysosomal structures within the Golgi complex, and acinar lumen membranes were contracted. Cleavage of GP2, a glycosyl phosphatidylinositol-anchored protein, was associated with the pH-dependent activation of HRP uptake. These studies demonstrate that acinar lumen pH regulates endocytic but not exocytic activity at the APM and suggest that alkalinization of the acinar lumen by duct cells is required for retrieval of exocytic membranes into the acinar cell via vesicular uptake mechanisms. The role of acid-base interactions within the acinar lumen provides a novel basis for understanding the cellular and luminal defects observed within the exocrine pancreas in cystic fibrosis.

Animals↗
PubMedDate not supplied

[Chronic sinusitis and nasal polyp as the initial manifestation of cystic fibrosis].

We report the case of a fourteen years old girl suffering from cystic fibrosis of pancreas, whose first clinic symptoms were chronic sinusitis and nasal polyp. Her most characteristic features were normal height growth without manifestations of pancreatic insufficiency or chronic endobronchial infections. Normal spirometry. PC 20 histamine > or = 16 mEq/ml. Negative skin test (prick) to common inhalants and sweat chloride concentration ranging between 92 and 110 mmol/l.

Adolescent↗
PubMed2001

150 mM HCO3(-)--how does the pancreas do it? Clues from computer modelling of the duct cell.

Cystic fibrosis (CF) takes its name from the pathological changes that occur in the pancreas. Cystic fibrosis transmembrane conductance regulator (CFTR) is highly expressed in the pancreatic ductal epithelium and plays a key role in ductal HCO(3)(-) secretion. In humans, the pancreatic duct secretes near isotonic NaHCO(3). Experimental data suggests that HCO(3)(-) secretion occurs via apical Cl(-)/HCO(3)(-) exchangers working in parallel with Cl(-) channels (CFTR and calcium activated chloride channels, CaCC). Programming the currently available experimental data into our computer model (based on network thermodynamics) shows that while the anion exchanger/Cl(-) channel mechanism will produce a relatively large volume of a HCO(3)(-)-rich fluid, it can only raise the luminal HCO(3)(-) concentration up to about 70 mM. To achieve secretion of about 150 mM NaHCO(3) it is necessary to modulate the properties of the apical membrane transporters as the secreted fluid flows down the ductal system. On the basis of our computer simulations, we propose that HCO(3)(-) secretion occurs mainly via the exchanger in duct segments near the acini (luminal HCO(3)(-) concentration up to about 70 mM), but mainly via channels further down the ductal tree (raising luminal HCO(3)(-) to about 150 mM). We speculate that the switch between these two secretory mechanisms is controlled by a series of luminal signals (e.g. pH, HCO(3)(-) concentration) acting on the apical membrane transporters in the duct cell.

Animals↗
PubMed1991

Selective deficiency of pancreatic amylase.

Two patients with specific pancreatic amylase deficiency are described. The greatly reduced pancreatic amylase activity was not due to an enzymatically inactive amylase molecule but to an almost complete absence of the molecule itself. The findings are of diagnostic importance as they show that low pancreatic amylase activity in serum or duodenal aspirates, or both, does not necessarily represent chronic exocrine pancreatic disease such as chronic pancreatitis, carcinoma of the pancreas, or cystic fibrosis but may be an isolated finding. In one of our patients a familial occurrence was shown, indicating a congenital deficiency.

Adult↗
PubMed1997

Models of exocrine pancreatic pathologies: a microscopical point of view.

The objective of this review is to emphasize the contribution of optical and electronic microscopy to the study of the normal and pathological rat pancreas. These basic techniques used to explore the pancreatic morphology are capital to precisely localize specific enzymes or proteins in cellular subcompartments, to establish the normal or the pathological state of the gland, and to detect and describe unusual structures that appear under certain experimental conditions.

Adrenal Cortex Hormones↗
PubMed1990

[Otorhinolaryngologic involvement in cystic fibrosis].

