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Objective: Acute pancreatitis (AP) is a disease whose pathogenesis remains largely obscure. Genetic research has focussed attention upon the role of the pancreatic protease/protease inhibitor system. The aim of this study was to investigate the prevalence of genetic variants of the trypsin inhibitor, SPINK1, in acute pancreatitis., Methods: We genotyped 468 patients with AP and 1117 healthy controls for SPINK1 alterations by single-strand conformation polymorphism analysis and by melting curve analysis using fluorescence resonance energy transfer probes., Results: The c.101A>G (p.N34S) variant was detected in 24/936 alleles of patients and in 18/2234 alleles of healthy controls (odds ratio=3.240; 95% confidence interval: 1.766-5.945; P<0.001). In the UK patients, the mean age of patients with N34S was 11.9 years younger compared with N34S negative patients (P=0.023), but this was not apparent in the German patients. Allele frequencies for the c.163C>T (p.P55S) variant did not differ between patients and controls., Conclusion: The SPINK1 N34S variant is associated with acute pancreatitis. This supports the importance of premature protease activation in the pathogenesis of AP and suggests that mutated SPINK1 may predispose certain individuals to develop this disease.

Epidemiological studies have demonstrated a variety of potential environmental factors that may alter susceptibility to chronic pancreatitis (CP) through oxidative/xenobiotic stress; however, a direct causal and mechanistic role has not been established. We aimed (1) to determine the prevalence of functional genetic polymorphisms in the antioxidant enzymes, glutathione S-transferase GSTM-1, GSTP-1, and GSTT-1, manganese superoxide dismutase, and catalase in CP and (2) to reveal evidence of oxidative stress in patients with CP by measuring whole-blood glutathione redox status. In total, 122 patients with CP (75 alcohol-induced [A1CP], 33 idiopathic [ICP], and 13 hereditary) and 245 age- and sex-matched controls were recruited. The prevalence of the functional GSTT-1 genotype (GSTT-1*A) was significantly higher in CP (88.5%) compared to healthy controls (76%; chi2 = 7.26, P = 0.007). Stratification to disease etiology demonstrated that the GSTT-1*A genotype was also significantly more prevalent among patients with ICP (94%; P = 0.02; 95% CI, 0.04-9.16) but not in those with A1CP. In 22 patients with stable CP, the whole-blood glutathione concentration (median [IQR]: 72 micromol/L [21-181 micromol/L]) and the glutathione redox ratio (GSH/GSSG) (median [IQR]: 9 (3-77]) were significantly reduced compared to those in 20 healthy volunteers (median [IQR]: 815 micromol/L [679-1148 micromol/L], P < 0.001, and 96 [52-347], P = 0.005, respectively). We conclude that the GSTT-1 functional genotype is associated with ICP. Evidence of altered glutathione redox status suggests that this disease modification may be a consequence of oxidative stress or the bioactivation of xenobiotics.

Background: Cyclooxygenase-2 (COX-2) is a key modulatory molecule in inflammation and neoplasia. Increasing evidence suggests a role for COX-2 in pancreatic cancer (PAC). However, expression of COX-2 in pancreatic intraepithelial neoplasia (PanIN), the precursor lesion of PAC which is often present in chronic pancreatitis (CP), has received little attention., Method: COX-2 immunostaining was performed on sections of PAC (n = 26), CP (n = 34), PanIN (n = 68) and normal pancreas (n = 11). Sections were also stained for macrophages (CD68), activated pancreatic stellate cells (alphaSMA), and collagen (Sirius Red) as markers of fibrosis. Semiquantitative scoring was based on the extent and intensity of immunostaining., Results: COX-2 expression was increased in PAC compared to normal (p = 0.02) with 89% of cases exceeding COX-2 immunostaining in normal ducts. In PanIN lesions, COX-2 expression increased with escalating severity of the PanIN change (p < or = 0.01). COX-2 expression was increased in PanIN-2/3 compared to normal pancreas and CP (p < or = 0.001). In ducts of CP, COX-2 expression did not differ from that in normal tissue. There was no association between COX-2 expression and clinicopathological variables., Conclusion: The high level of COX-2 expression in PanIN lesions suggests that this enzyme could be a therapeutic target at a non-invasive stage of pancreatic carcinogenesis and feasible for chemoprevention in CP., (Copyright 2005 S. Karger AG, Basel and IAP.)

Objective: Soluble CD14 is derived from a membrane glycoprotein, and it enhances endothelial cytokine responses to lipopolysaccharide. We studied the role of soluble CD14 in the pathogenesis of the systemic inflammatory response associated with acute pancreatitis, to determine whether altered expression was due to a functional C-260T polymorphism in the CD14 promoter gene or altered monocyte heterogeneity., Design: Prospective case-matched study., Setting: Tertiary pancreatic treatment unit in the United Kingdom., Subjects: Patients with pancreatitis and controls., Interventions: DNA from 117 patients with pancreatitis (34 severe) and 263 controls underwent CD14 genotyping using restriction fragment length polymorphism-polymerase chain reaction., Measurements and Main Results: Peripheral venous blood samples at 24 and 72 hrs after the onset of abdominal pain were analyzed for sCD14 levels. Isolated peripheral blood mononuclear cells were phenotyped for CD14/CD16 receptor expression using immunofluorescence flow cytometry. Disease severity was assessed using Atlanta criteria, Acute Physiology Scores, and C-reactive protein.Soluble CD14 levels were higher in severe (24-hr median, 66.6 ng/mL; 72-hr median, 72.2 ng/mL) compared with mild attacks (24-hr median, 50.7 ng/mL; 72-hr median, 49.7 ng/mL, p < .001), although the latter was similar to controls (median, 51 ng/mL). Furthermore, soluble CD14 levels correlated with Acute Physiology Scores (p < .001) and C-reactive protein (p = .01).Peripheral blood mononuclear cells CD14++ (p = .008), CD14+/16+ (p = .003), and CD16++ (p = .015) receptor densities were all increased in severe attacks at 24 hrs. Early CD14+/16+ receptor density correlated with sCD14 (p < .001), Acute Physiology Scores (p < .001), and C-reactive protein (p = 0.006). The CD14 genotype prevalence in acute pancreatitis was similar to controls and failed to correlate with any variables studied., Conclusions: Increased soluble CD14 expression is associated with the systemic inflammatory response to acute pancreatitis and an expansion of the proinflammatory CD14+/CD16+ monocyte subset. Its targeted disruption may afford some benefit in preventing the development of systemic complications.

