Four novel mutations in the thiazide-sensitive Na-Cl co-transporter gene in Japanese patients with Gitelman's syndrome.

BACKGROUND: Gitelman's syndrome (GS) is an autosomal recessive disorder resulting from inactivating mutations in the thiazide-sensitive Na-Cl co-transporter (NCCT) gene. To date, almost 90 mutations have been identified. It is possible that there is a population-specific distribution of mutations. In this study, we analysed mutations in the NCCT gene of seven Japanese patients with GS. METHODS: Peripheral blood mononuclear cells were isolated from patients with GS, their family members and healthy control subjects. A mutation analysis of the NCCT gene was performed completely by direct automated sequencing of polymerase chain reaction-amplified DNA products. In patients with a deletion or splice site mutation, we undertook cDNA sequence analysis. RESULTS: We identified nine mutations. Five of them [c.185C>T (Thr60Met), c.1712C>T (Ala569Val), c.1930C>T (Arg642Cys), c.2552T>A (Leu849His) and c.1932delC] have been reported in Japanese patients, but not in GS patients from other ethnic groups. The remaining four mutations [c.7A>T (Met1Leu), c.1181_1186+20del26, c.1811_1812delAT and IVS16+1G>A] were novel. In cDNA derived from a patient with c.1181_1186+20del26, a deletion of exon 9 and a frameshift at the start of exon 10 were observed. In cDNA derived from patients with IVS16+1G>A, an additional 96 bp insertion between exons 16 and 17 was observed. Six out of seven patients were compound heterozygotes, and the remaining one carried a single heterozygous mutation. CONCLUSIONS: We found four novel mutations in the NCCT gene in seven Japanese patients with GS. Moreover, our study suggests that the distribution of mutations in the NCCT gene in Japanese GS patients potentially differs from that in other populations.     

Successful Combination Therapy of Radical Liver Resection With 5-Fluorouracil/leucovorin,Oxaliplatin, Plus Bevacizumab for Ascending Colon Cancer With Pulmonary and 43 Liver Metastases: Report of a Case

At the time of diagnosis, 20% to 25% of patients with colorectal cancer already have liver metastases, the presence of which is a most important prognostic factor. A 64-year-old man was admitted to our hospital for investigation of anemia and multiple liver tumors. Examinations revealed ascending colon carcinoma with more than 40 liver metastases and 2 lung metastases. We performed right hemicolectomy with lymph node dissection, which was followed by 5-fluorouracil/leucovorin, oxaliplatin, plus bevacizumab (FOLFOX-BV). After 4 courses of chemotherapy, the lung metastases were in complete remission and the liver metastases had shrunk. We suggested the option of radical liver resection, but the patient declined initially as he had not suffered any severe side effects of FOLFOX-BV. After 23 courses of the chemotherapy, he agreed to undergo hepatectomy. We performed extended right lobectomy with partial left and caudal lobe resection. All of the macroscopic metastatic lesions were resected. Histopathologically, viable cancer cells were recognized in 7 of the 43 liver metastatic lesions. Postoperatively, FOLFOX-BV was restarted and continued for 10 months. At the time of writing, 15 months after the hepatectomy, the patient was well without evidence of recurrence of the cancer.     

Limited value of perineural invasion in radical prostatectomy specimens as a predictor of biochemical recurrence in Japanese men with clinically localized prostate cancer

The objective of this study was to determine whether the presence of perineural invasion (PNI) in radical prostatectomy specimens could be a useful prognostic parameter in Japanese men with prostate cancer. Between January 1995 and September 2003, 202 Japanese men underwent radical retropubic prostatectomy for prostate cancer without any neoadjuvant therapies prior to surgery. We retrospectively analyzed the relationship between PNI in radical prostatectomy specimens and other prognostic factors, and also assessed the significance of PNI in biochemical recurrence after radical prostatectomy. The presence of PNI was significantly related to clinical stage, pathological stage, Gleason score, seminal vesicle invasion, lymph node metastasis and tumor volume, but not pretreatment serum prostate specific antigen value. During the observation period, biochemical recurrence occurred in 20 patients (3 in patients without PNI and 17 in those with PNI), and the biochemical recurrence-free survival rate in patients with PNI was significantly lower than that in patients without PNI. In addition to-PNI, pathological stage, seminal vesicle invasion, lymph node metastasis and tumor volume were significantly associated with the biochemical recurrence-free survival rate; however, among these five factors, only seminal vesicle invasion was an independent predictor of biochemical recurrence on multivariate analysis. Despite a significant association between several prognostic parameters, PNI was not an independent predictor of biochemical recurrence; therefore, it may not provide an additive effect to consider the presence of PNI in predicting the prognosis of Japanese men who underwent radical prostatectomy if there are other conventional parameters available.     

