Dotlike Hemosiderin Spots Are Associated With Past Hemorrhagic Strokes in Patients With Lacunar Infarcts

BACKGROUND AND PURPOSE: Dotlike hemosiderin spots ongradient-echo T2(*)-weighted magnetic resonance imaging of the brain have been histologically diagnosed as old microbleeds associated with small vessel disease (SVD). The authors hypothesize that the presence of many dotHSs may be correlated with the fragility of small vessels and the recurrence of SVD, including lacunar infarction and deep intracerebral hemorrhage (ICH). METHODS: To investigate how dotHSs are related to past history of SVD, the number of subcortical or deep dotHSs was investigated in 146 patients with lacunar infarctions (95 men, 51 women, age 38 to 90 [66.6+/-9.4] years). They were divided into 2 subgroups according to history of deep ICHs or lacunar infarctions. The odds ratio (OR) for past history was estimated from logistic regression analyses with the number of subcortical or deep dotHSs as well as other factors. RESULTS: Of 146 patients with lacunar infarctions, 11 had past symptomatic ICHs and 19 had past symptomatic lacunar infarctions. An elevated rate of history of ICH was found for lacunar infarction patients with many deep dotHSs (>or=3; OR, 9.1; 95% confidence interval, 1.6-51, P=.015). However, history of lacunar infarction was not significantly associated with the number of subcortical or deep dotHSs. CONCLUSIONS: Our findings suggest that many deep dotHSs on T2(*)-weighted magnetic resonance imaging may be correlated with deep ICH-lacunar infarction type of SVD recurrence but not lacunar infarction-lacunar infarction type.     

Coexistence of amyotrophic lateral sclerosis and argyrophilic grain disease: A non‐demented autopsy case showing circumscribed temporal atrophy and involvement of the amygdala

We report a case of a 68‐year‐old right‐handed man with sporadic amyotrophic lateral sclerosis (ALS) and argyrophilic grain disease (AGD) having a 22‐month duration. His initial symptoms were dysarthria and swallowing difficulty at the age of 67. Subsequently bulbar palsy and pyramidal signs developed. His cognitive functions including face recognition, personality, and behavior were not changed compared with that of before the disease onset. However, magnetic resonance imaging disclosed severe right side‐predominant temporal atrophy. The neurological diagnosis was bulbar type ALS. Pathological examination disclosed histological evidence of ALS, including loss of Betz cells and lower motor neurons, corticospinal tract degeneration, and Bunina bodies. In addition, severe neuronal loss in the bilateral temporal cortex with an anterior gradient was found. Ubiquitin‐positive inclusions were encountered in the spinal anterior horn cells and hippocampal dentate gyrus, while few ubiquitin‐positive inclusions were noted in the affected temporal cortex. The amygdala, especially the basolateral nuclear group, was severely affected by neuronal loss with tissue rarefaction. Moderate neuronal loss was encountered in the parahippocampal gyrus, and to a lesser degree, in the ambient gyrus. Unexpectedly, many argyrophilic grains, coiled bodies, tau‐positive bush‐like astrocytes, pretangles, and ballooned neurons were found in the limbic system and temporal cortex. In the hippocampus, selective tau accumulation with minor neurofibrillary changes was observed in CA2 neurons. The present case suggests that (i) ALS and AGD do rarely coexist, and (ii) when ALS patients have severe temporal atrophy, not only ALS with dementia but also concurrent AGD should be considered in the differential diagnosis.     

HMG-CoA reductase inhibitor cerivastatin prolonged rat cardiac allograft survival by blocking intercellular signals.

BACKGROUND: The development of atherosclerotic cardiovascular complications caused by hyperlipidemia is a common and serious problem for long-term survivors of organ transplantation. However, adhesion molecules such as intercellular adhesion molecule (ICAM)-1 and lymphocyte function-associated antigen (LFA)-1 are involved in allograft rejection, possibly by providing costimulatory signals. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor cerivastatin has been shown to suppress ICAM-1 expression in acute inflammatory responses. METHODS: In this study, we evaluated the immunosuppressive effects of cerivastatin in rat cardiac allografts. The hearts of Fischer rats were transplanted heterotopically into Lewis rats. Cerivastatin (2 mg/kg) was administrated intraperitoneally to recipients for 7 consecutive days from the day before transplantation. RESULTS: Graft survival in the cerivastatin-treated group (n = 8) was significantly longer than in controls (n = 10) (24.6 +/- 2.2 days vs 10.2 +/- 1.3 days, p < 0.05). Mixed lymphocyte reaction (MLR) showed that on Day 8 after grafting, the proliferative response of alloreactive T cells against F344 alloantigen in cerivastatin-treated rats was significantly more suppressed than in Lewis rats. The Interleukin-2 concentration of supernatant in MLR cultures in the cerivastatin-treated group was lower than in the control group. Immunohistochemical analysis showed that the percentage of CD4-positive cells to infiltrating mononuclear cells was less prominent in the cerivastatin-treated group (9.8% +/- 2.2%) than in the control group (20.9% +/- 3.2%). CONCLUSIONS: The HMG-CoA reductase inhibitor cerivastatin effectively suppressed acute graft rejection, possibly by blocking intercellular signals via ICAM/LFA-1, and cerivastatin may be a candidate for treating patients with hyperlipidemia who undergo organ transplantation.     

