Effects of hypertension and type 2 diabetes mellitus on the risk of total cardiovascular events in Japanese patients with hypercholesterolemia: implications from the Japan Lipid Intervention Trial (J-LIT).

Hyperlipidemia, hypertension, and diabetes mellitus (DM) are well-established risk factors for cardiovascular disease. We analyzed the cardiovascular events in hyperlipidemic patients with or without DM who were administered open-labeled simvastatin in groups stratified by blood pressure level using data from the Japan Lipid Intervention Trial (J-LIT). Hyperlipidemic patients with DM (n=6,288) had significantly more cardiovascular events than those without DM (n=33,933). The incidence rates of total cardiovascular events in the Non-DM and DM groups were 15.40 and 25.76 per 1,000 patients for the 6-year period, respectively. The relative risk of total cardiovascular events in the DM vs. the Non-DM group was 1.68, and the relative risk was significantly higher in the DM than in the Non-DM group. The relative risks of total cardiovascular events were significantly higher in DM and Non-DM patients whose systolic blood pressure (SBP) was greater than or equal to 130 mmHg compared to that of Non-DM patients whose SBP was less than 130 mmHg, and in DM and Non-DM patients whose diastolic blood pressure (DBP) was greater than or equal to 80 mmHg compared to that of Non-DM patients whose DBP was less than 80 mmHg. In all groups stratified by SBP and DBP, relative risks of total cardiovascular events were higher in DM patients than in Non-DM patients. For patients with hypercholesterolemia and DM, blood pressure should be strictly controlled in order to prevent both coronary events and stroke. These results are in good agreement with the JNC 7 and the ESH/ESC guidelines for DM patients, which recommended that the SBP and DBP be less than 130 and 80 mmHg, respectively.     

Effect of systemic zinc administration on delayed neuronal death in the gerbil hippocampus

The divalent cation zinc has been reported to possess several physiological properties such as blocking apoptotic cell death through an inhibitory effect on Ca²⁺-Mg²⁺ endonuclease activity, or modulating the neurotoxicity via glutamate receptor subtypes. In the present study, we investigated the effect of peripherally injected zinc on delayed neuronal death seen in the hippocampus after transient global ischemia, in order to elucidate a possible beneficial role on zinc in ischemic neuronal cell death. Forty-five adult Mongolian gerbils of both sexes underwent transient bilateral clipping of the common carotid arteries for 3 min. In the pretreated animals, ZnCl₂ (20 mg/kg) was injected subcutaneously once, 1 h before ischemia (superacute group; n=6) or twice at 24 and 48 h before ischemia (subacute group; n=14). Histological survey was carried out 3 days later by in situ DNA fragmentation method and 4 days later by hematoxylin-eosin staining by semiquantatively counting dead neurons in the CA1 sector. Subacute zinc pre-administration significantly reduced the nuclear damage and subsequent neuronal death; however, superacutely pre-administered zinc did not protect hippocampal neurons against ischemia but it did not aggravate the effect of ischemia, either. The present study suggested that transfer of exogenous zinc into the intracellular space is required for neuroprotection, presumably via the anti-endonuclease activity.     

A case of embryonal carcinoma arising in the basal ganglia of the cerebrum]

The occurrence sites of intracranial primary germ cell tumors are most often the pineal and suprasellar regions. The histological type observed most frequently in these tumors is germinoma. Cases of embryonal carcinoma arising in the basal ganglia are rarely reported. To our knowledge, only 4 such cases have been previously reported in the literature. A case of an embryonal carcinoma arising in the basal ganglia is reported. A 17-year-old boy was admitted to our hospital on July 30, 1988 because of headache and vomiting, and a right hemiparesis. On admission, physical inspection showed no abnormalities and neurological examination revealed obtunded consciousness, a right central facial paresis and a right hemiparesis with Hoffman and Babinski reflexes. Noncontrast CT scan showed a large mass of low-to slightly high-density in the region of the left basal ganglia accompanied with midline shift and ventricular dilatation. Enhancement of the lesion was made by contrast CT scan. It was not homogeneous. Cerebral angiogram displayed a contralateral shift and an unrolling of the anterior cerebral artery, a lateral stretch of middle cerebral artery, a downward stretch of anterior choroidal artery and a tumor stain fed by the Heubner artery. On August 3, left frontotemporal craniotomy was performed. The tumor was totally removed in a piecemeal manner using microsurgical techniques. Histopathological diagnosis was mixed-type of germ cell tumor comprising embryonal carcinoma and teratoma. Postoperative CT scan showed complete disappearance of the tumor. A course of radiation of 4950 rads and two courses of a combination chemotherapy with cis-platinum, vinblastine and bleomycin were given within 3 months after the operation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Risk of basal cell carcinoma in relation to alcohol intake and smoking.

We prospectively investigated whether alcohol intake and smoking affect the risk of basal cell carcinoma (BCC) in subjects from the United States Radiological Technologists (USRT) cohort study. We evaluated 68,371 radiological technologists certified during 1926-1982 who were free of cancer at the time they answered a first questionnaire (1983-1989) and who completed a second questionnaire (1994-1998). The first questionnaire provided baseline information on numerous risk factors, including smoking and alcohol intake, and the second provided self-reported cancer diagnoses. During 698,190 person-years of follow-up, we identified 1,360 cases of BCC: 1,036 in women and 324 in men. Cox proportional hazards regression indicated that the trend in BCC was significantly associated with increased alcohol intake (P for trend = 0.001). Compared with those who reported no alcohol consumption, those who drank <1-2, 3-6, 7-14, and >14 drinks/week had multivariate risks of 1.1 [95% confidence interval (CI), 0.9-1.3], 1.3 (95% CI, 1.1-1.5), 1.4 (95% CI, 1.2-1.7), and 1.0 (95% CI, 0.7-1.6), respectively. We found no clear association between smoking and BCC. This is the second large prospective study to report a significant but nonmonotonic trend in increased risk associated with alcohol consumption.     