Serum periostin levels are correlated with progressive skin sclerosis in patients with systemic sclerosis

Background Periostin, a matricellular protein, serves as a regulator of wound healing and fibrosis. The role of periostin in the pathogenesis of systemic sclerosis (SSc) is unknown. Objective To determine periostin levels in association with severity of skin fibrosis in patients with SSc. Methods Expression of periostin was immunohistochemically examined in skin obtained from patients with SSc and healthy controls. Enzyme‐linked immunosorbent assay was performed to evaluate serum periostin levels in association with clinical characteristics in 56 patients with SSc [diffuse cutaneous SSc (dSSc), n = 16; and limited cutaneous SSc (lSSc), n = 40] and 66 healthy controls. Results Periostin was strongly expressed in the affected dermis from patients with SSc. Periostin was colocalized in α‐smooth muscle actin‐positive myofibroblasts and platelet endothelial cell adhesion molecule‐1‐positive endothelial cells in SSc dermis. Serum levels of periostin in patients with dSSc were markedly elevated compared with those in patients with lSSc and control subjects. Patients with lSSc had increased periostin levels compared with healthy controls. In addition, significantly higher levels of periostin were observed in patients with dSSc with disease duration ≤ 5 years compared with those with disease duration > 5 years. Furthermore, the modified Rodnan total skin thickness score (MRSS) was positively correlated with periostin levels in patients with SSc. Serial analysis revealed a correlation between periostin and MRSS; namely, MRSS decreased in line with decreased periostin levels in some patients with dSSc as the disease progressed. Conclusion An elevated periostin level in patients with SSc is associated with severity of skin sclerosis. Periostin may be a potential biomarker for progressive skin fibrosis in SSc.     

Masticatory performance in older subjects with varying degrees of tooth loss

Objectives

The purpose of this study was to establish the factors influencing the masticatory performance of older subjects with varying degrees of tooth loss and associated numbers of posterior occlusal contacts.

Methods

The subjects consisted of 1274 independently living people aged 60 years and over. Individuals with partially or fully edentulous arches without a denture replacement or those having any symptoms related to an oral problem were excluded from the study participants. Masticatory performance, maximal occlusal force and stimulated whole saliva were measured. Subjects were grouped into three categories by posterior occlusal contact, according to the Eichner Index. Group A had contacts in four support zones; group B had one to three zones of contact or contact in the anterior region only; and group C had no support zones at all, although a few teeth could still remain.

Results

The masticatory performance in groups B and C was found to be 81% and 50% of that of group A, respectively. The multiple linear regression analysis showed that in all the groups, occlusal force was significantly associated with masticatory performance. In groups A and B, the number of residual teeth was significantly associated with masticatory performance, whereas in group C, it had no significant relationship with masticatory performance. Salivary flow rate had a significant correlation with masticatory performance only in group C.

Conclusions

Declines in occlusal contact, occlusal force and salivary flow appear to be associated with reduction of masticatory performance in older adults. However, the crucial factors for masticatory performance varied, depending on the phase of occlusal collapse.     

Food-dependent exercise-induced anaphylaxis: influence of concurrent aspirin administration on skin testing and provocation

BACKGROUND: Provocation tests in patients with food-dependent exercise-induced anaphylaxis (FDEIA) are often negative, even after a sufficient quantity of the implicated food and exercise have been taken. OBJECTIVES: To investigate the effect of aspirin in provocation tests and in skin prick testing (SPT) of patients with FDEIA. Gluten as a major allergen in wheat-dependent FDEIA was also investigated. METHODS: Provocation tests and SPT with suspected foods were performed in 12 patients with FDEIA. Provocation tests were performed with combinations of foods, exercise and aspirin. Detection of gluten-specific IgE was also performed by the CAP System FEIA radioallergosorbent test, SPT and a histamine release test. RESULTS: The SPT reaction was enhanced by pretreatment with oral aspirin in five of eight (62.5) patients. Aspirin facilitated provocation in five of seven (71%) patients tested. Ingestion of wheat and aspirin without exercise provoked symptoms in two patients. Aspirin provoked symptoms even with a small amount of wheat and exercise in one patient. Only the combination of aspirin, wheat and exercise provoked anaphylaxis in one patient. Specific IgE, SPT and/or the histamine release test with gluten were positive in nine of 11 patients with wheat-dependent FDEIA. CONCLUSIONS: Aspirin enhances symptoms of FDEIA, and prior ingestion of aspirin under controlled conditions can be used to confirm FDEIA. In practice, such patients should avoid aspirin ingestion. Gluten appears to be the major allergen in these patients with wheat-dependent FDEIA.     

Segmental pulmonary vein antrum isolation using the "large-size" lasso catheter in patients with atrial fibrillation.

BACKGROUND: The limited efficacy and complications of segmental ostial pulmonary vein isolation (PVI) for treating atrial fibrillation (AF) have been discussed so, in the present study the feasibility and efficiency of performing segmental pulmonary vein (PV) antrum isolation to treat AF were assessed. METHODS AND RESULTS: A total of 187 patients with drug-refractory AF (paroxysmal 120, persistent 67) underwent segmental PVI guided by circumferential 20-electrode catheters (Lasso). Radiofrequency (RF) current was delivered either at the ostium using a regular Lasso (15-20 mm in diameter, 70 patients: Group 1) or at the antrum using a larger Lasso (25-30 mm in diameter, 117 patients: Group 2). A significantly wider region had to be ablated, with a longer RF application time, to isolate all 4 PVs in Group 2 patients than in Group 1 patients. Although the rate of recurrence of AF after the initial session was equal in both groups, a significantly greater number of patients were free from AF after a mean of 1.4 procedures in Group 2 than in Group 1 (93% vs 76% for paroxysmal AF, 78% vs 48% for persistent AF). CONCLUSIONS: Segmental antral PVI using large-sized Lasso catheters was found to be more effective and safer than ostial PVI for the treatment of AF.