alpha-chymotrypsin and Calcinosis

Topics: Animals; Calcinosis; Chronic Disease; Chymotrypsin; Humans; Pancreatic Juice; Pancreatitis; Proteins; Rats

The diagnosis of chronic pancreatitis remains challenging in early stages of the disease. This report defines the diagnostic criteria useful in the assessment of patients with suspected and established chronic pancreatitis. All current diagnostic procedures are reviewed, and evidence-based statements are provided about their utility and limitations. Diagnostic criteria for chronic pancreatitis are classified as definitive, probable, or insufficient evidence. A diagnostic (STEP-wise; survey, tomography, endoscopy, and pancreas function testing) algorithm is proposed that proceeds from a noninvasive to a more invasive approach. This algorithm maximizes specificity (low false-positive rate) in subjects with chronic abdominal pain and equivocal imaging changes. Furthermore, a nomenclature is suggested to further characterize patients with established chronic pancreatitis based on TIGAR-O (toxic, idiopathic, genetic, autoimmune, recurrent, and obstructive) etiology, gland morphology (Cambridge criteria), and physiologic state (exocrine, endocrine function) for uniformity across future multicenter research collaborations. This guideline will serve as a baseline manuscript that will be modified as new evidence becomes available and our knowledge of chronic pancreatitis improves.

Topics: Calcinosis; Cholangiopancreatography, Magnetic Resonance; Chymotrypsin; Diagnosis, Differential; Disease Progression; Endoscopy, Digestive System; Endosonography; Evidence-Based Medicine; Feces; Humans; Incidence; Pancreatic Elastase; Pancreatic Function Tests; Pancreatic Neoplasms; Pancreatitis, Alcoholic; Pancreatitis, Chronic; Risk Factors; Secretin; Sensitivity and Specificity; Severity of Illness Index; Smoking; Steatorrhea; Tomography, X-Ray Computed

In a previous study, the authors have shown that rather than variants in trypsinogen gene(s), mutations in pancreatic secretory trypsin inhibitor (encoded by SPINK1) and cathepsin B (CTSB) are associated with tropical calcific pancreatitis (TCP). Recently, chymotrypsin C (CTRC) variants that diminish its activity or secretion were found to predict susceptibility to chronic pancreatitis (CP). The authors analysed CTRC variants in a large, ethnically matched case-control TCP cohort.. The authors sequenced all eight exons and flanking regions in CTRC in 584 CP patients (497 TCP, 87 idiopathic CP) and 598 normal subjects and analysed the significance of association using χ(2) test. The authors also investigated interaction of CTRC variants with p.N34S SPINK1 and p.L26V CTSB mutations.. The authors identified 14 variants in CTRC, of which non-synonymous variants were detected in 71/584 CP patients (12.2%) and 22/598 controls (3.7%; OR 3.62, 95% CI 2.21 to 5.93; p=6.2 × 10(-8)). Rather than the commonly reported p.K247_R254del variant in Caucasians, p.V235I was the most common mutation in Indian CP patients (28/575 (4.9%); OR 7.60, 95% CI 2.52 to 25.71; p=1.01 × 10(-5)). Another pathogenic variant, p.A73T was identified in 3.1% (18/584) patients compared with 0.3% (2/598) in controls (OR=9.48, 95% CI 2.19 to 41.03, p=2.5 × 10(-4)). The authors also observed significant association for the synonymous variant c.180C>T (p.(=)) with CP (OR 2.71, 95% CI 1.79 to 4.12, p=5.3 × 10(-7)). Two novel nonsense mutations, p.G242AfsX9 and p.W113X were also identified exclusively in CP patients. No interaction between CTRC variants and p.N34S SPINK1 or p.L26V CTSB mutations was observed.. This study on a large cohort of TCP patients provides evidence of allelic heterogeneity and confirms that CTRC variants play a significant role in its pathogenesis.

Topics: Calcinosis; Carrier Proteins; Case-Control Studies; Cathepsin B; Chymotrypsin; Genetic Predisposition to Disease; Genotype; Humans; Mutation; Pancreatitis, Chronic; Trypsin Inhibitor, Kazal Pancreatic