Background & Aims: Genetic variations in antioxidant metabolism may explain varying biological responses to acute pancreatitis (AP). We studied the contribution of oxidative stress to the pathogenesis of severe pancreatitis by examining the prevalence of functional gene polymorphisms of antioxidant enzymes and evidence of heightened oxidative stress., Methods: DNA from 320 patients with AP (90 severe) and 263 controls was genotyped for glutathione S-transferase (Mu-1 [M-1], theta-1 [T-1], and pi-1 [P-1: Ile-105Val]), manganese superoxide dismutase (Ala-9Val), and catalase (C-260T) polymorphisms. Erythrocyte reduced glutathione (GSH) concentration was determined 24 and 72 hours after the onset of pain in 46 patients (11 severe). Disease severity was assessed using Atlanta clinical criteria, Acute Physiology Scores (APS), and peak serum C-reactive protein levels., Results: The functional GSTT-1*A genotype was more prevalent in severe (96%) compared with mild attacks of AP (78%; odds ratio [OR], 5.9; 95% confidence interval [CI ], 2-17; P < 0.0001) and controls (76%; OR, 6.6; 95% CI, 2.3-18.7; P < 0.0001). Compared with null genotype, GSTT-1*A was associated with higher peak C-reactive protein levels (184 vs. 94 g/dL; P = 0.0005) and APS (24 hours, P = 0.04; 48 hours, P = 0.015). Reduced glutathione (GSH) at 24 hours was lower in mild (median, 382 nmol/g) and severe attacks (median, 407 nmol/g) compared with controls (median, 3685 nmol/g; P < 0.001). Levels increased at 72 hours in mild (P = 0.012) but not severe attacks and inversely correlated with APS (r = -0.49; P = 0.04)., Conclusions: The functional GSTT-1*A genotype was associated with severe attacks of pancreatitis. Heightened oxidative stress characterized by glutathione depletion may be of importance in mediating the progression from mild to severe pancreatitis.

Background: Severe acute pancreatitis is associated with an early increase in intestinal permeability and endotoxemia. Endotoxin is a potent stimulator for the production and release of procalcitonin and its components (calcitonin precursors; [CTpr]). The aim of this study is to evaluate the role of plasma CTpr as an early marker for gut barrier dysfunction in patients with acute pancreatitis., Methods: Intestinal permeability to macromolecules (polyethylene glycol 3350), serum endotoxin and antiendotoxin core antibodies, plasma CTpr, and serum C-reactive protein (CRP) were measured on admission in 60 patients with acute pancreatitis. Attacks were classified as mild (n = 48) or severe (n = 12) according to the Atlanta criteria., Results: Compared with mild attacks of acute pancreatitis, severe attacks were significantly associated with an increase in intestinal permeability index (median: 0.02 vs. 0.006, P < 0.001), the frequency of endotoxemia (73% vs. 41%, P = 0.04), and the extent of depletion of serum IgM antiendotoxin antibodies (median: 43 MMU vs. 100 MMU, P = 0.004). Plasma CTpr levels were significantly elevated in patients with severe attacks compared with mild attacks on both the day of admission and on day 3 (median: 64 vs. 22 fmol/mL, P = 0.03; and 90 vs. 29 fmol/mL, P = 0.003 respectively). A positive and significant correlation was observed between the admission serum endotoxin and plasma CTpr levels on admission (r = 0.7, P < 0.0001) and on day 3 (r = 0.96, P < 0.0001), and between plasma CTpr on day 7 and the intestinal permeability index (r = 0.85, P = 0.0001). In contrast, only a weak positive correlation was observed between peak serum levels of CRP and plasma CTpr on admission (r = 0.3, P = 0.017) and on day 7 (r = 0.471, P = 0.049), as well as between CRP and each of the admission serum endotoxin (r = 0.3, P = 0.03) and the intestinal permeability index (r = 0.375, P = 0.007)., Conclusions: In patients with acute pancreatitis, plasma concentrations of CTpr appear to reflect more closely the derangement in gut barrier function rather than the extent of systemic inflammation.

Background: Previous reports of laparoscopic cholecystectomy (LC) in patients with biliary pancreatitis suggested increased operative difficulty, high rates of conversion, and greater morbidity and mortality., Methods: Between 1990 and 1997, LC was performed for biliary pancreatitis in 63 patients (Group I) and for other causes in 829 patients (Group II)., Results: Patients with biliary pancreatitis were significantly older (median age 57 vs 50 years, p = 0.009), with greater co-morbidity (ASA III/IV 24% vs 11%, p = 0.008). The groups were comparable with respect to the frequency of previous abdominal operations, acute inflammation of the gallbladder, and the frequency of bile duct calculi detected by intraoperative cholangiography. Moderate to severe adhesions involving the gallbladder were significantly more frequent in patients with biliary pancreatitis (46% vs 29%, p = 0.004). No significant differences were observed between the two groups with respect to intraoperative (1.5% Group I vs 6.0% Group II, p = 0.109) or postoperative complications (10% vs 8%, p = 0.426), conversion rate (0 vs 2.7%, p = 0.181), or duration of operation (median 92 vs 85 min, p = 0.33)., Conclusion: Despite increased age and co-morbidity and more frequent adhesions, our data showed no evidence that intraoperative or postoperative complications were more frequent in patients with biliary pancreatitis than in other patients undergoing LC.

Introduction: Hypocalcemia is not uncommon during acute pancreatitis and is associated with a poor outcome. Whilst the mechanisms responsible for its development remain unclear, there is evidence to implicate endotoxemia in other models of sepsis., Aim: To investigate the potential role of systemic endotoxin exposure in the development of hypocalcemia in patients with acute pancreatitis., Methodology: Adjusted serum calcium was measured daily, and the lowest value within 72 hours of admission for acute pancreatitis was determined. Serum endotoxin and both IgG and IgM antiendotoxin core antibodies (EndoCAbs) were measured on admission. Attacks were classified as mild (n = 51) or severe (n = 21) according to the criteria of the Atlanta International Symposium of 1992., Results: Hypocalcemia was significantly more frequent (86% versus 39%, p < 0.001) and reached significantly lower levels during severe attacks than during mild attacks (median [interquartile range], 2.06 [1.78-2.17] mmol/L, versus 2.23 [2.15-2.30] mmol/L; p < 0.001). Endotoxemia was present in a significantly greater proportion of patients with severe disease (71% versus 41%; p = 0.037), and serum IgM and IgG EndoCAbs were significantly depleted during severe attacks in comparison with mild attacks (p = 0.007 and p = 0.039, respectively). A negative and significant correlation was observed between endotoxemia and both the admission and lowest serum concentrations of adjusted calcium (r = -0.424 and p = 0.022; r = -0.383 and p = 0.037, respectively), and the latter correlated significantly with serum IgG EndoCAb concentrations (r = 0.251; p = 0.036)., Conclusion: Systemic endotoxin exposure appears to play a significant role in the development of hypocalcemia in patients with acute pancreatitis.

