Effect of Sodium-Glucose Cotransporter-2 Inhibitor Administration on Cardiac Rehabilitation in Patients with Type 2 Diabetes Mellitus with Heart Failure.

Cardiac rehabilitation in patients with diabetes mellitus and heart failure may be affected by anti-diabetic drugs. However, there are few reports on the effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors on cardiac rehabilitation. Thus, we retrospectively investigated the patient backgrounds and effects of cardiac rehabilitation in 44 patients admitted to our hospital with heart failure and pre-existing diabetes mellitus. Our results showed that the patients tended to be older, and those who received SGLT2 inhibitors had lower systolic blood pressure and left ventricular ejection fraction on admission than those who did not. Cardiac rehabilitation significantly improved the Short Physical Performance Battery (SPPB) score in all patients, and there was no significant difference in body mass index or in body weight. There were no significant differences in SPPB score at admission, discharge, or change from admission to discharge with or without SGLT2 inhibitors. These results suggest that SGLT2 inhibitors do not affect the change in SPPB scores. SGLT2 inhibitors may thus be used safely without affecting cardiac rehabilitation while adhering to the necessary safety precautions.

Elevation of matrix metalloproteinases and interleukin-6 in the culprit coronary artery of myocardial infarction.

BACKGROUND: Interleukin-6 (IL-6) and metalloproteinases (MMPs) are involved in the instability of vulnerable plaque associated with the induction of acute myocardial infarction (AMI). We examined the regional changes of cytokines, MMPs and adhesion molecules in patients with AMI to elucidate how these factors are involved in the onset of AMI. MATERIALS AND METHODS: One hundred and twenty-two patients with AMI were included. Blood was aspirated from the culprit coronary artery with a thrombectomy catheter, and was also sampled from peripheral veins during the coronary intervention. Control samples were obtained from the peripheral blood of age-matched patients. RESULTS: The serum levels of IL-6 (P < 0.05), tumour necrosis factor-alpha (P < 0.005), MMP-1 (P < 0.001), MMP-13 (P < 0.001), soluble intercellular adhesion molecule-1 (P < 0.005), and soluble vascular cellular adhesion molecule-1 (P < 0.05) in peripheral blood were significantly higher in the AMI group than in the controls. Aspirated serum contained significantly higher levels of IL-6 (P < 0.001), MMP-1 (P < 0.001), and MMP-13 (P < 0.05) compared to the peripheral blood of AMI. Serum IL-6 levels were significantly higher in the aspirated than in the peripheral blood in the patients hospitalized within 6 h and 6-12 h, but were similar in the aspirated and peripheral blood of the patients hospitalized 12-24 h after the onset of AMI. There were no differences between the aspirated serum and peripheral blood in the levels of interleukin-1beta and MMP-2. CONCLUSIONS: The levels of MMP-1, MMP-13 and IL-6 were higher in the culprit coronary artery than in the peripheral blood. These factors appear to be involved in the early stage of AMI.

A case of symptomatic Morgagni's hernia and a review of Morgagni's hernia in Japan (263 reported cases).

An 81-year-old female patient was admitted to the emergency room of our hospital with complaints of respiratory distress, abdominal ache, nausea, and intermittent vomiting. A plain X-ray of the abdomen and chest revealed air-fluid levels on the abdomen and the right side of the chest. Laboratory tests showed severe acidemia with a blood base excess level of -24.9 mmol/L. Since the patient was considered to have acute intestinal obstruction due to transverse colon herniation into the thorax through a foramen of Morgagni, emergency surgery was performed. Operative findings revealed that the retrosternal diaphragm had a defect of 5 cm in diameter and 20 cm in length with the transverse colon herniated into the thorax. The diaphragm defect was sutured first, and partial resection of the transverse colon was performed. After the operation, the patient had no symptoms and no recurrence has been observed during the 1-year follow-up. There have been 263 reported cases of Morgagani hernia in Japan. The case of the Morgagni hernia is reported here with some bibliographical comments.

Postprandial changes in LDL phenotypes in patients with myocardial infarction.

