Haplotype-based, case-control study of the receptor (calcitonin) activity-modifying protein (RAMP) 1 gene in essential hypertension.

The adrenomedullin receptor is a complex molecule that comprises the calcitonin-receptor-like receptor (CRLR) and the receptor-activity-modifying protein (RAMP). RAMP1 is a vasodilation factor, and RAMP1-deficient mice (RAMP1(-/-)) exhibit inflammatory responses with a significant transient increase in serum calcitonin-gene-related peptide levels and proinflammatory cytokines when compared with RAMP1(+/+) mice. The purpose of the present study was to investigate the relationships between essential hypertension (EH) and RAMP1 gene single-nucleotide polymorphisms (SNPs) or haplotypes in a Japanese population via a case-control study. Based on a database search of the National Center of Biotechnology Information website and the HapMap project, we chose six RAMP1 gene SNPs and performed an association study involving 263 patients with EH and 267 age-matched normotensive (NT) subjects. There was no significant difference between the EH and NT groups with regard to overall distribution of genotypes or SNP alleles. However, the haplotype-based case-control analysis revealed that there was a significant difference between the EH and NT groups with regard to overall distribution of the allele combinations at three SNPs-rs3754701-rs3769048-rs10199956-(P=0.002). The T-A-T haplotype was significantly more common in the EH group (10.3%) than in the NT control group (6.1%) (P=0.047). These results suggested that this T-A-T RAMP1 gene haplotype might have utility as a genetic marker for EH and that the RAMP1 gene or a neighbouring gene may be associated with increased susceptibility to EH.

Cost-effectiveness of cognitive remediation and supported employment for people with mental illness: a randomized controlled trial.

BACKGROUND: Little is known about the economic benefits of cognitive remediation and supported employment (CR + SE). The present study aimed to investigate the cost-effectiveness of CR + SE compared with traditional vocational services (TVS). METHOD: Individuals with mental illness and low cognitive function were recruited at six sites in Japan. A total of 111 participants were randomly allocated to the CR + SE group or the TVS group. Clinical and vocational outcomes were assessed at baseline and 12-month follow-up. Service utilization data were collected monthly. The data on outcomes and costs were combined to examine cost-effectiveness. RESULTS: The data were obtained from a total of 92 participants. The CR + SE group resulted in better vocational and clinical outcomes (employment rate, 62.2%; work tenures, 78.6 days; cognitive improvement, 0.5) than the TVS group (19.1%, 24.9 days and 0.2). There was no significant difference in mean total costs between the groups (CR + SE group: $9823, s.d. = $6372, TVS group: $11 063, s.d. = $11 263) with and without adjustment for covariates. However, mean cost for medical services in the CR + SE group was significantly lower than that in the TVS group after adjusting covariates (Β = -$3979, 95% confidence interval -$7816 to -$143, p = 0.042). Cost-effectiveness acceptability curves for vocational outcomes illustrated the high probabilities (approximately 70%) of the CR + SE group being more cost-effective than TVS when society is not willing to pay additional costs. CONCLUSIONS: CR + SE appears to be a cost-effective option for people with mental illness who have low cognitive functioning when compared with TVS.

The relationship between serum calcium level and early-phase insulin secretion in normoglycemic and pre-diabetic individuals.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is linked to altered calcium metabolism. However, little is known about the relationship between serum calcium levels and early-phase insulin secretion in subjects with normoglycemic tolerance (NGT) or prediabetes (preDM). METHODS: In this gender-separated cross-sectional study, 352 subjects with NGT (215 men and 137 women; age: 48.8±9.1 years and 51.6±6.7 years, respectively) and 316 subjects with preDM (231 men and 85 women; age: 52.5±8.6 years and 54.2±8.0 years, respectively) were examined. Following a 75-g oral glucose tolerance test, early-phase insulin secretion was estimated using the insulinogenic index (IGI) [ΔInsulin(30-0 min)/ΔGlucose(30-0 min)]. RESULTS: Simple linear regression analysis showed that IGI was positively correlated with serum calcium and albumin-adjusted calcium levels in men with NGT and preDM. However, IGI was not correlated with calcium levels in women with NGT and preDM. Multivariate linear regression analysis of men with NGT revealed that the albumin-adjusted calcium level was the major predictor of IGI, responsible for 5.1% of its variation (P=0.003). In addition, in men with preDM, the albumin-adjusted calcium level was one of the predictors of IGI, responsible for 3.8% of its variation (P=0.004). These associations were independent of age, BMI, and HbA1c. CONCLUSIONS: In non-diabetic Japanese men, serum calcium levels significantly correlate with early-phase insulin secretion. Serum calcium levels may be an independent predictor of ß-cell function in men.