Background: Calcitonin precursors are sensitive markers of inflammation and infection. The aim of this study was to evaluate the role of plasma calcitonin precursor levels on the day of admission in the prediction of severity of acute pancreatitis, and to compare this with the Acute Physiology And Chronic Health Evaluation (APACHE) II scoring system., Methods: Plasma concentrations of calcitonin precursors were determined on admission in 69 patients with acute pancreatitis. APACHE II scores were calculated on admission. Attacks were classified as mild (n = 55) or severe (n = 14) according to the Atlanta criteria. Plasma calcitonin precursor levels were determined with a sensitive radioimmunoassay., Results: On the day of hospital admission, plasma levels of calcitonin precursors were significantly greater in patients with a severe attack compared with levels in those with a mild attack of pancreatitis (median 64 versus 25 fmol/ml; P = 0.014), but the APACHE II scores were no different (median 9 versus 8; P = 0.2). The sensitivity, specificity, positive predictive and negative predictive values, and accuracy for the prediction of severe acute pancreatitis were 67, 89, 57, 93 and 85 per cent respectively for plasma calcitonin precursor levels higher than 48 fmol/ml, and 69, 45, 23, 86 and 50 per cent respectively for an APACHE II score greater than 7. Differences in the specificity and accuracy of the two prognostic indicators were significant (P < 0.001 and P = 0.001 respectively). A plasma calcitonin precursor concentration of more than 160 fmol/ml on admission was highly accurate (94 per cent) in predicting the development of septic complications and death., Conclusion: The assay of plasma calcitonin precursors on the day of admission to hospital has the potential to provide a more accurate prediction of the severity of acute pancreatitis than the APACHE II scoring system.

Background and Aims: Nitric oxide represents a potential key mediator of the local and systemic manifestations of acute pancreatitis (AP) in experimental models but its role in human disease is uncertain. We therefore sought to assess if systemic nitric oxide (NO) production is elevated in severe AP and determine whether this is a reflection of biochemical severity or endotoxin exposure., Patients and Methods: Patients were recruited within 72 hours of pain onset. NO derived nitrite excretion determined from a 24 hour sterile urine collection was correlated with intestinal macromolecular permeability (polyethylene glycol excretion ratio), markers of systemic endotoxin exposure (IgG:IgM endotoxin core antibody (EndoCAb) ratio), disease severity, and the magnitude of systemic inflammation (peak C reactive protein (CRP) and Acute Physiology and Chronic Health Evaluation score II (APACHE-II))., Results: In patients with a severe attack (n=20), nitrite excretion was increased significantly compared with patients with a mild attack (n=45, 20.6 micro g v 15.65 micro g; p<0.00) and the latter with healthy controls (n=20, p=0.004). Nitrite excretion correlated strongly with both intestinal permeability (r=0.7, p=0.006) and EndoCAb ratio (r=0.7, p<0.01) but not with CRP or APACHE-II scores (p>0.1)., Conclusions: Total urinary nitrite excretion is increased in patients with severe AP, and may not be simply a reflection of systemic inflammation, but potentially a consequence of endotoxin mediated upregulation of inducible NO synthase activity.

Introduction: Sepsis is the main cause of late mortality in patients with severe acute pancreatitis and is largely attributed to secondary infection of pancreatic necrosis with gram-negative enteric organisms. This is commonly preceded by a significant increase in intestinal colonization with such microbes and with early increases in intestinal permeability, thus suggesting a mechanism of bacterial translocation. Whilst cultures of blood specimens from these patients often remain sterile, it is conceivable that bacteria might translocate in small volumes with detrimental effects but elude detection by standard microbial culture techniques., Aims: To investigate the incidence and frequency with which bacterial DNA may exist in the systemic circulation of patients with acute pancreatitis and to relate that to disease severity, changes in intestinal permeability, and systemic endotoxin exposure., Methodology: Blood samples were obtained at admission and on days 3 and 7 from 26 patients with acute pancreatitis (seven with severe cases) and from 10 healthy controls for DNA extraction and standard microbial cultures. Polymerase chain reaction techniques were used to amplify a gene region (16S ribosomal RNA) found in all bacteria. Levels of serum endotoxin and antibodies to endotoxin core (EndoCAb) were measured at admission, and intestinal permeability to the macromolecule polyethylene glycol 3350 was determined within 72 hours of the onset of symptoms., Results: Blood cultures yielded and enterococci for one patient with a severe attack and coagulase-negative staphylococci for another patient with a mild attack. No bacterial DNA was found in any of the samples. Endotoxemia was detected in 20 patients (five with severe cases), and levels of serum IgM EndoCAb were depleted in patients with severe attacks but remained relatively unchanged during mild attacks (p = 0.033). Intestinal permeability was significantly increased in patients with severe attacks of acute pancreatitis but remained unchanged during mild attacks (p < 0.05)., Conclusions: Whilst severe attacks of acute pancreatitis are associated with early derangement in gut barrier function and systemic endotoxin translocation, there is no molecular evidence for associated bacterial "translocation."

Intestinal barrier failure and subsequent bacterial translocation have been implicated in the development of organ dysfunction and septic complications associated with severe acute pancreatitis. Splanchnic hypoperfusion and ischemia/reperfusion injury have been postulated as a cause of increased intestinal permeability. The urinary concentration of intestinal fatty acid binding protein (IFABP) has been shown to be a sensitive marker of intestinal ischemia, with increased levels being associated with ischemia/reperfusion. The aim of the current study was to assess the relationship between excretion of IFABP in urine, gut mucosal barrier failure (intestinal hyperpermeability and systemic exposure to endotoxemia), and clinical severity. Patients with a clinical and biochemical diagnosis of acute pancreatitis were studied within 72 hours of onset of pain. Polyethylene glycol probes of 3350 kDa and 400 kDa were administered enterally, and the ratio of the percentage of retrieval of each probe after renal excretion was used as a measure of intestinal macromolecular permeability. Collected urine was also used to determine the IFABP concentration (IFABP-c) and total IFABP (IFABP-t) excreted over the 24-hour period, using an enzyme-linked immunosorbent assay technique. The systemic inflammatory response was estimated from peak 0 to 72-hour plasma C-reactive protein levels, and systemic exposure to endotoxins was measured using serum IgM endotoxin cytoplasmic antibody (EndoCAb) levels. The severity of the attack was assessed on the basis of the Atlanta criteria. Sixty-one patients with acute pancreatitis (severe in 19) and 12 healthy control subjects were studied. Compared to mild attacks, severe attacks were associated with significantly higher urinary IFABP-c (median 1092 pg/ml vs. 84 pg/ml; P < 0.001) and IFABP-t (median 1.14 microg vs. 0.21 microg; P = 0.003). Furthermore, the control group had significantly lower IFABP-c (median 37 pg/ml; P = 0.029) and IFABP-t (median 0.06 microg; P = 0.005) than patients with mild attacks. IFABP correlated positively with the polyethylene glycol 3350 percentage retrieval (r = 0.50; P < 0.001), CRP (r = 0.51; P < 0.001), and inversely with serum IgM EndoCAb levels (r = -0.32; P = 0.02). The results of this study support the hypothesis that splanchnic hypoperfusion contributes to the loss of intestinal mucosal integrity associated with a severe attack of pancreatitis., (Copyright 2003 The Society for Surgery of the Alimentary Tract, Inc.)

