Serial angiographic follow-up beyond 10 years after coronary artery bypass grafting.

BACKGROUND: The long-term prognosis and serial angiographic follow-up beyond 10 years in patients who underwent coronary artery bypass grafting (CABG) have not been fully studied in Japan. METHODS AND RESULTS: In the present study data from 71 patients who underwent CABG before 1992 were analyzed. Thirty patients had a saphenous vein graft (SVG) only group, and the remaining 41 had a left internal thoracic artery graft to the left anterior descending coronary artery (LITA) group; 6 patients died from malignancy, which was the most common cause of death after CABG. The major adverse cardiac events (MACE) were defined as cardiac death, Q-wave or nonQ-wave myocardial infarction, and congestive heart failure. The MACE-free rate was significantly higher in the LITA group than in the SVG group (p < 0.05). However, among the patients with an ejection fraction < 0.40, there was no significant difference in MACE-free rate between the 2 groups. The LITA patency rate was significantly higher than that for SVG (p < 0.05) and the SVG patency rate was lower in the patients with hyperlipidemia (p < 0.05); cholesterol-lowering therapy improved the SVG patency rate. CONCLUSION: The long-term outcome of CABG was favorable, particularly if using an arterial graft. Although the patency rate was lower for the SVG than LITA, the patient's lipid profile might be an important factor in the SVG patency rate.     

Repeated ambulatory monitoring reveals an evening rise in blood pressure in a Japanese population

Recent studies have revealed 2 peaks in the onset of cardiovascular events, 1 in the morning and another in the evening. We evaluated whether blood pressure (BP) also rises in the morning/evening and identified the determinants of evening BP rise using 24‐hour ambulatory BP monitoring for 7 consecutive days. We identified 2 BP peaks, 1 in the morning (0‐3 hours after waking) and 1 in the evening (9‐12 hours after waking). Subjects were subclassified according to the extent of evening BP rise: those in the top quartile (≥6.45 mm Hg, n = 34; ER group) vs all others. After adjustment for age, sex, and 24‐hour systolic BP, evening BP rise was associated with the use of antihypertensive medications [odds ratio (OR), 3.57; 95% confidence interval (CI), 1.46‐8.74; P = .01] and estimated glomerular filtration rate (OR, 0.96; 95% CI, 0.93‐0.99; P = .04), confirming its association with antihypertensive medication use and renal dysfunction.     

PAPILLARY CARCINOMA OF THE THYROID

Twenty-one papillary thyroid carcinomas (PTCs), grouped into predominantly papillary (14 cases), predominantly follicular (5 cases), and extremely follicular, i.e., follicular variant (2 cases) types, were studied in comparison with three cases each of follicular lesions including follicular carcinoma, follicular adenoma, adenomatous goiter and Graves'disease. Histochemical, im-munoperoxidase, and electron microscopic analyses demonstrated no remarkable differences between the predominantly papillary and predominantly follicular PTCs, but the presence of common characteristics distinct from those of the follicular lesions. These two types of PTCs showed less glycogen, more mucoid material, more epidermal keratin, less thyroid hormone with relative predominance of T₃ over T₄, and more interdigitating reticulum cells (IDCs) than most of the follicular lesions. Ultrastructurally, the tumor cells of these PTCs had markedly irregular nuclei, a vesicular chromatin pattern, and small basally located lysosomes, in contrast with the cells in the follicular lesions which had smooth round nuclei, more heterochromatin, and apical or dispersed lysosomes of various sizes. The follicular variant PTCs showed some mixed features, such as glycogen in the follicular portion and mucoid material in metastatic papillary foci, positive keratin and IDCs but greater amounts of thyroid hormone, and a rather intermediate type of ultrastructure with only mildly irregular but vesicular nuclei and large apical as well as small basal lysosomes. These findings cytologically support the WHO definition of papillary carcinoma that includes tumors with variable mixtures of papillary and follicular patterns. However, separate consideration may be necessary with regard to the follicular variant. ACTA PATHOL. JPN. 37: 1563-1579, 1987.     

