Nobu Hattori

Effects of Insulin on Vasoconstrictive Responses to Norepinephrine and Angiotensin II in Rabbit Femoral Artery and Vein

To determine whether insulin has a vasodilator action on the artery and vein, the effects of insulin at varying concentrations (120 μU/ml, 1.2 mU/ml, 12 mU/ml, and 120 mU/ml) on vasoconstriction by norepinephrine (NE) and angiotensin II (ANG II) were studied in the isolated rabbit femoral artery and vein. Helical strips were suspended in an organ bath filled with modified Krebs solution (pH 7.4), were gassed with 95% O2/5% CO2 at 36°C, and isotonic contractions were measured. Insulin significantly and dose dependently inhibited the vasoconstriction induced by NE (10−8 M for the artery and 10−7 M for the vein) at ≥1.2 mU/ml for both the artery and vein and the vasoconstriction induced by ANG II (3 × 10−10 M for the artery and 3 × 10−9 M for the vein) at ≥1.2 mU/ml for the artery and ≥12 mU/ml for the vein. The results indicate that insulin has an inhibitory effect on NE- and ANG II–induced contraction in both the artery and vein, and this appeared to be a contributory factor in the hypotensive effect observed in diabetic patients treated with insulin.

HLA Antigens in Japanese Patients with Primary Biliary Cirrhosis and Autoimmune Hepatitis

22 Japanese patients with primary biliary cirrhosis and 12 patients with autoimmune hepatitis were studied for HLA antigens. In the patients with primary biliary cirrhosis, HLA-DR2 showed a statistically higher frequency compared to the controls (68 versus 30%, chi 2 corr. = 7.660, p less than 0.007, p corr. less than 0.042, RR = 5.00). In the patients with autoimmune hepatitis, HLA-A10 showed a somewhat higher frequency compared to the controls (50 versus 19%, chi 2 corr. = 4.824, p less than 0.05, p corr. NS, RR = 4.36). In the DR locus, DR2 and DR4 showed tendencies toward increased frequency, but these were not statistically significant.

Growth of Hepatocellular Carcinoma into the Right Atrium: Report of Five Cases

Five patients had hepatocellular carcinoma growing into the right atrium. Clinically, all patients had edema in the legs, venous dilatation in the abdominal wall, ascites, and dyspnea. Paroxysmal aggravation of dyspnea and its alleviation by a left decubitus position were noted in three patients. Three patients developed shock after a change in posture. A gallop rhythm in the cardiac murmur was detected in two. Pathologically, all livers had hepatocellular carcinoma and macronodular cirrhosis. At autopsy, a tumor thrombus was found that completely occluded the right hepatic vein and extended into the inferior vena cava and right atrium, partially occluding the inferior vena cava. Antemortem diagnosis of right atrial tumor thrombi in patients with primary hepatocellular carcinoma is difficult, but the condition should be suspected when dyspnea, abnormal cardiac sounds, and shock develop.

Pharmacokinetics of famotidine, a new H2-receptor antagonist, in relation to renal function

SummaryThe pharmacokinetics of a new, potent H2-receptor antagonist, famotidine, 20 mg i.v. was studied in 7 subjects with normal renal function and in 24 patients with varying degrees of renal impairment. The volume of distribution at steady state was 1.14 l/kg in normal subjects and was not altered in renal failure. The half-life of elimination was 2.59 h in normal subjects and was unchanged in mild renal failure (creatinine clearance, CLCR 90–60 ml/min/1.48 m2) but was increased to 4.72 h in moderate renal failure (CLCR 60–30 ml/min/1.48 m2), and to 12.07 h in severe renal failure (CLCR below 30 ml/min/1.48 m2). The cumulative urinary excretion and renal clearance of famotidine were correspondingly reduced in patients with impaired kidney function. In normal subjects and in patients with mild to moderate renal failure, about 70% of famotidine was excreted through the kidney, mainly by tubular secretion. In patients with a CLCR above 60 ml/min/1.48 m2 the normal daily dose of famotidine can be employed, but in those with a CLCR between 60 and 30 ml/min/1.48 m2 the dose should be reduced by half, and in patients with a CLCR below 30 ml/min/1.48 m2 a reduction by three quarters of the normal dose is recommended.

Myotonic dystrophy: Ambulatory electrocardiogram, electrophysiologic study, and echocardiographic evaluation

Myotonic dystrophy is frequently associated with functional and anatomic derangements in the myocardium. Ten myotonic dystrophy patients (seven men and three women, ages ranging from 35 to 58 years) were evaluated with a 12-lead ECG, 24-hour Holter monitor recording, invasive electrophysiologic studies, and echocardiographic examination. Nine patients displayed abnormalities in the conduction system. ECG and Holter monitor abnormalities were first-degree atrioventricular block (n = 8), second-degree atrioventricular block (n = 1) (Wenckebach type), complete left bundle branch block (n = 2), left anterior fascicular block (n = 5), left posterior fascicular block (n = 1), sinus bradycardia (n = 6), sick sinus syndrome (n = 2), frequent premature ventricular complexes (n = 4), and ventricular tachycardia (n = 2). Electrophysiologic study abnormalities included AH interval less than or equal to 140 msec (n = 7), AH interval greater than 140 msec (n = 3), HV interval greater than 60 msec (n = 9), and ventricular tachycardia induction (n = 1). Echocardiographic examination revealed mitral valve prolapse (n = 6). We conclude that diffuse conduction abnormalities were seen in a majority of our patients with myotonic dystrophy. Ventricular arrhythmias, including ventricular tachycardia, were seen in some of these patients, and mitral valve prolapse was a frequent finding.

