Third Department Of Internal Medicine Research Articles

[OP.8A.01] NEWLY DIAGNOSED DIABETES MELLITUS IS ASSOCIATED WITH INCREASED LEVELS OF ERYTHROCYTE MICROPARTICLES

Objective: Patients with Diabetes Mellitus (DM) carry a high burden of cardiovascular damage and high risk of early thrombotic events. It is currently unknown how early this damage occurs and if it preexists in naive newly diagnosed DM patients. Design and method: We sought to determine the thrombotic tendency of patients with known cardiovascular risk factors. To this end we used sophisticated, novel markers of atherosclerotic and thrombotic damage: platelet (PLTs) and erythrocyte (RBCs) microparticles. Consecutive patients of the Micro- and Macro-vascular disease Clinic of Third Department of Internal Medicine at Papageorgiou General Hospital of Thessaloniki were included in the study. A thorough medical history was taken and a blood sample was drawn. A 24-hour urine collection was performed to assess the presence of microalbuminuria. Furthermore, PLTs and RBCs were determined using flow cytometry according to specific protocol. Cardiovascular risk factors were evaluated with emphasis on hypertension, newly diagnosed DM, dyslipidemia, smoking and body mass index. Results: Our study sample consisted of 45 patients aged 52.5 ± 11.9 years, 19 men: 26 women, with mean systolic / diastolic blood pressure: 132.7 ± 16.8 / 83.3 ± 13.7 mmHg. Newly-diagnosed DM was found in 19 patients, while untreated hypertension in 16. Multiple linear regression analysis showed that DM makes the strongest contribution to high RBCs values (beta: 0,673, p = 0,021) after the effect of cardiovascular risk factors is controlled for. No significant predictor of PLTs could be identified. Conclusions: In our study, RBCs strongly correlated with the presence of DM at the very early stages of the disease, despite the small sample size. Current knowledge suggests that RBCs consist a robust indicator of thrombotic tendency. The fact that PLTs did not correlate with the presence of DM in our study may, at least in part, reflect the multifactorial role of platelets not only in the thrombotic but also in the inflammatory process of atherosclerosis. Larger studies are needed to determine the value of PLTs and RBCs in patients with cardiovascular risk factors.

974 DIAGNOSTIC ALGORITHM FOR HEPATOCELLULAR CARCINOMA (HCC) IN HYPOVASCULAR NODULE OF THE LIVER; A MULTICENTER NATIONWIDE STUDY

974 DIAGNOSTIC ALGORITHM FOR HEPATOCELLULAR CARCINOMA (HCC) IN HYPOVASCULAR NODULE OF THE LIVER; A MULTICENTER NATIONWIDE STUDY N. Izumi, K. Tsuchiya, O. Matsui, M. Sata, R. Kuromatsu, F. Moriyasu, Y. Imai, Y. Aoyagi, H. Iijima, S. Arii. Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Radiology, Kanazawa University Graduate School of Medicine, Kanazawa, Department of Gastroenterology and Hepatology, Kurume University School of Medicine, Kurume, Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Third Department of Internal Medicine, Niigata University Graduate School of Health Sciences, Niigata, Department of Ultrasound, Hyogo University of Medicine, Nishinomiya, Department of Surgery, Tokyo Medical and Dental University, Tokyo, Japan E-mail: nizumi@musashino.jrc.or.jp

Fluctuations in thrombopoietin, immature platelet fraction, and glycocalicin levels in a patient with cyclic thrombocytopenia

