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.     

The relationship between the soluble Klotho protein and the residual renal function among peritoneal dialysis patients

Background

Klotho has been investigated as an anti-aging protein that is predominantly expressed in the distal convoluted tubules in the kidneys and in the choroid plexus of the brain. The purpose of the present study was to determine the relationship between the soluble form of Klotho and renal function in chronic peritoneal dialysis (PD) patients, a relationship which remains poorly understood.

Methods

The soluble Klotho levels in the serum, urine, and peritoneal dialysate obtained from thirty-six PD patients were determined by a sandwich enzyme-linked immunosorbent assay system.

Results

The amount of urinary excreted soluble Klotho over 24?h ranged from 1.54 to 1774.4?ng/day (median 303.2?ng/day; interquartile range [IR] 84.1–498.5), while the serum soluble Klotho concentration ranged from 194.4 to 990.4?pg/ml (mean 553.7?±?210.4?pg/ml). The amount of urinary Klotho excretion was significantly correlated with residual renal function. However, there was no apparent correlation between the serum soluble Klotho levels and the residual renal function. Klotho was also detected in the 24-h dialysate collections. There was a significant correlation between the peritoneal Klotho excretion and the amount of albumin contained in the dialysate collections (r?=?0.798, p?Conclusions The total amount of urinary excreted Klotho, but not the serum level of soluble Klotho, may be a potential biomarker for assessing the residual renal function among PD patients. Whether our findings are also valid for chronic kidney disease patients overall should therefore be evaluated in greater detail.     

High plasma pentosidine level is accompanied with cardiovascular events in hemodialysis patients

Background

Cardiovascular disease is a major complication in patients with end-stage renal disease (ESRD). The accumulation of advanced glycation end products (AGEs) is facilitated in these patients. The aim of this study was to investigate the relationship between circulating AGEs and cardiovascular events in hemodialysis patients.

Methods

The plasma level of pentosidine, a well-defined AGEs, was measured in 110 hemodialysis patients who were prospectively followed for 90?months. The relationship between plasma pentosidine level and cardiovascular events was assessed using Kaplan-Meier and Cox regression analysis.

Results

Thirty-nine cardiovascular events (14 coronary heart disease and 25 strokes) occurred during the follow-up period. Multivariable Cox proportional hazard analysis showed that plasma pentosidine levels (HR 1.040, 95% CI 1.022–1.058, p?p?p?Conclusion The plasma pentosidine level predicts cardiovascular events in hemodialysis patients. The effects of lowering circulating AGE levels on cardiovascular events should be examined in ESRD patients.     

Concomitant aortic valve and ascending aorta replacement with moderate hypothermic circulatory arrest to treat an aortic bicuspid valve with post-stenotic dilatation

We recommend concomitant surgery for aortic valve replacement (AVR) and ascending aortic replacement using moderate hypothermic circulatory arrest (CA) for post-stenotic dilatation complicated by an aortic bicuspid valve. Cardiopulmonary bypass (CPB) was established from the right atrium to the dilated ascending aorta. As soon as the rectal temperature decreased to 28?°C, CA was commenced and the open distal anastomosis of a polyester prosthesis, without any cerebral perfusion, was completed. AVR was then carried out during rapid re-warming with CPB using a side arm of the prosthesis. This procedure exhibited safe and satisfactory results. There are many benefits of carrying out the procedure in this way; it avoids the requirement for cannulation to a calcified aortic arch, provides a good operative field, for an easier distal anastomosis and suturing at the valve site, and reduces the risk of further dilatation or dissection of the residual ascending aorta in the later phase.     

Bulk femoral head autograft without decortication in uncemented total hip arthroplasty: seven- to ten-year results

Superolateral acetabular bone defect is a serious challenge in uncemented total hip arthroplasty for acetabular dysplasia. We report a bulk bone autografting technique without decortication of the acetabulum and femoral head contact surfaces in 22 joints. Mean follow-up time was 8.3 years, and survival rates were 100% for loosening and revision end points. The preoperative Japanese orthopedic association hip score increased from 49.5 to 94.0. Although trabecular bridging and graft remodeling occurred in all cases, complete trabecular reorientation was observed in only 15 joints. Eccentric polyethylene wear was observed in 8 of 22 joints, and osteolysis, in 1 joint. Our technique is easy to perform, and midterm results were favorable; thus, we conclude that it may be an effective option for bulk bone autografting.     

