Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
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Gene/Protein
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Target Concepts:
Gene/Protein
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Enzyme
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Query: UMLS:C0149521 (
chronic pancreatitis
)
7,199
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The peptide hormones
neurotensin
(NT) and cholecystokinin (CCK) are commonly attributed with a physiological role in the stimulation of exocrine pancreatic secretion. However, on the other hand, little is known about the effect of diminished exocrine pancreatic function and of the resulting maldigestion on postprandial plasma levels of these two gastrointestinal peptides. We investigated, therefore, the effect of enzyme substitution therapy on the magnitude and time course of plasma concentrations of both hormones in patients suffering from severe
chronic pancreatitis
. Pancreatic insufficiency led to elevated NT-concentrations, in response to a standard meal, which could be reduced by enzyme replacement therapy. Prior to enzyme therapy, the mean integrated postprandial release of NT amounted to 2800 +/- 250 pg/ml after 60 min in patients with severe
chronic pancreatitis
. This amount was significantly reduced to 1250 +/- 150 pg/ml after 60 min after enzyme therapy, compared to 810 +/- 90 pg/ml after 60 min in healthy volunteers after the standard meal. The integrated postprandial CCK level in patients investigated was significantly lower (35 +/- 4.8 pmol/L after 60 min) without any substitution therapy, compared to the integrated peptide amount in healthy volunteers (145 +/- 13.5 pmol/L after 60 min). Enzyme therapy in patients suffering from
chronic pancreatitis
led to an increased postprandial CCK-level (80 +/- 9.6 pmol/L after 60 min). Elevated CCK-plasma concentrations have not been demonstrated in these patients with pancreatic insufficiency. We therefore suggest that CCK might not play a major role in feedback regulation in patients with
chronic pancreatitis
. However, in light of elevated NT plasma concentrations in patients with
chronic pancreatitis
, NT-mediated influence on the pancreas deserves further study.
...
PMID:Plasma concentrations of neurotensin and CCK in patients with chronic pancreatitis with and without enzyme substitution. 171 70
Thirty-three patients with
chronic pancreatitis
were studied in an effort to correlate release of gastrointestinal hormones (GIH) with the degree of pancreatic insufficiency. A prospective examination was conducted of fat-stimulated release of pancreatic polypeptide (PP), cholecystokinin (CCK), and
neurotensin
. Seventy-two-hour fecal fat determination, endoscopic retrograde pancreatography (ERP), and the bentiromide-PABA test were used to correlate the clinical stage of disease. The ERP was classified as positive only if the changes were advanced (or "marked") according to the Cambridge Classification. Five patients were defined to have mild disease, 13 moderate, and 15 severe. Any patient with clinical evidence of
chronic pancreatitis
and ERP changes that were less than advanced and had normal fecal fat and bentiromide tests received a grade of mild. Patients with one abnormal test were graded moderate, and those with two or three abnormal results were graded severe. In the 33 patients, the integrated 60-minute release of pancreatic polypeptide (PP) was 37.4 +/- 6.1 ng-60 min/ml in those five patients with mild disease, 102.3 +/- 10.3 ng-60 min/ml in the 13 patients with moderate disease, and 7.6 +/- 2.2 ng-60 min/ml in the 15 patients with severe disease. The integrated 60-minute release of
neurotensin
was 3.8 +/- 0.4 ng-60 min/ml in mild disease, 2.0 +/- 0.3 ng-60 min/ml in moderate disease, and 0.2 +/- 0.1 ng-60 min/ml in severe disease. CCK release did not correlate with the severity of disease. Enhanced release of PP appeared to correlate well with moderate stage of
chronic pancreatitis
, and depressed PP release with severe disease. Stimulated levels of PP and
neurotensin
appear to be useful in the diagnosis and staging of
chronic pancreatitis
. It is concluded that measurement of fat-stimulated release of PP and
neurotensin
may be useful to assess severity of disease in patients with
chronic pancreatitis
.
...
PMID:Diagnostic role of gastrointestinal hormones in patients with chronic pancreatitis. 376 78
Given an indication for surgery in patients with
chronic pancreatitis
, such as distal common bile duct obstruction, duodenal stenosis, or dilated pancreatic duct with stones and congestion, the surgeon must decide the type of operation to perform. A duodenopancreatectomy, the Whipple procedure, is widely considered to be the gold standard. It is highly effective in relieving pain and eliminating the structural abnormalities noted above. Duodenum-preserving resection of the head of the pancreas (DPRHP) seems to be an attractive alternative to pancreaticoduodenectomy (PD) in the treatment of
chronic pancreatitis
. In a clinical prospective randomized trial the efficiency of both operative methods was investigated. Between 7/1987 and 12/1993 43 patients were randomly assigned to undergo either a Whipple procedure (n = 21) or DPRHP (n = 22). Data on postoperative course, mortality, and postoperative morbidity were compiled. As concerns long-term results, postoperative hormonal status (insulin,
neurotensin
, cholecystokinin, gastrin) was checked, basal and stimulated with a standardized meal, using standard hormonal assay kits. All patients with PD survived, whereas one with DPRHP died from peritonitis. Patients with DPRHP had a significant more rapid convalescence (16.5 vs. 21.7 days). The range for postoperative follow-up is from 36 months to 5.5 years. In the DPRHP group 18 patients are in good condition. Two had diabetes and one developed carcinoma. In the PD group one died from hepatic coma, 14 are in good condition and 6 developed diabetes. All gained body weight with an average of 6.4 vs. 4.9 kg, DPRHP vs. PD. A difference between DPRHP and PD was obvious for the postoperative hormonal status. Results are satisfactory in both groups. For patients with DPRHP however, we see a quicker convalescence and a significant benefit as concerns postoperative hormonal status.
