We studied non-hospitalized 30-69 y-old Japanese subjects to ascertain the influences of a 677C-T methylene-tetrahydrofolate reductase (MTHFR) genotype, nutri-tional intake and lifestyle-related factors on plasma homocysteine (Hcys) and serum folate concentrations. Hcys was higher and serum folate was lower in males than in females (p<0, 01). The Hcys concentration was higher in the VV group than in the AA and AV groups for both males and females. However, a relatively low serum folate concentration of 18±7 nmol/L was found in the entire male group as compared with 22±10 nmol/L in all females. In the female subjects, serum folate concentrations differed among MTHFR geno-types, being lowest in the VV group. In all male subjects, log folate intake per 1, 000 kcal was a significant positive predictor of log serum folate concentration (p<0.01), while in females the log vitamin C intake per standard body weight was a significant positive variable (p<0.001) predicting the log serum folate concentration. Smokers had significantly lower serum folate concentrations, regardless of dietary folate intake. High folate and vitamin C consumptions, appears to be beneficial to normal and heterozygous MTHF genotype sub-jects for maintaining serum folate concentrations. Even a 400μg daily intake of folate might be less than what is needed, especially for homozygous MTHFR subjects and smokers, to maintain an adequate serum folate concentration.
Chronic thromboembolic pulmonary hypertension (CTEPH) is a serious disease that induces hypoxemia and pulmonary hypertension, eventually leading to respiratory failure and right heart failure. We evaluated the results of surgical treatment in patients undergoing circulatory arrest under profound hypothermia.Between February 1995 and June 1999, 24 cases of CTEPH were surgically treated. The age of patients (11 males and 13 females) ranged from 21 to 71 years (mean 49+/-15 years). Because of hypoxemia, severe pulmonary hypertension (mean pulmonary artery pressure 45+/-7 mmHg ), and low cardiac output, the functional class of these patients was New York Heart Association (NYHA) III or IV. Following a median sternotomy, profound hypothermia was induced using cardiopulmonary bypass, and pulmonary thromboendarterectomy in the bilateral pulmonary arteries was performed under intermittent circulatory arrest. Surgery was performed emergently in four patients.Of these 24 patients, 2 of 20 patients who underwent elective surgery and 3 of 4 patients who underwent emergent surgery died in the hospital. Symptoms of CTEPH markedly improved in 18 patients who survived the surgery. Pulmonary arterial pressure was decreased to 16+/-6 mmHg, and cardiac output was increased.When CTEPH is resistant to medical treatment, surgical treatment is useful. When surgical indications are carefully selected, pulmonary thromboendarterectomy using intermittent circulatory arrest under profound hypothermia is quite effective for treating CTEPH.
In two studies on the same group of patients we evaluated noninvasive methods of assessing atherosclerosis and determined the effect of the new calcium channel-blocking agent monatepil on the progression of early atherosclerosis in humans. Computed tomography (CT) of the lower abdominal aorta and ultrasonography of the carotid arteries were used as noninvasive methods to determine the extent of atherosclerosis. To evaluate the CT images, we developed a new medical image analysis program. This enabled aortic calcification volume (ACV) to be quantified using plain CT images, and aortic wall volume (AWV) and aortic wall and calcification volume (AWCV) to be quantified from contrast CT images. Interobserver coefficients of variation of ACV, AWV, and AWCV (n = 8) were 4.7, 2.4, and 5.0%, respectively. In the monatepil study, the effect of the drug on serum lipid profiles was evaluated. Preliminary results show that shortly after monatepil administration, total serum cholesterol levels decreased significantly from 253.8 +/- 35.6 to 244.8 +/- 38.6 mg/dL (P < .009) and triglyceride levels tended to decrease. A positive correlation between the change in total cholesterol and changes in mean platelet volume was found (P = .028). Fasting immunoreactive insulin levels decreased in the four patients in which they were determined. Although this is a preliminary study, results indicate that CT of the lower abdominal aorta in combination with our new analysis program may be a precise, reproducible means of assessing early atherosclerosis. We have also shown that monatepil significantly decreases total cholesterol levels. However, the long-term effects of monatepil on the progression of atherosclerosis remain to be determined.