Cyclic thrombocytopenia (CT) is an uncommon disorder characterized by periodic fluctuations in platelet count, resulting in alternating episodes of thrombocytopenia and normal platelet counts. Its pathogenesis remains unclear. Here, we report the case of a 65-year-old man with CT who was initially diagnosed with idiopathic thrombocytopenic purpura (ITP) concomitant with chronic thyroiditis. ITP was diagnosed 12 years ago in the absence of periodic fluctuations in platelet counts. He had been treated with corticosteroids; underwent splenectomy; and subsequently been treated with azathioprine, vincristine, high doses of dexamethasone, and herbal medicine. He had not received antibiotic eradication therapy for Helicobacter pylori because there was no evidence of infection with this organism. Since his symptoms did not improve, the treatments were discontinued, and he was placed under observation. He complained of mild bleeding symptoms, such as petechiae and purpura, which occurred intermittently for several months before he presented to us to undergo detailed investigations. His platelet count varied between 3 9 10/ll and 30 9 10/ll approximately every 3–4 weeks. His white blood cell count and hemoglobin concentration remained unchanged. To elucidate the mechanism underlying this disease, we evaluated the serum thrombopoietin (TPO) level, immature platelet fraction (IPF), plasma glycocalicin index normalized for the individual platelet count (GCI), and T helper (Th)1/Th2 ratio. The serum TPO level was measured with a human TPO ELISA kit (R&D Systems Inc., Minneapolis, MN, USA). The serum levels of TPO, a principal regulator of megakaryogenesis and thrombopoiesis, are thought to be regulated via receptor-mediated clearance by platelets and megakaryocytes. The median serum TPO concentration in healthy individuals is 51 pg/ml. The plasma glycocalicin level was measured with a Glycocalicin EIA kit (Takara Bio Inc., Ohtsu, Japan). The GCI was calculated as proposed by Steinberg et al. [1]: GCI = glycocalicin level 9 250 9 10/individual platelet count (/ll). Glycocalicin is a proteolytic fragment of the a-chain of glycoprotein Ib, a platelet membrane. The GCI reflects the rate of platelet destruction [2]. The mean GCI in healthy individuals is 1.27 (range 0.87–1.77). The IPF was determined to reliably quantify reticulated platelet counts by using a fully automated hematology analyzer XE-2100 equipped with special software IPF Master (Sysmex, Kobe, Japan). Reticulated platelets are RNA-rich immature platelets and are thought to reflect the ability of the bone marrow to produce platelets. Therefore, the IPF, as a surrogate marker of the reticulated platelet count, reflects the rate of thrombopoiesis [3]. The mean IPF in healthy individuals is 2.0% (range 0.5–5.7%). The Th1/Th2 ratio was determined by using flow cytometry analysis to measure the ratio of CD4? cells containing intracellular interferon-c to those containing interleukin-4. The fluctuations in the TPO levels, percentage of IPF, and GCI were synchronous and inversely proportional to those in the platelet counts (Fig. 1). In the thrombocytopenic phase, elevated GCI indicated platelet destruction in this patient. Thrombopoiesis was simultaneously accelerated in response to TPO. Consequently, the IPF, which is as an indicator of thrombopoiesis, increased. In the present case, CT seemed to be closely associated with cyclic increases in platelet destruction. However, the mechanism of cyclic platelet destruction remains to be elucidated. Th1/Th2 balance is T. Yujiri (&) Y. Tanaka M. Tanaka Y. Tanizawa Third Department of Internal Medicine, Yamaguchi University School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505, Japan e-mail: yujirit@yamaguchi-u.ac.jp

Anti‐fibrotic therapy: Are matrix metalloproteinases friends or foes?

Hepatology ResearchVolume 39, Issue 8 p. 748-750 Anti-fibrotic therapy: Are matrix metalloproteinases friends or foes? Hitoshi Yoshiji, Hitoshi Yoshiji Third Department of Internal Medicine, Nara Medical University, Nara, JapanSearch for more papers by this author Hitoshi Yoshiji, Hitoshi Yoshiji Third Department of Internal Medicine, Nara Medical University, Nara, JapanSearch for more papers by this author First published: 30 July 2009 https://doi.org/10.1111/j.1872-034X.2009.00573.xCitations: 2Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Citing Literature Volume39, Issue8August 2009Pages 748-750 RelatedInformation

‘The Mentor's Quality Determines the Probability of Success of the Young Researcher’: An Interview with Prof. Makoto Otsuki

In this interview, Professor Makoto Otsuki points out the importance of mentorship during young researchers' development. Dr. Otsuki, a Professor and Chair of the Third Department of Internal Medicine at the University of Occupational and Environmental Health, has contributed significantly to the field of pancreatic physiology. In addition, his epidemiological research has been fundamental for understanding the pathogenesis of pancreatitis and establishment of the guidelines for its diagnosis and improvement of case fatality.