Interim evidence of the renoprotective effect of the angiotensin II receptor antagonist losartan versus the calcium channel blocker amlodipine in patients with chronic kidney disease and hypertension: a report of the Japanese Losartan Therapy Intended for Global Renal Protection in Hypertensive Patients (JLIGHT) Study

Background. Insufficiency of renal function and high blood pressure influence each other and eventually result in life-threatening endstage renal disease. It has been proposed that proteinuria per se is a determinant of the progression of chronic kidney disease (CKD). The therapeutic strategy for patients with proteinuric CKD and hypertension should therefore be targeted with a view not merely toward blood pressure reduction but also toward renoprotection. Methods. We examined the effect of the angiotensin (AT)₁ receptor antagonist losartan and the calcium channel blocker amlodipine, throughout a period of 12 months, on reduction of blood pressure and renoprotection. This was done by assessing amounts of urinary protein excretion, serum creatinine (SCr), and creatinine clearance (CCr) in patients with hypertension (systolic blood pressure [SBP] 140mmHg or diastolic blood pressure [DBP] 90mmHg) and CKD (male, body weight [BW] 60kg: 1.5 SCr < 3.0mg/dl; female or male BW < 60kg: 1.3 SCr < 3.0mg/dl), manifesting proteinuria of 0.5g or more/day. Losartan was administered once daily at doses of 25 to 100mg/day, and amlodipine was given once daily at 2.5 to 5mg/day. No antihypertensive combination therapy was allowed during the first 3-month period. Results. A 3-month interim analysis revealed that, despite there being no difference in blood pressure between the two groups, there was a significant reduction in 24-h urinary protein excretion in the losartan group (n = 43), but there was no change in the amlodipine group (n = 43). Analysis of stratified subgroups with proteinuria of 2g or more/day and less than 2g/day showed that losartan lowered proteinuria by approximately 24% in both subgroups, while amlodipine lowered proteinuria by 10%, but only in the subgroup of less than 2g/day (NS). SCr and CCr did not change throughout the period of 3 months in either group. No severe or fatal adverse event was experienced in either group during the study period. Conclusions. Losartan appeared to be efficacious for renoprotection in patients with proteinuric CKD and hypertension, with the mechanism being independent of its antihypertensive action.     

Predictors of improvement in low back pain after lumbar decompression surgery: Prospective study of 140 patients

Background

Lumbar decompression surgery is often used to treat neurological symptoms of the lower extremity as a result of lumbar disease. However, this method also leads to the improvement of the accompanying low back pain (LBP). We studied the extent of LBP improvement after lumbar decompression surgery without fusion and the associated preoperative factors.

Union versus nonunion after posterolateral lumbar fusion: a comparison of long-term surgical outcomes in patients with degenerative lumbar spondylolisthesis

It has been reported that in patients undergoing posterolateral lumbar fusion (PLF), the fusion status is not related to the short-term operative results. To determine whether the fusion status influences the long-term operative results of PLF, we retrospectively examined the surgical outcomes of uninstrumented PLF for a minimum of 8 years (average, 9.5 years), by comparing cases exhibiting union with those exhibiting nonunion. Uninstrumented PLF was performed for the treatment of lumbar canal stenosis (LCS) with degenerative spondylolisthesis. Since nine patients were lost to final follow-up, the study included 42 patients, and the follow-up rate was 82.4%. The mean age of the patients was 64.1 years (range 46–77 years). Eight patients exhibited fusion at the L3–4 level and 34 patients, at the L4–5 level. The fusion status was assessed using plain radiographs. The clinical outcomes were evaluated using the Japanese Orthopaedic Association (JOA) scores. Nonunion was noted in 26% (11/42) of the patients. There were no statistically significant differences between the groups exhibiting union and nonunion with respect to age, sex, preoperative JOA score, or preoperative lumbar instability. The union group achieved better operative results than the nonunion group at the 5-year and final follow-up (P = 0.006 and 0.008, respectively) although there was no significant difference in the percent recovery at 1 and 3-year follow-up (P = 0.515 and 0.506, respectively). A stepwise regression analysis revealed that the best combination of predictors for percent recovery at the time of final follow-up included the fusion status and the presence of comorbid disease. The results indicate that the fusion status following PLF is a critical factor influencing the long-term but not short-term operative results in the treatment of LCS with degenerative spondylolisthesis.     

A case of transient bioprosthetic valve regurgitation and hemolysis devoloping early after surgery using Carpentier-Edwards valve.

The Carpentier-Edwards pericardial bioprosthesis has been markedly improved in the long-term results and valve-related complications including valve dysfunction, compared to the previous generation bioprosthesis. We report a patient in whom transient prosthetic valve regurgitation and hemolysis occurred early after mitral valve replacement using a Carpentier-Edwards pericardial bioprosthesis and were resolved by preservative therapy. The patient was a 77-year-old female diagnosed with severe mitral valve stenosis and insufficiency. She underwent mitral valve replacement with a Carpentier-Edwards pericardial bioprosthesis. Opening and closing of the three leaflets looked good on intraoperative transesophageal echocardiography (TEE). The only prosthetic valve regurgitation was evident at the central region where the leaflets form coaptation, and no abnormal findings were seen. Serum lactate dehydrogenase (LDH) was decreased to 405 U/l after surgery. However, LDH again began to increase on the 3rd day after surgery and it increased to 1,830 U/l on the 14th day after surgery. Hemolytic urine was detected on 10th day after surgery. PVL was not detected, but moderate abnormal regurgitation from the outside of the stent pocket was detected on TEE. Revision of valve replacement was considered, but LDH thereafter to 393 U/l on 41st day after surgery. The TEE was repeated, and only a trace of central jet was detected without abnormal regurgitation, unlike the previous examination. The patient did not develop any complications thereafter and was discharged on 47th day after surgery. LDH was nearly normal at the time of discharge.