Search

Objectives: We describe the methodology of Post-Acute Pancreatitis Pancreatic Exocrine Insufficiency (PAPPEI), a prospective, observational, multicenter cohort study. The objectives of PAPPEI are to estimate the incidence rate of post-acute pancreatitis (AP) pancreatic exocrine insufficiency (PEI), define factors that determine the development of post-AP PEI, and evaluate the impact of post-AP PEI on nutritional status and quality of life., Methods: Enrollment started in June 2017 in 3 expert academic centers in the United States. Data were collected during hospitalization (baseline) at 3 and 12 months after enrollment. Fecal elastase-1 was used to assess PEI. Study questionnaires are completed by patient interview and review of electronic medical records. Blood is obtained to evaluate vitamin deficiencies and nutritional markers., Results: As of August 2020, 77 subjects have completed the baseline evaluation. The median age was 58 years (interquartile range, 39-67 years), 38% were male, and 90% were white. The etiology of AP was biliary in 39 subjects (51%), and 51 subjects (66%) had mild AP. Three- and 12-month follow-up data have been collected in 29 and 13 subjects, respectively., Conclusion: The PAPPEI study aims to expand our understanding of post-AP PEI incidence, including its impact on nutritional status and quality of life., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: The aim of this study was to investigate if pancreatic steatosis measured by proton density fat fraction (PDFF) is associated with exocrine pancreatic function defined by fecal elastase concentrations., Materials and Methods: A total of 1458 volunteers (777 women; age range, 21-88 years) underwent magnetic resonance imaging of the pancreas, and organ fat content was quantified by using confounder corrected PDFF. Exocrine pancreatic function was categorized by fecal elastase levels using defined cutoffs: greater than 200 μg/g normal function (n = 1319) and 200 μg/g or less impaired function (n = 139). Statistical analysis to correlate pancreatic fat content with fecal elastase included linear regression, and analyses were adjusted for known confounders for pancreatic steatosis, such as age, sex, and body mass index., Results: Overall mean (±standard deviation) of pancreatic fat content was 7.50% ± 3.78%. Pancreatic fat content was significantly higher in subjects with impaired pancreatic exocrine function (9.36% ± 4.95%) compared with subjects with normal function (7.30% ± 3.59%; P < 0.01). Linear regression analyses showed an inverse correlation between pancreatic fat and fecal elastase levels over the whole study population (beta, -7.19 [standard error, 1.39]; P < 0.01) as well as in the subgroup of subjects with normal function (-4.26 [1.32]; P < 0.01). Among subjects with impaired pancreatic exocrine function, a trend toward an inverse relation was detected (-1.28 [0.84]; P < 0.13)., Conclusions: An inverse correlation between PDFF of the pancreas and fecal elastase suggests an association between pancreatic steatosis and impaired pancreatic exocrine function.

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.

Objectives: Clinical and morphological criteria are not precise enough to diagnose early chronic pancreatitis (CP). We investigated if short endoscopic pancreas function testing as a part of routine upper endoscopy could improve clinical diagnostics., Methods: Patients with suspected CP underwent modified secretin-stimulated upper endoscopy (short endoscopic secretin test, or EST). Duodenal juice was collected during 15 minutes starting 30 minutes after stimulation. A modified scoring system for CP after Layer with bicarbonate and fecal elastase 1 (FE1) was used. We tested with receiver operating characteristic curves the diagnostic accuracy of bicarbonate and FE1 and with analysis of variance how precise the 2 parameters can discriminate the groups., Results: Fifty-two patients aged 19 to 67 years and 25 healthy controls aged 19 to 64 years were included. Twenty-four patients fulfilled the modified Layer Score for CP or non-CP. The overall accuracy of the EST versus FE1 test was 85%/71%, with positive and negative predictive values of 100%/79% and 80%/69%, respectively., Conclusions: Short EST is rapid and easy to perform and can be incorporated in daily routines. We demonstrate that EST is superior to FE1 in the assessment of pancreatic insufficiency and may prove to be useful in diagnosing early or mild CP.