Background: Platelet activating factor (PAF) is believed to amplify the activity of key mediators of the systemic inflammatory response syndrome (SIRS) in acute pancreatitis, resulting in multiorgan dysfunction syndrome. We tested the hypothesis that a potent PAF antagonist, lexipafant, could dampen SIRS and reduce organ failure in severe acute pancreatitis., Methods: We conducted a randomised, double blind, placebo controlled, multicentre trial of lexipafant (100 mg/24 hours intravenously for seven days commenced within 72 hours of the onset of symptoms) involving 290 patients with an APACHE II score >6. Power calculations assumed that complications would be reduced from 40% to 24%. Secondary end points studied included severity of organ failure, markers of the inflammatory response, and mortality rate., Findings: Overall, 80/138 (58%) patients in the placebo group and 85/148 (57%) in the lexipafant group developed one or more organ failures. The primary hypothesis was invalidated by the unexpected finding that 44% of patients had organ failure on entry into the study; only 39 (14%) developed new organ failure. Organ failure scores were reduced in the lexipafant group only on day 3: median change -1 (range -4 to +8) versus 0 (-4 to +10) in the placebo group (p=0.04). Systemic sepsis affected fewer patients in the lexipafant group (13/138 v 4/148; p=0.023). Local complications occurred in 41/138 (30%) patients in the placebo group and in 30/148 (20%) in the lexipafant group (20%; p=0.065); pseudocysts developed in 19 (14%) and eight (5%) patients, respectively (p=0.025). Deaths attributable to acute pancreatitis were not significantly different. Interleukin 8, a marker of neutrophil activation, and E-selectin, a marker of endothelial damage, decreased more rapidly in the lexipafant group (both p<0.05); however, absolute values were not different between the two groups., Interpretation: The high incidence of organ failure within 72 hours of the onset of symptoms undermined the primary hypothesis, and power calculations for future studies in severe acute pancreatitis will need to allow for this. Lexipafant had no effect on new organ failure during treatment. This adequately powered study has shown that antagonism of PAF activity on its own is not sufficient to ameliorate SIRS in severe acute pancreatitis

Background: The diagnosis, early assessment, and management of severe acute pancreatitis remain difficult clinical problems. This article presents the consensus obtained at a meeting convened to consider the evidence in these areas. The aim of the article is to provide outcome statements to guide clinical practice, with an assessment of the supporting evidence for each statement., Method: Working groups considered the published evidence in the areas of diagnosis, assessment of severity, nonoperative treatment, and surgical treatment of severe acute pancreatitis. Outcome statements were defined to summarize the conclusions on each point considered. The findings were discussed and agreed on by all participants. A careful assessment was made of the strength of the available evidence (proven, probable, possible, unproven, or inappropriate)., Findings and Conclusions: There is reliable evidence to support much current practice. Clear guidance can be given in most areas examined, and several areas were identified where further investigation would be helpful. Diagnosis using plasma concentrations of pancreatic enzymes is reliable. Rapid advances are taking place in the assessment of severity. Several new therapeutic strategies show real promise for the reduction of morbidity and mortality rates. Surgical debridement is required for infected pancreatic necrosis, but is less often necessary for sterile necrosis.

Sepsis accounts for 80% of deaths from acute pancreatitis. This study aimed to investigate early changes in intestinal permeability in patients with acute pancreatitis, and to correlate these changes with subsequent disease severity and endotoxemia. The renal excretion of enterally administered polyethylene glycol (PEG) 3350 and PEG 400 was measured within 72 hours of onset of acute pancreatitis to determine intestinal permeability. Severity was assessed on the basis of APACHE II scores and C-reactive protein measurements. Serum endotoxin and antiendotoxin antibodies were measured on admission. Eight-five patients with acute pancreatitis (mild in 56, severe in 29) and 25 healthy control subjects were studied. Urinary excretion of PEG 3350 (median) was significantly greater in patients who had severe attacks (0.61%) compared to those with mild disease (0.09%) and health control subjects (0.12%) (P <0. 0001), as was the permeability index (PEG 3350/400 excretion) (P <0. 00001). The permeability index was significantly greater in patients who subsequently developed multiple organ system failure and/or died compared with other severe cases (0.16 vs. 0.04) (P = 0.0005). The excretion of PEG 3350 correlated strongly with endotoxemia (r = 0.8; P = 0.002). Early increased intestinal permeability may play an important role in the pathophysiology of severe acute pancreatitis. Therapies that aim to restore intestinal barrier function may improve outcome.

The proportion of peripheral blood mononuclear cells expressing the T helper cell phenotype and levels of antiendotoxin core antibody, interleukin (IL) 6 and C-reactive protein (CRP) were determined within 48 h of admission in a group of 29 patients with acute pancreatitis (16 mild, 13 severe attacks). There was a significant decrease in the proportion of T helper cells (12.2 versus 34.9 per cent, P < 0.01) and significant increases in levels of IL-6 (69.5 versus < 10 pg/ml, P < 0.01) and CRP (119 versus 30.5 mg/l, P < 0.01) in severe compared with mild attacks. During the convalescent stage at 3 months after admission, severe attacks were characterized by a significant increase in the proportion of T helper cells compared with the acute period (22.4 versus 10.6 per cent, P < 0.01). A persistently low proportion of T helper cells was associated with residual pancreatic necrosis. The presence of circulating endotoxin was demonstrated in two mild and two severe attacks using the Limulus amoebocyte lysate assay, and abnormal levels of antiendotoxin core antibodies were found in 70 and 92 per cent of mild and severe attacks respectively. There was a strong inverse correlation between levels of CRP and the proportion of T helper cells in severe disease (r = -0.76, P = 0.004). Translocation of endotoxin from the gastrointestinal tract may partly explain the abnormal levels of T helper cells, IL-6 and CRP.

Discussion over the role of enzyme therapy in patients with acute pancreatitis is based upon theoretical considerations rather than hard data. In this respect, it differs little from most other treatments used in the management of acute pancreatitis, although, in the case of enzyme treatment, the lack of data results largely from a dearth of experimentation to prove its efficacy rather than from equivocal or negative results.

