Expression of the TGF-β–ALK-1 Pathway in Dura and the Outer Membrane of Chronic Subdural Hematomas

Neovascularization of the outer membrane plays a critical role in the development and enlargement of chronic subdural hematomas (CSHs) and vascular endothelial growth factor (VEGF) may promote their progression. However, the precise mechanisms remain to be determined. We focused on the signaling pathway upstream of VEGF, transforming growth factor β (TGF-β), and activin receptor-like kinase 1 (ALK-1) to identify the mechanisms underlying the neovascularization of the outer membrane of CSH. Retrospective comparative study was conducted on 15 consecutive patients diagnosed as CSH with burr-hole drainage. Dura and the outer membrane were collected. We immunohistochemically examined the expression of VEGF, integrin-α, TGF-β, and ALK-1 on the outer membrane and dura of CSH and compared our findings with control samples and the signal intensity of hematomas on computed tomography (CT) scans. VEGF and integrin-α expression was markedly up-regulated in both the dura and outer membrane of CSH, the expression of TGF-β and ALK-1 in the dura was slightly increased in the dura and markedly up-regulated in the outer membrane. There was no significant correlation between their expression and CT density. Here we first report the expression of TGF-β and ALK-1 in the outer membrane and dura mater of CSH. We suggest that the TGF-β–ALK-1 pathway and VEGF affect neovascularization and the progression of CSH.     

Associations of Education With Overall Diet Quality Are Explained by Different Food Groups in Middle-aged and Old Japanese Women

BackgroundThe disparity of overall diet quality by personal educational attainment has been a public issue. However, it remains unknown which food groups contribute to the disparity. This cross-sectional study assesses which food groups explain associations between education and overall diet quality in Japanese women.MethodsA total of 3,788 middle-aged (mean age, 47.7 years) and 2,188 older women (mean age, 74.4 years), who lived in 47 prefectures in Japan, provided data on their education (low, middle, and high) and dietary intakes from a diet history questionnaire. A diet quality score (possible score 0–70) was calculated based on seven food components. Mean diet quality scores, with adjustment for lifestyle and neighborhood variables, were estimated by education using a general linear model, and Dunnett’s multiple comparison was conducted. Additionally, mean scores of each food component were estimated by education and compared using the same manner.ResultsAfter adjustment for lifestyle and neighborhood variables, mean diet quality score of high or middle education was higher than low education for both generations. Middle-aged women with high and middle education had higher scores of ‘milk’, ‘snacks, confection, and beverages’, ‘fruits’, and ‘vegetable dishes’ than those with low education. Older women with high and middle education had higher scores of ‘sodium from seasonings’ and ‘fruits’ than those with low education.ConclusionsThis study suggests that positive associations between education and diet quality are explained by different food groups in middle-aged and older Japanese women, which are independent of lifestyle and neighborhood variables.Key words: education, diet quality, Japanese     

Is acute subdural hematoma reduced during the agonal stage and postmortem?

The issue of proper use of postmortem computed tomography (PMCT) in forensic fields is currently being actively discussed. The PMCT image has specific findings that differ from the antemortem image, and it is essential to understand and interpret postmortem changes in order to utilize PMCT properly. In this article, we present two cases of acute subdural hematoma (ASDH) in which images were obtained both ante- and postmortem. These images showed marked reduction of hematoma and diminishing midline shift between the agonal and postmortem periods, without evacuation of the hematoma. Attention should be paid to this phenomenon because key findings in determining cause of death could disappear if investigating the cause of death takes too long in cases that prove to be ASDH. In other words, this phenomenon potentially becomes a risk for misdiagnosis when we decide the cause of death without knowing the details of the circumstances of death.     

Cutaneous squamous cell carcinoma,thyroid cancer and Langerhans cell histiocytosis in a patient with X‐linked recessive Mendelian susceptibility to mycobacterial diseases with a nuclear factor‐κB essential modifier mutation

Nuclear factor (NF)‐κB essential modifier (NEMO), also known as IκB kinase subunit‐γ (IKKγ), is a pivotal molecule in the NF‐κB signaling pathway. Mutations of NEMO cause incontinentia pigmenti and X‐linked ectodermal dysplasia with immunodeficiency. Mendelian susceptibility to mycobacterial diseases (MSMD), which confers an almost selective predisposition to mycobacterial infection, is also caused by NEMO mutations. We herein report the first case of a patient with X‐linked recessive (XR) MSMD who developed cutaneous squamous cell carcinoma, thyroid cancer and Langerhans cell histiocytosis. The relationship between NEMO mutation and oncogenesis is discussed.     