The relationship between serum uric acid levels and ß-cell functions in nondiabetic subjects.

High serum uric acid (UA) levels are believed to be an independent risk factor for the development of diabetes. We aimed to investigate the relationship between serum UA concentrations and early-phase insulin secretion following a 75 g oral glucose tolerance test (OGTT) in nondiabetic subjects. We enrolled 570 Japanese subjects (354 males and 216 females, aged 50.5 ± 8.9 years and 52.6 ± 7.3 years, respectively), who underwent the 75 g OGTT during their annual health examination. The OGTT confirmed their nondiabetic status. Insulin secretion was estimated by the disposition index (DI) [(Δ insulin/Δ glucose (0-30 min) × (1/HOMA-IR)], which is an adjusted measure of ß-cell function relative to variations in insulin sensitivity. Simple linear regression analysis showed negative correlations between serum UA levels and DI, when examined in the whole study population and female subjects only (r = -0.209, p < 0.001 and r = -0.232, p < 0.001, respectively). However, in male subjects, UA levels did not correlate with DI. In females, multivariate linear regression analysis revealed that serum UA levels were the major predictors of DI, explaining 16.4% of its variation (p < 0.001). Serum UA levels significantly correlate with early-phase insulin secretion in nondiabetic Japanese women. It may be an independent risk factor for predicting ß-cell function in women.

Effects of short-term intensive glycemic control on insulin, glucagon, and glucagon-like peptide-1 secretion in patients with Type 2 diabetes.

BACKGROUND: Short-term intensive insulin therapy (IIT) in patients with Type 2 diabetes mellitus (T2DM) has beneficial effects on insulin secretion. However, IIT effect on glucagon and glucagon-like peptide-1 (GLP-1) secretion is unknown. AIM: We evaluated short-term intensive glycemic control effects on insulin, glucagon, and GLP-1 secretory dynamics in T2DM. MATERIALS AND METHODS: Twenty-six patients with T2DM were hospitalized and treated with IIT for 10-14 days. A meal tolerance test was performed before and after IIT and the differences in serum immunoreactive insulin (IRI) and C-peptide immunoreactivity (CPR) as well as plasma glucagon and active GLP-1 levels were evaluated. RESULTS: Glycoalbumin levels decreased significantly from 23.0% before to 19.6% after IIT (p<0.001). However, pre- and post-IIT, IRI and CPR levels were not significantly different; post-IIT glucose levels were significantly decreased. The post-IIT glucagon levels at 0 and 60 min were lower than pre-IIT levels. Moreover, post- IIT area under the curve (AUC) of glucagon significantly reduced from 6755 ± 996 pg/dl · 60 min to 5796 ± 1074 pg/dl · 60 min (p<0.001). Furthermore, post-IIT GLP-1 levels and AUC were significantly higher than pre-IIT values. CONCLUSIONS: Our results suggest that patients with T2DM who received shortterm IIT demonstrated decreased postprandial glucagon levels and increased GLP-1 levels following a meal tolerance test.

The utility of endoscopic ultrasonography and endoscopy in the endoscopic mucosal resection of early gastric cancer.

OBJECTIVE: To clarify the usefulness of endoscopic ultrasonography (EUS) and endoscopy in the endoscopic mucosal resection (EMR) of early gastric cancer. Patients/Methods-EMR was performed in 61 patients with early gastric cancer over the past five years. The accuracy of the assessment of the depth of cancerous invasion was studied in 49 patients who had EUS before EMR. Forty eight patients were treated with endoscopy alone; in these patients, EUS and endoscopic findings correlated with the clinical course. RESULTS: Forty six patients showed no changes in the submucosal layer or deeper structures on EUS. Pathologically these included 37 patients with mucosal cancer and nine with submucosal cancer showing very slight submucosal infiltration. Three patients showed diffuse low echo changes in the submucosal layer on EUS; pathologically, these included two with submucosal cancer and one with mucosal cancer with a peptic ulcer scar within the tumour focus. Of 48 patients receiving endoscopic treatment alone, 45 showed no tumour recurrence or evidence of metastases on EUS and endoscopy. Three cases of recurrence were observed. Two of these patients had a surgical gastrectomy, and one was re-treated endoscopically. In the former cases, the surgical results correlated well with assessment by EUS and endoscopy. In addition, the latter patient who was re-treated endoscopically after evaluation with EUS and endoscopy has so far had no recurrence. CONCLUSION: The combined use of EUS and endoscopy is effective in diagnosing the depth of cancerous invasion in patients undergoing EMR as well as in clarifying changes both within and between anatomic levels during follow up.