BACKGROUND: Low-density lipoprotein (LDL) particle size is strongly affected by both fasting and postprandial triglyceride levels. We report here that the LDL phenotype shifts toward the smaller phenotype during oral fat tolerance tests (OFTTs) in some patients with myocardial infarction (MI); a condition closely associated with postprandial increases of triglyceride and remnant-like particles (RLPs). METHODS: Oral fat tolerance tests were performed on 63 MI patients with fasting serum triglyceride levels of less than 2.25 mmol L-1 (= 200 mg dL-1). Remnant-like particles and other serum lipids were compared among patients characterized by three LDL phenotypes based on nondenaturing gradient gel electrophoresis: pattern A (large LDLs, peak LDL particle size > or = 260 A), pattern I (intermediate-sized LDLs, LDL size > 255 A, < 260 A), and pattern B (small, dense LDLs, LDL size < or = 255 A). RESULTS: The LDL size decreased significantly in patients with the highest tertile of areas under the incremental curves (AUICs) of triglycerides above the fasting levels. The LDL phenotype shifted toward the smaller phenotype after a fat load in three of eight patients with pattern A and in seven of 35 patients with pattern I. The AUICs of triglyceride-rich lipoproteins were significantly higher in these patients than in the patients exhibiting little change in LDL size, whereas the fasting metabolic parameters were similar among the patients of the same LDL phenotype in the fasting state. CONCLUSION: These results suggest that alimentary lipaemia plays an important role in the remodeling of LDL particles into the more atherogenic small, dense LDLs in patients with MI.

[Morphological and histological studies of in-stent restenosis in seven types of stents implanted in porcine coronary arteries].

OBJECTIVES: Differences in the mechanism of restenosis after stenting between coil and tubular stents were examined in porcine coronary arteries using histological and immunohistochemical methods. METHODS: Twenty-four pigs underwent balloon-induced injury in the left anterior descending coronary artery. Two weeks later, seven different stents clinically available in Japan (Coil stents: GR I, GR II, Wiktor, Cordis; Tubular stents: gfx, Multilink, Palmaz-Schatz) were implanted in the injured site. Four weeks after the stent implantation, the pigs were sacrificed for histological examination and for morphometrical analysis of the lumen, neointima, media and adventitia. Immunohistochemical studies using anti-proliferating cell nuclear antigen (PCNA), anti-alpha-smooth muscle actin and anti-macrophage antibody were also performed. RESULTS: The coil stents formed eccentric, and the tubular stents formed concentric neointimal proliferation. Although there was no difference in the area of neointima between the stents, the area of lumen in the tubular stents was bigger than that in the coil stents (p < 0.01), because the vascular area was bigger in the tubular stents (p < 0.05). Immunohistochemical examination found many PCNA-positive cells in the proliferated neointima, especially in the area around the stent strut. Many of these cells around the stent strut were positively stained by anti-macrophage antibody. Other cells positively stained for PCNA were confirmed as smooth muscle cells. CONCLUSIONS: Tubular stents maintained a wider lumen than coil stents, because negative remodeling after stenting was less in the tubular stents. Implantation of stents with less negative remodeling is very important to prevent restenosis after stenting.

Synthesis and structure-activity relationships of a new class of 1-oxacephem-based human chymase inhibitors.

1-Oxacephem derivatives were synthesized and evaluated as a novel series of chymase inhibitors. Structure-activity relationship studies of 1-oxacephems led to compound 34, which exhibited 6 nM inhibition of human chymase and high selectivity for human chymase compared to other serine enzymes.

1-Oxacephem-based human chymase inhibitors: discovery of stable inhibitors in human plasma.

1-Oxacephem derivatives were evaluated as a novel series of chymase inhibitors. The structure-activity relationship studies of 1-oxacephems led to compounds 15, which exhibited 27 nM inhibition of human chymase and improvement of stability in human plasma (t 1/2 1.5 h).

[Colorectal cancer in spouses of colorectal cancer patients].

Married couples share home environments and life style for years. In the case of colorectal cancer, an association with insulin resistance was reported. We determined the presence of the insulin-resistance syndrome (IRS, 1 or more of the following: body mass index of > 25 kg/m2, diabetes, or hyperlipidemia) in 84 colorectal cancer patients, of whom 61 patients (73%) had IRS. The incidence of the distal colorectal cancer, which has been declining in the United States, was significantly higher in the IRS group than in the non-IRS group (75.4 vs 52.2%, p = 0.0400). Some mechanisms may promote the progression of mucosal lesions to invasive cancers in the distal colorectum. There were no significant differences with respect to the age (64.6 +/- 9.4 vs 64.3 +/- 11.3 yr, p = 0.8298), height (159 +/- 9 vs 157 +/- 8 cm, p = 0.1375), and body mass index (22.2 +/- 3.6 vs 22.4 +/- 2.7 kg/m2, p = 0.6364) between the patients and their spouses. In 84 couples in whom colorectal cancer develops at least in one may then not illustrate the nursery rhyme: "Jack Sprat could eat no fat, His wife could eat no lean...". The spouses had been married for an average of 38 years, and in 30 spouses who had been followed in a colorectal cancer screening, 5 developed colorectal cancer. To diminish the incidence of colorectal cancer in Japan, we might advise screening colonoscopy to the spouses of colorectal cancer patients, or déjà vu all over again?