Survey of Japanese dermatological vasculitis specialists on cases of cutaneous arteritis (cutaneous polyarteritis nodosa)

We developed a questionnaire to examine the findings of cutaneous arteritis among dermatological specialists experienced in vasculitis as certified by the Committee for guidelines for the management of vasculitis and vascular disorders of the Japanese Dermatological Association. We sent a questionnaire to 12 dermatological facilities identified through the revised Committee for guidelines for the management of vasculitis and vascular disorders of the Japanese Dermatological Association. Retrospective data obtained from 84 patients at the 12 dermatological facilities between 2012 January 2016 December were evaluated. The 84 patients were categorized into two groups, a systemic steroid treatment group (group 1, n = 52) and a no systemic steroid treatment group (group 2, n = 32). C-reactive protein in group 1 patients was significantly higher than that in group 2 patients. Frequency of fever, arthritis, myalgia- and peripheral neuropathy in group 1 was significantly higher than that in group 2. We propose that these symptoms could serve as early markers for the transfer from cutaneous arteritis to systemic polyarteritis nodosa. We further suggest that patients who are subsequently associated with cerebral hemorrhage and infarction, who are originally diagnosed as having cutaneous arteritis, could progress to systemic polyarteritis nodosa. The study demonstrated that it is important for dermatologists to detect these findings early in order to establish an accurate diagnosis and a timely treatment.     

Possible pro‐inflammatory role of heparin‐binding epidermal growth factor‐like growth factor in the active phase of systemic sclerosis

Heparin‐binding epidermal growth factor (EGF)‐like growth factor (HB‐EGF) is a member of the EGF family growth factors, which affects multiple aspects of the wound healing process such as epithelialization, wound contraction and angiogenesis. In our study, we measured the serum HB‐EGF levels of 51 systemic sclerosis (SSc) patients, which showed a significant increase compared with those of 20 normal subjects. Further analysis revealed a positive correlation between the HB‐EGF level and pulmonary ground‐glass score but no correlation between the former and pulmonary fibrosis score. Other findings include: a significant increase of serum sialylated carbohydrate antigen KL‐6 levels and significant shortness of disease duration in the diffuse cutaneous SSc patients with elevated HB‐EGF levels; and significantly higher HB‐EGF levels in the presence of Raynaud's phenomenon, in that of telangiectasia, and in the absence of contracture of phalanges in all SSc patients. We then evaluated HB‐EGF mRNA levels of fibroblasts harvested from skin samples of the SSc patients and those of foreskin‐derived fibroblasts treated with transforming growth factor‐β, both of which were significantly higher than each control. In conclusion, we speculate that HB‐EGF plays a pro‐inflammatory role in the active skin and lung lesions of SSc.     

A randomized trial of a primary care-based disease management program to improve cardiovascular risk factors and glycated hemoglobin levels in patients with diabetes

PURPOSE: To assess the efficacy of a pharmacist-led, primary care-based, disease management program to improve cardiovascular risk factors and glycated hemoglobin (A(1C)) levels in vulnerable patients with poorly controlled diabetes. METHODS: A randomized controlled trial of 217 patients with type 2 diabetes and poor glycemic control (A(1C) level >or=8.0%) was conducted at an academic general medicine practice from February 2001 to April 2003. Intervention patients received intensive management from clinical pharmacists, as well as from a diabetes care coordinator who provided diabetes education, applied algorithms for managing glucose control and decreasing cardiovascular risk factors, and addressed barriers to care. Control patients received a one-time management session from a pharmacist followed by usual care from their primary care provider. Outcomes were recorded at baseline and at 6 and 12 months. Primary outcomes included blood pressure, A(1C) level, cholesterol level, and aspirin use. Secondary outcomes included diabetes knowledge, satisfaction, use of clinical services, and adverse events. RESULTS: For the 194 patients (89%) with 12-month data, the intervention group had significantly greater improvement than did the control group for systolic blood pressure (-9 mm Hg; 95% confidence interval [CI]: -16 to -3 mm Hg) and A(1C) level (-0.8%; 95% CI: -1.7% to 0%). Change in total cholesterol level was not significant. At 12 months, aspirin use was 91% in the intervention group versus 58% among controls (P <0.0001). Intervention patients had greater improvements in diabetes knowledge and satisfaction than did control patients. There were no significant differences in use of clinical services or adverse events. CONCLUSION: Our comprehensive disease management program reduced cardiovascular risk factors and A(1C) levels among vulnerable patients with type 2 diabetes and poor glycemic control.