Objective: The objective of this study was to assess pancreatic exocrine function (PEF) and morphology in patients recovering from a first episode of acute pancreatitis (AP)., Methods: Sixty-five eligible patients recovering from AP and 70 healthy volunteers were enrolled in this study. We evaluated PEF by fecal elastase 1 (FE-1) and used ultrasonography to detect pancreatic morphology for all patients and 40 controls., Results: Exocrine pancreatic insufficiency (EPI) incidence in the severe and mild AP subgroups was 60.5% and 39.5%, respectively. The FE-1 level in patients who had undergone surgical care was significantly lower compared with the controls (P < 0.01), whereas no difference was observed between the alcoholic and nonalcoholic groups (P > 0.05). Surprisingly, the defecation change correlated with the EPI level. In these patients, a stepwise recovery was observed over the following 2.4 years. Compared with the controls, the diameter of pancreatic duct was enlarged, and abdominal pain during recovery was found to be the independent risk factor for pancreatic duct expansion, although a significant difference was not exhibited between the AP subgroups concerning FE-1 concentration (P = 0.591)., Conclusions: Our results indicated that many AP patients may have long-lasting EPI and an expanded main pancreatic duct; thus, routine evaluation of PEF is warranted.

Objective: Exocrine function has been described in patients with diabetes. We hypothetized that patients with exocrine dysfunction have pancreatic atrophy., Methods: This is a cohort study of hospitalized patients. Thirty-five patients were selected after detection of impaired exocrine function in routine tests, and 17 patients were matched for age and body mass index to the previous cohort. The pancreatic volume was evaluated on sections of computed tomographic scans of the pancreas. Other investigations included a glucagon stimulation test and determination of fecal elastase-1 concentration and chymotrypsin activity., Results: Fifty-two patients participated in this study, 24 with type 1 diabetes and 28 with type 2 diabetes. Duration of diabetes was 15 years (5-26 years; median [interquartile range]). The pancreatic volume, 42 cm (25-57 cm), was decreased in most patients. It did not differ in patients with type 1 diabetes compared with those with type 2 diabetes. It was decreased in patients treated with insulin and in those with low elastase-1 concentration or low chymotrypsin activity. In the multiple linear regression analysis, the pancreatic volume correlated with chymotrypsin activity and stimulated C-peptide., Conclusions: We have unraveled a link between 2 old observations in patients with diabetes: atrophy of the pancreas and exocrine deficiency. These observations give credence to the reality of the exocrine dysfunction in patients with diabetes.

Purpose of Review: We review important new clinical observations in chronic pancreatitis made in the last year., Recent Findings: Cholecystokinin-stimulated endoscopic pancreatic function testing has low specificity for diagnosis of early chronic pancreatitis, likely because of correctable technical limitations or failure to exclude confounding diseases. Fecal elastase 1 is a poor test for diagnosing pancreatic malabsorption. A 2-week trial of corticosteroids may differentiate autoimmune pancreatitis (AIP) from pancreatic cancer in select patients. A genetic screen may help to predict relapse of AIP. Repeated, 6-month visits to counsel against alcohol use may reduce recurrent attacks of alcoholic pancreatitis. A five-component antioxidant cocktail may reduce the frequency of pain in chronic pancreatitis by 1.5 days per month., Summary: Researchers this last year have further characterized clinical aspects of chronic pancreatitis that may lead to improved detection of early chronic pancreatitis and AIP, risk stratification and application of risk-lowering strategies to prevent relapses in AIP or the development of recurrent (and possibly chronic) alcoholic pancreatitis and new evidence that antioxidants may have a modest effect on reducing the dominant symptom in chronic pancreatitis, abdominal pain.

