Teruo Nakamura

Pancreatic endocrine and exocrine function and salivary gland function in autoimmune pancreatitis before and after steroid therapy.

Introduction Autoimmune pancreatitis (AIP) is a distinct clinical entity in which an autoimmune mechanism may be involved in pathogenesis. Aim To investigate salivary gland function in addition to pancreatic endocrine and exocrine function in patients with AIP, and to determine changes occurring after steroid therapy. Methodology Fasting serum glucose levels, oral glucose tolerance tests or glycosylated hemoglobin values were examined in 19 patients with AIP. N-benzoyl-L-tyrosyl-p-aminobenzoic acid excretion test, sialochemistry and parotid gland scintigraphy were performed in 8 patients. Results Eight patients had evidence of DM. Steroid therapy subsequently improved insulin secretion and glycemic control in 3 of 5 patients treated. Pancreatic exocrine function was reduced in 88% of patients. Impaired pancreatic exocrine function improved after steroid therapy in 3 of 6 patients treated. The 3 patients also showed treatment-related improvement in endocrine function. Concentration of &bgr;2-microglobulin in saliva was significantly raised in patients with AIP compared with controls (P < 0.05). Ratio of cumulative peak count to injected radionuclide and washout ratio in parotid scintigraphy in patients with AIP was significantly lower than those of controls (P < 0.01). Salivary gland dysfunction improved after steroid therapy in all 5 patients treated. Conclusions Pancreatic endocrine and exocrine and salivary gland function were frequently impaired in patients with AIP, and steroid therapy was occasionally effective for these dysfunctions.

Altered Postprandial Insulin Requirement in IDDM Patients With Gastroparesis

OBJECTIVE To evaluate the effect of gastric emptying on postprandial insulinrequirement in insulin-dependent diabetes mellitus (IDDM) patients with and without gastroparesis. RESEARCH DESIGN AND METHODS Postprandial insulin requirement and gastric emptying were simultaneously evaluated in five IDDM patients with gastroparesis and in six control IDDM patients without gastroparesis. Postprandial insulin requirement after test-meal intake was assessed by measuring the insulin infusion rate during a 4-h feedback control with an artificial endocrine pancreas device (Biostator, Life Science Instruments, Miles, Elkhart, IN). Gastric solid and liquid emptyings were evaluated during the Biostator study by measuring the disappearance rate of 99mTc in the stomach and in the time course of plasma acetaminophen concentration, respectively. RESULTS Total insulin requirement during the first 120 min after the test-meal intake was significantly lower in the gastroparetic patients than in the control patients. The gastroparetic patients showed no apparent postprandial peak for insulin infusion rate during the 4-h study, although the peak rate was observed within 120 min after the test-meal intake in the control patients. The disappearance of 99mTc in the stomach was significantly slower, and plasma acetaminophen concentrations were significantlylower in the gastroparetic patients compared with those in the control patients, respectively. CONCLUSIONS The results suggest that IDDM patients with gastroparesis, accompanied by impaired solid and liquid emptying, have an altered postprandial insulin requirement.

Erythromycin Derivative Improves Gastric Emptying and Insulin Requirement in Diabetic Patients With Gastroparesis

OBJECTIVE To evaluate the effect of the erythromycin derivative EM523L on gastric emptying and postprandial insulin requirement in insulin-dependent diabetic patients with severe gastroparesis. RESEARCH DESIGN AND METHODS In six IDDM patients with severe gastroparesis (two men and four women, mean age 44.5 years [range 36–53]), the insulin infusion pattern during feedback control with an artificial endocrine pancreas device (Biostator) after intake of a test meal, the retention rate of residual isotope (99mTc-labelled Sn-colloid) in the stomach, and the time-concentration curve of plasma acetaminophen as the marker for liquid emptying were studied with EM523L or a control placebo RESULTS Time courses of insulin infusion rates peaked within 120 min after intake of the test meal in the EM523L phase, whereas no apparent peak rates were observed in the control phase. The total amount of insulin required in the first 90 min postprandial was significantly greater in the EM523L phase than in the control phase. EM523L significantly decreased the residual isotope ratio in the stomach at ≥50 min postprandial and increased the plasma acetaminophen concentrations at 30–120 min postprandial, compared with respective values in the control phase. CONCLUSIONS Preliminary results obtained from a small number of patients suggest that EM523L or erythromycin analogs, which have agonistic activity to motilin receptors as well as no antibacterial effect, may be useful to accelerate gastric emptying and improve insulin requirement patterns, thereby establishing more stable glycemic control.

