Diagnosis and management of pancreatic exocrine insufficiency (PEI) in primary care: consensus guidance of a Canadian expert panel.

BACKGROUND: Pancreatic exocrine insufficiency (PEI) results in maldigestion due to inadequate activity of pancreatic enzymes in the small bowel. PEI can arise from a variety of medical conditions that reduce enzyme synthesis within the pancreatic parenchyma or from secondary factors that may occur despite optimal parenchymal function, such as pancreatic duct obstruction or impaired or poorly synchronized enzyme release. PURPOSE: To provide practical guidance for primary care physicians managing patients who are at risk of PEI or who present with symptoms of PEI. METHODS: For each of six key clinical questions identified by the authors, PubMed searches were conducted to identify key English-language papers up to April 2017. Forward and backward searches on key articles were conducted using Web of Science. Clinical recommendations proposed by the co-chairs (P.D. and C.T.) were vetted and approved based on the authors? FINDINGS: The most characteristic symptom of PEI is steatorrhea ? voluminous, lipid-rich stools; other common signs and symptoms include unexplained weight loss and deficiencies of fat-soluble vitamins and other micronutrients. Pancreatic enzyme replacement therapy (PERT) can relieve symptoms and long-term sequelae of PEI. Diagnosis of PEI and initiation of PERT are usually the responsibility of gastroenterology specialists. However, primary care physicians (PCPs) are well positioned to identify potential cases of PEI and to participate in the collaborative, long-term management of patients already seen by a specialist. CONCLUSIONS: In this document, a panel of Canadian gastroenterologists has conducted a critical review of the literature on PEI and PERT and has developed practical diagnostic and treatment recommendations for PCPs. These recommendations provide guidance on identifying patients at risk of PEI, the triggers for PEI testing and referral, and best practices for co-managing patients with confirmed PEI.

Maintenance of clinical benefit in Crohn's disease patients after discontinuation of infliximab: long-term follow-up of a single centre cohort.

BACKGROUND: Tumour necrosis factor-blockade with infliximab has advanced the treatment of Crohn's disease. While infliximab is efficacious, it remains to be determined whether patients who enter clinical remission with an anti-tumour necrosis factor therapy can have their treatment stopped and retain the state of remission. AIM: To assess in patients with Crohn's disease who obtained infliximab-induced remission, the proportion who relapsed after infliximab discontinuation. METHODS: This longitudinal cohort study examined patients from a University-based IBD referral centre. Forty eight patients with Crohn's disease in full clinical remission and who then discontinued infliximab were followed up for up to 7 years. Crohn's disease relapse was defined as an intervention with Crohn's disease medication or surgery. RESULTS: Kaplan-Meier analysis of the proportion of patients with sustained clinical benefit demonstrated that 50% relapsed within 477 days after infliximab discontinuance. In contrast, 35% of patients remained well, and without clinical relapse, up to the end of the nearly 7-year follow-up. CONCLUSIONS: In patients with Crohn's disease with an infliximab-induced remission, stopping infliximab results in a predictable relapse in a majority of patients. Nevertheless, a small percentage of patients sustain a long-term remission.

Polymerization of a vitelline envelope (VE)-like structure produced by using fractionated VE extracts from carp eggs.

Fractionation of vitelline envelope (VE) extracts from carp eggs made possible the efficient polymerization of a VE-like structure. The structure corresponded to the fourth layer of the VE or fertilization envelope (FE), and its organization was achieved by reassembly in vitro after solubilization of the sheets composed of filamentous substances or network-like aggregates which were induced by a cortical alveolus sialoglycoprotein or thrombin. The sialoglycoprotein was a serine proteinase and immunolocalized only in the structure at the periphery of cortical alveoli, not in the VE and yolk granules. Ultrastructural features of the VE-like structure suggested that reassembly in vitro occurred via several intermediates in the process of polymerization. A polyclonal antibody produced against one of the assembled VE components, a 64 kDa protein, more intensely immunostained the outer periphery of the VEs than other areas, and immunoelectron microscopy showed that immunogold particles specifically labeled reassembled VE-like structures and major skeletons of the networks or network-like sheets. The protein with a molecular weight of 64 kDa was found to be a DNase. Thus, these results suggest a new approach to investigating not only the FE assembly process in vitro but also the organizing relationship between the major skeleton of the VE or FE and other additional constituents.