Aggressive non-Hodgkin's lymphoma after successful eradication of Helicobacter pylori and regression of gastric lymphoma of mucosa-associated lymphoid tissue.

A 57-year-old woman presented to our clinic with low-grade gastric lymphoma of mucosa-associated lymphoid tissue (stage IE) and Helicobacter pylori infection. She received a 2-week course of omeprazole and clarithromycin, resulting in eradication of H. pylori and histological disappearance of the lymphoma. However, 9 months later (May 1996), multiple mass lesions were found around the pancreas and hepato-duodenal ligament on abdominal computed tomography. Inguinal lymph node biopsy revealed aggressive nodal type B-cell non-Hodgkin's lymphoma, diffuse large cell type. She received chemotherapy with cyclophosphamide, adriamycin, vincristine, and prednisolone, but failed to achieve remission and died in December 1996. There was no evidence of recurrent gastric lymphoma. This case emphasizes the importance of performing follow-up examinations to detect other neoplasms in patients with gastric lymphoma of mucosa-associated lymphoid tissue.

Incidence of peptic ulcer in men is inversely correlated with blood pressure: study in an apparently healthy Japanese population.

OBJECTIVE: To study the role of autonomic nervous innervation in the etiology of peptic ulcer, we investigated the blood pressure in patients with peptic ulcer. METHODS: In 100,085 Japanese adults who were undergoing health screening examinations, including barium meal study, there were endoscopic evaluation-confirmed diagnoses of gastric ulcer in 769 cases and of duodenal ulcer in 344 cases. The blood pressure in those patients was compared with that in 57,208 normal Japanese controls with no gastrointestinal abnormalities, as confirmed by barium meal study. RESULTS: The blood pressure of younger and middle-aged men with gastric and duodenal ulcer were lower than those of normal control men. In women, except for the diastolic pressure of those in their 50s, the blood pressure in patients with peptic ulcer and normal controls did not differ significantly. The incidence of duodenal ulcer or of gastric ulcer in men was inversely related to the systolic and diastolic pressure. No definite relationship in this respect was seen in women. CONCLUSIONS: An inverse relationship was observed between the occurrence of peptic ulcer and the blood pressure level in Japanese men, but not in women. The relationship may be mediated by an inhibitory effect of the sympathetic nervous system on ulcer formation in hypertensive subjects. The reason for the sex difference in this respect is unknown.

The coexistence of esophageal submucosal tumor and carcinoma.

The coexistence of esophageal submucosal tumor and carcinoma has been reported only in very few cases up to now, and the relationship between them is unclear. To elucidate the incidence and the pathogenesis of their coexistence, endoscopy and endoscopic ultrasonography (EUS) were sequentially performed in 95 patients who were suspected of having a submucosal tumor of the esophagus. EUS revealed 83 submucosal tumors and 12 cases of extraluminal compression. Two cases of esophageal carcinoma were observed in the series. In one patient, intraepithelial carcinoma was present on a leiomyoma originating in the muscularis mucosae, and in the other patient, multiple superficial carcinomas were presented.

A proposed staging system for primary gastric lymphoma.