Isolation and characterization of a digoxin transporter and its rat homologue expressed in the kidney

Digoxin, which is one of the most commonly prescribed drugs for the treatment of heart failure, is mainly eliminated from the circulation by the kidney. P-glycoprotein is well characterized as a digoxin pump at the apical membrane of the nephron. However, little is known about the transport mechanism at the basolateral membrane. We have isolated an organic anion transporter (OATP4C1) from human kidney. Human OATP4C1 is the first member of the organic anion transporting polypeptide (OATP) family expressed in human kidney. The isolated cDNA encodes a polypeptide of 724 aa with 12 transmembrane domains. The genomic organization consists of 13 exons located on chromosome 5q21. Its rat counterpart, Oatp4c1, is also isolated from rat kidney. Human OATP4C1 transports cardiac glycosides (digoxin, K(m) = 7.8 microM and ouabain, K(m) = 0.38 microM), thyroid hormone (triiodothyronine, K(m) = 5.9 microM and thyroxine), cAMP, and methotrexate in a sodium-independent manner. Rat Oatp4c1 also transports digoxin (K(m) = 8.0 microM) and triiodothyronine (K(m) = 1.9 microM). Immunohistochemical analysis reveals that rat Oatp4c1 protein is localized at the basolateral membrane of the proximal tubule cell in the kidney. These data suggest that human OATP4C1/rat Oatp4c1 might be a first step of the transport pathway of digoxin and various compounds into urine in the kidney.     

Simvastatin-tacrolimus and simvastatin-cyclosporin interactions in rats

The effect of simvastatin (SV)-tacrolimus (TL) and simvastatin-cyclosporin (CyA) interactions on creatine phosphokinase levels and renal and hepatic function were investigated in rats. Animals were divided into seven groups; (1) SV (150 mg kg⁻¹ oral) alone, (2) SV+TL (150 mg kg⁻¹ oral+0.5 mg kg⁻¹ intraperitoneal (i.p.)), (3) TL (0.5 mg kg⁻¹ i.p.) alone, (4) SV+CyA (150 mg kg⁻¹ oral+10 mg kg⁻¹ oral), (5) CyA (10 mg kg⁻¹ oral) alone, (6) control vehicle for oral administration, and (7) control vehicle for i.p. administration. A marked reduction in body weight and mortality was observed in the (SV+CyA) and (SV+TL) groups. Plasma creatine kinase levels in the (SV), (TL), (SV+CyA) and (SV+TL) groups, 7 days postadministration, were significantly higher compared with those before administration (p <0.05). The plasma urea nitrogen levels in the (TL), (SV+CyA) and (SV+TL) groups after 7 days of administration were significantly higher than those of the controls. In addition, a marked increase in the plasma levels of alanine and aspartate amino transferases were observed in the (SV+CyA) groups. © 1998 John Wiley & Sons, Ltd.     

Kinetics of hepatic transport of 4-methylumbelliferone in rats. Analysis by multiple indicator dilution method

Hepatic elimination of 4-methylumbelliferone (4-MU), which has been used as a model compound for conjugative metabolism, was studied by means of a multiple indicator dilution (MID) method in the isolated perfused rat liver. Using this method, three intrinsic hepatic clearances, CLint,inf, CLint,eff, and CLint,seq, which represent the influx, efflux, and sequestration processes, respectively, were obtained. When the dose was increased from a low dose (50 micrograms/rat liver) to a high dose (3000 micrograms/rat liver), the hepatic availability of 4-MU increased from 0.11 to 0.73. With increasing dose, the CLint,eff value increased approximately two times, while the CLint,seq value decreased to approximately one-third. The remarkable dose dependence of hepatic availability was due to nonlinearity in both CLint,eff and CLint,seq values. However, the CLint,inf value was almost independent of dose. The dose-dependent change in CLint,seq might be explained by the saturation of conjugative metabolism of 4-MU, while the increase in the CLint,eff value with increasing dose might be partly explained by the nonlinear tissue binding of 4-MU, since the tissue unbound fraction determined by an ultrafiltration method using liver homogenate increased approximately 1.5 times at higher concentration of 4-MU compared to that at lower concentrations. In addition, based on a comparison of the individual intrinsic clearances, i.e., CLint,inf, CLint,eff, and CLint,seq, the major determining process of the apparent hepatic intrinsic clearance of 4-MU is thought to be the sequestration process at the high dose. However, at the low dose, the membrane transport process (influx and efflux processes) as well as the sequestration process also determine the apparent hepatic intrinsic clearance.