Epidural malignant lymphomas of the spine: collected experiences with epidural malignant lymphomas of the spinal canal and their treatment

Retrospective study of 13 patients treated by the authors. To examine the course of the disease of malignant lymphoma (ML) presenting in the epidural area of the spine. Department of Neurosurgery, Third Department of Internal Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary. The epidural presentation in eight patients was heralded by motor signs (paraparesis and plegia), in one by a lesion of the posterior columns of the spinal cord (ataxia), and in three by pain. One patient was free of complaints and symptoms. The affected epidural area was diagnosed previously by myelography and computerized tomography (CT), and later by magnetic resonance (MR), over the course of which the location was verified as thoracic in eight patients, cervical in one, and lumbar in four. The authors recommended surgical intervention in 9 out of 13 cases, in seven cases of Hodgkin's and six cases of non-Hodgkin's lymphoma. Seven patients were treated for recognized manifestations of malignant lymphoma while six were diagnosed by intraoperative-histological examination. The decompression operations for tumors resulted in limited improvement in seven patients (reduction in pain and return of ability to walk). Four patients were not operated on, two of which had significant improvement in their neurological symptoms. Paraparesis remained unchanged in one patient. One patient remained symptom-free. The authors emphasize the importance of interdisciplinary consultation and weighing individual priorities in the indications for operation on epidural ML.

Elevated BALF concentrations of α- and β-defensins in patients with pulmonary alveolar proteinosis

Defensins are endogenous antibiotics and regulators of inflammation, immunity and wound repair. Their concentrations are substantially increased in bronchoalveolar lavage fluid (BALF) of patients with infectious lung diseases. alpha-defensin (HAD) levels are also elevated in patients with idiopathic pulmonary fibrosis (IPF) and correlated with the decline in pulmonary function tests, suggesting the association of defensins with the pathogenesis of interstitial lung diseases. The aim of this study was to determine the profile of defensins in interstitial lung diseases. Serum and BALF levels of HAD and beta-defensin 1 and 2 (HBD-1, and -2) were measured by radioimmunoassay in 63 patients with interstitial lung diseases, including idiopathic pulmonary alveolar proteinosis (PAP), IPF, nonspecific interstitial pneumonia (NSIP), cryptogenic organizing pneumonia (COP) and pulmonary sarcoidosis, and in 9 healthy volunteers as controls. Levels of HAD in BALF of patients with PAP were significantly higher than those in controls and patients with COP and sarcoidosis. Serum levels of HAD in all groups were significantly higher than those in controls. Levels of HBD-1 and -2 in BALF of patients with PAP were extremely high in all subjects. Serum levels of HBD-1 were higher in all patient groups, with the exception of those with PAP, and those of HBD-2 were also higher in patients with IPF and sarcoidosis, compared with controls. BALF of PAP patients, but not IPF patients and controls, expressed antimicrobial activity against Pseudomonas aeruginosa and Staphylococcus aureus. Our findings suggest different kinetics of HAD and HBD-1 and -2 in serum and BALF of interstitial lung diseases and that these antimicrobial peptides in the airway lumen may contribute to prevention of bacterial airway infections in PAP.

Lactoferrin inhibits hepatitis B virus infection in cultured human hepatocytes: Koji Hara, Masanori Ikeda, Satoru Saito, Shuhei Matsumoto, Kazushi Numata, Third Department of Internal Medicine, Yokohama City University of Medicine, Yokohama Japan; Katsuaki Tanaka, Department of Internal Medicine Gastroenterological Center, Yokohama City University Medical Center, Yokohama Japan; Hisahiko Sekihara, Third Department of Internal Medicine, Yokohama City University of Medicine, Yokohama Japan

