Fusao Kawakami

Plasma brain natriuretic peptide levels in normotensive Type 2 diabetic patients without cardiac disease and macroalbuminuria

To clarify the relationship of the plasma brain natriuretic peptide (BNP) levels to diabetic complications, we studied plasma BNP levels in 100 normotensive diabetic patients without clinical cardiac disease and macroalbuminuria. The values of plasma BNP levels were not significantly different between patients with microalbuminuria and those with normoalbuminuria (12.2 +/- 2.0 vs. 12.3 +/- 1.3 pg/ml, means +/- S.E.M.), and neither were the BNP levels of patients with and without retinopathy significantly different (15.7 +/- 3.4 vs. 11.4 +/- 1.0 pg/ml). BNP levels of the subjects with cerebral vascular disease (CVD) were not statistically different from those of subjects without CVD (17.5 +/- 5.5 vs. 11.7 +/- 1.0 pg/ml), although mean BNP value of subjects with CVD was higher than that of subjects without it. With regard to peripheral vascular disease (PVD), BNP levels of the subjects with PVD were not statistically different from those of subjects without PVD (13.5 +/- 2.3 vs. 12.1 +/- 1.2 pg/ml). We also studied radial arterial oxygen tension of 45 patients and compared these levels between those with and without diabetic complications. However, we could not find statistical differences between them. In conclusion, our study suggests that BNP and arterial oxygen tension levels will not be affected by retinopathy, microalbuminuria, CVD, and PVD in normotensive diabetic patients without clinical cardiac disease and macroalbuminuria. Therefore, when normotensive diabetic patients without macroalbuminuria show increased plasma level of BNP, we should examine their cardiac function in detail, considering subclinical cardiac disease.

Prevalence and clinical features of diabetes mellitus secondary to chronic pancreatitis in Japan; a study by questionnaire

The prevalence and clinical features of diagnosed mellitus secondary to chronic pancreatitis (CP) were assessed from northern (Hokkaido) to southern (Okinawa) Japan by means of a questionnaire to elucidate whether WHO-classified malnutrition-related diabetes mellitus (MRDM) exists in Japan. Of a total 17,500 diabetic patients, only two (0.011%)-one fibrocalculous pancreatic diabetes (FCPD) and one protein-deficient pancreatic diabetes (PDPD) - exhibited MRDM characteristics. A total of 649 CP were collected and classified into 268 cases with chronic alcoholic pancreatitis (CAP), 150 cases with chronic calcified pancreatitis (CCP) and 231 cases with other CP. The prevalence of diabetes mellitus was found to be 50.7% in CAP, 72.7% in CCP and 22.8% in other CP. Among all diabetics, 56.6% was noninsulin-dependent (NIDDM) and 26.4% insulin-dependent (IDDM). IDDM was most frequent in CP. Satisfactory and less than satisfactory glycemic control was obtained in approximately three quarters of all subjects. Only one quarter showed poor glycemic control. Insulin treatment was frequent in CAP (52.2%) and CCP (61.7%), but less in other CP (27.5%). The prevalence of diabetic retinopathy was observed in 33.1% of all subjects, nephropathy 21.0% and neuropathy 36.3%, respectively. The prevalence of complications, including macroangiopathy tended to be higher in CAP and CCP (40.3 and 56.9%) than in other CP (31.4%).

Intrahepatic cholangiocarcinoma with increased serum CYFRA 21-1 level.

Abstract: CYFRA 21-1 is a fragment of cytokeratin 19 (CK 19). Four patients with large intrahepatic (or peripheral) cholangiocarcinoma (CC) and high serum levels of CYFRA 21-1 (normal, ≤2 ng/ml) are reported. CYFRA 21-1 levels exceeded 9 ng/ml in all 4 patients. Carcinoembryonic antigen (CEA), was high in 1 (CEA; normal range, ≤5.0 ng/ml) and carbohydrate antigen 19-9 (CA 19-9) was high in 3 (CA19-9; normal range, ≤36 U/ml). We also measured serum levels of CYFRA 21-1 in 13 patients with hepatocellular carcinoma (HCC) more than 5 cm in diameter. Levels of CYFRA 21-1 exceeded 2 ng/ml in 9 of the HCC patients and were higher than 9 ng/ml in 2 of the HCC patients. Levels of alpha fetoprotein (AFP) and/or protein induced by vitamin K absence or antagonist II (PIVKA II) were elevated in all HCC patients (AFP, PIVKA II, respectively; normal range, ≤10.0 ng/ml and ≤0.1 AU/ml) CYFRA 21-1 levels were measured twice or three times during the clinical course in 2 CC patients and in 6 HCC patients, and increased gradually with tumor growth in the 2 CC patients and in 3 of the 6 HCC patients. Marked increases in serum CYFRA 21-1 levels in patients with large liver cancers, particularly in those with normal levels of AFP and PIVKA II, would suggest the existence of intrahepatic CC rather than HCC.

Gastric T-cell lymphoma presenting with epithelioid granulomas mimicking tuberculosis in regional lymph nodes.