BACKGROUND: Although primary gastric lymphoma is the most common extranodal lymphoma, no specific staging system exists. METHODS: The authors reviewed 98 cases histologically classified according to the Working Formulation, including low grade B-cell lymphoma of mucosa-associated lymphoid tissue type. Survival rates were calculated by the Kaplan-Meier method according to T, N, and M of the general rules of the International Union Against Cancer TNM system. The definitions of these categories are as follows: T1, tumor invades the lamina propria or submucosa; T2, the muscularis propria; T3, the subserosa; T4, the serosa without invasion of adjacent structures; T5, adjacent structures; N0, no regional lymph node metastasis; N1, perigastric lymph nodes within 3 cm of the edge of the primary tumor; N2, perigastric lymph nodes more than 3 cm from the edge of the primary tumor or in lymph nodes along the left gastric, common hepatic, splenic, or celiac arteries; N3, paraaortic and hepatoduodenal lymph nodes and/or other intraabdominal lymph nodes; N4, beyond N3; M0, no distant metastasis; and M1, positive. RESULTS: The overall 5-year survival rate was 83.5%; it was 100% in T1, 82.4% in T2, 84.2% in T3, 52.9% in T4, and 33.3% in T5; 93.9% in N0, 90.5% in N1, 66.2% in N2, and 44.4% in N3/N4; and 86.0% in M0 and 25.0% in M1. Based on these results, the authors proposed a new staging system as follows: Stage I, T1/N0, N1/M0; Stage II, T1/N2/M0, T2,T3/N0,N1,N2/M0; Stage III, T4,T5/any N/M0, any T/N3, N4/M0; and Stage IV, any T/any N/M1. According to this system, the 5-year survival rate significantly decreased as the stage progressed: 100% in Stage I, 88.9% in Stage II, 52.1% in Stage III, and 25.0% in Stage IV. In Stages I and II, survival rates were not significantly different whether chemotherapy was done or not, whereas in Stage III all patients treated with surgery alone died. CONCLUSIONS: This staging system is useful for assessing prognosis of and deciding a therapeutic plan for primary gastric lymphoma.

Superficial esophageal carcinoma: evaluation by endoscopic ultrasonography.

OBJECTIVES: The aim of this study was to evaluate the usefulness of endoscopic ultrasonography (EUS) in the staging of superficial esophageal carcinoma (SEC). METHODS: We examined the histopathologic findings of 28 patients with SEC which was confirmed in the postoperative histologic evaluation. The EUS results preoperatively estimated were compared with them. RESULTS: There were nine patients with mucosal carcinoma (two intraepithelial carcinomas and seven carcinomas limited to the mucosal layer) and 19 patients with submucosal carcinoma. The mucosal carcinomas revealed no lymph node metastasis or vessel permeation, whereas the submucosal carcinomas revealed lymph node metastasis (71%) and vessel permeation (lymphatic, 58%, vascular, 21%). The accuracy rates of depth of invasion by EUS were mucosa, 67% (6/9); submucosa, 79% (15/19); and total, 75% (21/28). EUS could not detect microinvasion to the submucosa. The overall accuracy rate of EUS in the evaluation of periesophagogastric lymph node metastasis was 72%: sensitivity 58% and specificity 85%. CONCLUSIONS: It has been clinically proved important to differentiate mucosal carcinoma from submucosal carcinoma in the staging of SEC, and EUS is recommended in differentiating between them.

Prevalence of gallbladder polyps among apparently healthy Japanese: ultrasonographic study.

The prevalence of gallbladder polyps was investigated in apparently healthy Japanese who underwent abdominal ultrasonography as part of their health screening examination. The polyps found were differentiated from gallstones, adenomas, or carcinomas as much as possible, and were considered to be cholesterol polyps. The prevalence of such gallbladder polyps was higher among males in every decade of age evaluated. The subjects with gallbladder polyps were more obese than the control group without gallbladder polyps, on abdominal ultrasonograms. The prevalence of gallbladder polyps rose in accordance with a rise in obesity index. At each range of obesity index, the prevalence of gallbladder polyps was higher among males. The prevalence of gallbladder polyps was highest among the middle-aged (40- and 50-yr-old) males, similar to the curve of the obesity index. In females, the obesity index increased with age, with no accompanying rise in the prevalence of gallbladder polyps. These data suggest that obesity contributes to the formation of cholesterol polyps of the gallbladder.

[Endoscopic ultrasonography in the assessment of invasive cardiac cancer].

The aim of this study was to assess the accuracy and limitation of Endoscopic ultrasonography (EUS) in the preoperative evaluation of the cardiac cancer (cancer in the area less than 2 cm from the esophago-gastric junction). EUS was preoperatively performed in 20 patients with cardiac cancer. These cases were visualized by the water immersion method and balloon contact method. The results were correlated with the histology of resected specimens. EUS was accurate in assessing the depth of tumor infiltration. Over all accuracy of EUS for cardiac cancer was 90%. Recognition of ultrasonographic patterns had enabled us to judge the mode of tumor infiltration whether expansive or infiltrative. Microscopical spread over 5 mm to the esophagus of the cardiac cancer could be detected by EUS. EUS was accurate in diagnosing thoracic lymph nodes (No. 110, 111, 112) metastasis of the cardiac cancer (accuracy 86%). EUS was valuable in the clinical diagnosis of the cardiac cancer.