Lactoferrin inhibits hepatitis B virus infection in cultured human hepatocytes: Koji Hara, Masanori Ikeda, Satoru Saito, Shuhei Matsumoto, Kazushi Numata, Third Department of Internal Medicine, Yokohama City University of Medicine, Yokohama Japan; Katsuaki Tanaka, Department of Internal Medicine Gastroenterological Center, Yokohama City University Medical Center, Yokohama Japan; Hisahiko Sekihara, Third Department of Internal Medicine, Yokohama City University of Medicine, Yokohama Japan

Sphingosine 1-phosphate inhibits DNA synthesis induced by growth factors in cultured rat hepatocytes with activation of the small GTpase Rho via G protein-coupled receptor EDG5: Hitoshi Ikeda, Mikio Yanase, Yukiko Inoue, Tomoaki Tomiya, Masahiro Arai, Kazuaki Tejima, Kayo Nagashima, Department of Gastroenterology, University of Tokyo, Tokyo Japan; Hiroaki Satoh, Department of Diabetes & Metabolism, University of Tokyo, Tokyo Japan; Yutaka Yatomi, Department of Laboratory Medicine, Yamanashi Medical University, Yamanashi Japan; Soutarou Sakurada, Yoh Takuwa, Department of Physiology, Kanazawa University School of Medicine, Kanazawa Japan; Kenji Fujiwara, Third Department of Internal Medicine, Saitama Medical School, Saitama Japan

Sphingosine 1-phosphate inhibits DNA synthesis induced by growth factors in cultured rat hepatocytes with activation of the small GTpase Rho via G protein-coupled receptor EDG5: Hitoshi Ikeda, Mikio Yanase, Yukiko Inoue, Tomoaki Tomiya, Masahiro Arai, Kazuaki Tejima, Kayo Nagashima, Department of Gastroenterology, University of Tokyo, Tokyo Japan; Hiroaki Satoh, Department of Diabetes & Metabolism, University of Tokyo, Tokyo Japan; Yutaka Yatomi, Department of Laboratory Medicine, Yamanashi Medical University, Yamanashi Japan; Soutarou Sakurada, Yoh Takuwa, Department of Physiology, Kanazawa University School of Medicine, Kanazawa Japan; Kenji Fujiwara, Third Department of Internal Medicine, Saitama Medical School, Saitama Japan

Efficacy of inchin-ko-to (TJ-135), a Japanese herbal, medicine, in the treatment of liver cirrhosis, as evaluated with rat models: Mie Inao, Satoshi Mochida, Atsushi Matsui, Youlutuz Yusufu, Shoji Mashiba, Yuichiro Eguchi, Yanhong Wang, Sumiko Nagoshi, Kenji Fujiwara, Third Department of Internal Medicine, Saitama Medical School, Saitama Japan

Efficacy of inchin-ko-to (TJ-135), a Japanese herbal, medicine, in the treatment of liver cirrhosis, as evaluated with rat models: Mie Inao, Satoshi Mochida, Atsushi Matsui, Youlutuz Yusufu, Shoji Mashiba, Yuichiro Eguchi, Yanhong Wang, Sumiko Nagoshi, Kenji Fujiwara, Third Department of Internal Medicine, Saitama Medical School, Saitama Japan

The significance of angiopoietin/tie receptors system in reconstruction of the hepatic sinusoids after partial hepatectomy in rats: Hiroyuki Kimura, Satoshi Mochida, Mie Inao, Atsushi Matsui, Sumiko Nagoshi, Kenji Fujiwara, Third Department of Internal Medicine, Saitama Medical School, Saitama Japan

The significance of angiopoietin/tie receptors system in reconstruction of the hepatic sinusoids after partial hepatectomy in rats: Hiroyuki Kimura, Satoshi Mochida, Mie Inao, Atsushi Matsui, Sumiko Nagoshi, Kenji Fujiwara, Third Department of Internal Medicine, Saitama Medical School, Saitama Japan

