Sequential monitoring of serum IL-6, TNF-α, and IFN-γ levels in a CAEBV patient treated by plasma exchange and immunochemotherapy

We report the case of a female patient with chronic active Epstein?CBarr virus infection (CAEBV) accompanied by hemophagocytic syndrome (HPS). On admission, she presented with severe liver dysfunction and disseminated intravascular coagulation with elevation of serum IL-6, TNF-??, and IFN-?? levels. Plasma exchange (PE) followed by immunochemotherapy with prednisolone, cyclosporine A, and VP16 was performed. PE decreased serum cytokine levels dramatically and improved liver function. Following immunochemotherapy, CAEBV became inactive. Four months after discharge, however, CAEBV relapsed with HPS, and serum cytokine levels were extremely elevated again. There was no response to immunochemotherapy, and the patient died 1?day after admission. We examined the cytokines in five additional untreated-CAEBV patients and determined that they were elevated above the normal level in all patients. These results suggest that inflammatory cytokines may have roles in the development of CAEBV, and that their depletion can be an effective treatment for this disease.     

Factors affecting independence in eating among elderly with Alzheimer's disease

Aim: In elderly patients with dementia, disturbed eating behavior is understood to be a core symptom or a behavioral and psychological symptom of dementia (BPSD). The purpose of the present study was to investigate the factors affecting self‐feeding in elderly patients with Alzheimer's disease (AD). Methods: A total of 150 AD patients who were hospitalized in dementia wards, or were residents of institutions or group homes were enrolled. The patients underwent an eating behavior examination, cognitive assessment, neurological examination and vital function tests. The eating behavior examination consisted of observation of the patients at mealtime. Items assessing eating behavior included the number of feeding cycles, stopping of eating or agitation and dysfunction. Results: Logistic regression analysis carried out to identify factors with a significant effect on decreased independence in eating were difficulty in beginning a meal (OR = 14.498, CI = 2.067–101.690), presence of dysphagia signs (OR = 5.214, CI = 1.031–26.377) and the severity of dementia (OR = 4.538, CI = 1.154–17.843). Conclusion: The present study is the first to generate objective data showing that difficulty in beginning a meal is a factor that hinders independence in eating in AD, in addition to the presence of dysphagia signs and the severity of dementia. Assisting AD patients in maintaining eating independence might be effectively achieved by eliminating environmental factors that interfere with beginning a meal, and by providing assistance that will promote beginning a meal. The present results show the necessity of developing effective methods for assisting elderly patients with AD. Geriatr Gerontol Int 2012; 12: 481–490.     

Visual acuity outcomes of anti-VEGF treatment for neovascular age-related macular degeneration in clinical trials

Japanese Journal of Ophthalmology - Anti-VEGF treatment for neovascular age-related macular degeneration (nAMD) has been evaluated in clinical trials. To select the best anti-VEGF drug and the best...     

Effects of metal cation doping in CeO2 support on catalytic methane steam reforming at low temperature in an electric field

Catalytic methane steam reforming was conducted at low temperature using a Pd catalyst supported on Ce_1−xM_xO₂ (x = 0 or 0.1, M = Ca, Ba, La, Y or Al) oxides with or without an electric field (EF). The effects of the catalyst support on catalytic activity and surface proton hopping were investigated. Results show that Pd/Al-CeO₂ (Pd/Ce_0.9Al_0.1O₂) showed higher activity than Pd/CeO₂ with EF, although their activity was identical without EF. Thermogravimetry revealed a larger amount of H₂O adsorbed onto Pd/Al-CeO₂ than onto Pd/CeO₂, so Al doping to CeO₂ contributes to greater H₂O adsorption. Furthermore, electrochemical conduction measurements of Pd/Al-CeO₂ revealed a larger contribution of surface proton hopping than that for Pd/CeO₂. This promotes the surface proton conductivity and catalytic activity during EF application.

Temperature dependence of electron/ion conductivity of Pd/CeO₂ and Pd/Al-CeO₂ under wet conditions with application of an electric field.     

Treatment When Prognostic Factors Do Not Match St. Gallen Recommendations: Profiling of Prognostic Factors among HR(+) and HER2(−) Breast Cancer Patients

Background

The St. Gallen consensus provides treatment recommendations for breast cancer based on prognostic factors. Although many patients’ prognostic patterns are not easily matched with the prognostic patterns listed in the St. Gallen consensus, there has been no systematic investigation reporting the gap between treatment recommendations and actual postoperative treatment choices in clinical practice.

