[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.

Relationship between LDL receptor activity and development of coronary heart disease in Japanese cases with heterozygous familial hypercholesterolemia.

To assess the clinical significance of low density lipoprotein (LDL) receptor activity on the development of coronary heart disease (CHD) in patients with heterozygous familial hypercholesterolemia (FH), we determined the binding, internalization and degradation of 125I-LDL using skin fibroblasts from 66 Japanese cases with heterozygous FH over 30 years old. Although the LDL receptor activity showed a wide variation in the subjects with heterozygous FH, it negatively correlated with the serum LDL-cholesterol levels (r = -0.407, p less than 0.01 for internalization; r = -0.384, p less than 0.01 for degradation). There was no difference in the levels of serum total- and LDL-cholesterol between the CHD (+) (positive) and the CHD (-) (negative) groups, while the serum high density lipoprotein (HDL)-cholesterol level was lower in the CHD (+) group than in the CHD (-) group (p less than 0.01). The mean receptor activity (degradation) of the CHD (+) group was significantly lower than that of the CHD (-) group (p less than 0.05). Stepwise linear discriminant analysis disclosed that not the level of LDL-cholesterol but the LDL receptor activity could also be a discriminator of CHD in patients with heterozygous FH as well as age, serum HDL-cholesterol level and a smoking habit. In conclusion, LDL receptor activity of cultured fibroblasts may also be one of the factors involved in the development of CHD in patients with heterozygous FH.

A 31-year-old woman with homozygous familial hypercholesterolemia without significant lesions in the coronary 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.

Primary cortisol resistance accompanied by a reduction in glucocorticoid receptors in two members of the same family.

This report describes studies of a man suspected of having primary cortisol resistance. This conclusion is based on his high plasma cortisol levels and high 24-h urinary 17-hydroxycorticosteroid and cortisol excretion, plus the fact that he had no manifestations of Cushing's syndrome. Among family members tested, his mother also had hypercortisolemia. Both mother and son had high levels of unbound plasma cortisol, but their plasma ACTH concentrations were within the normal range. Both were partially resistant to dexamethasone adrenal suppression, and both had mild hypertension without hypokalemia. To study this apparent end-organ resistance to cortisol, we examined the glucocorticoid receptors in peripheral mononuclear cells. Using whole cell assays, glucocorticoid receptors in both patients were found to have reduced total binding capacity. We conclude that these two patients, members of the same family, have primary cortisol resistance accompanied by a reduced number of glucocorticoid receptors.

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.

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.

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.

Revaluation of the vectorcardiographic criteria in cases of myocardial infarction: a comparative study of the vectorcardiogram, the left ventriculogram and the scintigram.

The results of vectorcardiograms were compared with those of the left ventriculograms and scintigrams with thallium-201 in cases of myocardial infarction to confirm the vectorcardiographic criteria of the present authors. The percentage of agreement between the VCG and scintigram was 82.5% and higher than the percentage of agreement between the VCG and the left ventriculogram. The percentage of disagreement between the negative finding in the VCG and the positive finding in the scintigram was 5.1% and consequently, a close relation was found between the VCG and scintigram. However, as the possibility of infarction was high in cases in which the scintigram finding was positive, the vectorcardiographic criteria in cases in which the VCG findings were negative were rechecked and partially corrected. Consequently the percentage of negative findings were decreased to 3.2%. Our next step was to perform the following prospective study which confirmed that the disagreement found in the corrected criteria (1.0%) was in fact less than what had been observed in the initial criteria (5.0%). Accordingly, it can be concluded that the corrected vectorcardiographic criteria in myocardial infarction may be the more reliable and useful in determining the location of the infarcted area.