Objectives: To correlate magnetic resonance cholangiopancreatography (MRCP) and magnetic resonance imaging (MRI) findings of the pancreas with the pancreatic exocrine function determined by fecal elastase 1 concentration., Methods: Magnetic resonance imaging and MRCP findings of 81 consecutive patients with clinically suspected chronic pancreatitis and 21 healthy volunteers were evaluated. All subjects underwent MRI/MRCP and fecal elastase 1 testing within 1 to 4 weeks' interval. Magnetic resonance cholangiopancreatography images were evaluated according to Cambridge classification. Magnetic resonance imaging of the pancreas was assessed for pancreatic size, signal, and arterial enhancement., Results: All volunteers had normal fecal elastase 1 levels (>200 microg/g) and normal MRI/MRCP findings. Thirty-one of 56 patients revealed MRI and/or MRCP findings despite normal fecal elastase 1 concentration. Four of 25 patients revealed normal MRI and MRCP findings despite low fecal elastase 1 concentration (<200 microg/g). Magnetic resonance imaging findings of size (P = 0.00001), arterial enhancement (P = 0.00001), and parenchymal signal (P = 0.001) were significantly different among the control group, patients with normal fecal elastase 1 levels, and patients with low fecal elastase 1 levels. Magnetic resonance cholangiopancreatography findings (P = 0.00001), pancreatic size (P = 0.00001), arterial enhancement (P = 0.014), and parenchymal signal (P = 0.004) on MRI correlated with the fecal elastase 1 concentration., Conclusions: Magnetic resonance imaging/MRCP findings correlate with fecal elastase 1 concentration and may precede pancreatic exocrine insufficiency in the early stages of chronic pancreatitis.

Objectives: Infected pancreatic necrosis (IPN) is a serious complication of acute pancreatitis. Data concerning survivors' quality of life and pancreatic functions are scarce. Follow-up of the patients with alcohol and biliary etiology of IPN treated with open necrosectomy was performed., Methods: Twenty-eight survivors after operative treatment (Bradley procedure) of IPN were followed up 24 to 96 months after discharge from the hospital (10 biliary and 18 alcohol patients). Their exocrine and endocrine pancreatic functions and quality of life (Functional Assessment of Chronic Illness Therapy scale) were evaluated. Pancreatic tissue remaining after necrosectomy was visualized by use of contrast-enhanced computed tomography (CT)., Results: In 44.4% of alcohol-induced IPN patients, the presence of the whole pancreas was shown on the follow-up CT, contrary to the biliary group, where the partial lack of the pancreas was observed in all cases. Pancreatic tissue calcifications were present on CT in 8 patients of alcohol-induced acute pancreatitis group only. Median stool elastase 1 concentrations were 318.1 U/mL in the biliary group and 238.3 U/mL in the alcohol-induced group (not significant). The Functional Assessment of Chronic Illness Therapy scale showed significantly higher social/family and emotional well-being in patients with biliary acute necrotizing pancreatitis., Conclusions: Patients after alcohol-induced IPN had lower quality of life compared with biliary etiology. Biliary and alcohol-induced IPN patients after surgical treatment have nonsignificant differences of endocrine and exocrine pancreatic functions.

Objective: To define the possible effects of gastric electrical stimulation (GES) for gastroparesis on pancreatic function, we performed 2 related human studies., Methods: Fecal elastase values were compared in 2 patient groups: (1) GES devices ON and (2) GES devices OFF and (2) in 3 control groups: (1) no response (NR) to prokinetic medications, (2) positive response (RES) to medications, and (3) normal controls. Polypeptide levels in 7 of 9 GES patients with device ON and OFF, elastase results, GI symptoms (TSS), and heart rate variability (HRV) were compared by paired t tests and/or ANOVA and reported as mean +/- SE., Results: Elastase was different for GES-ON and OFF (508.0 +/- 92.2 vs. GES-OFF 378.6 +/- 87.4, P < 0.05). Elastase was lower in medication NR and RES than in normal controls. Postprandial pancreatic polypeptide was greater with GES ON than OFF (P = 0.07). HRV revealed a lower percentage of change with device ON versus OFF (44.2 +/- 5.5 vs. 48.5 +/- 5.2, P = 0.08) and lower TSS with ON versus OFF (15.9 +/- 4.5 vs. 25.7 +/- 5.3, P < 0.05)., Conclusions: GES improves exocrine pancreatic release, effects autonomic control, and improves GI symptoms, suggesting a possible role for GES in the treatment of pancreatic insufficiency associated with gastroparesis.

