Bayou virus-associated hantavirus pulmonary syndrome in Eastern Texas: identification of the rice rat, Oryzomys palustris, as reservoir host

OBJECTIVE: To validate the safety of gadolinium-diethylenetriamine pentaacetic acid (GD-DTPA) by measuring its effect on pancreatic capillary perfusion and acinar injury in acute pancreatitis. BACKGROUND: Contrast-enhanced computed tomography (CECT) is proposed as a gold standard for early evaluation of acute necrotizing pancreatitis. However, iodinated contrast media used for CECT have been shown in these circumstances to reduce pancreatic capillary flow and increase necrosis and mortality. Recent reports suggest that post-GD MRI provides images comparable to CECT in the assessment of severe acute pancreatitis. METHODS: Necrotizing pancreatitis was induced in 14 Wistar rats by intraductal glycodeoxycholic acid (10 mM/L) and intravenous caerulein (5 microg/kg/h) over 6 hours. Intravital microscopic quantitation of pancreatic capillary blood flow was performed using fluorescein isothiocyanate-labeled erythrocytes after induction of pancreatitis and 30 and 60 minutes after an intravenous bolus of either Ringer's solution or GD-DTPA (0.2 mL/kg). RESULTS: The two study groups were comparable with regard to mean arterial pressure, heart rate, arterial blood gases, hematocrit, amylase, lipase, and trypsinogen activation peptide production throughout the experiment. GD-DTPA did not reduce capillary flow (1.93 +/- 0.05 nL/capillary/min) compared to animals infused with Ringer's solution (1.90 +/- 0.06 nL/capillary/min). CONCLUSIONS: Intravenous injection of GD-DTPA does not further impair pancreatic microcirculation or increase acinar injury in acute necrotizing pancreatitis. Because of this advantage over CT contrast medium, further development of MRI as a staging tool in acute pancreatitis seems desirable.     

Renal revascularisation by gastroduodenal-renal bypass as treatment of renal artery stenosis

The functioning part of parenchyma, isolated from the organ and its duct system due to the presence of pancreatitis or injury is the source filling the pseudocyst cavity and the cause which supports the pancreatic fistula existence. Possibility of pancreatic pseudocyst simulation in experiment on dogs was proved. An experimental cyst cavity decompression was done with the help of the tunnel conducted via papilla between the cyst and the main duct.     

Chronic pancreatitis: diagnosis

Chronic pancreatitis is a chronic, inflammatory process leading to destruction of the exocrine tissue, filorosis, and in some patients a loss of endocrine function. Because chronic pancreatitis results in a permanent destruction of pancreatic tissue, exocrine and/or endocrine pancreatic insufficiency may follow. However, owing to the tremendous reserve of pancreatic function, insufficiency may be subclinical at least in the beginning of the disease. The diagnosis of chronic pancreatitis is not difficult; it is based on a typical medical history, specific imaging procedures, and pancreatic function testing. The main differential diagnosis is to separate chronic pancreatitis form pancreatic carcinoma. In the present summary, the different imaging procedures and pancreatic function tests are discussed.     

Effect of recombinant platelet-activating factor acetylhydrolase on two models of experimental acute pancreatitis

BACKGROUND & AIMS: Recent reports suggest that platelet-activating factor (PAF) plays a role in pancreatitis and pancreatitis-associated lung injury. In this study, the effects on these processes of termination of PAF action by recombinant PAF-acetylhydrolase (rPAF-AH) were investigated. METHODS: Rats were given rPAF-AH and then infused with a supramaximally stimulating dose of cerulein to induce mild pancreatitis. Opossums underwent biliopancreatic duct ligation to induce severe pancreatitis, and rPAF-AH administration was begun 2 days later. RESULTS: In mild, secretagogue-induced pancreatitis, rPAF-AH given before the cerulein reduced hyperamylasemia, acinar cell vacuolization, and pancreatic inflammation but did not alter pancreatic edema or pulmonary microvascular permeability. In severe, biliopancreatic duct ligation-induced pancreatitis, rPAF-AH delayed and reduced the extent of inflammation and acinar cell injury/necrosis and completely prevented lung injury even though the rPAF-AH administration was begun after the onset of pancreatitis. CONCLUSIONS: PAF plays an important role in the regulation of pancreatic injury but not pancreatic edema or increased pulmonary microvascular permeability in mild, secretagogue-induced pancreatitis. PAF plays a critical role in the regulation of progression of pancreatic injury and mediation of pancreatitis-associated lung injury in severe biliary pancreatitis. Amelioration of pancreatitis and prevention of pancreatitis-associated lung injury can be achieved with rPAF-AH even if treatment is begun after pancreatitis is established.     