Relation between Estrogen Receptor and Malignancy of Thyroid Cancer

The relationship between the histological grade of dedifferentiation of thyroid cancer and estrogen receptors (ER) was examined immunohistochemically. Thyroid cancers were from postmenopausal females of almost the same mean age (69-73 years old) and within the same period of time (1974–1983). ER immunoreactivity located in the nucleus of the epithelium was found in all 6 well differentiated papillary cancers, and 5 of them (83.3%) showed ER-immunoreactive (ER-IR) cells amounting to 20 or more per visual field (x 100) under a light microscope. Of the 6 cases of poorly differentiated papillary cancer, 5 (83.3%) had 1-19 ER-IR cells per visual field. ER-IR cells were negative in 5 out of 6 cases (83.3%) of anaplastic cancers. Thus, the number of ER-IR cells tended to decrease with the degree of atypism of thyroid cancer (P < 0.001).     

Inhibition of IL-2 synthesis by donor-pecific suppressor T cells in a renal transplant recipient

Abstract A study was conducted to elucidate the mechanism of donor-pecific Mixed Lymphocyte Reaction (MLR and Cell Mediated Lymphotoxicity (CML) unresponsiveness in a renal transplant recipient with a long-term well-functioning kidney. The peripheral blood lymphocytes (PBL) of the recipient, who had not shown rejection since his transplantation 5 years previously, and those of his mother (donor), his father and two healthy third parties were examined. MLR, CML, semimicro MLR in a double chamber, interleukin-2 (IL-2) synthesis assay and limiting dilution assay were performed. This recipient showed donor-pecific MLR and CML unresponsiveness. IL-2 assay showed that the PBL of the recipient produced less IL-2 against the donor than against the father and the third parties. The addition of exogenous recombinant IL-2 (rIL-2; Takeda Co.) to the priming MLR caused a recovery of CML against the donor. A limiting dilution assay indicated that cytotoxic T cell precursor (CTLp) frequencies against the donor and father did not differ. The suppressor assay in a double chamber indicated that the PBL of the recipient stimulated by the donor PBL had a non-pecific suppressive effect on MLR, CML and IL-2 synthesis of the PBL across the Major Histocompatibility Complex (MHC) barrier. This suppressive effect was abolished by OKT3 or OKT8 monoclonal antibody and complement. Thus, the recipient had donor-pecific suppressor T cells that produced a humoral non-pecific suppressive factor only when stimulated by the donor PBL, and this factor suppressed PLR and CML by inhibiting IL-2 synthesis of the PBL.     

Inhibition of warm ischemic injury to rat liver, pancreas, and heart grafts by controlling the nutritional status of both donor and recipient

In this study, we tested the effect of donor fasting with or without the use of an essential fatty acids deficiency (EFAD) diet in the recipient using rat heart, pancreas, and liver transplant models. We then compared the survivals, tumor necrosis factor alpha (TNF-α) response, and white cell accumulation in rats in order to clarify the mechanisms of the beneficial effect of donor fasting and recipient EFAD. It was found that when the grafts were obtained from fasted donors and then transplanted into fed recipients, the survival rate was significantly higher for all three grafts than for those obtained from fed rats and transplanted into fed rats. The best survival was seen for pancreas grafts obtained from fasted donors and then transplanted into EFAD recipients. TNF-α secretion was significantly suppressed in both fasted and EFAD rats, and both the total cell count and neutrophil count were suppressed in EFAD rats. These results clearly indicate that in addition to liver grafts, both heart and pancreas grafts obtained from fasted animals are more tolerant to warm ischemic injury. Furthermore, the combination of donor fasting and recipient EFAD acts synergistically to inhibit the post-transplantation inflammatory reaction (through decreased TNF-α secretion and white cell accumulation), thus resulting in an improved survival.     

Quantitative analysis of the suppressive effect on the light rise of the hypertonic solution

We previously reported the hyperosmolarity response (a decrease of the ocular standing potential by hyperosmolarity) as a new clinical test of the retinal pigment epithelium (RPE) activity. In the present study a hypertonic solution (Fructmanit, 1.4 × 10³ m0sm/1) was intravenously injected for 20 min in proportion to a subject's total blood volume (TBV). At the injection speed of 5, 10, and 15% of the subjects' TBV per hour the mean amplitude of the hyperosmolarity response in normal subjects was 19.7, 30.1 and 36.4% respectively. The amplitude of the hyperosmolarity response depends on the logarithm of the dose of the hypertonic solution within the range of the dose tested.We previously found that hyperosmolarity suppresses the light rise. The present study investigated this suppressive effect in a quantitative manner. The light rise (a full-field illumination of 1.2 × 10³ cdl/m²) was dose-dependently suppressed by Fructmanit. The mean of the light rise to dark trough ratio in normal subjects was 1.81 with no osmotic stress, and 1.64, 1.41 and 1.29 respectively at the injection speeds of 5, 10, and 15%. The suppression of the light rise by hyperosmolarity is compatible with the view that the hyperosmolarity response and the light rise share the basal membrane of the RPE as the main site of their generation.