Vay Liang W. Go

Relations between Pancreatic Enzyme Outputs and Malabsorption in Severe Pancreatic Insufficiency

Abstract To investigate the functioning reserve capacity of the exocrine pancreas, we studied the relations of steatorrhea and creatorrhea to lipase and trypsin outputs in 17 patients with chronic ...

The triad of gastric leiomyosarcoma, functioning extra-adrenal paraganglioma and pulmonary chondroma

The association of three uncommon neoplasms — gastric leiomyosarcoma, functioning extra-adrenal paraganglioma and pulmonary chondroma — in two patients and the occurrence of two of these tumors in ...

Measurement of Gastric Functions During Digestion of Ordinary Solid Meals in Man

A method of measuring gastric secretions and emptying rates after ingestion of an ordinary (solid-liquid) meal has been developed and validated. The technique quantifies movements of volume across the pylorus using constant duodenal perfusion with a nonabsorbable marker, polyethylene glycol (PEG), which, in turn, quantifies emptying into the duodenum of another marker, [14C]PEG, incorporated in the meal. Acid and pepsin outputs can be determined without manipulation of the intragastric pH. Employing this method, we have simultaneously quantified acid, pepsin, and total secretory outputs; rates of gastric emptying of meal and secretions; and serum gastrin levels during digestion. These data characterize physiological responses to ordinary food in health.

Long-term outcomes of autoimmune pancreatitis: a multicentre, international analysis

Objective Autoimmune pancreatitis (AIP) is a treatable form of chronic pancreatitis that has been increasingly recognised over the last decade. We set out to better understand the current burden of AIP at several academic institutions diagnosed using the International Consensus Diagnostic Criteria, and to describe long-term outcomes, including organs involved, treatments, relapse frequency and long-term sequelae. Design 23 institutions from 10 different countries participated in this multinational analysis. A total of 1064 patients meeting the International Consensus Diagnostic Criteria for type 1 (n=978) or type 2 (n=86) AIP were included. Data regarding treatments, relapses and sequelae were obtained. Results The majority of patients with type 1 (99%) and type 2 (92%) AIP who were treated with steroids went into clinical remission. Most patients with jaundice required biliary stent placement (71% of type 1 and 77% of type 2 AIP). Relapses were more common in patients with type 1 (31%) versus type 2 AIP (9%, p<0.001), especially those with IgG4-related sclerosing cholangitis (56% vs 26%, p<0.001). Relapses typically occurred in the pancreas or biliary tree. Retreatment with steroids remained effective at inducing remission with or without alternative treatment, such as azathioprine. Pancreatic duct stones and cancer were uncommon sequelae in type 1 AIP and did not occur in type 2 AIP during the study period. Conclusions AIP is a global disease which uniformly displays a high response to steroid treatment and tendency to relapse in the pancreas and biliary tree. Potential long-term sequelae include pancreatic duct stones and malignancy, however they were uncommon during the study period and require additional follow-up. Additional studies investigating prevention and treatment of disease relapses are needed.

Curcumin exerts multiple suppressive effects on human breast carcinoma cells

In our study, we present experimental evidence suggesting that curcumin exerts multiple different suppressive effects on human breast carcinoma cells in vitro. Our experiments demonstrate that curcumins antiproliferative effects are estrogen dependent in ER (estrogen receptor)‐positive MCF‐7 cells, being more pronounced in estrogen‐containing media and in the presence of exogenous 17‐β estradiol. Curcumin inhibits the expression of ER downstream genes including pS2 and TGF‐β (transforming growth factor) in ER‐positive MCF‐7 cells, and this inhibition is also dependent on the presence of estrogen. Curcumin also decreases ERE (estrogen responsive element)‐CAT activities induced by 17‐β estradiol. In addition, we demonstrate that curcumin exerts strong antiinvasive effects in vitro that are not estrogen dependent in the ER‐negative MDA‐MB‐231 breast cancer cells. These antiinvasive effects appear to be mediated through the downregulation of MMP‐2 (matrix metalloproteinase) and the upregulation of TIMP‐1 (tissue inhibitor of metalloproteinase), 2 common effector molecules that have been implicated in regulating tumor cell invasion. Our study also demonstrates that curcumin inhibits the transcript levels of 2 major angiogenesis factors VEGF (vascular endothelial growth factor) and b‐FGF (basic fibroblast growth factor) mainly in ER‐negative MDA‐MB‐231 cells.

Somatostatin and Somatostatin Analogue (SMS 201-995) in Treatment of Hormone-Secreting Tumors of the Pituitary and Gastrointestinal Tract and Non-Neoplastic Diseases of the Gut

Somatostatin is a peptide synthesized in many tissues that can act as a neurotransmitter, a systemic hormone, or a local hormone, and inhibits the secretion of hormones or other cell products. A long-acting synthetic analogue of somatostatin (SMS 201-995) has been developed which when administered subcutaneously has a biologic half-life of 90 to 120 minutes and can be administered 2 or 3 times per day. SMS 201-995 can lower plasma concentrations of growth hormone and somatomedin-C in patients with pituitary acromegaly, but no controlled trials to assess symptomatic response or change in tumor size have been done. In patients with pituitary thyrotropin-producing pituitary tumors, SMS 201-995 has been remarkably effective in producing biochemical and clinical responses and is the drug of first choice in this syndrome when tumor resection is not possible. In patients with the carcinoid syndrome, SMS 201-995 effectively reduces diarrhea, is the best available drug for treatment of carcinoid flush (effective in approximately 90% of cases), and is useful in treating carcinoid crisis. Eighty-five percent of patients with pancreatic islet cell tumors that produce vasoactive intestinal peptide will respond to SMS 201-995 with a reduction in diarrhea that often has been resistant to all other therapy. SMS 201-995 may also be useful in treating the symptoms in some patients with glucagonomas, growth hormone releasing hormone-producing tumors and insulinomas. Whether SMS 201-995 has a significant effect on gut neuroendocrine tumor growth remains uncertain. Certain nonmalignant diseases of the gut respond to somatostatin, including secretory diarrhea and fistulas of unknown cause. In general, SMS 201-995 has proved safe with few significant side effects, but whether the long-term use of the drug will result in an iatrogenic form of the somatostatinoma syndrome is uncertain.

