Effect of H. pylori on COX-2 expression in gastric remnant after distal gastrectomy

BACKGROUND/AIMS: Helicobacter pylori infection is known to induce gastritis, oxidative stress, and cyclooxygenase (COX)-2 expression in the gastric mucosa. However, the effect of H. pylori infection on remnant gastritis has not been studied. We investigated whether the severity of remnant gastritis and COX-2 expression were affected by H. pylori infection after distal gastrectomy. METHODOLOGY: The study included 97 patients with gastric cancer who underwent curative distal gastrectomy with lymphadenectomy in our department between May 1999 and April 2001. All patients underwent endoscopic examination 2 weeks before and 12 weeks after surgery. The presence of H. pylori infection was determined by urease activity, hematoxylin-eosin staining, and immunochemical staining. Histologic remnant gastritis was graded based on the degree of neutrophil infiltration using the updated Sydney System. COX-2 expression was estimated immunohistochemically. RESULTS: Both the degree of neutrophil infiltration and the level of COX-2 expression were significantly higher in patients with than without H. pylori (p<0.05). There was a significant correlation between the degree of neutrophil infiltration and the degree of COX-2 expression (p<0.001). CONCLUSIONS: H. pylori eradication may become a treatment for preventing both remnant gastritis as well as remnant gastric carcinoma after distal gastrectomy.     

Perioperative management of benign hepatic tumors in patients with glycogen storage disease type Ia

Glycogen storage disease type Ia (GSD-Ia; von Gierke disease) is an inherited disorder caused by glucose-6-phosphatase deficiency, and there have been some reports of hepatic tumors in patients with this disease. We report two patients with benign hepatic tumors with GSD-Ia. One is a 19-year-old man who underwent segmentectomy 4 for a focal nodular hyperplasia, and the other is a 31-year-old woman who underwent segmentectomies 3, 5, and 6 for hepatic adenomas. Two significant perioperative complications, resulting from the carbohydrate metabolic disorders, hypoglycemia and metabolic acidosis, occurred in both patients. We managed the metabolic complications successfully by administering a sufficient volume of glucose intravenously. Close perioperative monitoring of blood glucose and lactate concentrations is essential in the perioperative management of patients with GSD-Ia. The intravenous administration of glucose, starting with a smaller dose and then increasing the dose, is adequate management for lactic acidosis with or without hypoglycemia during the perioperative period.     

Prevalence and correlates of carotid atherosclerosis among elderly Japanese men

We determined intima-media thickness (IMT) and diameter of carotid artery and estimated their correlations with cardiovascular risk factors in 1129 men aged 60-74 years, who participated in a cardiovascular risk survey in three Japanese communities. The multivariate odds ratios (95% confidence interval) for the maximum IMT > or = 1.1 mm in the common carotid artery (CCA) were 1.3 (1.1-1.5) per 4 years of age, 1.8 (1.4-2.5) for hypertension, 1.4 (1.2-1.7) for a 34.4 mg/dl increase in serum total cholesterol, 0.7 (0.6-0.8) for a 14.7 mg/dl increase in serum HDL-cholesterol, and 2.4 (1.1-5.0) for history of stroke, while the maximum IMT > or = 1.5mm in the internal carotid artery (ICA) were 1.6 (1.4-1.8) per 4 years of age, 1.9 (1.5-2.4) for hypertension, 1.6 (1.2-2.1) for current smoking, and 3.5 (1.6-7.6) for history of stroke. Age, height, hypertension, current smoking, ethanol intake and history of coronary heart disease were independent determinants of both the outer and inner CCA diameter. Maximum IMT correlated positively with the outer diameter and inversely with the inner diameter in the CCA. Carotid atherosclerosis suggests to be a risk factor for stroke among Japanese elderly men, although future prospective studies are required to confirm this finding.     

Detailed glomerular ultrastructure in Japanese type 2 diabetic patients by the quick-freezing and deep-etching method

Mesangial expansion and glomerular basement membrane (GBM) thickening did not correlate with urinary albumin excretion (UAE) in type 2 diabetic patients in our previous studies; therefore, it was necessary to elucidate more detailed ultrastructural changes in the early stages of diabetic nephropathy (DN) in type 2 diabetic patients. The quick-freezing and deep-etching (QF–DE) method allows us to examine three-dimensional ultrastructures of human renal glomeruli in vivo at high resolution. The QF–DE method was applied to six type 2 diabetic patients without definable renal diseases other than DN. Four patients were normoalbuminuric (NA) and the other two were microalbuminuria (MA). Three control specimens were the normal parts from nephrectomies due to renal cell carcinomas. Electron microscopic morphometric analyses provided quantitative glomerular structural changes. Replica membranes were prepared by the QF–DE method, and diameters of mesh structures at the GBM and mesangial matrix (MM) were measured on electron micrographs as previously described. By the QF–DE method, both the GBM middle layer and MM were composed of polygonal meshwork structures. The mesh pores of the GBM and MM were more enlarged and irregular in shape in NA diabetic patients than those of the controls, and these ultrastructural changes became more obvious in MA patients. The mesh diameters of the GBM and MM in the diabetic patients were also larger than those of the controls. Such a mesh diameter of the GBM was well correlated with the amount of UAE, while the mesh diameter of MM showed a slight correlation with UAE. Although there were small number of subjects in the present study, the detailed ultrastructural changes in NA and MA type 2 diabetic patients, which had not been disclosed by conventional electron microscopy, were revealed by the QF–DE method. Increased mesh diameters of GBM might be related with the increase of UAE.     