The splice-pattern of CD44 is altered in chronic pancreatitis exhibiting dysplastic changes

Recent studies have shown that several splice variants of CD44, might be involved in tumor progression. Since chronic pancreatitis is suggested to be a risk factor for pancreatic cancer we investigated the splice pattern of CD44 in chronic pancreatitis to elucidate the role of CD44 in pancreas tumorigenesis. The expression of CD44-isoforms was examined in 40 specimens of chronic pancreatitis and 12 specimens of normal pancreas by immunohistochemistry, Westernblotting and exon specific RT-PCR. Pancreatic cancer tissue from two patients who developed pancreatic cancer 2 and 3 years following surgery for chronic pancreatitis were analyzed. Strong expression of CD44s was found in all cells, whereas the expression of CD44v6 was restricted to ductal cells. Westernblotting revealed an overexpression of CD44v6 in chronic pancreatitis as compared to normal pancreas. Exon specific analysis revealed an altered splice pattern of CD44, similar to that in pancreatic cancer, in 12.5% of the chronic pancreatitis specimens. Both patients who developed pancreatic cancer after chronic pancreatitis exhibited this altered splice pattern in both, chronic pancreatitis and pancreatic cancer. These results suggest that variant forms of CD44-mRNA might be expressed in early dysplastic alterations in chronic pancreatitis.     

Protective effect of calcitonin gene-related peptide against caerulein-induced pancreatitis in rats

The stimulation of sensory nerves by capsaicin exhibits the protective effect against caerulein-induced pancreatitis whereas deactivation of these nerves aggravates pancreatic damage evoked by overdose of caerulein. Calcitonin-gene related peptide (CGRP) has been identified as the prominent mediator of sensory nerves. The aim of the present study was to examine the influence of CGRP on the course of caerulein-induced pancreatitis (CIP). CIP led to a significant decrease in DNA synthesis and pancreatic blood flow (PBF) by 48% and 50% respectively, as well as a significant increase of pancreatic weight, plasma amylase concentration and development of the histological signs of pancreatic damage expressed as edema, leukocyte infiltration and vacuolization. Treatment with CGRP (2 x 10 micrograms/kg s.c.) attenuated the pancreatic tissue damage in caerulein-induced pancreatitis and completely reversed the deleterious effect of the ablation of sensory nerves on caerulein-induced pancreatitis. We conclude that CGRP exerts protective effect against caerulein-induced pancreatitis and is able to reverse the damage caused by deactivation of sensory nerves. Vasodilatation and preservation of pancreatic blood flow are involved in this effect.     

Role of secondary prevention in congestive heart failure due to coronary artery disease

BACKGROUND: It is unknown whether genetic factors predispose patients to idiopathic pancreatitis. In patients with cystic fibrosis, mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene typically cause pulmonary and pancreatic insufficiency while rarely causing pancreatitis. We examined whether idiopathic pancreatitis is associated with CFTR mutations in persons who do not have lung disease of cystic fibrosis. METHODS: We studied 27 patients (mean age at diagnosis, 36 years), 22 of whom were female, who had been referred for an evaluation of idiopathic pancreatitis. DNA was tested for 17 CFTR mutations and for the 5T allele in intron 8 of the CFTR gene. The 5T allele reduces the level of functional CFTR and is associated with an inherited form of infertility in males. Patients with two abnormal CFTR alleles were further evaluated for unrecognized cystic fibrosis-related lung disease, and both base-line and CFTR-mediated ion transport were measured in the nasal mucosa. RESULTS: Ten patients with idiopathic chronic pancreatitis (37 percent) had at least one abnormal CFTR allele. Eight CFTR mutations were detected (prevalence ratio, 11:1; 95 percent confidence interval, 5 to 23; P<0.001). In three patients both alleles were affected (prevalence ratio, 80:1; 95 percent confidence interval, 17 to 379; P<0.001). These three patients did not have lung disease typical of cystic fibrosis on the basis of sweat testing, spirometry, or base-line nasal potential-difference measurements. Nonetheless, each had abnormal nasal cyclic AMP-mediated chloride transport. CONCLUSION: In a group of patients referred for evaluation of idiopathic pancreatitis, there was a strong association between mutations in the CFTR gene and pancreatitis. The abnormal CFTR genotypes in these patients with pancreatitis resemble those associated with male infertility.     