The proliferation of rat hepatocytes is regulated by an interaction of p53 with specific growth factors: Yukiko Inoue, Tomoaki Tomiya, Mikio Yanase, Masahiro Arai, Hitoshi Ikeda, Kazuaki Tejima, Kayo Nagashima, Itsuro Ogata, Department of Gastroenterology, University of Tokyo, Tokyo Japan; Kenji Fujiwara, Third Department of Internal Medicine, Saitama Medical School, Saitama Japan

The proliferation of rat hepatocytes is regulated by an interaction of p53 with specific growth factors: Yukiko Inoue, Tomoaki Tomiya, Mikio Yanase, Masahiro Arai, Hitoshi Ikeda, Kazuaki Tejima, Kayo Nagashima, Itsuro Ogata, Department of Gastroenterology, University of Tokyo, Tokyo Japan; Kenji Fujiwara, Third Department of Internal Medicine, Saitama Medical School, Saitama Japan

Anandamide as a candidate factor for impared liver regeneration in fulminant hepatic failure by inducing apoptosis of hepatocytes: Satoshi Mochida, Yanhong Wang, Mie Inao, Atsushi Matsui, Sumiko Nagoshi, Kenji Fujiwara, Third Department of Internal Medicine, Saitama Medical School, Saitama Japan

Anandamide as a candidate factor for impared liver regeneration in fulminant hepatic failure by inducing apoptosis of hepatocytes: Satoshi Mochida, Yanhong Wang, Mie Inao, Atsushi Matsui, Sumiko Nagoshi, Kenji Fujiwara, Third Department of Internal Medicine, Saitama Medical School, Saitama Japan

The expression of osteopontin in hepatocytes in chronic liver disease patients and its association with liver fibrosis: Atsushi Matsui, Satoshi Mochida, Yuichiro Eguchi, Mie Inao, Sumiko Nagoshi, Kenji Fujiwara, Third Department of Internal Medicine, Saitama Medical School, Saitama Japan

The expression of osteopontin in hepatocytes in chronic liver disease patients and its association with liver fibrosis: Atsushi Matsui, Satoshi Mochida, Yuichiro Eguchi, Mie Inao, Sumiko Nagoshi, Kenji Fujiwara, Third Department of Internal Medicine, Saitama Medical School, Saitama Japan

Reply:

We appreciate the comments of Luedde et al.1 We read the interesting article reported by Luedde et al.2 In the partial hepatectomy (PH) experiments using knockout mice for various cyclin-dependent kinase (Cdk) inhibitors, the authors have shown that a loss of p18INK4C alone did not influence Cdk4 activity, but the lack of p21CIP1/WAF1 led to Cdk 4 activation. On the other hand, we have reported that the kinase activity of Cdk4 was higher in p18INK4C-negative hepatocellular carcinomas (HCCs) than in p18INK4C-positive ones.3 Based on the results, we concluded that p18INK4C expression might play an important role in the development of HCC through the upregulation of Cdk4 activity. These two reports appear to be contradictory. However, our experiments are different from the study of Leudde and colleagues. The reasons are as follows. Liver regeneration after PH reflects the proliferation of normal hepatocytes, and the process is completed after one week. Thus, changes induced by liver regeneration after PH are quite short, and are reversible. On the other hand, proliferation of HCC is a chronic and continuous process in transformed cells (cancer cells), and it is irreversible. Therefore, although the kinetic changes of cell cycle-related molecules in liver regeneration after PH provide important hints for the mechanism of hepatocarcinogenesis, they may not be directly applied to the proliferation of cancer cells. To solve this problem, it may be necessary to study Cdk 4 activity in carcinogen-induced HCC of p18INK4C knockout animals. It has been shown that the expression of p21CIP1/WAF1, p27 KIP1 and p57KIP2 were frequently downregulated in HCC.4, 5 Therefore, we agree with the suggestion that the effect on Cdk4 activity in HCC may be caused by a simultaneous loss of p18INK4C, p21CIP1/WAF1 and/or p27KIP2. In the future, it will be needed to determine what Cdk inhibitors influence Cdk4 activation in HCC. In addition, we would like to address the following point. Luedde et al. have stated that a loss of p18INK4C expression alone did not influence Cdk4 activation after PH. However, a clear band corresponding to the retinoblastoma protein phosphorylated at Ser-780 was visible 36 and 48 hours after PH in p18INK4C knockout animals (Fig. 5C in the text of Luedde et al.2). This result suggests that a loss of p18INK4C alone may also influence Cdk4 activation in liver regeneration after PH. We previously reported that the overexpression of Cdk4 was detected in HCC of Long Evans cinnamon rats and human.6, 7 In addition, Pascale et al.8 have also demonstrated that the overexpression of cyclin D1/Cdk4 complex occurred in chemically induced HCC of Fischer 344 rats. Conversely, it has been shown that Cdk6 protein was not increased in HCC.4, 5 Therefore, we assume that the amount of Cdk4 (cyclin D/Cdk4) may be higher than that of Cdk 6 (cyclin D1/Cdk6), and p18INK4C may dominantly interact with Cdk4 rather than with Cdk6 in p18INK4C-positive HCCs, suggesting that p18INK4C in HCC may contribute only to the up-regulation of Cdk4. Finally, expression levels of p18INK4C, p21CIP1/WAF1, p27KIP1, p57KIP2 and other Cdk inhibitors should be evaluated to examine their functional collaboration in the development of HCC. Tsutomu Masaki M.D.*, Asahiro Morishita M.D.*, Shigeki Kuriyama M.D.*, * Third Department of Internal Medicine, Kagawa University School of Medicine, Kagawa, Japan.