Activated proteases in plasma are complexed by alpha 2-macroglobulin. Although the complexes retain peptidase activity, they are usually eliminated promptly by mononuclear phagocytes. In severe acute pancreatitis, almost 30% of plasma alpha 2-macroglobulin becomes complexed, suggesting impaired clearance. In the present study, plasma [methyl-14C]trypsin clearance and monocyte phagocytosis were investigated. Attacks complicated by major organ-system failure, pancreatic pseudocyst, abscess, or necrosis were graded severe (median Ranson score 5.5). Plasma [methyl-14C]trypsin half-life was significantly increased in severe attacks (N = 7, median 21.1 min), compared to mild attacks (N = 14, median 15.4 min, P < 0.05) and healthy controls (N = 4, median 10.8 min, P < 0.02). Monocyte phagocytosis was significantly lower in severe attacks (N = 9, median 3.6%) compared to mild attacks (N = 20, median 20.8%, P < 0.01) and healthy controls (N = 8, median 26.9%, P < 0.01). Plasma [methyl-14C]trypsin half-life and monocyte phagocytosis were significantly inversely correlated (r = -0.51, P < 0.01). Impaired clearance of circulating trypsin in acute pancreatitis is potentially deleterious but may be reversed by stimulating mononuclear phagocytes.

In a small percentage of patients with acute pancreatitis, recurrent attacks of pain and hyperamylasaemia occur when feeding is commenced. Recurrences of this type may occur because the pancreas is still swollen and inflamed, and indicate the need for a longer period of "pancreatic rest" before food is introduced. Alternatively, they may reflect the presence of "mechanical" factors leading to the recurrent pancreatitis, such as a gallstone in the common bile duct, a pseudocyst of the pancreas, or pancreatic duct obstruction. Successful resolution of the pancreatitis may require treatment of underlying causative factors. A stone in the pancreatic duct (probably a gallstone) was found to be the cause of recurrent acute pancreatitis in an elderly patient with severe cardiovascular disease, who was unfit for surgery. Pancreatitis settled after percutaneous drainage of the pancreatic duct, the technique described.

Plasma values of C reactive protein, alpha 1 proteinase inhibitor, alpha 2 macroglobulin, and complexed alpha 2 macroglobulin have been determined in serial samples from 27 patients with acute pancreatitis. Complexed alpha 2 macroglobulin was measured by a novel enzyme linked immunosorbent assay with a monoclonal antibody specific for the complexed form. Patients with severe illness had lower concentrations of total alpha 2 macroglobulin and higher concentrations of complexed alpha 2 macroglobulin than those with mild illness, and in the majority of severe attacks the abnormal amounts of complexed alpha 2 macroglobulin were present throughout the eight days of the study. The proportion of total alpha 2 macroglobulin in the uncomplexed form, however, was generally greater than 90%, and in 26% of the mild cases completely normal concentrations of uncomplexed alpha 2 macroglobulin (greater than 99% of total) were found throughout the eight days of the study. This suggests that exhaustion of alpha 2 macroglobulin in plasma is unlikely to be a major factor in the pathogenesis of acute pancreatitis.

This study examines the possible role of excessive leukocyte stimulation in the pathogenesis of acute pancreatitis. Levels of tumor necrosis factor alpha (TNF-alpha) and elastase-alpha 1 proteinase inhibitor (E-alpha 1PI) have been measured as markers of macrophage and neutrophil activation, respectively, in serial plasma samples from 27 patients with acute pancreatitis. Levels of TNF-alpha did not support the possibility of excessive macrophage activation, but raised levels of E-alpha 1PI in patients with either the mild or severe form of the illness indicated the activation of neutrophils. Whether this is a consequence of the illness or is a contributory factor in the pathogenesis is not clear.

Objective: To evaluate dynamic contrast enhanced computed tomography for detecting and localising pancreatic necrosis in acute pancreatitis., Design: Prospective evaluation with blind reporting of scans., Setting: Single teaching hospital., Patients: 60 Consecutive patients with acute pancreatitis suspected to have pancreatic necrosis because of major organ system failure (13); slow recovery five to seven days after admission with raised scores on the acute physiological and chronic health evaluation (APACHE-II) system (27); or findings on previous ultrasonography or computed tomography (20)., Main Outcome Measure: Pancreatic necrosis proved histologically--that is, greater than 30 g necrotic tissue debrided at laparotomy (for life threatening sepsis or peritonitis) or necropsy., Results: Dynamic computed tomography correctly localised pancreatic necrosis in 11 patients (confirmed at laparotomy in nine and at necropsy in two). Of nine patients with low enhancement of peripancreatic tissues alone, eight recovered after conservative management; necropsy confirmed viable pancreas and necrosis of peripancreatic fat in one patient. Of 40 patients with normal contrast enhancement, none required laparotomy to debride pancreatic necrosis., Conclusion: Dynamic contrast enhanced computed tomography seems to be a safe and accurate method of identifying and localising pancreatic and peripancreatic necrosis, which cannot be predicted accurately by conventional imaging techniques.

Sera from patients of biliary, alcoholic, and idiopathic acute pancreatitis with severity scored from 1 to 5 based on the Ranson criteria were tested for proinsulin/insulin degrading activity. Proinsulin degrading activity by normal controls was 8 +/- 4% as compared with 22-78 +/- 17% with a mean of 45% by the patient sera. An order of magnitude increase of proinsulin degrading activity was accompanied by an order of magnitude increase of immunoreactive pancreatic cationic trypsin(ogen) and (pro)elastase-2 as determined by radioimmunoassay with day 1 sera. Proinsulin degrading activity also showed a negative correlation with the clinical time course and dropped to normal by 6 days after admission. The decrease of proinsulin degrading activity was concomitant with a decrease of serum immunoreactive pancreatic serine proteases. High-performance liquid chromatography analysis of the proteolysis products showed the appearance of insulin and smaller peptides with no proinsulin conversion intermediates. Ninety to ninety-eight percent of proinsulin degrading activity was inhibited by anti-alpha 2-macroglobulin (alpha 2-M) antiserum, or (Ac)Eglin-C(J141), and 52% by an elastase and chymotrypsin-specific inhibitor, MeOSuc-Ala-Ala-Pro-boroVal-pinacol. E64c, TLCK, alpha 1-protease inhibitor (alpha 1-PI), or Trasylol inhibited proinsulin degrading activity by 10-17%, and anti-cathepsin B antiserum by 9%. The observed proinsulin degrading activity did not correlate with the Ranson's scores, age, sex, etiology, total serum immunoreactive insulin, calcium, albumin or alpha 2-M but had a negative correlation with serum alpha 1-PI (r = -0.55) and a positive correlation with serum esterase activity (r = .62).(ABSTRACT TRUNCATED AT 250 WORDS)

The prognostic value of three predictive indices was compared in 436 attacks of acute pancreatitis in 418 patients. The outcome of an attack was graded as uncomplicated (324), complicated (70), or fatal (41); 1 attack was excluded because of puncture of the caecum. The overall mortality rate was 9.4%. Clinical assessment on admission identified only 34% of patients whose attack was severe (ie, complicated or fatal). Multiple laboratory criteria and peritoneal lavage were more sensitive (61% and 53%, respectively) while retaining diagnostic accuracy (79% and 74%). An erroneous diagnosis of pancreatitis was corrected by the findings on lavage in 5 patients. The major advantage of peritoneal lavage over multiple laboratory criteria was the shorter delay between admission to the study and determination of severity (median 4 v 24 h), but visceral puncture during insertion of the cannula occurred in 2 of 253 patients (0.8%). When used together, the three indices correctly predicted 82% of the attacks with a severe outcome and identified all patients destined to die within 10 days of admission.