Emergency postcoital contraception

Pancreatitis may be acute or chronic, mild or severe. Acute necrotizing pancreatitis remains the most serious form of acute pancreatitis and accounts for the majority of complications. Although there is an established nomenclature for pancreatitis and pancreatic fluid collections, such as pancreatic pseudocysts, it is not widely understood or recognized by gastroenterologists. Because the management options for the treatment of pancreatic fluid collections continues to evolve with an increased use of endoscopic therapy, gastroenterologists will be increasingly called on to treat patients with pancreatitis and its complications. This article addresses and summarizes pancreatic fluid collections and their management, with an emphasis on endoscopic drainage.     

Resolution of panniculitis after placement of pancreatic duct stent in chronic pancreatitis

The association of panniculitis and pancreatitis is well described. However, panniculitis remains a relatively uncommon manifestation of pancreatic inflammation. We report a case in which treatment of pancreatitis by the placement of a pancreatic stent led to simultaneous resolution of both the pancreatitis and the associated panniculitis. There are no other reports in the literature demonstrating resolution of panniculitis subsequent to stent placement or definitive surgery.     

Missed curable carcinoma of the pancreas presenting as chronic pancreatitis

We present a case of pancreatic malignancy which presented as chronic pancreatitis. The diagnostic difficulties are discussed. We recommend that when there is any doubt about a diagnosis of chronic pancreatitis with a pancreatic mass, then early resection is appropriate.     

Absence of K-ras mutations in the pancreatic parenchyma of patients with chronic pancreatitis

BACKGROUND: Human pancreatic cancers exhibit a high frequency of K-ras mutations. METHODS: In this study we used oligonucleotide specific hybridization to compare the frequency of K-ras mutations in genomic DNA samples prepared from 21 normal pancreatic tissues, 26 chronic pancreatitis tissues, and 24 pancreatic cancers. RESULTS: None of the DNA samples from normal or chronic pancreatitis tissues exhibited a K-ras mutation at codons 12 or 13 of K-ras. In contrast, 17 of 24 DNA pancreatic cancers harbored a K-ras mutation. Validity of the methodology was confirmed by genotyping 7 human pancreatic cancer cell lines. Analysis of focal areas of proliferation from 5 chronic pancreatitis and 5 pancreatic cancer samples processed by selective ultraviolet radiation fractionation (SURF), a procedure used to enrich DNA isolation from foci of proliferating cells, revealed complete concordance with total genomic DNA analysis. CONCLUSIONS: These findings indicate that the pancreatic parenchyma in patients with chronic pancreatitis most frequently does not possess a K-ras mutation.     

The risk of pancreatic cancer following pancreatitis: an association due to confounding?

BACKGROUND & AIMS: Chronic pancreatitis has been suggested as a causal risk factor for pancreatic cancer in a recent study. The aim of this study was to clarify the relationship between chronic pancreatitis and pancreatic cancer. METHODS: All patients in the Swedish inpatient Register with a discharge diagnosis of pancreatitis from 1965 to 1983 were identified. They were stratified into subcohorts as follows: (1) one episode of unspecified pancreatitis (n = 823); (2) one episode of acute pancreatitis (n = 24,753); (3) recurrent pancreatitis (n = 7328); and (4) chronic pancreatitis (n = 4546). We also identified those with associated diagnoses indicating gallbladder disease or alcoholism. The patients were followed up through record linkage to the nationwide Swedish Cancer Register, Death Register, and Migration Register. RESULTS: After exclusion of cancers occurring in the first year, there were excess risks for pancreatic cancer in all subcohorts. However, the risks declined with time in all subcohorts. A persistent excess risk after 10 years was restricted to patients with associated alcohol abuse (standardized incidence ratio, 3.8; 95% confidence interval, 1.5-7.9). CONCLUSIONS: The findings are not consistent with reports that pancreatitis is causally associated with a long-term risk of pancreatic cancer. Selection bias, alcohol consumption, and smoking may contribute to some of the patterns of risk that have been observed.     