Association of HLA and Autoantibodies Against the Exocrine Pancreas in Type 1 Diabetes

Department of Internal Medicine, Ohtsu Red Cross Hospital, Shiga, Japan Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan Department of Internal Medicine, Ohtsu Red Cross Hospital, Shiga, Japan

In Memory of Yukitaka Miyachi

Dr. Yukitaka Miyachi graduated from the Medical School of the University of Tokyo, Japan, in 1963; four years later he received his Ph. D. degree from the Graduate School of the same University. He subsequently did his residency in Medicine and fellowship in Endocrinology and Metabolism at the Third Department of Internal Medicine, University of Tokyo Medical School. He joined the National Institutes of Health as a visiting fellow in 1971, and continued his research in the field of the hypothalamic-pituitary-adrenal axis under the supervision of the late Dr. M. B. Lipsett for two years, before returning to his native country as an Associate Professor of Internal Medicine.

難治性潰よう性口内炎が初発症状と考えられた急性型成人Ｔ細胞白血病の１例

In March 1999, a 70-year-old man presented with ulceration of the oral mucosa and difficulty in swallowing accompanied by pain.Clinically, the oral ulcerations were characterized by a punched-out appearance, and the circumscribed lesions showed a trend toward bleeding with pain. The clinical diagnosis was herpetic gingivostomatitis.After admission, the patient received systemic antiviral agents (aciclovir), and corticosteroid ointment was applied to the oral lesions. Despite treatment, the oral ulcers remained unchanged, and the patient had a fever of unknown origin. Microscopic examination of a specimen of the oral ulcer revealed no definitive evidence of viral infection. On immunological examination, anti-ATLA was positive, and PPD reaction was negative. Subpopulation analysis of blood lymphocytes showed an increase in CD 4-positive cells and an increased CD 4/CD 8 ratio.Viral esophagitis was confirmed histopathologically by gastrointestinal examination. These findings suggested severe immune deficiency. A diagnosis of acute adult T-cell leukemia (ATL) was made at the Third Department of Internal Medicine of our university hospital. Chemotherapy for ATL was performed; however, the patient died of respiratory dysfunction caused by ATL cell infiltration of the lung in May 2000.