Correlation between pancreatic endocrine and exocrine function and characteristics of pancreatic endocrine function in patients with diabetes mellitus owing to chronic pancreatitis

SummaryConclusionPancreatic endocrine capacities are remarkably disturbed in patients with pancreatic diabetes owing to calcific pancreatitis as opposed to those owing to noncalcific pancreatitis. Insulin secretion in calcific pancreatitis resembled, that in insulin-dependent diabetes mellitus (IDDM), whereas insulin secretion in noncalcific pancreatitis resembled that in non-IDDM (NIDDM). The involvements of acinar cell and ductal cell function closely correlate with endocrine function (insulin and glucagon secretions) in chronic pancreatitis (pancreatic diabetes).BackgroundWe sought to clarify the differences of pancreatic endocrine function between pancreatic diabetes and primary diabetes, and to verify the correlations between pancreatic exocrine and endocrine dysfunction in patients with chronic pancreatitis.MethodsUrinary C-peptide (CPR) excretion and fasting plasma glucagon levels in patients with pancreatic diabetes owing to calcific pancreatitis (19 cases) and owing to noncalcific pancreatitis (14 cases) were studied in comparison with those in patients with insulin-dependent diabetes mellitus (IDDM, 23 cases), noninsulin-dependent diabetes (NIDDM, 18 cases), and in healthy controls (11 cases). In addition, pancreatic exocrine function was investigated in patients with chronic pancreatitis (calcific and noncalcific) and in healthy controls. The correlation between pancreatic exocrine and endocrine function was studied.ResultsThe urinary CPR excetion in controls was 94.9±20.5 μg/d. The urinary CPR excretion in calcific pancreatitis was 12.8±7.4 μg/d and it resembled that in IDDM (9.4±5.8 μg/d). The urinary CPR excretion in noncalcific pancreatitis was 41.5±30.1 μg/d, being similar to that in NIDDM (49.3±21.0 μg/d).The plasma glucagon level in calcific pancreatitis was 64.1±15.9 ρg/mL, which was significantly lower than the values in IDDM (111.2±50.2 ρg/mL) and NIDDM (96.7±21.9 ρg/mL). The plasma glucagon level in calcific and noncalcific pancreratitis (88.4±29.6 ρg/mL) were significantly lower than that in controls (12.9±21.6 ρg/mL).The residual capacities of acinar cells and ductal cells were strongly correlated with urinary CPR excretion and plasma glucagon concentration.

Pancreatic Steatorrhea, Malabsorption, and Nutrition Biochemistry : A Comparison of Japanese, European, and American Patients with Chronic Pancreatitis

This article reports on Steatorrhea, daily food intake, and fecal substances other than fecal fat (e.g., neutral sterols, bile acids, short-chain fatty acids) in pancreatic exocrine dysfunction arising from chronic pancreatitis (CP) in Japanese, European, and American patients. Changes in upper small intestinal pH and lipase secretion, plasma fatty acid profiles, serum fat-soluble vitamin levels and symptoms of their deficiency, and nutritional status are discussed in detail. Treatment of pancreatic Steatorrhea is described. Throughout this study, we compared characteristics of maldigestion and malabsorption in these patient populations and our study revealed that fecal fat excretion reflected quantitative differences in fat consumption, plasma fatty acid profiles reflected quantitative and qualitative differences in fish oil consumption, and there were no differences in pancreatic exocrine dysfunction among these three groups. Since differences in fecal fat excretion and plasma fatty acid profiles appear to depend on dietary fats, the pathology and treatment of CP patients should be evaluated and the findings used to prescribe treatments.

Chronic pancreatitis in the elderly in Japan.

Background/Aim: Although the elderly comprise an increasingly large segment of the population, little has been written about chronic pancreatitis in this age group in Japan. In this study, we analyzed the clinical features of elderly Japanese patients with chronic pancreatitis and compared them with those of late-onset chronic pancreatitis patients in Western countries. Methods: Subjects were 182 patients (162 males and 20 females) with chronic pancreatitis. They were divided into two groups: early-onset group (onset <65 years of age, n = 119) and late-onset group (onset ≧65 years of age, n = 63). Clinical findings and follow-up data were examined for each group. Results: Alcohol abuse was the most common etiological factor in early-onset pancreatitis patients. In the late-onset group, the frequencies of idiopathic and autoimmune pancreatitis increased. Furthermore, the age at onset of autoimmune pancreatitis was >60 years in 94% of the cases. The late-onset group was more likely to have painless disease, and calcification of the pancreas and steatorrhea were rare in this group. Major causes of death were malignancy and malnutrition in each group. Conclusions: Early- and late-onset chronic pancreatitis showed different clinical features. Clinicians should consider autoimmune pancreatitis in the differential diagnosis in elderly patients with obstructive jaundice.

The Effects of Serum Albumin and Related Amino Acids on Pancreatic Lipase and Bile Salts Inhibited Microbial Lipases.

The activities of microbial lipases were inhibited by bile salts in a non-emulsifying assay system. To protect lipase activities from inactivation, the effects of proteins and amino acids were investigated. Bovine serum albumin (BSA) and α-lactalbumin (α-LA) stored the bile salts inhibited microbial lipases. Among N-end amino groups contained in BSA, L-histidine restored the activities of the bile salts inhibited microbial lipases. On the other hand, pancreatic lipase activity was stimulated by not only BSA, but L-histidine and L-aspartic acid as N-end amino groups of BSA and additionally accelerated it in combination with bile salts.