Clinical effects of anticancer drugs to pancreatic diseases as protein synthesis inhibitors

The anticancer drugs, like 5-Fluorouracil, which are believed to interfere with enzyme protein synthesis in the exocrine cells of pancreas were administered intravenously to fifteen patients with various pancreatic diseases. The improvement of clinical symptoms and the diminution of serum and urinary amylase levels were observed in four cases with acute pancreatitis and two cases with chronic relapsing pancreatitis. The postoperative complications, namely the formation of pancreatic fistula and the rupture of pancreaticojejunostomy, or the aggravation of concomitant pancreatitis were not observed in three cases with benign surgical pancreatic diseases and six cases with pancreatic carcinoma. Furthermore, the diminution of amylase and protein output of pancreatic juice from canulae inserted into pancreatic ducts were observed.     

Plasma alpha 2-macroglobulin-trypsin complexlike substance (MTLS) in pancreatic disease

alpha 2-macroglobulin-trypsin complexlike substance (MTLS) was determined in plasma of pancreatic and nonpancreatic diseases using a two-step enzyme immunoassay to study the diagnostic and pathophysiological significance of MTLS. Plasma levels of MTLS in acute pancreatitis (mean +/- SD = 265.6 +/- 346.2 ng/ ml, n = 9), calcified chronic pancreatitis (128.6 +/- 257.4, n = 13), and noncalcified chronic pancreatitis (13.5 +/- 12.5, n = 10) were significantly higher than that in controls (3.6 +/- 1.8, n = 81). In other diseases such as gastric cancer, hepatoma, diabetes mellitus, and gallstones, MTLS values were not different from those of control. Plasma MTLS values showed low correlation with serum trypsin, elastase 1, pancreatic amylase, lipase, and pancreatic secretory trypsin inhibitor (PSTI). The elevation of plasma MTLS values in acute pancreatitis suggests that plasma MTLS levels reflect that protease is inappropriately activated in pancreatic acinar cell and released into the circulation and that the determination of MTLS can be useful for diagnosis and pathophysiology of acute pancreatitis and chronic pancreatitis.     

Endoscopic retrograde cholangiopancreatography in the evaluation of pancreatic disease

Endoscopic retrograde cholangiopancreatography (ERCP) was carried out in 98 patients with unexplained abdominal pain or known pancreatitis with recurrent pain. Patients with jaundice were excluded from the study. In 38 patients with a clinical diagnosis of pancreatitis, the radiological findings on ERCP were graded according to the criteria of Kasugai et al. Advanced pancreatitis was found in 20 patients (52,5%), moderate changes in 7 (18,4%) and minimal-change pancreatitis in 6 (15,8%). ERCP had normal pancreatic function tests. In 35 patients investigated for unexplained abdominal pain, changes consistent with pancreatitis were found in 7, pancreatic carcinoma in 5, a duodenal ulcer in 2, gallstones in 1 and a duodenal tumour in 1. ERCP was normal in 19 patients. A comparison of the findings on ERCP and the standard secretin-cholecystokinin pancreatic function test was available in 52 patients. There was a good agreement between the two tests in the patients with advanced or moderate pancreatitis as revealed by ERCP, but less agreement in the patients with minimal-change pancreatitis. A few patients with clinical pancreatitis and abnormal ERCP had normal pancreatic function tests. ERCP increases the diagnostic yield in patients suspected of having pancreatitis and is at present the only reliable method of diagnosing pancreatic carcinoma which is not evident by other non-operative techniques. ERCP is also of value in the assessment of the severity of pancreatitis and is a necessary investigation before pancreatic surgery to confirm or exclude cyst formation or the site of duct obstruction. The finding of an unsuspected cyst at ERCP necessitates early operation because of the danger of introducing infection during the procedure.     