Fos plays no role in apoptosis of epithelia in the mouse male accessory sex organs and uterus

Roles of Fos in apoptosis of epithelia in the mouse male accessory sex organs and uterus were investigated using Fos-deficient mice. Normal 30- and 50-day-old and Fos-deficient 50-day-old male and female mice were castrated, and testosterone propionate and estradiol-17 beta were daily injected into male and female mice, respectively, for 5 days. An apoptotic index (a percentage of apoptotic cells) in the epithelium was examined from the day following the last injection (day 1) to day 8. The body weights and the weights of the ventral prostate (VP), coagulating gland (C), seminal vesicle (SV) and epididymis (Ep) and uterus of 50-day-castrated Fos-deficient mice on day 1 suggested that the development of these mice corresponded to that of 30-day-castrated normal mice at the most. The extents of apoptosis estimated by an apoptotic index in the VP, C, SV, Ep and uterus in 50-day-castrated Fos-deficient mice were comparable to those in 30-day-castrated normal mice. The extents of apoptosis in the SV, Ep and uterus in 30-day-castrated normal and 50-day-castrated Fos-deficient mice were similar to those in 50-day-castrated normal mice, while the extents of apoptosis in the VP and C in the former two groups of mice were less than those in the latter mice. The present results show that Fos-deficiency does not affect apoptosis in the SV, EP and uterus. However, the extents of apoptosis in the VP and C were less in 50-day-castrated Fos-deficient mice than in 50-day-castrated normal mice. This seems to be due to the retarded development of 50-day-castrated Fos-deficient mice, but not to a role of Fos in apoptosis.     

Comparison of the antidiabetic effects of linagliptin among groups with a normal renal function and a mild or severe renal impairment – retrospective observation study of Japanese patients with type 2 diabetes mellitus

Objective: The clinical course > 6 months after the initiation of linagliptin in patients with type 2 diabetes was compared among the groups divided by their renal function.

Methods: Two hundred and sixteen Japanese patients with type 2 diabetes treated with 5 mg once daily linagliptin were studied as the treated set. One hundred and forty-five subjects whose medications were not changed during the observation period were investigated as the full analysis set to assess the effectiveness. The subjects were divided into three groups based on an eGFR: eGFR ≥ 60, 59 – 45 and < 45 ml/min/1.73 m². The parameters were analyzed separately in the patients receiving monotherapy and additional therapy of linagliptin.

Results: The HbA1c (NGSP) levels significantly improved in both the patients receiving monotherapy and additional therapy. The changes in the HbA1c levels at 6 months were not significantly different between the groups with an eGFR ≥ 60, 59 – 45 and < 45 ml/min/1.73 m² receiving monotherapy (?1.0, ?0.8 and ?0.8%, respectively). Similarly, those were not significantly different between the different groups receiving additional therapy (?0.6, ?0.5 and ?0.7%, respectively).

Conclusions: Linagliptin is considered to be effective for patients with type 2 diabetes and renal impairment in the present analysis performed at our institution.     

Second allogeneic transplantation using umbilical cord blood for a patient with relapsed ALK+ anaplastic large cell lymphoma after allogeneic bone marrow transplantation in the era of ALK inhibitors: A case report

Rationale:Anaplastic lymphoma kinase (ALK) + anaplastic large cell lymphoma (ALCL) is considered as a good prognosis lymphoma. However, in an extremely rare subset of patients, ALK+ ALCL with leukemic presentations is known to be chemotherapy-resistant. Although several novel therapies have been tested, the standard therapy for relapsed/refractory ALK+ ALCL has not been established yet.Patient concerns:An 18-year-old female patient who had conventional chemotherapy- and Brentuximab Vedotin (BV)-resistant ALK+ ALCL with leukemic presentation. She was successfully treated with an ALK inhibitor, crizotinib. Crizotinib induced complete remission (CR) and bridged to allogeneic bone marrow transplantation (BMT).Diagnosis:However, her ALCL relapsed on day 60 after BMT and she developed high grade fever and lymphadenopathy.Intervention:Although crizotinib was given to the patient immediately after relapse, she developed grade 3 nausea and could not continue to take it. Then, we gave alectinib to the patient, which promptly induced sustained CR without any further chemotherapy. The patient received second stem cell transplantation using umbilical cord blood with myeloablative regimen in 2^nd CR.Outcomes:The patient has been in CR under maintenance therapy of alectinib for more than 16 months.Lessons:Both ALK inhibitors demonstrated drastic efficacy for our patient who had chemotherapy- and BV-resistant ALK+ ALCL with leukemic presentation. Alectinib showed less gastro-intestinal toxicity than crizotinib and the patient was able to take it even at the relatively early phase of stem cell transplantation.     

Results of a survey of community-acquired-pneumonia and evaluation of old and new Japanese Respiratory Society guidelines]

We evaluated the usefulness of domestic and foreign guidelines for the diagnosis and treatment of patients with community-acquired-pneumonia at 23 institutions in 6 prefectures of the Tohoku Area, from December 2003 to November 2004. Based on the old and new Japanese Respiratory Society (JRS) guidelines, we evaluated severity, clinical efficacy and detection of atypical pneumonia. As for severity, the old guidelines led to the diagnosis of an excessive number of 'severe' cases. On the other hand, patients were appropriately diagnosed as having mild, moderate, severe, or very severe disease based on the new JRS guidelines (2005). The severity classification often correlated with the Pneumonia Severity Index (PSI) of the IDSA guidelines. The efficacy rate for patients who were prescribed the recommended drug according to the old JRS guidelines was 85.7% and for those who did not use the recommended drug it was 68.7% (p < 0.001).