Bezafibrate improves hypertension and insulin sensitivity in humans.

We examined cellular membrane fatty acid composition and insulin sensitivity in patients with mild essential hypertension and hyperlipidemia, and investigated whether bezafibrate, a lipid-lowering drug, could improve elevated blood pressure and insulin sensitivity in these subjects by ameliorating cellular membrane fatty acid composition. Twenty-seven subjects were recruited. Twelve men with mild essential hypertension [systolic blood pressure (SBP) between 140 mmHg and 160 mmHg] and hypertriglyceridemia (plasma triglyceride concentration over 150 mg/dl) were designated the HL group. Fifteen men with mild essential hypertension and normotriglyceridemia (plasma triglyceride concentration below 150 mg/dl) were designated the NL group. Subjects in the HL group were given bezafibrate 400 mg/dl and those in the NL group were given placebo for 3 months. Bezafibrate significantly reduced SBP (140 +/- 2.6 to 131.8 +/- 2.6 mmHg, mean +/- SEM), diastolic blood pressure (DBP) (87.8 +/- 2.0 to 82.8 +/- 2.6 mmHg), fasting plasma triglyceride concentration (225.5 +/- 23.5 to 102.9 +/- 10.9 mg/dl), fasting plasma insulin concentration (9.6 +/- 0.8 to 7.1 +/- 0.8 microU/ml), and homeostasis model assessment scores (HOMA-R, 2.4 +/- 0.2 to 1.7 +/- 0.2), and significantly improved the insulin sensitivity index (56.0 +/- 3.0 to 70.7 +/- 4.8 mg x l2/mmol x mU x min) in the HL group. Regarding erythrocyte membrane fatty acid composition, bezafibrate reduced the percentages of saturated fatty acids (SFA) and increased the percentage of polyunsaturated fatty acids (PUFA). Plasma triglyceride concentrations were positively correlated with HOMA-R (r = 0.50, p < 0.01) and SFA (r = 0.39, p < 0.05), and negatively correlated with PUFA (r = -0.45, p < 0.05) before administration of placebo or bezafibrate. In conclusion, an improvement of hyperlipidemia by bezafibrate may be attributed to reduction of blood pressure and amelioration of insulin sensitivity. Abnormalities in membrane lipid composition may play an important role in these metabolic disorders.     

Cell surface phenotype of in vitro proliferating lymphocytes in HTLV-I-associated myelopathy (HAM/TSP)

The in vitro proliferation of peripheral blood lymphocytes (PBLs) without any mitogenic stimulation is one of the hallmarks of human T lymphotropic virus type I (HTLV-I) infection. Recent evidence suggests a difference in the degree of the phenomenon between HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and asymptomatic HTLV-I carriers (AC). In this article, we demonstrated several alterations in the features of the in vitro transformed lymphocytes between patients with HAM/TSP (n = 16) and AC (n = 8). The percentages of total CD8+ and CD8+CD28+ cells were significantly increased in the in vitro proliferating T lymphocytes derived from the patients with HAM/TSP when compared to those from AC. HAM/TSP was segregated from AC by the high degree of the proliferation of CD8+CD28+ cells. The expression of HTLV-I-specific antigens on the cultured PBLs was detected only in the subjects which showed low CD8+CD28+/CD4+ ratio of the in vitro proliferating lymphocytes. These findings suggest that this phenomenon distinguishes HAM/TSP from AC, not only in quantity but also in quality.     

A case of primary hypothyroidism with repeated episodes of respiratory failure

A case of repeated episodes of hypoventilatory respiratory failure accompanied with primary hypothyroidism was reported. A 76-year-old woman was admitted to our hospital due to both disturbance of consciousness and respiratory failure. A diagnosis of primary hypothyroidism complicated with hypoventilatory respiratory failure deterioration due to respiratory infection was made. Supplemental therapy of thyroid hormones improved her general condition, but respiratory failure recurred after interruption of a replacement drug. Cases of unexplained respiratory failure should be differentiated from respiratory failure induced by hypothyroidism.     

Invasion of the skull base by carcinomas: histopathologically evidenced findings with CT and MRI

The depth and extent of the invasion of the skull base by a tumor are the most critical information for successful en bloc resection of the tumor. The only means available for the evaluation of these factors are CT or MRI images. In order to clarify the ability of these imaging modes to delineate the invasion of the skull base, preoperative images of ten patients who underwent en bloc resection of skull base tumors at Kobe University Hospital were compared with the histopathological findings of the resected specimens. CT proved to be superior to MRI for evaluating bone destruction of the skull base. On the other hand, MRI provided more useful information about intracranial invasion than CT. As a hypertrophic linear shadow on Gd-enhanced MRI represented dural invasion or thickened dura mater adjacent to the tumor, this technique should be taken into consideration to determine the dural resection. We concluded that preoperative evaluation of the depth of skull base invasion by both CT and Gd-enhanced MRI is essential for planning complete tumor resection.     