...
PMID:[Pancreatic function and quality of life after resection of the head of the pancreas in chronic pancreatitis. A prospective, randomized comparative study after duodenum preserving resection of the head of the pancreas versus Whipple's operation]. 763 46
Three-dimensional magnetic resonance cholangiopancreatography is currently the most exciting new imaging technique for
chronic pancreatitis
. Endoscopy-assisted duodenal intubation during the secretin-cholecystokinin test reduces intubation time in difficult cases. The NBT-para-amino benzoic acid test has been refined to enhance its discriminant power. The cholesteryl-[C13]octanoate breath test and the faecal elastase test are newer highly sensitive and specific tubeless tests. Pain in
chronic pancreatitis
continues to be a vexing therapeutic issue. Enzyme treatment continues despite criticism.
Neurotensin
is the new suspected mediator of the feedback mechanism, which is downregulated by enzyme therapy. Steroid ganglion block is an exciting therapeutic tool for pain relief. Endoscopic pancreatic sphincterotomy, Dormia basketing and pancreatic stenting in conjunction with extracorporeal shock wave lithotripsy should be performed early in
chronic pancreatitis
to prevent parenchymal atrophy with ensuing exocrine and endocrine pancreatic dysfunction. The modified Puestow's procedure preserves endocrine and exocrine pancreatic functions besides relieving pain. Closed loop insulin infusion allows superior management of pancreatic diabetes following near total pancreatectomy. The standardised incidence rate of pancreatic cancer is 16.5 in patients with alcoholic
chronic pancreatitis
and 100 for tropical
chronic pancreatitis
. Aggressive treatment protocols combining neo-adjuvant chemoradiation and intra-operative radiation with surgery are being used to improve the prognosis in this dismal complication of
chronic pancreatitis
.
...
PMID:Chronic pancreatitis: diagnosis and treatment. 875 8
The role of
neurotensin
as a physiologic regulator of exocrine pancreatic secretion is known, but the hormone has only recently been recognized as important mitogen in vitro for human cancer cells. The aim of this study was to evaluate the variations of serum levels of
neurotensin
in pancreatic cancer. We studied 58 patients: 13 control subjects, 20 pancreatic cancer patients, 11
chronic pancreatitis
patients, and 14 cases of extrapancreatic disease. No differences were found between serum values of
neurotensin
in pancreatic cancer and control subjects or extrapancreatic disease. Significantly higher values were detected in
chronic pancreatitis
than in pancreatic cancer patients (P < 0.04). In
chronic pancreatitis
patients, the serum levels of
neurotensin
were correlated with serum amylase (r = 0.95, P < 0.01). Lower levels of
neurotensin
were found in stage IV pancreatic cancer than in stages I-II (t = 1.82, P < 0.04) and in grade II than in grade I (t = 2.21, P < 0.02). Significant correlations were found between serum levels of
neurotensin
and two indices of nutrition: albumin (r = 0.60, P < 0.05) and the percentage reduction in body weight (Z = 2.20, P < 0.02). No correlations were found between serum levels of the hormone and size of the neoplasm or the survival of patients. We can conclude that the serum variations of
neurotensin
do not seem to be related to the progression of human pancreatic cancer. The variation of serum levels of the hormone may be linked to a poor nutritional status of the patient.
...
PMID:Serum neurotensin in human pancreatic cancer. 906 Oct 71
By autoradiography,
neurotensin
(NT) binding is specifically detectable in pancreatic cancer, but not in the normal pancreas,
chronic pancreatitis
(CP), or other pancreatic disorders. In the present study, we investigated whether this is due to NT receptor-1 (NTR-1) mRNA up-regulation and whether NTR-1 mRNA could also be used as a specific diagnostic marker and treatment target in pancreatic cancer. Fifteen normal pancreas tissue samples, 20 CP samples, and 30 pancreatic cancer samples were studied. Expression and localization of NTR-1 mRNA was investigated by Northern blot analysis and in situ hybridization. Furthermore, consecutive tissue sections were analyzed for NTR-1 mRNA expression and NT binding. By Northern blot analysis, NTR-1 mRNA expression was 4.4-fold (P < 0.01) and 3.0-fold (P < 0.01) higher in pancreatic cancer and CP tissue samples, respectively, compared with normal controls. There was no difference in NTR-1 mRNA levels between CP and cancer samples (P > 0.05). In pancreatic cancer, the NTR-1 mRNA levels were higher in advanced tumor stage (stages III and IV) than early tumor stage (stages I and II; P < 0.05), but no difference was found between well/moderately differentiated (grades 1 and 2) and poorly differentiated/undifferentiated cancers (grades 3 and 4; P > 0.05). By in situ hybridization, NTR-1 mRNA signals were weakly present in the cytoplasm of acinar and ductal cells of the normal pancreas. Moderate to intense NTR-1 mRNA signals were present in the cytoplasm of acinar cells dedifferentiating into tubular complexes and degenerating acinar cells of CP samples. In the cancer samples, NTR-1 mRNA was moderately to intensely expressed in the cytoplasm of cancer cells. When on consecutive tissue sections NTR-1 mRNA expression was compared with the presence of NTR-1, measured by receptor autoradiography, a correlation was found in carcinomas but not in CP samples, in which no receptors were detectable by autoradiography. The enhanced expression of NTR-1 mRNA in pancreatic cancer cells further suggests that neuroendocrine hormones might modulate pancreas cancer cell behavior. However, its relatively high levels in CP excludes NTR-1 mRNA as a specific parameter for pancreatic cancer and for the differentiation of pancreatic cancer from CP.
...
PMID:Neurotensin receptor-1 mRNA analysis in normal pancreas and pancreatic disease. 1069 May 40