Effects of trichostatins on differentiation of murine erythroleukemia cells

The fungistatic antibiotics trichostatins (TS) A and C were isolated from culture broth of Streptomyces platensis No. 145 and were found to be potent inducers of differentiation in murine erythroleukemia (Friend and RV133) cells at concentrations of 1.5 X 10(-8) M for TSA and 5 X 10(-7) M for TSC. Differentiation induced by TS was cooperatively enhanced by UV irradiation but not by treatment with dimethyl sulfoxide. This enhanced activity was completely inhibited by adding cycloheximide to the culture medium 2 h after exposure to TS, suggesting that TS are dimethyl sulfoxide-type inducers of erythroid differentiation. No inhibitory effect of TS was observed on macromolecular synthesis in cultured cells.     

UFT for head and neck cancers: its tissue concentrations and effects on lymphocyte subpopulations

Summary UFT, a combination of the masked compound of 5-fluorouracil (FT-207) and uracil, was given to head and neck cancer patients for 1 week preoperatively and for 8 weeks postoperatively. Drug concentrations were examined in the surgically removed tissues. The concentrations of FT-207, 5-fluorouracil, and uracil were higher in tumor tissues than in normal tissues. The lymphocyte subpopulations were assessed by cytofluorometry with monoclonal antibodies. There was no evidence that adjuvant chemotherapy with UFT specifically suppresses immunocompetent cells. We therefore conclude that further clinical evaluation of adjuvant chemotherapy with UFT would be worthwhile.     

Combined aortic valve replacement and coronary artery bypass grafting with in situ arterial grafts for porcelain aorta.

Patients with porcelain aorta carry a high risk of cerebral as well as systemic embolism during cardiac surgery. Here we describe a case of severe aortic stenosis and coronary artery disease combined with the circumferentially calcified aorta. The patient was a 77-year-old man who successfully received four coronary artery bypass grafts with in situ arterial grafts without clamping the aorta and aortic valve replacement. Aortic valve replacement and two distal coronary artery anastomoses to the left circumflex artery and obtuse marginal branch were performed under cardiac arrest during hypothermic perfusion with endoaortic balloon occlusion, followed by partial endarterectomy and closure of the aorta buttressed with bovine pericardium under deep hypothermic circulatory arrest. While rewarming, the other two distal coronary anastomoses to the left anterior descending artery and diagonal branch were done on the beating heart in order to minimize cardiac arrest time. On-pump beating heart coronary artery bypass grafting (CABG) can be useful especially for combined complex cardiac surgery.     

The association of diet, obesity, and breast cancer in Hawaii.

A case-control study of the association of dietary fat and animal protein consumption with breast cancer was conducted between 1975 and 1980 on Oahu, Hawaii. Data from this study were used to explore the relation of selected foods and the interaction of nutrients and foods with other factors, such as body size, age at menopause, and ethnicity on the risk for breast cancer. The sample included 272 postmenopausal breast cancer cases and 296 neighborhood controls. Study participants included Japanese and Caucasian women, aged 45 to 74, who were residents of Oahu. There was a suggestion of a positive-dose response relation (P < 0.01) between sausage consumption and the odds ratio for breast cancer. Significant odds ratios for breast cancer were also found for higher intakes (above the 50th percentile) of diary items, sausage, and all meats combined. The dose-response relation for nutrients and foods tended to be stronger among women with a high Benn's index (kg/cm1.5182) compared to women with a low Benn's index. In general, subjects with high dietary intakes of fat and animal protein who were in the upper 50th percentile of body size were at the greatest risk for breast cancer. However, there was no evidence for an interaction between the dietary variables and body size, ethnic group, age at menarche, age at menopause, or age at first birth that would affect the odds ratio for breast cancer. These data suggest that women with both a high intake of foods rich in fat and animal protein and with a large body size are at increased risk for breast cancer.     

Polymorphism of renin-angiotensin system genes in progressive IgA nephropathy

Summary: Clinical studies revealed that angiotensin converting enzyme (ACE) inhibitor reduces proteinuria and attenuates progressive decline in renal function in IgA nephropathy. Recent studies by us and others have demonstrated that the homozygote of the D allele (DD) of the ACE insertion/deletion (I/D) polymorphism is a potential risk factor for poor prognosis in IgA nephropathy, and that this deletion polymorphism predicts the therapeutic efficacy of ACE inhibition on proteinuria and, potentially, on progressive deterioration of renal function in patients with the nephropathy.