Osteoporosis after gastrectomy: bone mineral density of lumbar spine assessed by dual-energy X-ray absorptiometry.

Although osteoporosis is a common clinical disorder associated with gastric surgery, long-term effects of gastrectomy on bone metabolism are still unclear. The purpose of this study was to clarify the incidence and risk factors of osteoporosis after gastrectomy using univariate and multivariate analyses of quantitative measurements. The study included 59 patients who had undergone gastrectomy more than 5 years before. There were 38 men and 21 women, aged 37-81 years, mean 64 years. Bone mineral density (BMD) of L2-L4 spine was measured using dual-energy X-ray absorptiometry (DXA). Absolute value of BMD (g/cm2) and age- and sex-matched BMD (%) were given. The mean BMD was 0.766 g/cm2, and the incidence of osteoporosis (BMD less than 0.70 g/cm2) was 37%: 18% in men and 71% in women. The mean age- and sex-matched BMD was 85.9%: 87.5% in men and 83.1% in women. Univariate and multivariate analyses revealed that BMD was significantly associated with the age and sex of patients, but was not influenced by the type of gastrectomy (partial versus total) and years after operation (< 20 versus 20 <). Our study clarified the fact that postgastrectomy osteoporosis was frequent in the aged or female patients. BMD should be evaluated after gastrectomy, especially in the aged and in women.

DNA oligomers having a diazapyrenium dication (DAP2+); synthesis and DNA cleavage activities.

Aiming at the creation of functionalized antisense DNA oligomers possessing site-selective DNA cleaving activity, viologen and a related compound, diazapyrenium dication (DAP2+), were selected and introduced into oligodeoxyribonucleotides as a functionalized molecule. The conjugation of these functionalized molecules with DNA proceeded smoothly by using standard H-phosphonate chemistry. A part of the DAP(2+)-tethered DNA oligomers was synthesized by a combination of solid support method and liquid phase technique. Viologen-tethered DNA oligomers showed no significant activity toward DNA cleavage in spite of their characteristic ESR spectra. On the other hand, it was observed that the DAP(2+)-tethered DNA oligomers formed more stable duplexes with their complementary strands than the corresponding wild type, and these molecules effectively cleaved the complementary strands at the specific site of 2-3 bases away from the modified phosphoramidate linkage. The effect of position and length of the linker arm on the selectivity in the cleavage reaction was also investigated, and it was found that introduction at the 3'- or 5'-end phosphate site is more favorable, probably due to duplex stabilization.

Volvulus of the ileum in adult diagnosed pre-operatively by helical 3-dimensioned computed-tomography.

A 46 year-old male who was strictly diagnosed as having volvulus of the ileum based on the pre-operative information brought by computed tomography (CT) and helical (spiral) 3-dimensioned computed tomography was surgically treated. The post-operative course was satisfactory and the patient is now under observation without any exacerbation of symptoms one year after surgery.

Long tube for obstructing left-sided colon cancer.

BACKGROUND: Obstructing left-sided colon cancer is now managed by immediate resection and primary anastomosis using intraoperative mechanical bowel irrigation. The aim of this study was to describe our new technique using a long tube for preoperative bowel decompression and intraoperative antegrade irrigation. METHODS: A long nasointestinal tube was inserted and a balloon was inflated with distilled water. The tube gradually went forward to the ileum end by peristalsis, and the small intestine became fully decompressed. At operation, antegrade colonic irrigation with warm saline was performed through this long tube without insertion of a Foley catheter. RESULTS: Immediate colonic resection and primary end-to-end anastomosis using layer-to-layer interrupted sutures was successfully performed in 4 patients with obstructing sigmoid colon cancer. CONCLUSIONS: This method avoids opening and closure of the cecum or ileum, and minimizes bacterial contamination. The technique is simple and easy, and useful for immediate resection and primary anastomosis of obstructing left-sided colon cancer.

Ileus with incarceration of Spigelian hernia.

An 85 year-old female with ileus due to incarceration of Spigelian hernia, which was diagnosed pre-operatively with the findings of the abdominal computed tomography and plain radiographic pictures, is reported. A simple hernioplasty was made by suturing the internal oblique and transverse muscles to the rectus sheath. The post-operative condition is satisfactory without any recurrence of hernia.

Carcinoid tumor of the ileum with intestinal obstruction.