Introduction: Indirect tests of exocrine pancreatic function are thought to be of little sensitivity and specificity in mild to moderate insufficiency as compared with direct function tests. Direct tests, which are claimed to be the "gold standard" of functional diagnosis, are too complicated to be performed on great numbers of patients and are not standardized., Aims: To characterize the use of an indirect function test (fecal elastase 1 measurements determined independently from a direct test), in this study we compared it with the gold standard of morphologic diagnosis, endoscopic retrograde cholangiopancreatography (ERCP)., Methodology: Data for 213 patients who underwent ERCP (104 males and 109 females; mean age, 54 years [8-89]) were collected prospectively, including fecal elastase 1 measurements and clinical and ERCP data., Results: Elastase 1 findings correlated with pancreatic duct changes (p < 0.05). At a cutoff point of 200 microg/g, the positive predictive value of elastase 1 measurement for moderate/severe duct changes was 90.4%, and for any duct changes it was 96.8%. The sensitivity was only 45.3% for any duct changes but 76.5% for severe changes. Specificity for moderate/severe changes was 86%., Conclusion: Fecal elastase 1 measurements appear to be valuable for characterizing patients at high risk for chronic pancreatitis, even if their sensitivity is lower than that of direct tests.

Atelectasis is a major cause of decreased arterial oxygenation after cardiopulmonary bypass (CPB). There is a close relationship between atelectasis and inflammatory responses. We therefore tested the hypothesis that neutrophil number and the concentrations of proinflammatory cytokines and elastase in plasma and bronchoalveolar lavage fluid correlate with changes in arterial oxygenation. Bronchoalveolar lavage was performed just after the induction of anesthesia and at the end of surgery in 80 patients undergoing CPB. Peripheral blood was sampled simultaneously. Arterial oxygenation was quantified by PaO(2)/fraction of inspired oxygen (FIO(2)) and intrapulmonary shunt (Q(s)/Q(t)). PaO(2)/FIO(2) and Q(s)/Q(t) decreased significantly at the end of surgery, whereas neutrophil number, interleukin (IL)-6, IL-8, tumor necrosis factor-alpha, and elastase concentrations in the lavage fluid increased significantly. The increase in neutrophil count from the lavage fluid correlated significantly with the increases in IL-8 and elastase concentrations. The increase in neutrophil number and IL-8 and elastase concentrations in the lavage fluid correlated significantly with PaO(2)/FIO(2) and Q(s)/Q(t) at the end of surgery. In contrast, none of the plasma values correlated with these variables. Significant correlation between immune mediators and decreased arterial oxygenation suggests that inflammatory responses in the distal airway are strongly related to a decrease in arterial oxygenation after CPB.

The aim of this study was to evaluate the controversial specificity of the plasma amino acid (AA)-consumption test in detecting pancreatic diseases by using two different quantitative methods. A total of 55 subjects: 13 healthy subjects, 13 patients with chronic pancreatitis (three mild/moderate, eight severe), 13 patients with pancreatectomy and complete suppression of the exocrine pancreatic secretion, eight patients with chronic liver disease (five with impaired synthetic function), and eight patients with chronic renal failure. Total plasma AAs were quantified by a colorimetric method (p-benzoquinone) in all subjects, at 0, 30, 45, and 60 min during and 30 min after minute 60 of i.v. cerulein infusion (50 ng/kg/h). Either total and individual AAs were quantified by chromatography (high-performance liquid chromatography; HPLC) in 10 healthy subjects, 10 patients with pancreatectomy, and 10 with chronic pancreatitis at 0 and 60 min after the start of the cerulein infusion. For the colorimetric method, healthy subjects had maximal percentage decreases of total AA concentrations not significantly different from those of patients with pancreatectomy and significantly higher than those of patients with chronic pancreatitis (p < 0.0001) or chronic liver disease (p < 0.001). Pancreatic function, as assessed by fecal elastase-1 test, was not significantly correlated to the maximal percentage decrease in total plasma AAs. For the chromatographic method, total AA concentrations were not significantly correlated to those determined by colorimetry. The concentration of each of the individual plasma AAs varied considerably in each group. Fecal elastase-1 values were normal (> or = 200 microg/g) in all patients without pancreatic disease and in only one of 11 patients with chronic pancreatitis and exocrine insufficiency. The type of method used can explain the different results of the AA-consumption test. This test is not very specific for the pancreas.

