Hiroto Mashiba

Significance of coronary artery tone in patients with vasospastic angina

To investigate the relation between basal coronary artery diameter and development of coronary artery spasm, the diameters of the proximal, middle and distal segments of the three major coronary artery branches, together with that of the left main trunk, were measured on a control angiogram and after ergonovine and nitrate administration in 30 patients with vasospastic angina without significant organic stenosis, and in 35 patients without ischemic heart disease. The percent change in coronary diameter after ergonovine and nitrate administration compared with the control diameter was used as an index of coronary vasoreactivity. In patients with vasospastic angina, coronary artery responses to both ergonovine and nitrate were greater in the spastic segments than in the other segments (p less than 0.05), and those of the coronary arteries without spasm were greater than those of the coronary arteries in patients without ischemic heart disease (p less than 0.01). There were no significant differences between the coronary artery diameters in the two groups after nitrate administration, and the control diameters were less in patients with vasospastic angina than in patients without ischemic heart disease. These observations indicate that a coronary vasomotion disorder, which involves increased basal coronary artery tone and hypersensitivity to vasoconstrictive stimuli, not only at a localized segment but also in the entire coronary artery tree, is present in patients with vasospastic angina. Clinically, evaluation of basal coronary artery tone may be useful for predicting the occurrence and location of coronary artery spasm.

Cause of Persistent Hypouricemia in Outpatients

We measured serum urate in 3,258 Japanese outpatients. Five of them had persistent hypouricemia. Three also had microhematuria. Four of the five patients were proven to have renal uricosuria with hypouricemia, but otherwise normal tubular function. When tested with both pyrazinamide and benzbromarone, 1 patient had a presecretory reabsorption defect, 2 had postabsorption defects, and 1 an enhanced renal tubular secretion of urate. These results suggest that persistent hypouricemia in outpatients is of very low incidence, is usually caused by an isolated metabolic error of urate transport, and is not related to drug ingestion or systemic disease.

A New Rapid Test for Detecting Anti–Helicobacter pylori Antibody Excreted into Urine

Background. Helicobacter pylori infection has been one of the most common infectious diseases in the world, whereas a gold standard for identifying its infection has not yet been established. The specific test will depend on the particular clinical, epidemiological, and scientific requirements. We recently developed a new type of rapid test to detect H. pylori antibody excreted into urine; the test requires only 20 minutes. The purpose of this study was to examine the accuracy of this rapid test.

Characteristics of 161 Patients With Cardiac Tumors Diagnosed During 1993 and 1994 in Japan

We investigated clinical and pathologic characteristics of 161 patients with primary or secondary cardiac tumors diagnosed between 1993 and 1994 in Japan. The increased use of cardiovascular imaging, especially echocardiography, contributed to the early identification of small cardiac tumors, resulting in a reduction of the serious complications such as embolization.

Lung Cancer Associated with Pulmonary Bulla

A few reports have suggested the possible association between lung cancer and bullous disease. We report a surgical case of lung adenocarcinoma located in close proximity to pulmonary bullae. A 48-year-old nonsmoker, asymptomatic male was found to have a pulmonary tumor mass and giant bulla in the right lung. Thoracotomy identified a tumor arising from a firm, scarred and contracted area close to the bulla wall. Based on this report and review of other cases in the literature, we emphasize the need for physicians to be aware of the potential development of lung cancer in patients with pulmonary bulla.

Mechanism of inhibition of the sodium current by bepridil in guinea-pig isolated ventricular cells.

1 Effects of bepridil, a sodium‐, calcium‐, and potassium‐antagonistic agent, on the Na+ current were studied by the whole cell voltage clamp technique (tip resistance = 0.5 MOhm, [Na]i and [Na]o 10 mmol T−1 at 20°C) 2 Bepridil produced tonic block (K drest = 295.44 μmol 1−1, Kdi = 1.41 μmol −1; n = 4) 3 Bepridil (100 μmol 1−1) shifted the inactivation curve in the hyperpolarization direction by 13.4 ±2.7 mV (n = 4) without change in the slope factor 4 In the presence of 50 μmol 1−1 bepridil, bepridil showed use‐dependent block at 2 Hz, whereas changes in pulse duration did not significantly effect this use‐dependent block (81% ±2% at 10 ms, 84% ±3% at 30 ms, 86% ±3% at 100 ms; n = 4) 5 After removal of fast inactivation of the Na+ current by 3 mmol 1−1 tosylchloramide sodium, bepridil (50 μmol 1−1) still showed use‐dependent block which was independent of the holding potential 6 The recovery time constant from the bepridil‐induced use‐dependent block was 0.48 s at holding potential of −100 mV and 0.51 s at holding potential of −140 mV 7 These results indicate that bepridil could bind to the receptor in the sodium channel through the hydrophobic and the hydrophilic pathway and leave the receptor through the hydrophobic pathway in the lipid bilayer. The binding and dissociation kinetics of this drug were shown to be fast, and the accumulation of the drug in the sodium channel appeared to be small. Bepridil is presumed to be safe in terms of adverse effects that result from drug‐accumulation in the sodium channel.

