Unique excitation–contraction characteristics of mouse myocardium as revealed by SEA0400, a specific inhibitor of Na<Superscript>+</Superscript>–Ca<Superscript>2+</Superscript> exchanger

The functional role of the sodium–calcium exchanger in mouse ventricular myocardium was evaluated with a newly developed specific inhibitor, SEA0400. Contractile force and action potential configuration were measured in isolated ventricular tissue preparations, and cell shortening and Ca²⁺ transients were measured in indo-1-loaded isolated ventricular cardiomyocytes. SEA0400 increased the contractile force, cell shortening and Ca²⁺ transient amplitude, and shortened the late plateau phase of the action potential. -adrenergic stimulation by phenylephrine produced a sustained decrease in contractile force, cell shortening and Ca²⁺ transient amplitude, which were all inhibited by SEA0400. Increasing the contraction frequency resulted in a decrease in contractile force in the absence of drugs (negative staircase phenomenon). This frequency-dependent decrease was attenuated by SEA0400 and enhanced by phenylephrine. Phenylephrine increased the Ca²⁺ sensitivity of contractile proteins in isolated ventricular cardiomyocytes, while SEA0400 had no effect. These results provide the first pharmacological evidence in the mouse ventricular myocardium that inward current generated by Ca²⁺ extrusion through the sodium–calcium exchanger during the Ca²⁺ transient contributes to the action potential late plateau, that -adrenoceptor-mediated negative inotropy is produced by enhanced Ca²⁺ extrusion through the sodium–calcium exchanger, and that the negative staircase phenomenon can be explained by increased Ca²⁺ extrusion through the sodium–calcium exchanger at higher contraction frequencies.     

Gastric cancer developing in the stomach after pylorus-preserving pancreaticoduodenectomy with pancreaticogastrostomy: Case report and review of the literature

A 59-year-old woman underwent surgery for uterine corpus cancer in March 1998. She also underwent pylorus-preserving pancreaticoduodenectomy with pancreaticogastrostomy for common bile duct cancer in November 1998. She was followed up at our outpatient clinic after pylorus-preserving pancreaticoduodenectomy. In November 2002, her carcinoembryonic antigen level became elevated and abdominal ultrasound revealed a huge tumor. Gastroscopy showed a Borrmann type 3 tumor at the anastomosis of the pancreaticogastrostomy, and a biopsy revealed adenocarcinoma. With a diagnosis of advanced gastric cancer, she underwent total gastrectomy, splenectomy, and residual pancreatectomy in January 2003. The pathologic .ndings revealed that the gastric cancer was separated from the pancreas, suggesting that the cancer had developed from the stomach. The present report describes a rare case of gastric cancer that had developed at the anastomosis of a pancreaticogastrostomy.     

Surgical treatment of thoracic aortic aneurysm in patients with concomitant coronary artery disease

Objective: Surgical treatment of thoracic aortic surgery in patients with coronary artery disease was investigated. Methods: Between 1990 and April 2003, 330 patients underwent elective thoracic aortic surgery. Fifty-six patients who underwent aortic root reconstruction were excluded and 274 patients were examined. Fifty-four (20%) patients showed concomitant coronary artery disease. Ten had undergone coronary revascularization previously; and 3 underwent coronary revascularization [2 coronary artery bypass grafting (CABG), 1 percutaneous transluminal coronary angioplasty (PTCA)] before aortic surgery. Twenty-three patients underwent elective CABG simultaneously and 2 patients had additional coronary artery bypass because of cardiac ischemia during operation. The number of patients who underwent thoracic aortic surgery including Asc Ao+AVR was 2, hemi arch 1, total arch 15, distal arch 5, distal arch+LV aneurysmectomy 1, and thoracoabdominal Ao 1. Two patients underwent coronary revascularization with arterial grafts and the others with SVG grafts. Results: There was one hospital death (4%). In patients without coronary bypass, 2 patients suffered cardiac ischemic events. Conclusion: Our thoracic aortic operations with concomitant CABG using SVG were overall successful. Our current strategies for thoracic aortic surgery in patients with concomitant coronary artery disease include conducting a dipyridamole myocardial perfusion-imaging test first in patients not at risk of coronary artery disease, and if the test is positive, coronary angiography is performed and aggressive coronary revascularization is conducted where possible.     