Fecal elastase-1 is a candidate for a sensitive noninvasive test detecting chronic pancreatitis. This prospective study enrolled 10 healthy male controls and 23 patients referred for tube testing of pancreatic function. It was designed (a) to correlate duodenal outputs and fecal concentrations of elastase-1 with duodenal outputs of amylase, lipase, trypsin, and chymotrypsin in the fed state (duodenal perfusion of a mixed liquid meal at 2.5 kcal/min for 150 min), (b) to compare the diagnostic accuracy of fecal elastase-1 and fecal chymotrypsin, and (c) to characterize the cyclical pattern of postprandial pancreatic secretion in healthy subjects and patients with chronic pancreatitis. Based on their enzyme responses to duodenal meal perfusion and imaging procedures, 12 patients were classified as having normal pancreatic function and 11 patients as having chronic pancreatitis. Duodenal enzyme outputs of elastase-1 were markedly lowered in chronic pancreatitis (p < 0.0001) and correlated well with the outputs of the other four enzymes (r > 0.71, p < 0.00001). Fecal concentrations of elastase-1 were also clearly reduced in chronic pancreatitis (p < 0.0001). Fecal chymotrypsin was less strongly associated with duodenal enzyme outputs (r = 0.33 to r = 0.587), whereas fecal elastase-1 correlated more precisely with the duodenal outputs of all five enzymes (r = 0.637 to r = 0.830, p < 0.00001). Sensitivity and specificity in the detection of chronic pancreatitis amounted to 0.64 and 0.95 for fecal elastase-1 and 0.27 and 0.95 for fecal chymotrypsin, respectively. In the postprandial state, peaks of enzyme secretion occurred at a frequency of about 1 peak/150 min. The amplitude but not the frequency of secretory peaks was markedly reduced in chronic pancreatitis (p < 0.01). We conclude that fecal elastase-1 clearly exceeds the sensitivity of fecal chymotrypsin in the diagnosis of chronic pancreatitis but does not reliably detect all cases with mild to moderate disease. The pattern of postprandial pancreatic secretion is cyclical, even with minimal secretory outputs in chronic pancreatitis.

Many tests are available to assess pancreatic function. The ideal test would be simple and have adequate sensitivity in mild to moderate chronic pancreatitis (MCP) and severe CP (SCP). Fecal pancreatic elastase 1 (FPE1) assay (ScheBo Tech) has been proposed as a reliable test to evaluate pancreatic exocrine function, with sensitivities of up to 100% in diagnosing CP. Cutoff values (microgram/g stool) of < 100 have been suggested as SCP, 100-200 as MCP, and > 200 as normal. The test's ability to detect MCP distinguished by the absence of steatorrhea, and its specificity among various etiologies of malabsorption, has not been fully evaluated. The aim of this study was to evaluate this assay in subjects including patients with SCP with steatorrhea, patients with MCP with no steatorrhea, healthy controls, and diseased controls with nonpancreatic malabsorption. Thirty-six subjects [15 healthy controls, 7 malabsorption controls, and 14 subjects with CP (7 MCP, 7 SCP)] had FPE1 assays. One hundred fifty-four assays for FPE1 were run for analysis. The intraassay and interassay intraclass correlation coefficients were 0.93 and 0.90, respectively. All SCP had values of < 100 micrograms/g but more than half of the MCP subjects had FPE1 levels within the normal range. The subjects with nonpancreatic malabsorption had FPE1 values ranging from 55 to > 500 micrograms/g of stool. Although the assay detected SCP with steatorrhea, it did not consistently separate the MCP patients from normals. The majority of those with nonpancreatic malabsorption had false-positive values. These results may differ from previously described data because of the purposeful inclusion of MCP subjects, documented by the lack of steatorrhea, and the inclusion of disease controls with nonpancreatic malabsorption. Although PE1 concentrates in the stool and is not significantly degraded, subtle changes in this enzyme, as in MCP, do not seem to be detectable by this assay. This group continues to be the most difficult group to diagnose clinically.

A valid control group is an essential part of any patient study. We asked whether burned children returning for reconstructive surgery could be used as "controls" in a study of seven proteolytic elements in the circulation. Functional levels of elastase, plasminogen, prekallikrein, antithrombin, alpha 2-antiplasmin, alpha 2-macroglobulin, and total proteolytic activity in 30 healthy unburned children were compared with levels in 29 patients admitted for reconstructive surgery an average of 7.9 years after burn. The two groups were not statistically different in distributions of sex and race but differed in mean age. Levels of six of the seven parameters were equal in the two groups. However, even when correction for the age difference was done between the groups, alpha 2-macroglobulin in the patients undergoing reconstructive surgery still was significantly less (p < 0.021) than in the unburned group. Therefore caution may be needed when readily available patients undergoing reconstructive surgery are used as "controls" in studies of patients with acute burns.