Pancreatic Dysfunction and Treatment Options

Pancreatic steatorrhea and pancreatic diabetes are the dominant symptoms of patients in the decompensated stage of chronic pancreatitis (CP). In this stage, the nutritional state is greatly disturbed and hypoglycemia and labile infection are involved. Pancreatic enzyme replacement therapy is the principal treatment method for pancreatic steatorrhea. Before initiating this therapy, dietary fat intake must be determined and pancreatic lipase and bicarbonate secretion function must be evaluated. Upper small intestinal pH is regulated by gastric acid secretion, and abnormal gastric emptying changes lipolysis. In addition, precipitation of bile acids in the upper small intestine and ileal brakes due to undigested fats and carbohydrates must be considered. Porcine pancreatin, bacterial lipase, and acid-resistant fungal lipase are used as enzymes for replacement therapy. Conventional, entero-coating, and enteric-coated microsphere preparations of porcine pancreatin are available for treatment and are formulated to protect against gastric acids, to dissolve enzymes at optimum pH, and to be emptied simultaneously with food from the stomach. Gastric acid secretion suppressants, such as H2 blockers or a proton pump inhibitor, can also be used concomitantly with pancreatin preparations. In consideration of both strengths and weaknesses of these preparations, types and dosages of enzyme replacement therapy should be carefully prescribed, and fecal fats should be examined repeatedly by a simple and rapid method during treatment. Attention should also be paid to changes in body weight and nutritional indices (e.g., nutritional parameters, fat-soluble vitamins). The relationship between carbohydrate maldigestion/malabsorption in CP patients and treatment of pancreatic diabetes are topics for future research.

Serum fatty acid composition in normal Japanese and its relationship with dietary fish and vegetable oil contents and blood lipid levels

A survey was conducted on 110 normal Japanese adults (55 men and 55 women) to determine their caloric intake, dietary fat content and its origin (animal, plant, or marine). In addition, their blood lipid levels and fatty acid compositions were examined. Men in their 30s-50s consumed 2,600-2,800 calories and 60 g of fats, while women in the same age range consumed 2,000-2,200 calories and 52-58 g of fats. In both sexes, caloric, fat, and cholesterol intakes were lower for those in their 60s but protein and crude fiber consumption remained generally unchanged. When the dietary fats were classified according to origin, men and women in their 30s were found to consume less oil of marine origin. This appeared to be the result of a western style diet for Japanese adults in their 30s. Compared with men, women exhibited lower blood lipid levels. As age increased, the total cholesterol level of the blood rose in women. Thus the blood lipid level was generally equal in the two groups in their 60s. There was a positive correlation between the blood eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) levels and dietary consumption of fish oil. The marine/plant lipid ratio was positively correlated with the blood EPA/arachidonic acid ratio. Therefore, it was believed that the origin of the dietary fats consumed is a factor in determining the blood fatty acid profile. The linoleic acid (18:2), arachidonic acid (20:4), and 18:2 + 20:4 contents were negatively correlated to the total cholesterol level in the blood but positively correlated to the HDL-cholesterol level. Polyunsaturated fatty acids (18:2 + 20:4 + 20:5 + 22:6) were negatively correlated with the blood triglyceride level. From the findings presented above, we concluded that dietary fats not derived from animal sources should be classified into fish and vegetable oils to evaluate their dietary significance. We also noted that Japanese in their 30s consume less fish oil, indicating the western trend in their dietary lipid consumption.

Histopathologic Study of Coexistent Pathologic States in Pancreatic Fibrosis in Patients with Chronic Alcohol Abuse: Two Distinct Pathologic Fibrosis Entities with Different Mechanisms

The distribution and clinicopathologic features of pancreatic fibrosis were studied histopathologically in 137 autopsy cases of chronic alcohol abuse. Fibrosis was observed in 90 of the cases and was classified as perilobular sclerosis (PS) and intralobular sclerosis (IS). Fibrosis of the PS type was irregular and sometimes patchy and extended into the intralobular area in advanced cases. In some advanced cases, complete replacement of the pancreatic tissue by extensive fibrosis was seen. Fibrosis of the IS type was uniformly distributed. The tissues in some cases showed prominently periacinar fibrosis. In these cases, the pancreatic parenchyma had not been completely replaced by extensive fibrosis. Clinicopathologic comparisons revealed the following results: accompanying liver cirrhosis was greater in the IS than in the PS of fibrosis. However, a higher frequency of protein plugs, pancreatic stones, extensive fibrosis replacement, peripancreatic fibrosis, splenic vein involvement, choledochus involvement, pseudocyst, and ductal hyperplasia was found in the PS type compared to the IS type. In conclusion, the findings on the perilobular and intralobular distribution of fibrosis and differences in various components or accompanying diseases in pancreatic fibrosis suggest that this entity shows two distinct pathologic patterns with differing mechanisms.