The W258X mutation in SLC22A12 is the predominant cause of Japanese renal hypouricemia

Recently, a urate transporter, hURAT1 (human uric acid transporter 1) encoded by SLC22A12, was isolated from the human kidney. hURAT1 is presumed to play the central role in reabsorption of urate from glomerular filtrate. In the present study, we analyzed SLC22A12 in seven unrelated Japanese patients with renal hypouricemia whose serum level of urate was less than 1.0 mg/dl, and their family members. We performed direct DNA sequencing of the exon and exon-intron boundaries of SLC22A12 using genomic DNA. Six of the seven patients (86%) possess mutations in SLC22A12. In five patients, a homozygous G to A transition at nucleotide 774 within exon 4 of SLC22A12, which forms a stop codon (TGA) at codon 258 (TGG), was identified (W258X). In one patient, the C to T transition within exon 3, which changes threonine at codon 217 to methionine (T217 M), and the W258X mutation were found (compound heterozygote). Thus, among 12 mutational alleles in six patients, 11 were the W258X mutation (92%). Family members with the heterozygous W258X mutation (carriers) show relatively low levels of serum urate. The present study demonstrates that homozygous W258X mutation is the predominant genetic cause of idiopathic renal hypouricemia in Japanese patients.     

Aortic regurgitation secondary to back-and-forth intimal flap movement of acute type A dissection.

We present an unusual case of acute type A dissection complicated with severe aortic valve insufficiency caused by prolapse of the tubular intimal flap into the left ventricular outflow tract, which was shown legibly by transesophageal echocardiography in the diastolic phase and by intraoperative macroscopic findings. The dissected ascending aorta was excised completely and replaced without any repairing of the aortic valve, resulting in a favorable outcome for the patient. Prolapse of an intimal flap from the aorta into the left ventricle represented a rare pathophysiology of aortic regurgitation in patients with aortic dissection.     

Arterial stiffness in predialysis patients with uremia

BACKGROUND: Hemodialysis patients have advanced arterial wall stiffening as shown by increased aortic pulse wave velocity (PWV), an independent predictor of cardiovascular mortality. We compared aortic PWV of uremic patients before starting hemodialysis treatment with that of patients on maintenance hemodialysis. METHODS: The subjects were 71 patients with end-stage renal disease (ESRD) before starting hemodialysis (predialysis group), 144 patients on maintenance hemodialysis, and 140 healthy control subjects. These three groups were all nondiabetic and comparable in age and gender. RESULTS: The hemodialysis group had greater aortic PWV than the healthy subjects, and the predialysis patients showed a still higher value than the hemodialysis group. Multiple regression analysis in the total subjects revealed that the presence of renal failure was significantly associated with increased aortic PWV independent of age, gender, blood pressure, body mass index, smoking, high-density lipoprotein (HDL) and nonhigh-density lipoprotein (non-HDL) cholesterol levels. In contrast, hemodialysis was associated with decreased aortic PWV independent of renal failure and the other factors. Further analyses in the combined uremic patients again indicated the favorable impact of hemodialysis on aortic PWV independent of the classical risk factors, use of antihypertensive medications, including angiotensin-converting enzyme inhibitors and calcium channel blockers, hematocrit, serum calcium, phosphorus, parathyroid hormone levels, and the use of calcium carbonate. Insulin resistance using homeostasis model assessment (HOMA-IR) was associated with increased aortic PWV. CONCLUSION: Aortic stiffening was present in uremic patients before starting hemodialysis treatment and no adverse effect of hemodialysis was observed, suggesting the important roles of renal failure and/or metabolic alterations secondary to renal failure in arterial stiffness in patients with uremia.     

Effects of cigarette smoking on iodine 123 N-isopropyl-p-iodoamphetamine clearance from the lung

Iodine 123 N-isopropyl p-iodoamphetamine (¹²³I-IMP), originally developed as a brain scanning agent, is also taken up by the lung. To evaluate the effects of cigarette smoking on the kinetics of IMP in the lung, we studied ¹²³I-IMP clearance from the lung in 18 volunteers (8 non-smokers and 10 smokers). After the injection of 111 MBq of ¹²³I-IMP into the medial cubital vein, the time-activity curve for 60 min and the regional activity using 1 frame per minute and a 64 × 64 matrix were obtained. The ¹²³I-IMP clearance curve was described as follows: C (t) = A ₁e^–k ₁ t+ A ₂e^–k ₂ t (A1, A ₂: intercepts, and k ₁, k ₂: slopes of the exponential components). ¹²³I-IMP clearance was delayed in smokers, and k ₂ was smaller in smokers. Also, a correlation between k ₁, k ₂, and the number of cigarettes smoked per day was found (r = –0.65, r = –0.74, respectively, P<0.01). In conclusion, this study suggests that the delayed clearance and retention of ¹²³I-IMP in the lung indicate lung metabolic disorders due to cigarette smoking.Offprint requests to: K. Kato     

Anti-ischemic actions of a new thromboxane receptor antagonist during acute myocardial ischemia in cats

Thromboxane A2 (TxA2) production increases significantly during acute myocardial ischemia. Since TxA2 induces platelet aggregation, coronary vasoconstriction, and has a direct cytolytic effect, thromboxane receptor antagonism would be expected to be beneficial in acute myocardial ischemia. Thirty minutes after ligation of the left anterior descending coronary artery (LAD) in anesthetized cats, the TxA2 receptor antagonist BM-13,177 or its vehicle was given as a bolus injection at 20 mg/kg, followed by continuous infusion of 20 mg/kg/hr for 4.5 hours. ST segment elevation declined significantly (p less than 0.02) after BM-13,177 treatment, suggesting a reduction in cellular ischemia. The loss in myocardial creatine kinase (CK) activity and in free amino-nitrogen concentration in the ischemic area was also significantly reduced (p less than 0.01). No significant changes in blood pressure or heart rate were seen with BM-13,177 during myocardial ischemia or in nonischemic control cats. Blood levels of BM-13,177 were sufficient to inhibit ex vivo platelet aggregation induced by the prostaglandin endoperoxide analog, U-46,619. Data from isolated cat coronary arteries suggest that BM-13, 177 antagonizes the thromboxane/endoperoxide receptor in coronary vascular smooth muscle. These experiments indicate that TxA2 plays a significant role in propagating the extension of ischemic damage, and that thromboxane receptor antagonism is an effective means of reducing the damage provoked by TxA2 in acute myocardial ischemia.     