The management of gallstones in patients with acute pancreatitis (AP) is controversial. This paper reports an analysis of 171 attacks of AP associated with gallstones. Whilst awaiting elective cholecystectomy 56% of patients had further symptoms and 1 died. Non-urgent operations during the same admission as the pancreatitis (n = 34) resulted in 2 deaths and 7 septic complications, but prediction of complications may be possible. Urgent surgery (n = 5) was followed by 3 deaths. This study suggests that in most patients, cholecystectomy should be performed as soon as the patient is adequately fit. Urgent removal of an impacted ampullary stone (preferably by endoscopic papillotomy) may be required in a small minority if severe pancreatitis fails to respond to medical treatment, or if cholangitis supervenes .

Diagnostic peritoneal lavage was carried out in 79 patients with acute pancreatitis, at a mean time of 7 h after admission to hospital. The presence of more than 10 ml of free peritoneal fluid, brown-coloured free fluid or mid-straw-coloured lavage fluid was the criterion used for the prediction of a severe attack by lavage. Prior to lavage the attack was assessed as mild or severe by the clinician and reassessed by him at 24 and 48 h. All attacks were finally classified as mild or severe by means of a simple clinical grading scheme. There were 61 mild and 18 severe attacks (including 4 deaths). Initial clinical assessment correctly predicted only 39 per cent of the severe attacks compared with a 72 per cent succwss rate for diagnostic lavage. All the mild attacks were correctly predicted by clinical assessment but lavage was wrong in 3 out of 61 cases (95 per cent success rate). By 48 h after admission clinical assessment was comparable to systems using multiple criteria in its predictive value, success rates being 83 per cent and 82 per cent respectively for prediction of severe attacks. We did not find either the presence of methaemalbumin in the serum or the presence of hypocalcaemia to be of additional value. Diagnostic peritoneal lavage was the most accurate early guide to severity, and correctly predicted all patients who developed shock or died.

The renal handling of calcium and phosphate, which normally reflects parathyroid hormone (PTH) activity, was studied during the first 5 days after admission to hospital in 18 patients with acute pancreatitis. The ionized calcium level in plasma was calculated from the total calcium, albumin, total protein and pH. Hypocalcaemia (Ca less than 1.08) was found in 6 patients and was associated with low urine calcium concentrations, hypophosphataemia and lower renal tubular reabsorption of phosphate. Although these changes were all consistent with an appropriate renal response to increased PTH production in the hypocalcaemic patients, measured levels of PTH were very variable. In one patient who developed tetany, calcium infusion resulted in a rise in plasma calcium and a reversal of renal changes, but had little influence upon PTH levels. We found no evidence that hypomagnesaemia or proteolytic degradation of PTH were factors in the aetiology of hypocalcaemia. The discrepancy between evidence of PTH activity from renal function and immunoassayable levels of PTH in plasma might indicate that the parathyroid response, although present, was inadequate to mobilize enough skeletal calcium to prevent hypocalcaemia; it underlines the need for caution in the interpretation of data fom radioimmunoassay techniques when taken in isolation in situations where they have not been fully evaluated.

Current trends in the treatment of gallstone pancreatitis require rapid diagnosis of cholelithiasis. This study evaluates the diagnostic potential of plasma aspartate aminotransferase (AST), alkaline phosphatase, and bilirubin on the day of admission to hospital in 215 attacks of acute pancreatitis. The optimal diagnostic cut-off level for AST was 60 IU/1. A transient elevation above 60 IU/1 was recorded in 111 (84.1%) of 132 attacks associated with gallstones, but in only 12 (14.5%) of 83 attacks without stones, and was unrelated to the severity of the attack. Elevated levels of alkaline phosphatase and bilirubin were also more common in attacks associated with gallstones but were less reliable for the identification of cholelithiasis than AST. As a sensitive indicator of hepatocyte disruption, the early and transient rise in plasma AST is consistent with the concept of transient ampullary obstruction in gallstone pancreatitis, and may be useful in identifying patients who require urgent surgical or endoscopic disimpaction.

A case is described demonstrating a stricture of the colon associated with acute pancreatitis and 20 similar cases found in the literature are reviewed. The colonic stenosis may be of short duration and largely due to oedema or more chronic with deposition of fibrous tissue. Many cases have been confused with a carcinoma both radiologically and at laparotomy. It is suggested that a conservative approach be adopted initially, resection being carried out if follow-up barium examination fails to show resolution of the stenosis.

It was felt that the apparent specificity of the amylase-to-creatine clearance ratio (ACCR) in several previous studies of pancreatitis might reflect a failure to utilize adequately ill control subjects. The ACCR and the renal clearances of beta 2-microglobulin (B2-m), similarly related to creatinine (BCCR) as well as the urinary concentration of albumin, were compared in 27 patients with acute pancreatitis, 8 with a perforated peptic ulcer and 7 with mild biliary colic, during the first 5 days in hospital. Acute pancreatitis was graded as mild (6), moderate (14) or severe (7), using a combination of clinical data, diagnostic peritoneal lavage and multiple criteria. Further assessment of the severity of the acute illness was obtained from measurement of C-reactive protein (C-RP). Lowest C-RP levels were found in the patients with mild pancreatitis and biliary colic, and highest levels in the patients with severe pancreatitis and perforated ulcer (P less than 0.002). Similarly, ACCR and BCCR levels were significantly lower in the two mild groups than in the two severe ones (P less than 0.01 and less than 0.002 respectively), although plasma amylase was raised only in patients with pancreatitis and plasma B2-m was similar in all groups. Electrophoresis of urine showed dense bands of tubuloprotein in patients from both severe groups. Urine albumin was higher in severe pancreatitis than in perforated ulcer (P less than 0.1), perhaps indicating a more specific glomerular lesion in pancreatitis. Thus a rise in amylase clearance appeared to be related to the severity of the acute illness, and may be a component of a non-specific tubuloproteinuria. In this study patients with a perforated peptic ulcer had increases in ACCR similar to those seen in patients with severe pancreatitis, and we are therefore doubtful whether ACCR has any role in the clinical diagnosis of pancreatic disease.