Increased serum triglyceride clearance and elevated high-density lipoprotein 2 and 3 cholesterol during treatment of primary hypertriglyceridemia with bezafibrate

Background Hypertriglyceridemia accompanied by low levels of high-density lipoprotein cholesterol (HDL-C) is a risk factor for coronary artery disease. High-density lipoprotein 2 (HDL 2) and 3 (HDL 3) are believed to suppress the progress of atherosclerosis through reverse cholesterol transport. As a result, peripheral tissues can be protected against excessive accumulation of cholesterol. Although bezafibrate is known to accelerate the increase of HDL-C, results are not standardized regarding increases of HDL 3 and HDL 2 subfractions. Objective This study assessed the effects of bezafibrate on serum triglyceride (TG) fractional clearance rate (K 2) and HDL 2 and HDL 3 cholesterol (HDL 2-C and HDL 3-C, respectively) levels in patients with primary hypertriglyceridemia (serum TG ≥150 mg/dL). Methods Outpatients with primary hypertriglyceridemia were enrolled in this 8-week study conducted at the Third Department of Internal Medicine, Nagoya City University Hospital (Nagoya, Japan). Oral bezafibrate was administered at a dose of 400 mg/d (200-mg tablet BID, morning and evening) for 8 weeks. After 8 weeks, serum levels of total cholesterol (TC), TG, HDL-C, HDL 2-C, and HDL 3-C were measured. A fat emulsion tolerance test to assess K 2 and measurements of plasma lipoprotein lipase (LPL) mass, LPL activity, and hepatic triglyceride lipase (HTGL) activity in postheparin plasma were performed before bezafibrate administration and after the course of treatment. Results Sixteen patients (10 men, 6 women; mean [SD] age, 54 [12] years [range, 30–69 years]; mean [SD] body mass index, 23 [2] kg/m 2) entered the study. The following findings were observed in male and female patients after 8 weeks of treatment. A statistically significant reduction was observed in mean serum TG level ( P<0.01). Significant increases were seen in HDL-C, HDL 2-C, and HDL 3-C (all P<0.01), K 2 ( P<0.01), and in plasma LPL mass ( P<0.01) and LPL activity ( P<0.05). TC level and HTGL activity did not change significantly. No adverse effects related to the use of bezafibrate were documented. Conclusions In this study, bezafibrate treatment resulted in significant decreases in serum TG level and significant increases in HDL 2-C and HDL 3-C levels and plasma LPL mass and activity. We hypothesize that bezafibrate may increase HDL 3-C by promoting TG-rich lipoprotein catabolism and may increase HDL 2-C by promoting the conversion of HDL 3 to HDL 2.

Use of telemedicine in periodic screening of diabetic retinopathy.

Telemedicine was used for taking ocular fundus images of diabetic patients, which were subsequently sent by electronic mail to experienced ophthalmologists at a university hospital. The ophthalmologists provided reports on the patients to the internists. The objective of the study was to evaluate the effectiveness of this telemedicine system. A total of 279 diabetic patients were admitted to the Third Department of Internal Medicine of Yokohama City University Hospital, School of Medicine, for blood sugar control or for education on lifestyle between April, 1999, and October, 2000. The subjects did not have eye disease nor diabetic retinopathy when evaluated by an ophthalmologist (at either Yokohama City University Hospital or other facility) within 3 months before enrollment in the study. After dilation of the pupil, fundus images were taken of each eye from four angles using a nonmydriatic fundus camera. The images were transmitted by electronic mail to the Division of Ophthalmology of Tokyo University Branch Hospital along with other patient information. The ophthalmologists there evaluated the images on the screen according to Fukuda's classification of diabetic retinopathy. They sent ophthalmologic reports to the internists at the Third Department of Internal Medicine of Yokohama City University Hospital, School of Medicine, and recommended whether the patient should be seen by his/her regular ophthalmologist earlier than the next scheduled visit. Fundus images were obtained at the time of admission, at 1, 3, and 6 months after discharge, and at every 6 months thereafter. Out of the images of 1170 eyes obtained at various time points from the 279 patients, 1076 (92.0%) were successfully evaluated by the ophthalmologists at the University of Tokyo, while 60 (5.1%) could not be evaluated and there was a communication problem for the images of 34 eyes. The ophthalmologists determined that 5 eyes of 3 patients required further evaluation by the patient's regular ophthalmologist based on the images transferred by telemedicine. No patient dropped out during the study period.