The exocrine and endocrine pathophysiology of chronic calcific pancreatitis of the tropics (CCPT) remains elusive. The objective of this study was to evaluate the spectrum and correlates of the exocrine and endocrine pancreatic dysfunction in CCPT. Thirty-seven consecutive patients with a clinico-radiological diagnosis of CCPT were stratified into three subgroups: CCPT-normal glucose tolerance (NGT), CCPT-abnormal glucose tolerance (IGT) and CCPT-diabetes mellitus (DM). Ten ketosis resistant young diabetic (KRDY) patients, 10 classical insulin dependent diabetes mellitus (IDDM) patients and 18 healthy matched controls were included for comparison. Fecal chymotrypsin (FCT) levels and blood C-peptide levels (basal and post i.v. glucagon stimulation) were estimated for assessing the exocrine and endocrine pancreatic functions, respectively. Sonography was performed to evaluate the pancreatic size and ductal diameter. Pancreatic exocrine-endocrine correlation was examined by studying the C-peptide/fecal chymotrypsin ratio (CP/FCT) (CP/FCT of normal controls = 1). Mean FCT levels in all 3 subgroups of CCPT (NGT: 3.4 micrograms/g; IGT: 0.82 microgram/g; DM: 2.4 micrograms/g) were very low (87-96% reduction in exocrine pancreatic dysfunction; mean FCT in healthy controls was 22.8 micrograms/g) (P < 0.0001). In contrast, KRDY and IDDM patients displayed 50-54% reduction in pancreatic acinar function (P < 0.001). Basal and stimulated C-peptide levels progressively fell in the 3 CCPT subsets (NGT: 0.23 and 0.46 > IGT: 0.14 and 0.29 > DM 0.10 and 0.14) (P < 0.01). CCPT patients exhibited pancreatic atrophy and ductal dilation (> 3 mm).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Age of Onset; Analysis of Variance; Blood Glucose; C-Peptide; Calcinosis; Chronic Disease; Chymotrypsin; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glucagon; Glucose Intolerance; Glucose Tolerance Test; Humans; Islets of Langerhans; Male; Pancreas; Pancreatitis; Reference Values; Tropical Climate; Ultrasonography

Over the last 10 years, a series of 144 consecutive patients with alcoholic recurrent pancreatitis have been studied prospectively at regular intervals with particular regard to exocrine function, calcifications, pancreatographic ductal changes, and histopathology of the pancreas. Based upon the long-term course, the patients were classified into two groups; group A (n = 95), those with chronic pancreatitis (78 of them with calcifications); and group B (n = 49), those with acute (nonprogressive) pancreatitis. The duration of disease from onset was 2-19 years (median, 9.7 and 8.3 years, respectively, in group A and B). The two groups were comparable at onset of the disease in age, sex, number of episodes of pancreatitis, and number of pseudocysts. In group A, all 95 cases fulfilled the strict diagnostic criteria of chronic pancreatitis within the period of observation (e.g., progressive exocrine insufficiency and/or typical morphological changes, particularly calcifications). In group B, the exocrine function remained normal over the entire period of observation. No histologic evidence of chronic pancreatitis was detected in five of seven large pancreatic specimens. Marked to moderate ductal changes were found in 10 of 16 patients in group B (despite normal exocrine function). Our data suggest that about one third of patients of the present series with alcoholic (recurrent) pancreatitis did not progress toward chronic (progressive) pancreatitis, although some demonstrated morphological alterations (except calcifications) in association with normally preserved exocrine function (residual scars?). The pathogenetic factor(s) responsible for progression (or nonprogression) of alcoholic (recurrent) pancreatitis to chronic pancreatitis remain(s) to be elucidated.

Topics: Acute Disease; Adult; Alcoholism; Calcinosis; Chronic Disease; Chymotrypsin; Feces; Female; Humans; Longitudinal Studies; Male; Middle Aged; Pancreas; Pancreatic Ducts; Pancreatic Pseudocyst; Pancreatitis; Prognosis; Prospective Studies; Recurrence

Topics: Acute Disease; Adult; Aged; Calcinosis; Chronic Disease; Chymotrypsin; Feces; Female; Humans; Male; Middle Aged; Pancreatitis

Tissues from twenty-four patients with focal hyperplastic gingival lesions containing calcification were stained for lysozyme (muramidase), alpha-1-antitrypsin, and alpha-1-antichymotrypsin. In eighteen of the twenty-four cases the tissues stained positively for lysozyme, and in all instances the tissues stained positively for alpha-1-antitrypsin and alpha-1-antichymotrypsin. These data suggest that the fibrous components of these lesions are derived from tissue histiocytes.

Topics: alpha 1-Antichymotrypsin; alpha 1-Antitrypsin; Calcinosis; Chymotrypsin; Gingival Hyperplasia; Gingivitis; Histiocytes; Histocytochemistry; Humans; Immunochemistry; Muramidase; Odontogenic Tumors

Topics: Calcinosis; Chronic Disease; Chymotrypsin; Humans; Lipase; Pancreatic Juice; Pancreatitis; Trypsin

Topics: Black People; Calcinosis; Chymotrypsin; Diagnosis; Feces; Humans; Pancreas; Pancreatic Diseases; Trypsin; Uganda