ENT involvement is very frequent in mucoviscidosis, particularly rhinitis and sinusitis. This prospective study, which spanned from September 1st, 1988 to August 31st, 1989 anc included 27 children with cystic fibrosis of pancreas was carried out with the intent of determining the incidence of the various associated diseases, their bacteriologic profile, and the optimal therapeutic procedure. Less than a child in 5 is symptomless when the nose and sinuses are affected. Polyposis is found to occur in 6/27 cases, and all children have sinus radio-opacities. Ear disease is rare (1/4 of cases) and is manifested by asymptomatic tubal dysfunction with minimal audiometric repercussions. Bacteriologic specimens of sputum and sinus purulent discharge show simultaneous germ positivity (10 times out of 11). Our therapeutic recommendations are based on our own experience as well as literature data, and are, in our opinion, only relevant for children with clinical signs of disease, as opposed to advocating systematic treatment of sinus foci found on X-ray.

Adolescent↗
PubMed1998

Calcium-activated chloride conductance in a pancreatic adenocarcinoma cell line of ductal origin (HPAF) and in freshly isolated human pancreatic duct cells.

Using the whole-cell patch-clamp technique, a calcium-activated chloride conductance (CACC) could be elicited in HPAF cells by addition of 1 microM ionomycin to the bath solution (66 +/- 22 pA/pF;Vm + 60 mV) or by addition of 1 microM calcium to the pipette solution (136 +/- 17 pA/pF; Vm + 60 mV). Both conductances had similar biophysical characteristics, including time-dependent inactivation at hyperpolarising potentials and a linear/slightly outwardly rectifying current/voltage (I/V) curve with a reversal potential (Erev) close to the calculated chloride equilibrium potential. The anion permeability sequence obtained from shifts in Erev was I > Br >/= Cl. 4,4'-Diisothiocyanatostilbene disulphonic acid (DIDS, 500 microM) caused a 13% inhibition of the current (Vm + 60 mV) while 100 microM glibenclamide, 30 nM TS-TM-calix[4]arene and 10 microM tamoxifen, all chloride channel blockers, had no marked effects (8%, -6% and -2% inhibition respectively). Niflumic acid (100 microM) caused a voltage-dependent inhibition of the current of 48% and 17% (Vm +/- 60 mV, respectively). In freshly isolated human pancreatic duct cells (PDCs) a CACC was elicited with 1 microM calcium in the pipette solution (260 +/- 62 pA/pF; Vm + 60 mV). The presence of this CACC in human PDCs could provide a possible therapeutic pathway for treatment of pancreatic insufficiency of the human pancreas in cystic fibrosis.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1997

Characterization of two distinct chloride channels in cultured dog pancreatic duct epithelial cells.

Cl- secretion by pancreatic duct epithelial cells (PDEC) regulates cellular HCO3- secretion, an important component of the exocrine pancreas. In cystic fibrosis, for example, impaired function of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel results in decreased pancreatic secretion and secondary pancreatic insufficiency. Studies of ion transport by PDEC have been hindered by the lack of a practical in vitro model. We have successfully cultured nontransformed dog PDEC on Vitrogen-coated permeable membranes overlying a feeder layer of myofibroblasts and report the characterization of Cl- channels in these cells. Cl- conductance, assessed through efflux of 125I from PDEC, was stimulated by agents acting via adenosine 3',5'-cyclic monophosphate (cAMP) or cytosolic Ca2+. The Cl- conductances activated by cAMP and Ca2+ were distinct, since they were differentially inhibited by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid and, to a lesser extent, by 5-nitro-2-(3-phenylpropylamino)benzoic acid and diphenylamine-2 carboxylate. Patch-clamp studies confirmed the presence of Cl- channels activated by cAMP and Ca2+, with differential inhibition by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid. The presence of CFTR Cl- channels in PDEC was confirmed by immunoblotting. These cultured PDEC are an optimal model for studies of pancreatic duct secretion.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed2003

CFTR and bicarbonate secretion by [correction of to] epithelial cells.

Defective HCO(3)(-) and fluid secretion are hallmarks of the pathophysiology of the pancreas of cystic fibrosis patients. Recently, impaired HCO(3)(-) secretion has been shown in most tissues known to express the cystic fibrosis transmembrane conductance regulator (CFTR). New results suggest that CFTR plays an important role in the transcellular secretion of HCO(3)(-).

Bicarbonates↗