Release of nonesterified fatty acids during cerulein-induced pancreatitis in rats

During acute pancreatitis, data obtained in vitro suggest that pancreatic lipase, acting on circulating or tissular triglycerides, might generate nonesterified fatty acids (NEFA) that could promote pancreatic and fat tissue necrosis. This work determined whether NEFA were actually produced in vivo in pancreatic tissue and in blood during cerulein-induced pancreatitis in rats. Intraperitoneal injections of cerulein induced pancreatitis. To promote the possible NEFA release by pancreatic lipase, a venous infusion of human very low density lipoprotein (VLDL) was used to cause hypertriglyceridemia. NEFA were measured in portal and aortic blood and in tissue extracts prepared from pancreas homogenates. NEFA did not increase either in peripheral or in portal blood. In pancreatic tissue, NEFA levels did not differ from controls. The major hypertriglyceridemia produced by human VLDL intravenous infusion neither altered the course of the disease nor promoted plasma NEFA release. The role commonly attributed to NEFA in acute pancreatitis seems questionable.     

Diagnostic features of chronic pancreatitis distal to benign and to malignant pancreatic duct obstruction

Differentiation between diffuse chronic pancreatitis and pancreatitis distal to a malignant or benign stenosis has important prognostic and therapeutic implications. We examined the retrograde pancreatograms of 64 patients with histologically confirmed diagnosis of diffuse chronic pancreatitis, chronic pancreatitis distal to a benign tumor and chronic pancreatitis distal to a malignant tumor. The nature of the stenosis was often difficult to determine from the shape of the pancreatic duct only. By using discriminant analysis it was possible to determine an allocation rule based on 8 criteria mainly derived from changes in the pancreatic ductuli. This allocation rule allowed the correct diagnosis to be made in 24 out of 26 patients with diffuse chronic pancreatitis (92%), 19 out of 20 patients with pancreatitis distal to a benign tumor (95%) and all 18 patients (100%) with pancreatitis distal to a malignancy.     

The behavior of mucopolysaccharide in the pancreatic juice in chronic pancreatitis

In order to study whether or not mucosubstance increases occur in the pancreatic juice of patients with chronic pancreatitis, hexosamine was measured in duodenal aspirates during the secretin phase (S-40) following pancreozymin-secretin stimulation in 16 normal subjects, 37 patients with chronic pancreatitis, 6 patients with alcoholism, 13 patients with gallstones, and 11 patients with peptic ulcer. The hexosamine concentrations in the pancreatic secretions showed a negative correlation with the bicarbonate concentrations and volume output. Rises in hexosamine concentration were seen in alcoholism and chronic pancreatitis, especially in alcoholic pancreatitis. This is probably intimately related with the repeated ingestion of large amounts of alcohol over long periods of time. Since high hexosamine values are noted in the relapsing type of chronic alcoholic pancreatitis, increases in viscosity due to mucosubstance increases in the pancreatic juice are probably related with the recurrence of acute attacks accompanying ductal stenosis or obstruction.     

Induction of apoptosis in pancreatic acinar cells reduces the severity of acute pancreatitis

1-Cyano-2-hydroxy-3-butene (CHB) has been reported to cause cell death in rat pancreatic acini. In this report, we describe the time-dependent effects of CHB on mouse acinar cell apoptosis and the effects of CHB-induced acinar cell apoptosis on the severity of secretagogue-induced acute pancreatitis in mice. CHB administration to mice resulted in a time-dependent increase in pancreatic apoptosis, which was maximal 12 hours after CHB administration. The severity of pancreatitis was significantly reduced by prior CHB administration and maximal protection was observed when the caerulein injections were started 12 hours after CHB administration. These observations indicate that induction of apoptosis can reduce the severity of pancreatitis and they suggest that induction of pancreatic acinar cell apoptosis may be beneficial in the clinical management of acute pancreatitis.