Preterm deliveries (PTDs) are a leading cause of neonatal morbidity and mortality in the world. Efforts to prevent PTD have been hampered by a poor understanding of the underlying pathophysiology, inadequate diagnostic tools, and generally ineffective therapies. There is increasing clinical and laboratory evidence that many PTDs result from premature activation of cells in the cervix, decidua, and fetal membranes in response to local mediators of maternal or fetal stress, ascending genital tract infection, and/or decidual hemorrhage. Putative mediators include peptide hormones (e.g. corticotropin releasing hormone (CRH)) and/or inflammatory-cytokines (e.g. interleukin-1, -6, and -8 (IL-1, -6 and -8)) which promote the production of oxytotic factors (e.g. prostanoids and endothelin) capable of eliciting uterine contractions and enhancing expression of proteases capable of initiating cervical change and/or membrane rupture. The identification of cervical, decidual, and/or chorionic extracellular matrix (ECM) proteins (e.g. collagen fragments and fetal fibronectin) and ECM-degrading proteases (e.g. collagenases and granulocyte elastase) in maternal serum and cervicovaginal secretions may provide new approaches to the detection of patients at high risk for PTD. In addition, our growing understanding of the pathogenic processes preceding PTD have led to new therapeutic approaches including antibiotic, anticytokine, and antiprotease treatments.

Background: This study was performed to biochemically assess and quantify the previously observed ultrastructural alterations in the collagen matrix of stunned myocardium., Methods and Results: The stunned myocardium was produced in 13 mongrel dogs by a series of 12 coronary artery occlusions of 5 minutes followed by 10-minute reperfusion periods, with a final reperfusion period of 90 minutes. Regional systolic function in the stunned myocardium was 17% of control. Relative end-diastolic length in the stunned region increased up to 8%. There was a nonuniform transmural loss of collagen. Hydroxyproline in the stunned endocardium was not different from control. The stunned midwall and epicardium demonstrated 12.5% (p less than 0.05) and 14.6% (p less than 0.005) decreases, respectively. All transmural layers in the stunned myocardium had significant increases in collagenase activity before procollagenase activation, averaging a 73.6% increase (p less than 0.025). Complete activation of all procollagenase forms with aminophenylmercuric acetate revealed no differences in fully activated collagenase between the stunned and normal regions. The lysosomal enzymes, elastase and cathepsin G, were not different between stunned and normal zone tissue. These results would tend to exclude exogenous sources of protease in the stunned myocardium at the 90-minute final reperfusion time frame. Collagen fibers were isolated from the stunned and normal zone tissue and underwent dansyl chloride reaction. Stunned collagen fibers had 9% greater dansyl labeling, suggesting greater numbers of exposed N-terminal amino acid residues on the fiber and compatible with greater enzymatic cleavage activity on the stunned collagen matrix. Tissue water content was consistently greater in the stunned region compared to the normal: a uniform transmural increase of approximately 1.7%., Conclusions: The stunned myocardium is characterized by both systolic dysfunction and diastolic expansion or dilatation. Endogenous procollagenase is activated by the ischemic process leading to degradation of the extracellular matrix. The underlying mechanisms may be relevant in ischemic enlargement of the heart and cardiomyopathy.

