Amelioration of chronic inflammation by ingestion of elemental diet in a rat model of granulomatous enteritis

The beneficial effect of elemental diet (ED) in the treatment of Crohn's disease is reported, although the exact mechanism for this remains to be elucidated. In this study the effects of ED on intestinal inflammation were investigated in a rat model of granulomatous enteritis. Intestinal inflammation was induced by a single intramural injection of peptidoglycan-polysaccharide (PG-PS) from group A streptococci into rat ileal Peyer's patches. A single injection of PG-PS in combination with fibrinogen, which retains PG-PS at the injection site, induced severe granulomatous inflammation associated with mucosal ulceration. Immunohistochemical study and immunocytochemical analysis of the cell suspension from Peyer's patches showed accumulation of macrophages and an increase in interleukin-2 receptor (IL-2R)-positive T cells after PG-PS treatment. Chemiluminescence (ChL) activity and nitrite and nitrate (NOx) levels in the mesenteric venous blood as well as Ca(2+)-independent (inducible) nitric oxide synthase (NOS) activity in Peyer's patches were increased by PG-PS treatment. In rats fed with ED, both macroscopic and histologic damage scores were significantly decreased as compared with those in rats fed with the control diet. ED inhibited the increase in the numbers of macrophages and IL-2R-positive T cells in Peyer's patches. Increased ChL activity, NOx levels, and Ca(2+)-independent NOS activity were also reduced significantly by feeding with ED. These data suggest that ED reduces progression of PG-PS-induced chronic intestinal inflammation by modulating activation of T cells, production of nitric oxide, and generation of oxygen free radicals.     

Pathological changes in pancreatic ducts from patients with chronic pancreatitis

The microsporidian Encephalitozoon hellem is being reported with increasing frequency in HIV-positive subjects, as an agent of disseminated microsporidiosis without involving the gastrointestinal tract. We describe a case of pulmonary microsporidiosis in a 27-year-old Italian man with AIDS who developed fever, cough, and dyspnea. A chest X-ray showed multiple bilateral pulmonary opacities and mediastinal lymph-node enlargement. Stained smears of bronchoalveolar lavage sediment showed oval structures consistent with microsporidian spores. Viral, bacterial and fungal cultures were repeatedly negative, whereas microsporidia were successfully cultured in human and bovine fibroblast cell lines. Analysis of electron micrographs indicated that the isolate belonged to the genus Encephalitozoon. Based on further immunological, biochemical and molecular studies it was characterized as E. hellem. Even though a temporary improvement with albendazole therapy was noticed, the patient deteriorated clinically and died of severe respiratory distress.     

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.     

Influence of long-term human recombinant erythropoietin treatment on secretion of pancreatic polypeptide and gastrin in hemodialysed patients with chronic renal failure

The study aimed to assess the influence of long-term rhu-EPO treatment on secretion of pancreatic polypeptide (PP) and gastrin. A total of 27 haemodialysed patients and nine healthy subjects were examined. Nine patients with uraemic anaemia were treated with rhu-EPO for 12 months (EPO group), while another nine patients did not receive rhu-EPO (non-EPO group), but were monitored biochemically and clinically as patients of the EPO group. The third group (HD) comparised nine haemodialysed patients with a haematocrit value > or = 30% without rhu-EPO therapy. In all subjects plasma levels of PP and gastrin were estimated before and after administration of a test meal. Patients of the EPO and non-EPO group were examined before and after 6 and 12 months of rhu-EPO therapy (EPO group) or clinical monitoring (non-EPO group) respectively, while only one test was performed in patients of the HD group and healthy subjects. Six months rhu-EPO therapy was followed by an decrease of basal plasma level of PP and increased response of gastrin to the test meal. After 12 months of rhu-EPO therapy basal plasma level of PP was still lower, the response of PP secretion to a test meal was higher, while that of gastrin secretion lower that the pretreatment ones. Our results suggest, that rhu-EPO treatment exerts effect on secretion of PP and gastrin. These alterations seem not to be related to improvement of the haematological status.     

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.     

Islet amyloid polypeptide in patients with pancreatic cancer and diabetes

Population-based psychiatric admission rates vary across geographic areas, but reasons for this variation are unknown. Insofar as Community Mental Health Centers (CMHCs) provide outpatient services that may deter the need for hospitalization, the presence and structural characteristics of CMHCs may have an impact on a population's psychiatric admission rates. This study uses small area analysis to examine how general hospital psychiatric admission rates are associated with CMHC characteristics. Based on a survey of all CMHCs in Iowa and corresponding small area variation data, it was found that population admission rates were higher in areas closer to the CMHC and lower in outlying catchment areas, adjusting for age, sex, and urban/rural differences in populations. There was little evidence that differences in staffing and service variables influenced admission rates, although greater CMHC staff coverage by social workers and psychiatric residents was associated with lower admission rates. The results suggest that CMHCs do not lower an area's hospitalization rate, and in fact, the presence of CMHCs may promote a "supplier-induced demand" phenomenon of higher admissions.     