Abstract: In patients with malignant lymphomas, a sarcoid reaction is occasionally observed. However, lymphoma-related granulomas with caseous necrosis are rare. We describe such a case of T-cell gastric lymphoma that was difficult to diagnose. A 50-year-old man was referred to our hospital because of abnormal gastric endoscopic findings: hypertrophic folds with narrowing of the gastric lumen and multiple ulcers in the body. Gastric biopsy specimens showed non-specific inflammation. An open biopsy of the enlarged gastric regional lymph nodes was performed. The sections revealed effacement of the normal architecture and replacement by numerous epithelioid granulomas accompanied by Langhans type giant cells with or without central caseous necrosis, strongly suggesting tuberculosis. However, mycobacteria and other causative organisms were not detected, and an anti-tuberculous regimen was ineffective. Repeat gastric biopsies were performed and, finally, atypical lymphocytes were observed infiltrating the mucosa. The patient was diagnosed with gastric T-cell lymphoma based on the results of immunohistochemical stainings. After chemotherapy, a total gastrectomy was performed. The diagnosis of gastric T-cell lymphoma with a sarcoid reaction was confirmed by histological findings of the sections. Namely, the gastric wall was replaced by atypical lymphocytes showing the phenotype of helper T cells, admixed with epithelioid granulomas with Langhans type giant cells. Thus, this case suggests that regional lymph nodes in gastric lymphomas may be present as epithelioid granulomas with caseous necrosis, mimicking tuberculosis.

Protein-losing enteropathy and pancreatic involvement in a case of connective tissue disease

SummaryA patient with connective tissue disease presenting with both protein-losing enteropathy and pancreatic involvement is reported. A 52-year-old female was admitted because of mild epigastralgia, anasarca and ascites. Serum albumin, transferrin and zinc, showed low levels. An Upper G.I. series and endoscopy showed thickened folds of the duodenum and the jejunum. Biopsy specimens revealed lymphangiectasia in edematous villi.99mTc-labeled human serum albumin scintigram showed abnormal radioactivity in the small intestine 90 minutes after intravenous injection, indicating protein-losing enteropathy. Hypoalbuminemia was ameliorated by glucocorticoid therapy, but recurred twice when glucocorticoid treatment was tapered. Hypoalbuminemia has not occurred since intestinal lymphangiectasia was improved with glucocorticoid treatment. Levels of elastase 1 and lipase were high in serum and ascites on admission. Endoscopic retrograde pancreatogrm showed no abnormalities. Serum pancreatic enzymes were also ameliorated by glucocorticoid therapy, but slightly high levels continued for about one year and a half. This case might have been diagnosed as systemic lupus erythematosus although mixed connective tissue disease was also suspected. There are few reports of protein-losing enteropathy and pancreatic involvement associated with connective tissue diseases. Protein-losing enteropathy and pancreatic involvement were ameliorated with glucocorticoid treatment, suggesting participation of immunological mechanisms.

Relationship of abdominal fat with metabolic disorders in diabetes mellitus patients

In this study, we examined the relationships of the fat distribution with the clinical parameters, microangiopathy, and coagulation disorders in Japanese diabetic patients, distinguishing between males and females. To investigate these relationships, the clinical parameters of the patients were compared with the total abdominal fat area (TFA), visceral fat area (VFA), subcutaneous fat area (SFA), BMI, and percent body fat. In addition, microangiopathies and coagulation disorders of the patients were also compared with the fat distribution. In the male patients, the insulin level, triglyceride (TG) level, and diastolic blood pressure significantly correlated with both VFA and SFA. The HDL cholesterol (HDL-Chol) level and systolic blood pressure also significantly correlated with VFA, but not with SFA. In the female patients, the insulin level, TG level, HDL-Chol level and systolic blood pressure significantly correlated with VFA. On the other hand, only the systolic and diastolic blood pressures significantly correlated with SFA. The fibrinogen and thrombin-antithrombin III complex (TAT) levels significantly correlated with VFA only in the female patients. The male patients with macroalbuminuria had significantly larger VFA than those with microalbuminuria or normoalbuminuria. However, SFA had no relation with the urinary albumin excretion rate. The multiple regression analysis showed that VFA was an independent variable associated with diabetic nephropathy in the male patients. In conclusion, VFA plays more important role than SFA in the metabolic disorders and diabetic nephropathy in the Japanese diabetic patients. In the female diabetic patients, VFA may be associated with disorders of coagulation and fibrinolysis.

Prevalence of vascular complications in untreated diabetics with obesity during an 18 year period

Prevalence of vascular complications in newly diagnosed untreated diabetic patients with obesity was studied over a period of 18 years. A total of 742 patients including 241 subjects with obesity (BMI greater than 25) were analyzed. Obese patients showed higher serum cholesterol and triglyceride and lower HDL-cholesterol levels than non-obese patients. Average prevalence of obesity is shown to be 32.5% with higher prevalence in women (37.8%) than in men (28.3%, P less than 0.01). No definite change is found in yearly prevalence throughout the observation period. Ischemic ECG findings and hypertension were observed more frequently in obese (35.8% and 34.9%, respectively) than in non-obese (25.2%, P less than 0.02; 24.5%, P less than 0.01, respectively) subjects, while diabetic retinopathy was less in obese patients (P less than 0.05). The prevalence of proteinuria was almost the same in obese and non-obese groups. These results coincide with the general concept that obesity may be responsible for the development of macroangiopathy in diabetes mellitus.