Kazuhiko Hirobe

Effects of probucol on homozygous cases of familial hypercholesterolemia

A marked reduction of serum cholesterol was obtained by treatment with probucol in heterozygous as well as in homozygous cases of familial hypercholesterolemia. A strict dietary regimen (low-fat, low-calories) intensified the hypocholesterolemic effect of the drug. The drug was also useful in diminishing the rebound of serum cholesterol after plasma exchange. Probucol reduced serum triglycerides in heterozygous cases of familial hypercholesterolemia, but there was a slight increase in triglycerides in homozygous cases. Treatment with probucol resulted in the regression of cutaneous and tendon xanthomas. Although it caused a decrease in HDL, it seems to be very effective in the treatment of familial hypercholesterolemia.

Noninvasive study of left ventricular performance in obese patients: influence of duration of obesity.

We studied the performance of the left ventricle in 35 obese patients by means of noninvasive methods, including echocardiography, carotid arterial pulse tracing, and phonocardiography. Patients were divided into two groups according to the duration of obesity: group 1 included patients who had been obese for less than 15 years, and group 2 comprised patients who had been obese for more than 15 years. There were no differences in the degree of obesity and cellularity of adipose tissue between two groups. Left ventricular dimension and wall thickness, stroke volume, and cardiac output were significantly greater in both groups of obese patients than in nonobese control subjects. Group 2 had a significantly increased end-diastolic dimension index (DdI, calculated as end-diastolic dimension/cube root of body surface area), stroke index (SI), and radius/wall thickness ratio (R/Th) of the left ventricle compared with group 1. Multiple regression analysis showed that DdI, SI, and R/Th correlated significantly with the duration of obesity. We conclude that alterations of cardiac performance in obese patients with left ventricular enlargement and wall thickening is attributed not only to the excess of body weight but also to the duration of obesity.

Coronary artery disease in heterozygous familial hypercholesterolemia

Serum lipids, lipoproteins and Achilles tendon thickness in 52 patients with heterozygous familial hypercholesterolemia (FH) were investigated in order to clarify what are the important factors for the development of coronary artery disease (CAD) in heterozygous FH patients. There were no significant differences in the average concentration of total cholesterol and triglyceride between the patients with and those without CAD. The HDL cholesterol (HDL-C) level was significantly lower in patients with CAD than in those without, and the HDL-C value was within the normal range in most of the patients with heterozygous FH, if not associated with CAD. Although most of the males aged over 50 years had CAD and a decreased level of HDL-C, many of the aged females were without signs of CAD. The HDL-C value of heterozygous FH patients with CAD was significantly lower compared with the age-matched group without CAD. The Achilles tendon was thicker in patients with CAD than in those without CAD, both for males and females, although it was less closely correlated with the incidence of CAD than HDL-C or the atherogenic index. A forecast concerning the development of CAD in heterozygous FH may be possible if we consider multiple parameters, such as HDL-C, atherogenic index, Achilles tendon thickness, etc.

A 31-year-old woman with homozygous familial hypercholesterolemia without significant lesions in the coronayry arteries

Cardiovascular complications were examined in a 31-year-old woman with homozygous familial hypercholesterolemia (FH) (LDL receptor defective type), who had had no clinical symptoms of coronary artery disease. She had delivered 2 children without any cardiac complications, and her exercise electrocardiogram showed no positive findings for ischemic heart disease. Coronary angiography showed no significant arterial lesions, and left ventriculography revealed good contraction of the left ventricle (ejection fraction: 67%). This is considered to be a very rare case of homozygous FH without significant lesions in the coronary arteries. This might be attributed at least in part to her dietary regimen consisting of a very low fat and low calorie diet, to the residual LDL receptor activity or to the low value of prothrombin time.

[7 years of annual mass screening for colorectal cancer in office workers--usefulness of 3-day RPHA method].

Immunological fecal occult blood test have been proved to be useful in the mass screening for colorectal cancer. Since 1986, we have started annual mass screening by the use of 3-day RPHA method and medical questionnaire for office workers over 40 yr old. During 7 yr, 261 out of 5386 examinees were testing positive for fecal occult blood, a test positive rate was 4.8% and 12 colorectal cancer (7: early, 5: advanced) were found. Among 12 cases, 10 were detected by positive results of RPHA test and 2 by questionnaires of symptoms or family history. The sensitivity and specificity of this method were calculated at 83.3% and 95.3% respectively. But as for advanced cancers, the sensitivity of this method was 100%. 75% of patients with colorectal cancer were over 55 yr old. The predictive value of positive test (PV) were much more higher in subjects with 2 or 3 times test positive (high risk group: PV = 14.3%) than in subject with only 1 time test positive (low risk group: PV = 0.6%). So it is considered to be reasonable that the high risk group (24% of total test positive) should be immediately undergone further examinations (Ba. enema or colonoscopy), and the low risk group should be undergone re-examinations of 3-day RPHA method. By this system, almost 50% of further examinations will be reduced. In conclusion, 3-day RPHA method with this further examination system is reasonable and efficient for screening of colorectal cancer in office workers, considering the high reliability in cancer detection and decreased further examinations.