Acute pancreatitis was induced in anaesthetised dogs in order to investigate the relative contribution of peritoneal ascitic fluid and thoracic duct lymph as routes of transfer of pancreatic enzymes from the inflamed gland to the blood. In eight animals the exudate from the gland was collected in a plastic bag and continuously drained away, and in a further eight it was allowed to accumulate within the peritoneal cavity. The thoracic duct was cannulated and in four of the animals of each group the lymph which drained was discarded; in the other four it was returned via a venous cannula. The initial rise of plasma amylase and lipase was probably because of the direct transfer of enzyme into veins draining the pancreas or peri-pancreatic tissues. Thereafter transfer of enzyme via the thoracic duct significantly influenced plasma concentrations of amylase and lipase. The majority of enzyme released from the gland accumulated within the peritoneal ascitic fluid, but this intraperitoneal accumulation did not appear to have a significant influence upon lymph or plasma concentrations of amylase or lipase.

alpha 2-macroglobulin is probably the most important of the antiproteases in plasma. In this study, the relationships of plasma alpha 2-macroglobulin to the clinical features of acute pancreatitis as well as to plasma levels of other antiproteases, immunoglobulins, and immunoreactive trypsin, were investigated in 55 patients with acute pancreatitis. The mean level of alpha 2-macroglobulin in 395 plasma samples from the patients was 2.12 g/liter compared with 2.41 g/liter in 29 healthy subjects and 2.93 g/liter in 17 patients with septicemia. Plasma levels were lower in 12 patients with severe pancreatitis than in 43 with mild attacks, and the lowest levels in three fatal attacks were less than half the mean of the normal range. Lowest levels were recorded at a mean time of 3 days after admission in the patients with mild attacks, at 5 days after admission in the patients with severe attacks, and 9 days after admission in those with fatal attacks. In contrast, plasma levels of the alpha 1-proteinase inhibitor antichymotrypsin and C-reactive protein increased to above normal levels during the attack, significantly more so in severe compared with mild attacks. Plasma levels of IgA, IgG, and IgM remained within the normal range or were increased. In patients with severe pancreatitis, plasma levels of immunoreactive trypsin remained elevated for longer than in those with mild attacks although there was little initial difference in the levels. These data suggest that decreasing levels of alpha 2-macroglobulin during the course of acute pancreatitis are due to a specific mechanism and unrelated, for the most part, to any generalized effect of pancreatitis on protein synthesis. The formation of rapidly cleared complexes between alpha 2-macroglobulin and active proteases is the most tenable explanation for the depletion of plasma levels, but the clinical significance of the changes remains unclear.

The plasma levels of certain digestive enzymes and protease inhibitors were determined in 40 patients with severe acute pancreatitis diagnosed as gallstone-induced (GP), alcoholic (AP), or idiopathic (IP). On admission, plasma levels of amylase and immunoreactive cationic trypsin(ogen) (IRCT) and elastase 2 (IRE 2) were found to be 50 +/- 10 ng/ml, 340 +/- 64 ng/ml, and 190 +/- 15 ng/ml, respectively, in all groups of patients. These enzymes levels remained high for the first 2 days following hospitalization and then decreased, although amylase and IRCT levels remained elevated above normal values throughout the study period (2 weeks). In general amylase and IRCT were lower in patients with concomitant ascites, pancreatic pseudocysts, or abscesses, and higher in patients who died, as compared to the pancreatitis group as a whole. In these patients, levels of immunoreactive alpha 1-protease inhibitor (alpha 1-PI) and alpha 2-macroglobulin (alpha 2-M) remained relatively constant at the lower end of the normal range throughout the study period. Inhibitor levels in plasma were unaffected by the etiology of pancreatitis or the occurrence of complications. A similar trend was seen with plasma levels of lysosomal hydrolases. The results indicate that in this group of patients, plasma levels of pancreatic digestive enzymes were reflective of the clinical features and severity of the disease, as well as the time following the acute attack that brought the patient to the hospital.

The value of the Acute Physiology and Chronic Health Enquiry (APACHE-II) score, the Simplified Acute Physiology score, and the Medical Research Council (MRC) sepsis score were compared with clinical assessment and Ranson and Imrie scores in the evaluation and monitoring of acute pancreatitis in 290 attacks. Attacks were graded mild (231) if uncomplicated, or severe (59) when major organ failure or a pancreatic collection occurred. Only APACHE-II scores were available at the time of admission; they correctly predicted outcome in 77% of attacks and identified 63% of severe attacks, compared with 44% achieved by clinical assessment. After 48 h, APACHE-II was most accurate, and correctly predicted outcome in 88% of attacks, compared with 69% for Ranson and 84% for Imrie scores. APACHE-II predicted 73% of pancreatic collections at 48 h, compared with 65% for Ranson and 58% for Imrie scores. In acute pancreatitis, APACHE-II may facilitate rapid selection of patients for intensive therapy or clinical trials, improve comparison between groups of patients, and indicate that a pancreatic collection is probable.

A tubeless pancreatic function test (BTP test) using N-benzoyl-l-tyrosyl-p-aminobenzoic acid was used to assess exocrine function from urinary recovery of p-aminobenzoic acid produced by hydrolysis of the peptide by chymotrypsin. Patients with acute pancreatitis were studied at various time intervals after the acute attack and compared with controls with abdominal pain that was not pancreatic in origin. The initial BTP test carried out in the convalescent period was abnormal in all of 30 patients with acute pancreatitis but normal in 10 patients with non-pancreatic abdominal pain and also in 8 patients who had recovered from an attack of acute pancreatitis 2-6 years previously. Results were improved or normal in 12 of 15 patients re-tested 1 year after the attack of pancreatitis, but 4 out of 6 still had abnormal results 2-6 months after the attack. The data suggest that an attack of acute pancreatitis may impair exocrine pancreatic function for several months.