Assembly in vitro of vitelline envelope components induced by a cortical alveolus sialoglycoprotein of eggs of the fish Tribolodon hakonensis.

Assembly in vitro of vitelline envelope (VE) components, which were precipitated by 50-70% saturated ammonium sulphate from VE extracts, was induced by the action of a sialoglycoprotein that is immunohistochemically localised in cortical alveoli of fish eggs and has serine proteinase activity. The VE components consisted of major bands of molecular mass about 150-120, 110-100, 70 and 27 kDa in addition to about 20 minor bands and contained a chorionic transglutaminase, visualised as two fluorescent bands by monodansylcadaverine staining. The VE component assembly in vitro was Ca(2+)-dependent, not induced if the sialoglycoprotein was pretreated with a serine proteinase inhibitor, and inhibited by the presence of p-chloromercuribenzoate, iodoacetamide or L-cysteine in the reaction medium system. Electron microscopy revealed that assembly in vitro of the VE components consisted of aggregates of network sheets, consisting of branching and anastomosing thin (approximately 27-52 nm) and thick (approximately 137-376 nm) filamentous substances. Separation by SDS-PAGE showed that a considerable number of VE components participated in the assembly in vitro in various amounts. These results suggest at least partial reproduction of the phenomena that occur in the process of fertilisation envelope (FE) formation, and provide a new approach to investigation of the process of FE assembly in vitro.

Purine metabolic enzymes in lymphocytes. II. Adenosine deaminase and purine nucleoside phosphorylase activities in the immune response.

ICR mice were immunized with sheep red blood cells (sRBC). Both adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) activities in spleen lymphocytes increased faster than the serum antibody titer and reached a peak one week after the immunization. ADA activity increased significantly in T lymphocytes but not in B lymphocytes collected from the spleens of the immunized mice. A statistically significant increase in PNP activity was found in both T and B lymphocytes from the spleens of the immunized mice. Spleen lymphocytes collected from ICR mice which had been immunized with mitomycin C-treated sarcoma 180 (S180) cells one week earlier showed cytotoxic activity against viable S180 cells. Both ADA and PNP activities in spleen lymphocytes of S180-immunized mice increased significantly, and both activities increased in T lymphocytes prepared from spleen of immunized mice. In contrast, an increase was found in PNP activity but not in ADA activity in B lymphocytes. These results suggest that an increase in both ADA and PNP activities may by necessary for the T-cell response in both humoral and cellular immune responses, and that an increase in PNP activity may be necessary for the B-cell response.

Purine metabolic enzymes in lymphocytes. I. Adenosine deaminase and purine nucleoside phosphorylase activities in mouse lymphocyte subpopulations.

The distribution of adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) activities in lymphoid organs and lymphocyte subpopulations in mice, and the effect of phytohemagglutinin P (PHA-P) and concanavalin A (Con A) on the enzyme activities were studied. ADA activity was distributed equally in cells from all organs used and no mouse strain differences were observed. In contrast, PNP activity varied with the mouse strain, being highest in C57BL/6 mice and lowest in BALB/c mice, and with the organ in ICR mice, being high in peripheral blood lymphocytes and spleen lymphocytes, low in mesenteric lymph node cells and absent or very weak in thymus cells. T and B lymphocytes were prepared from spleen of ICR mice. High ADA activity was found in both T and B lymphocytes, whereas PNP activity in the T lymphocytes was about one-third of that in the B lymphocytes. PNP activity in thymus cells was increased to the normal level of T lymphocytes in the spleens by cultivation without stimulant. The development of PNP activity in thymus cells was partially inhibited by Con A but was not affected by PHA-P. ADA activity in thymus cells was enhanced by in vitro stimulation with PHA-P but not with Con A. In contrast, in spleen lymphocytes the development of ADA activity was enhanced by stimulation with PHA-P and Con A, and that of PNP activity was enhanced by PHA-P but not by Con A.