Study of V1a vasopressin receptor gene single nucleotide polymorphisms in platelet vasopressin responsiveness.

There is a significant heterogeneity among individuals in terms of platelet aggregation response to arginine vasopressin (AVP). The aim of this study was to evaluate whether four single nucleotide polymorphisms (SNPs) in the promoter region of vasopressin V1a receptor gene (V1aR) could be used as genetic markers for divergent platelet aggregation response to AVP. Seventeen of 33 subjects showed more than 60% of maximum platelet aggregation and were classified as responders. Sixteen were classified as nonresponders because they had less than 30% aggregation. In a preliminary study, V1aR gene sequences were determined in two responders and two nonresponders. We found four SNPs in the promoter region of the V1aR gene: -6951G/A, -4112A/T, -3860T/C, and -242C/T. In all 33 subjects the genotypes of four SNPs were determined using either polymerase chain reaction (PCR) with allele-specific primers or PCR followed by restriction-fragment length polymorphism (RFLP). There were no differences in the AVP-induced aggregation between the subjects with and without variant alleles of each four SNPs. The genotype frequencies of four SNPs of V1aR were almost identical between AVP responders and nonresponders. These results suggest that the four SNPs in the promoter region of the V1aR gene may not be useful as genetic markers for platelet aggregation heterogeneity.

Clinical relationship of myocardial sympathetic nervous activity to cardiovascular functions in chronic heart failure: assessment by myocardial scintigraphy with 123I-metaiodobenzylguanidine.

The aim of this study was to clarify the relationship between cardiac sympathetic nervous activity (SNA) assessed by radioiodinated metaiodobenzylguanidine (123I-MIBG), an analogue of norepinephrine and cardiovascular functions in patients with chronic heart failure (CHF). Subjects were 17 patients with CHF. A dose of 111 MBq of 123I-MIBG was administered intravenously, and 5-minute anterior planar images were obtained 15 minutes (early image) and 3 hours (delayed image) after the injection. The heart/mediastinum (H/M) count ratio was defined to quantify cardiac 123I-MIBG uptake. The washout ratio (WR) of 123I-MIBG from the heart was calculated as follows: (early counts-delayed counts)/early counts x 100 (%). Echocardiography was performed on all patients within 1 week of 123I-MIBG scintigraphy to measure stroke volume index (SVI). Blood pressure and heart rate (HR) in the resting state were also recorded to calculate cardiovascular functions including cardiac output, pulse pressure (PP), and mean blood pressure. Significant linear correlations were found between the early H/M ratio of 123I-MIBG and SVI, and between the delayed H/M ratio of 123I-MIBG and SVI, respectively. WR of 123I-MIBG was correlated with HR, and was inversely correlated with SVI and with PP, respectively. It is likely that a decrease in SVI is associated with enhanced cardiac SNA in severe CHF. 123I-MIBG scintigraphy is effective in assessing the cardiac functional status and SNA in patients with CHF in vivo. Moreover, changes in PP and HR indicate well alteration in SNA.

A novel support system for patient immobilization and transportation for daily computed tomographic localization of target prior to radiation therapy.

PURPOSE: To develop a method for quick and smooth transportation of patients from a computed tomography (CT) table to a linear accelerator (linac) table for confirming tumor center before radiation therapy. MATERIALS AND METHODS: We developed a system using a subtable for patient immobilization that is transported via a customized stretcher. The patient lies on the subtable and is immobilized by a vacuum cushion and thermoplastic body cast. The subtable stretcher is used to carry the subtable from the CT table to the linac table. During transportation, the subtable is kept flat and shock to the subtable is carefully avoided. Between August 2001 and September 2002, a total of 9 patients with solitary upper lung tumors (superior to carina) were treated using this system. RESULTS: Intrafractional tumor motion along the x (left-right), y (anterior-posterior), and z axis (superior-inferior) ranged from -2 mm to 2 mm, -2 mm to 2 mm, and -5 mm to 3 mm, respectively. The standard deviation of intrafractional tumor motion along the x, y, and z axis ranged from 0.5 mm to 1.5 mm, 0 mm to 1.7 mm, and 0.6 mm to 3.5 mm, respectively. Interfractional setup errors along the x, y, and z axis ranged from -5 mm to 4 mm, -6 mm to 8 mm, and -6 mm to 6 mm, respectively, and we could reduce interfractional setup errors in the majority of treatment sessions. CONCLUSIONS: We developed a system that allows patients to be immobilized and transported to verify tumor location on a daily basis. This system is highly useful for reducing setup errors.

Reverse pharmacological effect of loop diuretics and altered rBSC1 expression in rats with lithium nephropathy.

BACKGROUND: Renal urinary concentration is associated with enhanced expression of rBSC1, a rat sodium cotransporter, in the thick ascending limb of Henle. Increased expression of rBSC1 was reported recently in nephrogenic diabetes insipidus induced by lithium chloride (Li nephropathy). However, the pathophysiological implication of altered rBSC1 expression has not yet been investigated. METHODS: Li nephropathy was induced in rats by an oral administration of 40 mmol lithium/kg dry food. In rats with reduced urinary osmolality to less than 300 mOsm/kg H2O, we examined the expression of rBSC1 mRNA and protein, plasma arginine vasopressin (AVP) and RNA expression of kidney-specific water channel, aquaporin-2 (AQP2), of collecting ducts. Rats with Li nephropathy were treated with furosemide (3 mg/kg body weight), which blocks the activity of rBSC1, and changes in urine concentration, plasma AVP, medullary accumulation of Li ions, and apical AQP2 expression were determined. RESULTS: Rats with Li nephropathy showed increased rBSC1 RNA and protein expression and reduced AQP2 RNA. In these rats, furosemide, which induces dilution of urine and polyuria in normal rats, resulted in a progressive and significant rise in urine osmolality from 167 +/- 11 (mean +/- SD) at baseline to 450 +/- 45 mOsm/kg H2O at three hours after administration, and significant oliguria. In the same rats, plasma AVP decreased significantly from 5.7 to 3.0 pg/mL. In addition, recovery of apical AQP2 expression was noted in a proportion of epithelial cells of the collecting ducts. Although Li+ in the renal medulla was slightly lower in rats with Li nephropathy treated with furosemide, statistical significance was not achieved. CONCLUSIONS: Our results suggest that dehydration or high plasma AVP results in an enhanced rBSC1 expression in Li nephropathy, and that rBSC1 expression is closely associated with the adverse effects of Li ions on collecting duct function.