Significant Clinical Differences in Primary Hyperparathyroidism Between Patients with and Those Without Concomitant Thyroid Disease

Purpose We evaluated the differences in diagnosis and treatment for primary hyperparathyroidism (pHPT) in patients with and those without concomitant thyroid disease.Methods One hundred and ten patients with pHPT underwent parathyroid localization and thyroid examination by ultrasonography (US) and sestamibi scintigraphy (MIBI). The clinical and biochemical findings, parathyroid localization, and operations performed were compared in 49 patients without thyroid disease and 61 patients with thyroid disease.Results Asymptomatic hypercalcemia was significantly more prevalent in patients with concomitant thyroid disease (88.5%) than in those without thyroid disease (49.0%) (P < 0.01). The mean serum calcium was significantly higher and the inorganic phosphate level was significantly lower in patients without concomitant thyroid disease than in those with concomitant thyroid disease (P < 0.05, P < 0.01, respectively). The pathologic parathyroid gland was identified significantly more often in patients without concomitant thyroid disease than in those with concomitant thyroid disease both by US and MIBI (P < 0.05). Unilateral exploration was performed more often in patients without thyroid disease than in those with thyroid disease (P < 0.01).Conclusion Primary hyperparathyroidism was diagnosed at an earlier stage in patients with concomitant thyroid disease. Thyroid disease concomitant with pHPT influenced parathyroid localization as well as the indication for minimally invasive parathyroidectomy.     

Thyroid evaluation in patients with primary hyperparathyroidism

We evaluated the efficacy of preoperative high-resolution ultrasonography (US) for diagnosing possible concomitant thyroid disease which affects the surgical management in patients with primary hyperparathyroidism (pHPT). One hundred and nine patients with sporadic pHPT underwent US with or without ultrasound-guided fine-needle aspiration biopsy (US-FNAB). Diagnosis of concomitant thyroid nodules by US and US-FNAB were compared with the histopathological findings. Of the 109 patients, 19 (17.4%) had malignant thyroid nodules, 26 (23.9%) had benign thyroid nodules alone, and 12 (11.0%) had diffuse goiter. The sensitivity, specificity, and accuracy of diagnosing 72 thyroid nodules were 91.3%, 91.8%, and 91.7% for US, 57.9%, 94.3%, and 81.5% for US-FNAB, and 95.7%, 91.8%, and 93.1% for combined US and US-FNAB, respectively. True positive/false negative ratio of US-FNAB diagnosis was significantly lower in nodules of 5-9 mm than nodules of 10 mm or more. Four unexpected thyroid cancers existed at a different site in 3 of the 39 patients with palpable thyroid disease. Five thyroid cancers were histopathologically confirmed in 5 (7.1%) of 70 patients without palpable thyroid disease. Eight (88.9%) of the 9 non-palpable thyroid cancers were accurately diagnosed by combined US and US-FNAB. Preoperative US is useful for evaluation of possible concomitant thyroid disease, especially for prediction of malignancy.     

13C enriched carbonate apatites studied by ESR: Comparison with human tooth enamel apatites

Conclusions The present ESR study on the¹³C enriched carbonate apatites suggested that the doublet signal of 146 gauss disposed on either side of the asymmetric signal is a hyperfine splitting due to¹³C. The doublet signal of 170 gauss which has been observed in enamel samples by several workers is tentatively attributed to another hyperfine splitting due to¹³C.     

Hepatic insulin resistance induced by chronic hindlimb ischemia

Peripheral vascular disease (PVD) has been reported to cause deterioration in insulin sensitivity. The precise mechanism of insulin resistance induced by PVD has not been clarified. To elucidate the mechanism causing impaired insulin action and glucose metabolism under peripheral ischemic conditions, we determined glucose turnover and glucose tolerance in hindlimb-ischemic (FAL) rats. The right femoral artery was ligated in hindlimb-ischemic (FAL) rats, while the artery was only exposed in the Sham operated (Sham) rats used as a control. Two weeks after the ligation, glucose tolerance was impaired and plasma insulin levels were significantly increased in FAL rats compared with Sham rats after intraperitoneal glucose loading (2 g kg(-1)). Under euglycemic hyperinsulinemic clamp conditions, the glucose infusion rate was significantly lower in FAL rats compared with Sham rats, but there was no significant difference in the glucose disappearance rate between the two groups. Hyperinsulinemia suppressed endogenous glucose production by 50% in Sham rats, while the suppression was 20% in FAL rats, indicating hepatic insulin resistance in FAL rats. mRNA analysis of isolated liver after the clamp experiment revealed that glucokinase mRNA, but not PEPCK and glucose-6-phosphatase mRNA, was significantly lower in FAL rats compared with Sham rats. In conclusion, chronic hindlimb ischemia impaired glucose tolerance associated with insulin resistance in the liver rather than the peripheral tissues.