Glucometabolic responses during Glucose Tolerance Test: A comparison between known diabetes and newly detected diabetes after acute myocardial infarction

Background

Glucose Tolerance Test (GTT) newly detects diabetes (new diabetes) in a substantial number of patients without a history of diabetes (known diabetes) after acute myocardial infarction (AMI). Patients with new diabetes have poor outcomes, despite their lower HbA1c levels.

Methods

This study consisted of 53 patients with new diabetes and 47 patients with known diabetes who underwent GTT 1 week after AMI. Sixty-eight patients with normal GTT and 78 patients with impaired glucose tolerance served as control. Plasma glucose and insulin were measured at fasting, 30 m, 60 m and 120 m after glucose load. Peak glucose-fasting glucose was used as a measure of glucose fluctuation. Homeostasis model assessment of insulin resistance and the Stumvoll's equations were used to assess insulin sensitivity and ß-cell function, respectively.

Results

Fasting glucose (115 ± 20 mg/dl versus 129 ± 41 mg/dl, p = 0.02) and hemoglobin A1C (5.7 ± 0.5% versus 6.7 ± 1.4%, p < 0.001) in new diabetes were significantly lower than known diabetes. Insulin sensitivity was similarly impaired in both new diabetes and known diabetes (3.2 ± 2.2 versus 3.0 ± 1.9, p = 0.58). Impairment of insulin secretion was less severe in new diabetes than in known diabetes. Peak glucose-fasting glucose was significantly greater in diabetic patients than inpatients with normal GTT (75 ± 30 mg/dl, p < 0.001) and impaired glucose tolerance (95 ± 24 mg/dl, p < 0.001), with no difference between new diabetes and known diabetes (156 ± 36 mg/dl versus 165 ± 57 mg/dl, p = 0.36).

Conclusions

These findings suggested that insulin resistance and exaggerated glucose fluctuation could be attributable to poor outcomes after AMI in patients with new diabetes.     

Risk factors for bleeding after endoscopic submucosal dissection of gastric epithelial neoplasm

Background: Although endoscopic submucosal dissection (ESD) is standard therapy in Japan for gastric epithelial neoplasm, the complication rate is unsatisfactory, with postoperative bleeding as the major complication. The aim of the present study was to determine risk factors for post‐ESD bleeding in patients with gastric epithelial neoplasm. Patients and Methods: The study included 764 patients in whom 924 gastric epithelial neoplasms were resected endoscopically between June 2005 and December 2009: the period during which preventative coagulation for all exposed vessels on the artificial ulcer with hemostatic forceps upon completion of ESD was performed routinely. We analyzed the risk factors for bleeding after ESD in relation to the various clinical factors. Results: The post‐ESD bleeding rate was 3.0%. Dialysis (vs no dialysis, P = 0.034), operation time ≥75 min (vs <75 min, P = 0.012) and poor control of bleeding during ESD (vs good control, P = 0.014) were significantly related to post‐ESD bleeding. Poor control of bleeding during ESD (vs good control; P = 0.04) and operation time ≥75 min (vs <75 min; P = 0.012) were significantly related to bleeding after second‐look endoscopy. Conclusions: Patients at high risk for post‐ESD bleeding in gastric epithelial neoplasm were those undergoing dialysis, those in whom operation time was ≥75 min, and those in whom bleeding during ESD was poorly controlled. The latter two are risk factors for bleeding even after second‐look endoscopy.     

Serum levels of platelet-derived growth factor-BB and vascular endothelial growth factor as prognostic factors for patients with fulminant hepatic failure

Background and Aims: In animal models for acute liver injury, the administration of some angiogenic factors such as vascular endothelial growth factor (VEGF) and granulocyte‐colony stimulating factor (G‐CSF) are shown to reduce liver injury and improve liver proliferative capacity. The aim of the present study was to assess the role of angiogenic factors in fulminant hepatic failure (FHF). Methods: Serum levels of nine angiogenic factors (angiopoietin‐2, follistatin, G‐CSF, hepatocyte growth factor [HGF], interleukin‐8, leptin, platelet‐derived growth factor [PDGF]‐BB, platelet endothelial cell adhesion molecule‐1 and VEGF) were measured using the Bio‐Plex Protein Array System in 30 patients, 17 of whom were diagnosed with FHF, 13 with acute hepatitis (AH), and 20 controls. Results: Serum levels of PDGF‐BB and VEGF were lower in FHF patients than AH patients and controls (PDGF‐BB; 2050 ± 1572 pg/mL vs 4521 ± 2419 pg/mL vs 8506 ± 5500 pg/mL, VEGF; 39 ± 38 pg/mL vs 144 ± 122 pg/mL vs 205 ± 121 pg/mL). By using univariate logistic regression models, serum levels of PDGF‐BB and VEGF were associated with poor outcomes. Serum PDGF‐BB levels were strongly correlated with serum VEGF levels (r = 0.70). Furthermore, serum PDGF‐BB levels were significantly correlated with platelet counts (r = 0.79), PT activity (r = 0.37) and D.Bil/T.Bil ratio (r = 0.50), while serum VEGF levels were significantly correlated with platelet counts (r = 0.68) and PT activity (r = 0.38). Conclusions: We consider that serum levels of PDGF‐BB and VEGF are worth investigating as biomarkers for predicting outcomes of FHF patients.     