The aim of this study was to determine whether neutrophil activation occurs in the fetal circulation in pregnancy-induced hypertension and to correlate this with evidence of neutrophil activation in the maternal circulation. Twenty-one normal pregnancies and 23 complicated by pregnancy-induced hypertension were studied in the third trimester. The mean length of gestation at delivery was significantly shorter (P less than .01) and the mean birth weight percentile was significantly lower (P less than .05) in the hypertensive group; otherwise the groups were comparable. Blood was obtained before cesarean delivery or established labor in the mothers and immediately after delivery from the umbilical vein. Plasma neutrophil elastase, which is released after neutrophil activation, was measured by radioimmunoassay as a marker for neutrophil activation. The mean (+/- standard error) concentration of neutrophil elastase in maternal plasma in the hypertensive group (35.9 +/- 4.7 ng/mL) was significantly higher than in the normal group (20.8 +/- 0.87 ng/mL) (P less than .005). The concentration of neutrophil elastase in umbilical venous plasma was not significantly different between the normal and hypertensive groups. However, significantly higher concentrations of neutrophil elastase were found in the umbilical venous plasma of pregnancies delivered vaginally compared with those delivered by cesarean (P less than .05) regardless of diagnosis. There was no correlation between maternal venous and umbilical venous plasma neutrophil elastase concentrations, birth weight percentile, plasma urate, or platelet count. These data suggest that neutrophil activation is confined to the maternal circulation in pregnancy-induced hypertension where it may contribute to vascular damage and dysfunction in areas such as the placental bed.(ABSTRACT TRUNCATED AT 250 WORDS)

By degrading antithrombin III, polymorphonuclear neutrophil (PMN) elastase can become a procoagulant. Because intravascular coagulation may accompany severe burn injury, this study examined burn wound exudates for PMN elastase and its physiologic inhibitor, plasma alpha 1-protease inhibitor (alpha 1-PI), as a step in evaluating their contributions to coagulopathy in patients with burns. Each of the nine exudates examined were inhibitory for PMN elastase. Chromatographic characterization of the inhibitor indicated that it was alpha 1-PI; its elution volume for four exudates was identical to that of pure alpha 1-PI. Confirmation of the inhibitor's identity was achieved by reaction of anti-alpha 1-PI antibody with each exudate and with inhibitory chromatographic fractions of exudates with the most inhibitory activity. Inhibitor potency, determined from dose-response curves against a standard PMN elastase activity, varied twentyfold among exudates. Only one exudate had catalytic activity with the PMN elastase substrate. Although this enzyme had elastase-like properties, it appeared to differ from PMN elastase. The presence of alpha 1-PI in the wound exudate suggests that this inhibitor may act to diminish fibrin formation from the level that might otherwise have been seen if excess elastase were free to degrade antithrombin III.

To better understand the role of granulocyte elastase (GE) in mediating tissue injury during sepsis, GE levels were measured in plasma and bronchoalveolar lavage fluid (BALF) in patients with septic shock (n = 16) and hemorrhagic shock (n = 30). Granulocyte elastase levels were compared to levels of alpha 1-protease inhibitor (alpha 1-PI). Results show that although plasma GE-alpha 1-PI complex was initially elevated in patients with hemorrhagic and septic shock, elevations in plasma GE-alpha 1-PI complex (831 +/- 241 micrograms/L) persisted in septic shock patients. alpha 1-Protease inhibitor levels in serum were increased, resulting in an inhibition of serum GE activity. Granulocyte elastase activity in BALF, however, was significantly higher in those patients with septic, as compared to hemorrhagic shock (31.4 +/- 25.8 versus 3.7 +/- 4.0 U/L, respectively). In addition GE levels were compared to other parameters, including respiratory index, blood neutrophil count, and plasma levels of endotoxin, fibronectin, and coagulation factor XIII. Significant correlations were observed between GE-alpha 1-PI and increased endotoxin concentration and decreased fibronectin and coagulation factor XIII levels. Significant correlation was found also between GE activity in BALF and respiratory index. These findings suggest that severe tissue damage occurred in patients with septic shock complicated by multiple-organ failure. Although GE activity appeared to be adequately inhibited by alpha 1-PI in blood, increased GE activity in local tissues, such as lung alveoli, may be responsible for significant local tissue injury during septic shock.

Changes in the macromolecular matrix of the intervertebral disc may predispose to biomechanical failure of the disc. Such changes would involve extracellular enzymes capable of altering the collagen and proteoglycan of the disc matrix. In this study, extracts from homogenates of both annuli fibrosi and nuclei pulposi of human lumbar discs were found to contain neutral collagenolytic, gelatinolytic, and elastinolytic enzymes in all samples assayed. The specific activity of the collagenase was higher in extracts from nuclear than from annular tissue, a difference not seen with gelatinase or elastase. The collagenase was present as both a latent and active enzyme, the other enzymes being fully active. Human intervertebral discs therefore contain enzymes capable of degrading their extracellular macromolecular matrix.