Fat-induced heal brake in humans: A dose-dependent phenomenon correlated to the plasma levels of peptide YY

BACKGROUND Upper gastrointestinal motility is regulated by the presence of nutrients in the distal gut. The present study evaluated whether lipid-induced ileal brake on gastric emptying (1) can be elicited by low fat concentrations; (2) is a dose-dependent phenomenon; and (3) is related to gastrointestinal peptide release. METHODS Seven patients were studied in the defunctionalized stage of total colectomy, on three separate occasions. On each study day, patients ate a meal labeled in the solid component; 30 minutes later, one of the following solutions was randomly infused into the ileal pouch: 0.9% saline, 2% oleic acid, and 20% oleic acid. Plasma concentrations of peptide YY (PYY), enteroglucagon, neurotensin, and motilin were measured. RESULTS Both oleic acid solutions slowed gastric emptying compared with saline (P < 0.001), the effect being dose dependent (P < 0.001). Ileal infusions did not modify neurotensin and enteroglucagon levels but induced a dose-dependent increase of PYY (P < 0.01) and a borderline decrease of motilin (P = 0.05) levels. Slower rates of gastric emptying were related to increased plasma concentrations of PYY (r = 0.615; P < 0.05). CONCLUSIONS This study shows that (1) the ileal brake on gastric emptying can be evoked by low doses of lipids in the distal ileum; (2) the delay of gastric emptying is related to the release of PYY; and (3) both phenomena are dose dependent.

Comparative Effects of Antacids, Cimetidine and Enteric Coating on the Therapeutic Response to Oral Enzymes in Severe Pancreatic Insufficiency

To provide a rational basis for pancreatic enzyme replacement therapy, we evaluated, in six patients with advanced pancreatic insufficiency, the effects of various treatment regimens on fecal fat and nitrogen balance and on duodenal recovery of ingested pancreatic enzymes after a solid test meal. The combination of cimetidine (an H2-receptor antagonist) and pancreatin, each given by mouth, produced significantly higher postprandial duodenal recoveries and concentrations of trypsin and lipase (P less than 0.05). Steatorrhea was reduced in all patients and abolished in four of the six. In the dosages used, neither enteric-coated enzymes nor supplemental neutralizing antacids were more effective than pancreatin alone in decreasing steatorrhea or improving duodenal enzyme delivery. Cimetidine may be a useful adjunct to oral pancreatic extract therapy in some patients with severe pancreatic insufficiency who fail to respond to pancreatic enzyme replacement alone.

Phytoestrogens Induce Differential Estrogen Receptor Alpha- or Beta-Mediated Responses in Transfected Breast Cancer Cells:

Increased intake of phytoestrogens may be associated with a lower risk of cancer in the breast and several other sites, although there is controversy surrounding this activity. One of the mechanisms proposed to explain the activity of phytoestrogens is their ability to bind and activate human estrogen receptor a (ERα) and human estrogen receptor β (ERβ). Nine phytoestrogens were tested for their ability to transactivate ERα or ERβ at a range of doses. Mammary adenocarcinoma (MCF-7) cells were co-transfected with either ERα or ERβ, and an estrogen-response element was linked to a luciferase reporter gene. Dose-dependent responses were compared with the endogenous ligand 17β-estradiol. Purified genistein, daidzein, apigenin, and coumestrol showed differential and robust transactivation of ERα- and ERβ-induced transcription, with an up to 100-fold stronger activation of ERβ. Equol, naringenin, and kaempferol were weaker agonists. When activity was evaluated against a background of 0.5 nM 17β-estradiol, the addition of genistein, daidzein, and resveratrol superstimulated the system, while kaempferol and quercetin were antagonists at the highest doses. This transfection assay provides an excellent model to evaluate the activation of ERα and ERβ by different phytoestrogens in a breast cancer context and can be used as a screening bioassay tool to evaluate the estrogenic activity of extracts of herbs and foods.

Catechin Content of 18 Teas and a Green Tea Extract Supplement Correlates With the Antioxidant Capacity

Our literature review of currently available data in the area of tea and cancer prevention demonstrated that there is more conclusive evidence for the chemopreventive effect of green tea compared with black tea. We suggest that this is due to a large variation of the flavanol content in tea, which is not taken into consideration in most of the epidemiological studies. It was the purpose of this study to determine the flavanol content of various teas and tea products and to correlate it with their radical scavenging activity. A modified oxygen radical absorbance capacity (ORAC) assay at pH 5.5 was utilized. The total flavavol content varied from 21.2 to 103.2 mg/g for regular teas and from 4.6 to 39.0 mg/g for decaffeinated teas. The ORAC value varied from 728 to 1686 trolox equivalents/g tea for regular teas and from 507 to 845 trolox equivalents/g for decaffeinated teas. There was a significant correlation of flavanol content to ORAC value (r = 0.79, P = 0.0001) for the teas and green tea extract. The large variation in flavanol content and ORAC value among various brands and types of tea provides critical information for investigators using tea in studies of nutrition and cancer prevention.