Terminal stage cardiac findings in patients with cardiac Fabry disease: an electrocardiographic, echocardiographic, and autopsy study

OBJECTIVES: Fabry disease is caused by deficiency of alpha-galactosidase A, and typically causes multi-organ dysfunction. Patients with manifestations limited to the heart, mainly left ventricular hypertrophy (LVH), have been reported as a disease variation. We have reported a 3% prevalence of this cardiac variant in men with LVH, which we designated 'cardiac Fabry disease'. The purposes of this study were to evaluate the terminal stage cardiac manifestations and autopsy findings in patients with cardiac Fabry disease. METHODS: We examined seven terminal stage patients with cardiac Fabry disease. During hospitalization, standard 12-lead electrocardiograms, Holter electrocardiograms, and echocardiograms were obtained. Autopsies were performed and macroscopic along with microscopic findings were evaluated. RESULTS: Six patients died of heart failure and one of ventricular fibrillation. Electrocardiograms revealed the presence of conduction abnormalities and nonsustained ventricular tachycardia. Echocardiograms and autopsy findings revealed LVH in all patients. Localized basal posterior wall thinning of the left ventricle was detected in the six patients who died of heart failure. All patients had severe left ventricular dysfunction. Histologically, myocardial cells, but not cardiac vascular endothelial cells, showed glycosphingolipid accumulation. No accumulation was observed in other organs or in systemic vascular endothelial cells. CONCLUSIONS: Severe left ventricular dysfunction with associated conduction disturbances and ventricular arrhythmias occur in patients with terminal stage cardiac Fabry disease. Furthermore, LVH is present and associated with thinning of the base of the left ventricular posterior wall. In contrast to typical Fabry disease, accumulation of glycosphingolipids was observed in myocardial cells but not in other organs.     

Change in the membranous lipid composition accelerates lipid peroxidation in young rat hearts subjected to 2 weeks of hypoxia followed by hyperoxia.

BACKGROUND: The effects of chronic hypoxia on cardiac membrane fatty acids and on lipid peroxidation were examined, as well as the effect of l-carnitine (LCAR), which suppresses lipid peroxidation, on this process. METHODS AND RESULTS: Four-week-old Sprague-Dawley rats were exposed to 10% oxygen for 14 days ("Hypoxia"), and then to 100% oxygen for 12 h (O2). LCAR (200 mg/kg) was administered by intraperitoneal injection daily for 2 weeks. Fatty acid composition, malondialdehyde (MDA) as a lipid peroxidation product, and antioxidants (superoxide dismutase (SOD), glutathione peroxidase and catalase) were measured. The concentration of linoleic acid was lower, and that of docosahexaenoic acid, which has more double bonds than linoleic acid, was increased in hypoxic hearts. SOD activity decreased in hypoxia, whereas MDA was unchanged, but significantly increased in "Hypoxia"+O2. LCAR reduced the increase in MDA, and had no effect on SOD activity or fatty acid composition. The administration of LCAR caused an increase in the ventricular levels of acetylcarnitine. CONCLUSIONS: These results suggest that chronic hypoxia changes the cardiac fatty acid composition of juvenile rats to fatty acids that contain more double-bonds and reduce SOD activity, and that lipid peroxidation was augmented by exposure to oxygen.     

Large cell neuroendocrine carcinoma arising from the left main bronchus

A 67-year-old man was referred to our hospital for a detailed medical examination of a bronchial polyp that was detected during chest computed tomography. Bronchoscopic examination revealed a tumor that almost occluded the main left bronchus. Nd-YAG laser treatment and tumor removal with biopsy forceps were conducted. On the basis of the histopathological and immunohistochemical features, large cell neuroendocrine carcinoma (LCNEC), T2aN0M0, stage IB was diagnosed. After induction chemotherapy with a combination of cisplatin and etoposide, a sleeve resection of the left main bronchus with telescoping bronchial anastomosis was performed. LCNEC typically occurs in the peripheral lung field, but here, we report a rare case of LCNEC arising from the left main bronchus.     