Response of sympathetic nervous system activity to exercise in patients with congestive heart failure.

Abstract. To investigate the serial sympathetic nervous system response to exercise, plasma norepinephrine (NE) and epinephrine (E) concentrations were measured at rest, during each stage of treadmill exercise, and immediately and 5 minutes after exercise in 68 congestive heart failure (CHF) patients (NYHA functional class I 24, II 25, III 19) and 30 normal subjects. Circulatory responses of NYHA class II patients increased at early stages of exercise. Systolic blood pressure and double product at peak exercise were significantly lower in NYHA class III patients. Plasma NE response of NYHA class I patients was similar to that of normal subjects. However, plasma NE at rest, and during and after exercise were significantly higher in NYHA classes II and III patients than in normal subjects and NYHA class I patients (peak NE (pg ml‐1); Normals: 547±37, I: 535±53, II: 867±87, III: 1033±157). There was no significant difference in plasma E levels among the four groups. NE response to exercise was augmented according to the severity of heart failure, which suggested compensatory activation of sympathetic nervous system activity. Circulatory responses were reduced in NYHA class III patients despite the exaggerated compensatory activation of the sympathetic nervous system. Blunted circulatory responses to increased NE concentration in NYHA class III patients might relate to a decreased cardiac responsiveness to sympathetic activity in severe CHF patients.

Evaluation of thyroid function in patients with isolated adrenocorticotropin deficiency

Thyroid hormone and thyrotropin (TSH) levels were evaluated before and after adrenal replacement in eight patients (six men and two women, 35-62 years old) with isolated adrenocorticotropin (ACTH) deficiency. Six patients (cases 1-6) showed TSH excess before treatment. Four patients (cases 1-4), who initially had subnormal thyroid hormone levels, showed resolution of biochemical features of primary hypothyroidism after treatment, although TSH excess has persisted in two patients (cases 1 and 2). Case 1 had an extremely high titer of antimicrosomal antibody (MCHA), and cases 2 and 3 showed histologically and cytologically chronic thyroiditis, despite negative results for MCHA and antithyroglobulin antibody, respectively. Two patients (cases 5 and 6), who had had normal thyroid hormone levels and did not show the significant rise in serum T3 in TSH releasing hormone testing, showed TSH normalization without changes in serum thyroid hormone levels after treatment. The other two patients (cases 7 and 8), who initially had normal TSH and thyroid hormone levels, did not show the significant changes in serum TSH and thyroid hormone levels after treatment. The prevalence of chronic thyroiditis coexistence in isolated ACTH deficiency may be higher than predicted. Therefore, TSH excess before adrenal replacement may be attributed to not only direct enhancement of TSH release due to chronic cortisol deficiency but also to thyroid dysfunction due to chronic thyroiditis. It is possible that hypothyroidism due to chronic thyroiditis can be improved only by adrenal supplementation.

Effect of β-hydroxybutyrate and acetoacetate on insulin and glucagon secretion from perfused rat pancreas

Abstract To elucidate the physiological significance of ketone bodies on insulin and glucagon secretion, the direct effects of β-hydroxybutyrate (BOHB) and acetoacetate (AcAc) infusion on insulin and glucagon release from perfused rat pancreas were investigated. The BOHB or AcAc was administered at concentrations of 10, 1, or 0.1 m m for 30 min at 4.0 ml/min. High-concentration infusions of BOHB and AcAc (10 m m ) produced significant increases in insulin release in the presence of 4.4 m m glucose, but low-concentration infusions of BOHB and AcAc (1 and 0.1 mM) caused no significant changes in insulin secretion from perfused rat pancreas. BOHB (10, 1, and 0.1 m m ) and AcAc (10 and 1 m m ) infusion significantly inhibited glucagon secretion from perfused rat pancreas. These results suggest that physiological concentrations of ketone bodies have no direct effect on insulin release but have a direct inhibitory effect on glucagon secretion from perfused rat pancreas.

Renal Hypouricemia Due to Enhanced Tubular Secretion of Urate Associated with Urolithiasis; Successful Treatment of Urolithiasis by Alkalization of Urine K+, Na+-Citrate

We encountered a case of hypouricemia with increases both in urate clearance (Cur) and in the ratio of Cur to creatinine clearance (Cur/Ccr), the normal daily urinary excretion of urate, and urolithiasis. Pyrazinamide markedly decreased Cur and Cur/Ccr, and both probenecid and benzbromarone markedly increased Cur and Cur/Ccr, however, benzbromarone did not increase either Cur or Cur/Ccr under pretreatment with pyrazinamide in the patient. Thus, the diagnosis was made of renal hypouricemia due to enhanced tubular secretion of urate. The urinary pH of the patient tended to be acidic. Three months after the start of alkalization of the patients urine by K+, Na(+)-citrate, both urolithiasis and the symptoms related to urolithiasis disappeared. These results suggest that renal hypouricemia due to enhanced tubular secretion of urate can result in urolithiasis and the alkalization of urine may be an effective treatment for uric acid stones.