Endogenous levels of somatostatin, C-peptide and insulin in acute pancreatitis

The authors compared in seven patients with acute pancreatitis the levels of endogenous somatostatin, insulin and C-peptide to assess their mutual correlation and relation to the development of the disease and serum amalyse levels. The results were compared with values recorded in 11 healthy volunteers. The levels of endogenous somatostatin were in patients with acute pancreatitis significantly higher (p < 0.05) than in the control group. The authors found an inverse relationship between the somatostatin and amylase level (correlation coefficient 0.75). They did not observe a significant correlation between somatostatin and insulin levels nor between somatostatin and C-peptide levels. The elevated somatostatin level may be due to the counteregulatory reaction during secretion, stimulated by endogenous or exogenous factors (cholecystokinin, alcohol, food).     

Insulin and glucagon response in patients with chronic pancreatitis

The oral glucose tolerance test and arginine infusion test were carried out on 22 patients with chronic pancreatitis and 11 normal control subjects. According to the glucose tolerance curve, the patients were divided into three groups; group I (normal or slightly impaired), group II (mildly diabetic) and group III (moderately diabetic). Markedly impaired insulin responses to oral glucose as well as to arginine infusion were observed in groups II and III. In group I, the mean plasma insulin levels during glucose tolerance test were the same as those in the controls, but the insulin response to arginine was reduced except in two cases. On the other hand, the glucagon levels during arginine infusion test were within the normal range in group I and slightly reduced in the other groups with diabetic glucose tolerance. The ratio of increment area of insulin to that of glucagon during arginine infusion in the patients was slightly decreased in comparison with the controls. Neither insulin nor glucagon response after arginine infusion showed a significant correlation with pancreatic exocrine function. It is concluded that in chronic pancreatitis insulin response to glucose as well as to arginine is markedly decreased, and that glucagon rise after arginine infusion is lowered compared with the controls.     

Antibody responses to Epstein-Barr virus, human herpesvirus 6 and human herpesvirus 7 in patients with chronic fatigue syndrome

To test for an association between chronic fatigue syndrome (CFS) and infections with Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6) and human herpesvirus 7 (HHV-7), antibodies to these viruses were tested in the serum from three groups of individuals: (1) 10 CFS patients with chronic fatigue beginning with a clinical pattern of acute infectious mononucleosis [IM; true chronic IM (CIM)]; (2) 10 CFS patients whose illness did not start with acute IM (non-CIM), and (3) healthy controls. High EBV antibody titers were demonstrated in most patients. Antibodies to ZEBRA, a product of the immediate early EBV gene BZLF1, were detected in the serum of CFS patients at a higher frequency than in healthy controls. Antibody titers to HHV-6 and HHV-7 were also higher in the patients with CFS than in the controls. These results are consistent with the view that CFS patients may have reactivations of EBV, HHV-6 and HHV-7.     

Cholecystokinin and pancreatic polypeptide release in diabetic patients with and without autonomic neuropathy

The present study was undertaken to investigate postprandial responses of cholecystokinin (CCK) and pancreatic polypeptide (PP) and their interrelationship in patients with diabetes mellitus (DM) with and without autonomic neuropathy (AN). Twenty-two patients with DM (seven with AN and 15 without AN) and 14 age-matched healthy controls were studied. AN was diagnosed according to several tests of cardiovascular autonomic function. CCK and PP plasma levels were measured by specific radioimmunoassays before and at several time points after the oral administration of a test meal. Basal CCK plasma levels in DM patients were normal, whereas basal PP plasma levels were increased (139 +/- 18 vs 72 +/- 7 pg/ml; P < 0.01). Integrated postprandial CCK response was increased in DM patients (208 +/- 27 vs 110 +/- 14 pmol/liter/2 hr; P < 0.05), mainly due to the patients with AN. Postprandial PP response was increased in DM patients without AN (37,273 +/- 5241 vs 13,418 +/- 3299 pg/ml/2 hr; P < 0.001) but not in those with AN (8887 +/- 3461 pg/ml/2 hr). Moreover, PP response was closely (P < 0.002) correlated with the degree of AN. A direct and linear correlation between postprandial CCK and PP responses was found in healthy controls (r = 0.78; P < 0.005) but not in DM patients. We conclude that the CCK response to a meal is increased in diabetic patients with AN, whereas the PP response is increased only with an intact autonomic nervous system.(ABSTRACT TRUNCATED AT 250 WORDS)     

Wirsung's duct and chronic pancreatitis. Changes in the morphology of the pancreatic ducts after pancreatic duct shunts. 23 cases followed-up

The authors study in chronic pancreatitis the morphology of Wirsung's duct in 31 patients who had undergone repeated operations, 23 of them were submitted in a first stage to an anastomosis between the pancreatic duct and the digestive tract. The main causes of failure were obstructions of the anastomosis, biliary complications and continuation of the pancreatic disease. The difference in prognosis between pancreatitis with a dilated pancreatic duct, and those with a filiform duct, is perhaps due to lesions of different histological appearance and course. The best results were obtained in patients able to give up alcohol and in whom it was possible to carry out a broader anastomosis on a dilated and unobstructed pancreatic duct.     