QUANTITATIVE ANALYSIS OF LOW‐DOSE ASPIRIN‐ASSOCIATED SMALL BOWEL INJURY USING A CAPSULE ENDOSCOPY SCORING INDEX

Aim: The major limitation of capsule endoscopy (CE) has been the lack of a standardized and validated severity scale for mucosal injury. The aim of the present study was to verify the usefulness of quantifying small bowel mucosal changes associated with giving low‐dose aspirin (LDA) using a CE scoring index. Methods: The CE score for small bowel mucosal injury was investigated to evaluate the severity of mucosal injury. Healthy volunteers and patients suspected of having small bowel disease were recruited for this study. The short‐term LDA group (V + S‐LDA group) consisted of volunteers who took low‐dose aspirin for 14 days; this group was then compared with healthy volunteers who did not receive LDA treatment (V‐Control group). The long‐term LDA group (L‐LDA group) consisted of patients with at least a 3‐month history of daily LDA use; this group was compared with non‐users of LDA (P‐Control group). Results: The CE score was significantly higher in the V + S‐LDA group than in the V‐Control group. In the V‐Control group, almost all the subjects were categorized as exhibiting a ‘normal’ change. ‘Mild’ changes were observed significantly more frequently in the V + S‐LDA group than in the V‐Control group. The CE score was significantly higher in the L‐LDA group than in the P‐Control group. ‘Mild’ or ‘moderate or severe’ changes were observed significantly more frequently in the L‐LDA group than in the P‐Control group. Conclusion: The CE scoring system was useful for evaluating LDA‐associated small bowel mucosal disease activity and for objectively scoring the small bowel inflammatory disease state.     

Transnasal ultrathin endoscopy for placement of a long intestinal tube in patients with intestinal obstruction

BACKGROUND: The technical difficulties related to the insertion of a long intestinal tube into the jejunum under fluoroscopy present a considerable problem in patients with an intestinal obstruction. OBJECTIVE: To evaluate the usefulness of endoscopic long intestinal-tube placement with the ultrathin esophagogastroduodenoscope (UT-EGD). DESIGN: A prospective randomized clinical trial was conducted. PATIENTS: Twenty-eight consecutive patients who presented with an intestinal obstruction were included in the study. INTERVENTION: The UT-EGD was inserted nasally into at least the second portion of the duodenum or beyond. After a guidewire was introduced through the working channel, with fluoroscopic guidance, the UT-EGD itself was carefully removed with the guidewire left in place. Next, a hydrophilic intestinal tube was advanced over the guidewire into the jejunum, and then the guidewire was removed. MAIN OUTCOME MEASUREMENTS: Primary end points are the total procedure time, the radiation exposure time, and the rate of complications, all compared with the conventional method. RESULTS: The mean (+/-SD) total procedure time was 18.7 +/- 8.4 minutes for the UT-EGD method and 39.5 +/- 15.0 minutes for the conventional method, with a significant time difference between the 2 methods (P < .0005). The mean (+/-SD) radiation exposure time was also shorter with the UT-EGD method (11.1 +/- 6.0 minutes) than with the conventional method (30.3 +/- 13.7 minutes) (P < .0005). There were no complications, except for mild nasal bleeding with each method. CONCLUSIONS: The UT-EGD method has definite advantages in the placement of a long intestinal tube for patients with an intestinal obstruction in comparison with the conventional method.     

Successful treatment of chronic granulomatous disease with fludarabine-based reduced-intensity conditioning and unrelated bone marrow transplantation

Allogeneic hematopoietic stem-cell transplantation (HSCT) for chronic granulomatous disease (CGD) with a reduced-intensity conditioning regimen can be expected to lead to less therapy-related mortality and late-onset impairment, whereas it has also been reported to increase the risk of unsustained mixed donor chimerism and late rejection after transplantation. Herein, we report a 4-year-old boy with CGD who was successfully treated with unrelated bone marrow transplantation with a reduced-intensity conditioning regimen (RIC). Fludarabine-based RIC, 4 Gy of total body irradiation, 120 mg/kg of cyclophosphamide, and 125 mg/m² of fludarabine, was adopted for transplantation, followed with 8.9 × 10⁸/kg mononucleated donor cells infused without T-cell depletion. Although hematopoietic engraftment was rapidly obtained by day +17, he developed unstable donor chimerism. After tacrolimus withdrawal, the patient showed grade III acute graft-versus-host disease (GVHD), and subsequently reached full donor chimerism by day +61. Twelve months post-transplant, the patient has remained well with stable and durable engraftment, 100% donor chimerism, and normal superoxide production, without the requirement of donor lymphocyte infusions (DLI).