Diagnostic peritoneal lavage was attempted in 96 out of a consecutive series of 168 attacks of acute pancreatitis, in order to evaluate its ability to predict severe disease. Lavage was successful in 89 instances, and resulted in relief of pain in many patients, and in one complication. Lavage indicated (by the presence of numerous organisms) that the diagnosis was incorrect in 1 patient with suspected acute pancreatitis; the correct diagnosis, biliary peritonitis, was revealed at post mortem examination. The severity of the attack was predicted by the clinician prior to lavage, and each attack was classified as mild or severe when the patient left hospital according to a simple clinical scheme. Although there was a strong correlations between severe attacks and the concentrations of G. O. T., albumin, protein, magnesium, potassium and phosphate in the lavage fluid, a simple and immediate classification based upon the physical features of the free peritoneal fluid and the lavage return fluid was adopted. The presence of brown free fluid, or more than 10 ml of free fluid, or mild-straw coloured lavage was taken as the lavage criterion of a severe attack. Of the 89 attacks with a successful lavage, 68 were classified as mild and 21 as severe according to the clinical outcome. Clinical assessment of the attack on the day of admission to hospital successfully predicted only 8 (38%) of the severe attacks, but 17 (76%) were correctly predicted by lavage, carried out at an average time of 7 hours after admission. False positive results of lavage were seen in only 4 (6%) of the 68 mild attacks. All attacks in which a shock-like illness developed, or which resulted in death (4) were predicted as severe by lavage. We feel that diagnostic lavage especially suited to select patients who may be expected to benefit from therapeutic peritoneal lavage.

We performed a multicenter, randomized, controlled clinical trial of therapeutic peritoneal lavage (2 liters per hour for three days) in 91 patients with severe acute pancreatitis. Patients were entered into the study if severe pancreatitis was indicated by multiple laboratory criteria or diagnostic peritoneal lavage. All patients received full supportive treatment. The median time between the onset of symptoms and randomization was 38 hours. Forty-six patients were assigned to the control group and 45 to the lavage group. There were 13 deaths (28 per cent) and 16 patients with major complications (35 per cent) in the control group, as compared with 12 deaths (27 per cent) and 17 patients with major complications (38 per cent) in the lavage group. Lavage did not appear to modify the length of survival, the incidence of pancreatic collections (pseudocysts or abscesses), or the plasma amylase concentration. Considering the statistical power of the design, we conclude that the outcome of severe pancreatitis was not greatly, if at all, influenced by the regimen of peritoneal lavage used in this study.

Forty-six gallbladders were examined for the number, weight, size and shape of their gallstones, and for the volume of flow, under conditions of constant pressure, that was transmitted by the cystic duct. Eighteen gallbladders were from patients who had previously suffered an attack of acute pancreatitis, and the other 28 were from control patients who had not had a known attack of pancreatitis. Cystic duct flow rates, which we assumed were related to cystic duct calibre, were greater in the pancreatitis group (mean = 282 ml/min) than in the controls (mean = 134 ml/min) (P less than 0.01). There were more stones in the gallbladders of the pancreatitis patients, and the mean stone weight was lower in this group (0.31 g compared with 0.74 g; P less than 0.02). Large stones were more frequently seen in the control gallbladders. Small, irregular or mulberry-shaped stones were the dominant stone type in 78 per cent of the pancreatitis group but in only 43 per cent of the controls (P less than 0.05). Thus a large-calibre cystic duct and numerous small stones with an irregular shape appeared to be more common in patients who had suffered acute pancreatitis, and may be factors in the pathogenesis of the attack.

Peritoneal fluid may be the source of multi-system failure during the initial stages of acute pancreatitis. The toxicity of human pancreatic ascitic fluid (HPAF) collected under sterile conditions from 12 patients with acute pancreatitis was investigated with the use of an in vitro preparation of mitochondria. Hepatocyte mitochondria from Sprague-Dawley rats were prepared by standard techniques. Mitochondrial oxidative activity was determined in glutamate-malate medium, with micromodification of the YSI Model 53 (Yellow Springs, Ohio) oxygen electrode system. The oxygen uptake of 150 to 200 microliter samples of mitochondria suspension (20 to 25 mg/ml) was monitored for 3 minutes, after which 3 microliter of 0.1 M adenosine diphosphate (ADP) was added to the chamber to induce state 3 respiration. Two minutes after the oxygen trace returned to state 4 respirations, 20, 40, or 80 microliter of the HPAF sample was introduced into the reaction vessel and the oxygen measurement continued for an additional 3 minutes. After this, 3 microliter of 0.1 M ADP again was added to the reaction chamber and the oxygen measurement continued. Control runs were made with reconstituted pooled human serum used in place of the HPAF samples. A significant (p less than 0.05) increase in state 4 respiration occurred in all 12 samples of HPAF. Addition of ADP showed a significant decline (p less than 0.05) in respiratory control ratio in all specimens. A dose-response curve was observed in 8 of 12 HPAF samples tested.(ABSTRACT TRUNCATED AT 250 WORDS)

A retrospective and prospective study was made of 82 attacks of acute pancreatitis occurring in 80 patients. Attacks were defined as mild (55) or severe (27) according to clinical criteria. Severe attacks were associated with significantly low levels of uncorrected calcium and calculated ionized calcium, both at the time of admission and 48 h later. Patients with severe attacks were found to have lower levels of parathyroid hormone than either those with mild attacks or other patients who had undergone an abdominal operation. These results indicate that severe pancreatitis is associated with true hypocalcaemia, and that deficiency of circulating parathyroid hormone may be a factor in its production.

In acute pancreatitis a toxic exudate accumulates within the peritoneal cavity, which contains activated pancreatic proteinases. Peritoneal lavage removes the exudate effectively, washing it away with large volumes of saline solution, but is of unproven therapeutic value and may have deleterious effects. These may be avoided by combining lower volume peritoneal washouts with intra-peritoneal installation of a proteinase inhibitor, although therapeutic effectiveness may be compromised by systemic absorption depending on the inhibitor selected. This latter effect was studied in fifteen patients with acute pancreatitis, treated by simple peritoneal washout and bolus intra-peritoneal administration of aprotinin (Trasylol) solution.

An enzyme linked immunosorbent assay (ELISA) for human pancreatic lipase was compared, for diagnostic sensitivity, to a chromogenic assay of total plasma amylase in 37 patients with acute pancreatitis. Data from patients were related to a control group of 38 patients with gastrointestinal disease but without pancreatic diseases. During the first 24 hours of admission, lipase was elevated 131 standard deviations (SD) above the mean of the control range compared to 25 SD for amylase (p less than 0.001). When amylase fell to within the control range (less than 531 iu/l) lipase was still elevated at a mean of 11 SD above the control mean. In patients followed for longer, lipase usually remained above normal for at least ten days, whereas amylase lay within 1 SD of the mean of the control samples in most plasma samples after 4 days. These data show that lipase is considerably more sensitive than total amylase for the diagnosis of acute pancreatitis.

A simple agglutination test for plasma immunoreactive lipase has been evaluated in 101 patients. A positive agglutination reaction was observed if, and only if, plasma lipase exceeded 300 micrograms/l. The test was positive in all 23 patients with acute pancreatitis who were tested on the day of admission to hospital, in one patient with a pancreatitic pseudocyst and in one patient with hyperamylasaemia and hyperlipasaemia due to a perforated duodenal ulcer. The simplicity and reliability of this test make it suitable as an urgent diagnostic investigation for acute pancreatitis.