Effect of duodenum-preserving resection of the head of the pancreas on endocrine and exocrine pancreatic function in patients with chronic pancreatitis

Two mobilizable cloning vectors, designated pABW1 and pAWB2, were constructed basing on the E. coli vector pBGS18 and oriT originating from RK2. In pABW2 the kanamycin resistance gene was replaced by a novel tetracycline resistance cassette derived from Tn1721. Both vectors, specific for E. coli, allow to perform the cloning steps in E. coli and then to efficiently transfer the constructs by conjugation to the host of choice. A vector which cannot propagate in the given host can be applied for identification of the host specific plasmid replicator regions. With the use of pABW2 we defined the minimal replicator region of pTAV202-a mini-derivative of the large pTAV1 plasmid of P. versutus. We also proved that RepC' encoded on this fragment is the principal initiator replication protein and that oriV is located along its coding sequence.     

Decrease in contents of pancreatic carboxyl ester lipase, phospholipase A2, and lingual lipase in rats with streptozotocin-induced diabetes

Fibrin glue has been used as a protective seal in normal and high-risk anastomoses to prevent leakage. The influence of fibrin adhesive on the healing colonic anastomosis in a control and high-risk model was tested. Resection and anastomosis of the left colon was performed in rats. In group Ia an end-to-end anastomosis was constructed with 12 7-O polypropylene sutures; in group Ib the anastomosis was sealed with fibrin adhesive. In group II an incomplete anastomosis was constructed with only 4 sutures at 90 degrees, therefore potentially leaking. In group IIb additional sealing with fibrin glue was performed. On Days 2, 4, and 7 body weight, adhesion formation, anastomotic bursting pressure, and collagen concentration were measured. The results showed increased adhesion formation after fibrin sealing. The anastomotic bursting pressure of incomplete anastomoses showed a significant increase after sealing on Day 2 only; on Day 4 and 7 no differences were found. Sealing of control anastomoses caused lower bursting pressures on Day 4. Collagen concentration is significantly reduced after fibrin sealing of normal anastomoses. We conclude that fibrin sealing of control anastomoses inhibits wound healing. Incomplete anastomoses are temporarily protected by fibrin glue sealing. Finally, fibrin sealing of the colon wound does not prevent adhesion formation.     

Helicobacter pylori infection in patients with chronic pancreatitis and duodenal ulcer

BACKGROUND: The prevalence of duodenal ulcer is high in patients with chronic pancreatitis. Patients with simple duodenal ulcer without chronic pancreatitis are mostly Helicobacter pylori-infected, and the prevalence of IgG seropositivity is > 95%. The prevalence of H. pylori infection in patients with chronic pancreatitis is not known. METHODS: IgG antibodies against H. pylori were measured in a cross-sectional survey of consecutive patients who had their exocrine pancreas function examined with a Lundh meal test in the period 1988-95 and in a control group of patients with simple duodenal ulcer. RESULTS: Twenty-seven per cent of the patients with chronic pancreatitis had duodenal ulcer during the observation period. The prevalence of IgG antibodies against H. pylori was 22% in patients with chronic pancreatitis without duodenal ulcer as compared with 27% with non-organic abdominal pain. The prevalence of IgG antibodies against H. pylori was 60% in patients with chronic pancreatitis complicated by duodenal ulcer as compared with 86% in controls with simple duodenal ulcer. CONCLUSIONS: H. pylori infection contributes but may not be the only cause of duodenal ulcer in patients with chronic pancreatitis.     

The characteristics of disorders in carbohydrate metabolism and insulin and C-peptide secretion in patients with chronic glomerulonephritis in developing chronic kidney failure

The authors studied hormonal regulation of carbohydrate metabolism by secretion of insulin, C-peptide in 86 patients with chronic glomerulonephritis with different functional condition of the kidneys. There was a decrease in glucose tolerance, basal and reactive hyperinsulinemia, elevated level of C-peptide (relative insulin insufficiency). Mechanism of arising changes in the carbohydrate and insulin metabolism is complex and multicomponent. This includes renal lesion and consequent inhibition of hormone metabolism. Intensification of glomerular filtration is associated with inhibition of filtration of insulin and C-peptide derivants. Accumulation of nitrogen metabolism products results in changed response of pancreatic beta-cells to glucose. General disturbances of metabolism are accompanied by increasing levels of hormonal and nonhormonal contrainsular substances.     