An 83 year-old female presenting with intestinal obstruction due to a carcinoid tumor of the small intestine is herein reported. The intra-operative findings revealed a stenotic lesion and ischemic changes of the ileum. A segmental jejunotomy was performed and a submucosal tumor was recognized as a causal lesion. Histopathological investigation demonstrated the features of carcinoid tumor.

Clinical results and prognostic factors of radiologically node-positive gastric carcinoma.

Lymph node metastasis determined by histologic examination is an important prognostic indicator in gastric carcinoma. However, prognostic value of lymph node metastasis detected by computed tomography (CT) is unknown. The aim of this study was to evaluate clinical results and prognostic factors of patients with radiologically node-positive gastric carcinoma. The study included 78 patients with primary gastric carcinoma and lymph node metastasis confirmed by CT. The level of lymph node metastasis was simply graded as follows: level I included perigastric nodes; level II included intermediate nodes along the left gastric, common hepatic, and celiac arteries; and level III included distant nodes along the hepatoduodenal ligament, pancreas, spleen, and abdominal aorta. Sixty patients (79%) had stage IV tumors showing one or more of the following: level III lymph node metastasis in 37, pancreatic invasion in 27, peritoneal dissemination in 23, and liver metastasis in 19. Overall 1- and 5-year survival rates were 29% and 6%, respectively, and the 1-year survival rate was significantly influenced by the level of lymph node metastasis on CT (55% for level I, 27% for level II, 7% for level III, P < 0.01). In patients with gastrectomy, prognostic factors were tumor size (<10 cm versus >10 cm, P < 0.01), gross type (localized versus infiltrative, P < 0.01), histologic type (well differentiated versus poorly differentiated, P < 0.01), and curability of the disease (curative versus noncurative, P < 0.01). Our study indicates that prognosis of patients with radiologically node-positive gastric carcinoma is poor because of high frequency of extensive tumor spreads. Patients having only positive level I nodes on CT are candidates for curative gastrectomy, which may offer long-term survival.

[Necrosis of the hepatocellular carcinoma nodule can aggravate metastasis].

Since the stroma of hepatocellular carcinoma is composed of sinusoid-like structures, cancer cells are readily released from the primary tumor with possible injurious consequences. A 63-year-old woman with hepatocellular carcinoma underwent percutaneous ethanol injection therapy. During this treatment, tumor thrombus developed in the right hepatic vein. Partial hepatic resection was performed. Six months later, multiple nodules appeared in the lung fields. Partial necrosis may have allowed the release of cancer cells from the primary tumor. Perioperative therapy should have an effect on intrahepatic micrometastases, because removal of the main tumor can be done surgically.

Bone mineral density in patients taking H2-receptor antagonist.

Osteoporosis after gastrectomy is a common clinical disorder. In gastrectomized patients, decreased gastric acidity may be associated with impaired calcium absorption. This study was undertaken to determine whether patients with chronic use of H2-receptor antagonists (HRA) had demonstrable decreases in bone mineral density (BMD). Thirty-three patients taking cimetidine, ranitidine, or famotidine for more than 2 years were analyzed. We measured BMD of L2-L4 using dual energy X-ray absorptiometry (DXA). Osteoporosis (BMD less than 0.70 g/cm2) was found only in three patients (9%). As compared with healthy controls, age- and sex-matched BMD ranged from 74.4% to 132.9%, with a mean of 97.0%, and was not influenced by the period of HRA use (<5 years versus >5 years or more). Although the age- and sex-matched BMD was different among the kinds of HRA (98.6% for cimetidine, 101.3% for ranitidine, and 85.5% for famotidine), the relationship between the BMD and type of drug was not significant by multivariate analysis. These results indicate that chronic use of HRA has little influence on the degree of BMD, and suggest that decreased gastric acidity is not always associated with osteoporosis after gastrectomy.

Increased serum CA19-9 in patients with xanthogranulomatous cholecystitis.

We present three cases of xanthogranulomatous cholecystitis (XGC) with an increased serum carbohydrate antigen 19-9 (CA19-9). All of the patients were elderly females and had gallstones lodged in the neck of the gallbladder. Preoperative serum CA19-9 levels were 709 U/ml, 87 U/ml, and 400 U/ml, respectively. A cholecystectomy with or without bile duct exploration was performed, and the histological diagnosis of XGC was made. Serum CA19-9 levels fell to normal levels in two patients who recovered uneventfully, but rose again in one patient who died of cholangitis. Clinicians must remember that XGC is a possible cause of increased serum CA19-9 levels.