A multi-center double-blind controlled trial of ursodeoxycholic acid for primary biliary cirrhosis.

SummaryA multi-center double-blind controlled trial of ursodeoxycholic acid (UDCA) for treatment of primary biliary cirrhosis (PBC) was carried out. Twenty two and 23 patients were treated with 600mg/day UDCA and placebo, respectively, for 24 weeks. In UDCA - treated patients, fall of serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and gamma glutamyltranspeptidase activities started within 4 weeks after start of the trial and continued throughout the trial period. The serum IgM level fell in 7 UDCA-treated patients examined but not in 10 placebo-treated patients examined. Serum bilirubin concentration showed no significant change at the end of the study in either of UDCA- and placebotreated group of patients. There was no significant difference between these two groups with respect to the frequency of improvement of pruritus. In UDCA-treated patients, serum bile acid composition changed markedly, though its concentation showed no significant change. The percentage of total bile acid which ursodeoxycholic acid took up increased, whereas those which cholic acid, chenodeoxycholic acid and deoxycholic acid took up were decreased.

Effects of long-term prazosin therapy on lipoprotein metabolism in hypertensive patients

Prazosin administration caused a significant and continuous antihypertensive effect when given as a single agent for 12 months. The daily dose was stabilized after three months at 6.0 mg per day. After 12 months of prazosin treatment, high-density lipoprotein cholesterol increased by 17 percent (p less than 0.005) and the cholesterol ratio increased by 19 percent (p less than 0.05), but total cholesterol was not significantly changed. There were no statistically significant changes in triglycerides, plasma renin activity, and plasma aldosterone concentration following treatment when compared with baseline levels. Prazosin monotherapy is concluded to have favorable effects on serum lipids and can be considered suitable for long-term antihypertensive therapy.

Peripheral Circulatory Effects of Insulin in Diabetes

Peripheral circulatory effects of insulin were studied in the diabetic patients with and without autonomic neuropathy. Forearm blood flow, calf venous vol ume and calf venous distensibility were measured by strain gauge plethysmo graphy. In the diabetic patients with autonomic neuropathy, mean blood pres sure fell from 96±5 to 88±5 mmHg after an intravenous injection of 4 U of monocomponent insulin (p < 0.001). Forearm vascular resistance decreased from 53.99±8.29 to 45.88±7.76 mmHg•ml -1•100ml-1•min-1 after insulin (p < 0.01). Insulin increased calf venous volume from 1.20±0.19 to 2.23±0.44 ml/100ml (p < 0.05) and calf venous distensibility from 0.039±0.004 to 0.082±0.016 ml/mmHg (p < 0.05). In contrast, in the diabetic patients without autonomic neuropathy, there were no significant changes in the mean blood pressure, forearm vascular resistance, calf venous volume and calf venous dis tensibility. Symptoms of hypoglycaemia did not occur in any patient. These results suggest that insulin has a vasodilator action on both resistance and capacitance vessels, which may be one of the main factors in insulin-in duced hypotension.

Significance of IgA deposits on the glomerular capillary walls in IgA nephropathy.

Based on immunofluorescence findings, 232 patients with IgA nephropathy were classified into two groups; one consisted of 88 patients (38%) with IgA deposits in the glomerular capillary walls together with the mesangial deposits (capillary type), and the other consisted of 144 patients (62%) with deposits confined to the mesangium (mesangial type). Electron microscopic findings revealed dense deposits on the capillary walls (subepithelial, 50%; intramembranous, 65%; and subendothelial, 24%) in 37 of 46 patients with capillary type and six of 47 with mesangial type (P less than .001). Crescent formation observed in greater than or equal to 10% of glomeruli was more frequently found in patients with the capillary type (30/88, 34%) than those with the mesangial type (9/144, 6%) (P less than .01), especially higher in those with subepithelial deposits (15/26, 57%). The capillary type patients showed heavier proteinuria (1.7 +/- 0.2 g/d) than the mesangial type patients (0.6 +/- 0.1 g/d) (P less than .05). Thirteen of the 14 patients in an acute exacerbation phase, manifested by an abrupt increase in urinary protein and development of macroscopic hematuria, showed capillary type IgA deposits. The ratio of patients with normal renal function in the fifth year after apparent onset was lower in the capillary type (74.0%) than in the mesangial type patients (96.9%) (P less than .05). These findings suggest that capillary IgA deposition is closely related to clinical and histologic activities of IgA nephropathy and is considered to be an important factor responsible for the progression of the disease, possibly through crescent formation.

Primary biliary cirrhosis and chronic pancreatitis in a patient with ulcerative colitis.

A 65-year-old Japanese woman had primary biliary cirrhosis (PBC) and chronic pancreatitis associated with ulcerative colitis. The association of PBC and ulcerative colitis may prove to be valid.