Regulation of migrating motor complexes by motilin and pancreatic polypeptide in human infants

In samples of wool from 1,229 differently colored newborn Astrakhan lambs, the total content of melanins and the proportion of pheomelanin in the total melanin were studied by the method of electron magnetic resonance spectometry. An analysis of the corresponding computer data base revealed that the distribution of the samples with respect to the proportion of pheomelanin had at least four characteristic maximums; 1-6, 9-10, 28-29, and 39% of pheomelanin. The former two maximums were characteristic for the brown and Karakalpak sur colors, and the latter two maximums, for red-brown kambar color. White hair tips, characteristic for the sur color, and the proportion of pheomelanin were combined almost independently; therefore the possibility is discussed of classifying these characters as independent phenes, and some variants of sur, as their combinations.     

Effect of pancreatic ductal and parenchymal changes on exocrine function in chronic pancreatitis

The effect of pancreatic ductal and parenchymal changes on exocrine pancreatic function was analyzed prospectively in 75 patients with chronic pancreatitis (CP). Endoscopic retrograde pancreatography (ERP), computed tomography (CT), and serum pancreolauryl test (PLT) were performed to evaluate the degree of ductal, parenchymal, and functional changes, respectively. Results were evaluated by stepwise multivariate logistic regression and are expressed as the odds ratio (OR). A strong association was found between the degree of ductal changes in ERP and the degree of exocrine functional impairment (OR = 5.8). However, the association between the degree of parenchymal changes in CT and the degree of pancreatic dysfunction was weaker and was clearly confounded by the degree of ductal changes. On the basis of these findings, we suggest that the development of exocrine pancreatic functional impairment in patients with CP depends primarily on the degree of ductal changes, while parenchymal abnormalities play a less important role.     

Mutations of the cystic fibrosis gene in patients with chronic pancreatitis

BACKGROUND: The pancreatic lesions of cystic fibrosis develop in utero and closely resemble those of chronic pancreatitis. Therefore, we hypothesized that mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene may be more common than expected among patients with chronic pancreatitis. METHODS: We studied 134 consecutive patients with chronic pancreatitis (alcohol-related disease in 71, hyperparathyroidism in 2, hypertriglyceridemia in 1, and idiopathic disease in 60). We examined DNA for 22 mutations of the CFTR gene that together account for 95 percent of all mutations in patients with cystic fibrosis in the northwest of England. We also determined the length of the noncoding sequence of thymidines in intron 8, since the shorter the sequence, the lower the proportion of normal CFTR messenger RNA. RESULTS: The 94 male and 40 female patients ranged in age from 16 to 86 years. None had a mutation on both copies of the CFTR gene. Eighteen patients (13.4 percent), including 12 without alcoholism, had a CFTR mutation on one chromosome, as compared with a frequency of 5.3 percent among 600 local unrelated partners of persons with a family history of cystic fibrosis (P<0.001). A total of 10.4 percent of the patients had the 5T allele in intron 8 (14 of 134), which is twice the expected frequency (P=0.008). Four patients were heterozygous for both a CFTR mutation and the 5T allele. Patients with a CFTR mutation were younger than those with no mutations (P=0.03). None had the combination of sinopulmonary disease, high sweat electrolyte concentrations, and low nasal potential-difference values that are diagnostic of cystic fibrosis. CONCLUSIONS: Mutations of the CFTR gene and the 5T genotype are associated with chronic pancreatitis.     

Determination of serum pancreatic polypeptide and its clinical significance in patients with end state renal failure

A screening program for the detection of Tay-Sachs disease (TSD) carriers in the ultra Orthodox community of Ashkenazi Jews has operated in Israel since 1986. The purpose of this program is the prevention of marriages of 2 heterozygotes. The screened individuals are mostly couples in the engagement process or students in religious high schools. Two mandatory requirements guide this program. First, anonymity of the tested individuals who are identified only by code numbers; second completion of the test results of couples in the engagement process within a few days. The screening program is performed by the determination of hexosaminidase A (Hex A) activity in serum which is repeated in serum and leukocyte extracts in couples where both partners were found in the heterozygote range in the initial tests. The minimal carrier frequency was estimated to be 1:26 or higher, which is higher then in the general Jewish Ashkenazi population. This higher carrier frequency apparently stems from the fact that most members of this community originate from central Europe where the TSD carrier frequency was previously reported to be the highest in the Ashkenazi population. Since the beginning of the screening program no TSD child has been born to newlywed couples of this community in Israel.