Cost disparity between open repair and endovascular aneurysm repair for abdominal aortic aneurysm: a single-institute experience in Japan

Purpose

We conducted this study to compare the cost of open surgical repair (OR) with that of endovascular aneurysm repair (EVAR) of an abdominal aortic aneurysm (AAA).

Methods

Between January 2007 and November 2008, 70 patients underwent open repair and 57 patients underwent EVAR. We evaluated the total cost, including that of the Diagnosis Procedure Combination (DPC), that of the surgical procedure, that of materials such as grafts and guide wires, and that of the anesthesia.

Results

The mean costs for OR versus EVAR were as follows: DPC, ??632370 versus ??490050, respectively, which was significant; anesthesia, ??123540 versus ??86220, respectively (P?Conclusions New technologies should not only be clinically effective, but also cost effective. EVAR is less invasive clinically, but the cost of endovascular prostheses and other materials remains high.     

Assessment of neuromuscular block at the orbicularis oris, corrugator supercilii, and adductor pollicis muscles

Purpose  

We studied neuromuscular block at the orbicularis oris, corrugator supercilii, and adductor pollicis muscles in anesthetized patients.     

Evaluation of complications related to therapeutic colonoscopy using the bipolar snare

Background

The complications with therapeutic colonoscopy reported to date have been associated with the monopolar snare, and the frequency of complications related to use of the bipolar snare is uncertain. This study aimed too investigate the incidence of bleeding and perforation associated with the bipolar snare and to identify the risk factors for bleeding.

Methods

Between October 2001 and December 2008, all patients with colorectal polyps treated using the bipolar snare were enrolled in this retrospective study. Clinical data were assembled from an electronic database. The incidence of bleeding and perforation was investigated, and the risk factors for bleeding also were determined using multivariate analysis.

Results

This study collected 4,719 patients with 10,513 lesions. Perforation occurred for eight patients (0.17%) and bleeding in 66 patients (1.4%). Age younger than 60?years was a significant risk factor for bleeding (P?P?P?P?P?Conclusions The complication rates for the bipolar snare appear to be comparable with those for the monopolar snare based on comparison of the results reported in the literature. Age (<60?years), lesion size (??10?mm), macroscopic type (pedunculated), and lesion location (rectum) are independent risk factors for bleeding.     

Long-term outcome for surgically treated cervical spondylotic radiculopathy and myelopathy

Long-term follow-up results were examined to verify the efficacy of anterior osteophytectomy for cervical spondylotic myelopathy and radiculopathy, in particular the outcome for patients with developmentally narrow cervical canals and patients with associated ossification of the posterior longitudinal ligament (OPLL). One hundred thirty-nine patients who had undergone anterior osteophytectomy with interbody fusion between 1976 and 1990 were followed up for 1 to 22.5 years (mean 11.4 years). Overall results evaluated by the neurosurgical cervical spine scale scoring and grading showed significant improvement in both improvement score (2.7 +/- 2.3) and improvement rate (52.3 +/- 45.7%). Lower extremity motor function improved in 66.1% of patients, upper extremity motor function in 82.0%, and sensory/pain function in 70.5%. Improvement ranged from one to three grades. Severely affected patients showed good recovery. Outcome for patients with narrow cervical canals (41 patients, 29.5%) did not differ significantly from that for patients with normal canals (98, 70.5%). Patients with associated OPLL (32 patients, 23.0%) had approximately the same outcomes as those with only spondylosis (107, 77.0%). Fifteen patients (10.8%) underwent reoperation because of myelopathy due to disc degeneration adjacent to the fused level (11 patients) or OPLL (4 patients). Anterior osteophytectomy with interbody fusion can achieve good outcomes in patients with cervical spondylotic myelopathy and radiculopathy, regardless of the size of the spinal canal and association with OPLL.     

Poor prognosis after lung resection for patients with adenosquamous carcinoma of the lung

BACKGROUND: We evaluated the prognosis of adenosquamous carcinoma of the lung after lung resection in comparison with other types of carcinoma. METHODS: We retrospectively reviewed charts of patients who underwent lung resection for lung cancer. RESULTS: Surgical outcomes for 30 patients with adenosquamous carcinoma of the lung, who were treated between 1976 and 1998, were compared with the surgical results for 1,219 patients similarly treated for adenocarcinoma or squamous cell carcinoma during the same period. Adenosquamous carcinoma comprised only 2.1% of 1,408 lung cancer cases treated by resection. The overall cumulative 5-year survival rate was only 6.2% for the patients with adenosquamous carcinoma, indicating a significantly poorer prognosis than for adenocarcinoma or squamous cell carcinoma. CONCLUSIONS: The cumulative survival rate for patients with adenosquamous carcinoma in pathologic stages IA to IIB was similar to that of patients with stage IIIA adenocarcinoma or squamous cell carcinoma.