Genetic alteration in carcinoid tumors of the lung.

Surgically resected specimens of 13 carcinoid tumors of the lung including nine typical carcinoids and four atypical carcinoids, and eight salivary gland type carcinomas (six mucoepidermoid carcinomas and two adenoid cystic carcinomas) were analyzed regarding p53 expression, loss of heterozygosity (LOH) in chromosome 3p, 9p, and K-ras mutation. The overexpression of p53 was identified in four atypical carcinoid tumors, one mucoepidermoid carcinoma, and one adenoid cystic carcinoma, however, none of typical carcinoids showed p53 immunoreactivity. LOH in 3p14 was demonstrated in three of seven informative cases in all tumors. LOH in 9p was demonstrated in two of five informative cases in all tumors. Two of three cases with LOH at 3p14 had a poor prognosis, one of which also had LOH at 9p. No mutation of the K-ras gene was observed in any of these tumors. These data thus indicate that p53 overexpression might distinguish atypical carcinoid tumors from typical tumors and might therefore be useful as an adjunct modality in the differential diagnosis of pulmonary carcinoid tumors. The presence of LOH at 3p14 or 9p may thus help to identify lung cancer patients with a poor prognosis.     

A trial of semiquantitative analysis of whole body bone scintigraphy in renal osteodystrophy

Four color processed whole body bone scintigraphy with 99mTc-methylene diphosphonate was performed in six patients on maintenance hemodialysis, and the results of semiquantitative colorimetric analysis were compared with those of a normal group. The difference between the two (control and patient group) was statistically significant (P less than 0.01). Furthermore, the effect of 1 alpha-hydroxyvitamin D3 treatment on renal osteodystrophy was evaluated by this method. The results indicated that this method provides a useful method for assessing the response of renal osteodystrophy to treatment. Two representative cases of renal osteodystrophy are presented to illustrate the usefulness of this approach to semiquantitative whole body bone scanning.     

Rotational acetabular osteotomy for acetabular dysplasia of the hip with a giant acetabular bone cyst: a case report

In acetabular dysplasia of the hip joint accompanied by a giant acetabular bone cyst, rotational acetabular osteotomy may cause serious complications, such as bone necrosis after surgery or fracture of the fragile acetabulum during the operation. In a patient with this condition, we performed a two-stage operation: first, autogenous bone grafting supplemented with hydroxyapatite filling, then rotational acetabular osteotomy (after new bone formation had been assured). Radiographs and CT scans showed favorable fusion of the grafted bone. Some 18 months after the second operation, arthrograms showed no inflow of contrast medium from the articular cavity into the bone cyst region, although this had been observed before treatment. Thus, an effective remodeling of bony congruency was indicated in the mobile acetabulum 5 years after the second operation. This two-stage operation appears to be useful for correcting acetabular dysplasia accompanied by a giant bone cyst and to carry a reduced risk of serious complications, such as deterioration of the articular surface of the acetabulum or necrosis of the translocated acetabulum.     

Renovascular hypertension: a unique cause of unilateral focal segmental glomerulosclerosis.

A 48-year-old man presented with malignant hypertension and massive proteinuria. Renal angiography showed complete obstruction of the left renal artery and 99mTc-mercaptoacetylglycine (MAG3) renography showed a nonfunctioning left kidney. Percutaneous transluminal renal angioplasty of the left renal artery was unsuccessful; hence, the patient underwent left nephrectomy because of uncontrolled hypertension and proteinuria. Histological examination of a right kidney specimen revealed lesions of focal segmental glomerulosclerosis with benign nephrosclerosis. In contrast, histology of the left kidney showed typical ischemic kidney with hypertrophy of arteriolar smooth muscle cells. The patient responded favorably to the nephrectomy, as his blood pressure and urinary protein dramatically decreased with no antihypertensive medication. This case illustrates the heterogeneous effect of the renin-angiotensin system on either kidney in patients with renovascular hypertension due to unilateral renal artery stenosis.     

A case-control study of breast cancer among Japanese women: with special reference to family history and reproductive and dietary factors

Summary To study the effects of family history and reproductive, anthropometric, and dietary factors on the risk of breast cancer among low risk populations, we conducted a hospital-based case-control study involving 908 patients with breast cancer and their matched controls, in Japan. A positive family history of breast cancer significantly increased the risk of breast cancer (odds ratio = 1.52, 95% confidence interval: 1.14–2.03). The risk further increased with increasing number of family members affected. Obesity, single marital status, fewer births, a late childbirth, and less consumption of green-yellow vegetables and dairy products were also associated with an increased risk of breast cancer. These associations were independent in multivariate analyses. There was no increase in risk associated with consumption of high fat foods. When analyzed by menopausal status, the association with family history of breast cancer, especially in the first degree of relatives, was more evident for premenopausal breast cancer. The associations with obesity and lower consumption of dairy products were more pronounced for postmenopausal breast cancer, while those with lower parity and single marital status were stronger for premenopausal breast cancer.