Methods

Four hundred seventy-one patients with hormone receptor-positive [HR(+)] and human epidermal growth factor receptor type 2-negative [HER2(?)] breast cancer were analyzed. These patients were classified into either the “crisp treatment group” or “fuzzy treatment group” based on the definitiveness of postoperative treatment selection based on St. Gallen treatment recommendations. The patients in the fuzzy treatment group were further classified into strata in which patients within each stratum shared the same prognostic factor patterns with similar recurrence rates.

Results

A total of 87.3 % of HR(+)HER2(?) patients were designated to the fuzzy treatment group. Four prognostic strata were constructed according to the survival tree model, and revealed that patients with poor prognostic profiles tended to receive endocrine therapy with chemotherapy. This suggests that postoperative chemotherapy is useful, although there was no statistical significance.

Conclusions

We constructed prognostic profiles of patients in the fuzzy treatment group and examined the recurrence rates associated with two treatment regimens within each prognostic profile. These findings are exploratory, but they may be useful for planning prospective studies of the effectiveness of postoperative treatment regimens among patients with a heterogeneous combination of prognostic factors.     

The mitochondrial protein frataxin is downregulated in hemodialysis patients

Background

The mitochondrial protein frataxin regulates iron metabolism for heme and iron sulfur cluster synthesis in the mitochondria and could be associated with the regulation of oxidative stress. To clarify the expression of frataxin and its association with uremia, we evaluated the mRNA and protein levels of frataxin in the polymorphonuclear leukocytes (PMNLs) of patients on hemodialysis (HD).

Methods

Uremic patients on HD (n = 18) and healthy control subjects (n = 18) were investigated. PMNLs were isolated by differential centrifugation. The mRNA levels of frataxin in isolated leukocytes were quantified by TaqMan real-time polymerase chain reaction. Frataxin protein expression in the cell lysate was evaluated using SDS-polyacrylamide gel electrophoresis and Western blotting.

Results

The frataxin/glyceraldehyde-3-phosphate dehydrogenase mRNA ratio in PMNLs from uremic patients was significantly lower than that in control subjects. Frataxin protein expression in uremic patients was also significantly lower than that in controls. Multiple regression analysis showed that frataxin mRNA levels were independently associated with the serum levels of both the oxidative stress marker malondialdehyde and the proinflammatory cytokine tumor necrosis factor-α.

Conclusion

The downregulation of frataxin seems to be linked with uremic status, which is usually associated with chronic inflammation and the acceleration of oxidative stress. Mitochondrial iron regulation may play a role in several comorbidities and in the poor prognosis in uremic patients. Further investigation is needed to elucidate whether reduced frataxin levels are linked to the pathological status of uremic patients and whether uremic substances affect frataxin expression.     

Contiguous ABCD1 DXS1357E deletion syndrome: Report of an autopsy case

Contiguous ABCD1 DXS1357E deletion syndrome (CADDS) is a contiguous deletion syndrome involving the ABCD1 and DXS1357E/BAP31 genes on Xq28. Although ABCD1 is responsible for X‐linked adrenoleukodystrophy (X‐ALD), its phenotype differs from that of CADDS, which manifests with many features of Zellweger syndrome (ZS), including severe growth and developmental retardation, liver dysfunction, cholestasis and early infantile death. We report here the fourth case of CADDS, in which a boy had dysmorphic features, including a flat orbital edge, hypoplastic nose, micrognathia, inguinal hernia, micropenis, cryptorchidism and club feet, all of which are shared by ZS. The patient achieved no developmental milestones and died of pneumonia at 8 months. Biochemical studies demonstrated abnormal metabolism of very long chain fatty acids, which was higher than that seen in X‐ALD. Immunocytochemistry and Western blot showed the absence of ALD protein (ALDP) despite the presence of other peroxisomal proteins. Pathological studies disclosed a small brain with hypomyelination and secondary hypoxic‐ischemic changes. Neuronal heterotopia in the white matter and leptomeningeal glioneuronal heterotopia indicated a neuronal migration disorder. The liver showed fibrosis and cholestasis. The thymus and adrenal glands were hypoplastic. Array comparative genomic hybridization (CGH) analysis suggested that the deletion was a genomic rearrangement in the 90‐kb span starting in DXS1357E/BACP31 exon 4 and included ABCD1, PLXNB3, SRPK3, IDH3G and SSR4, ending in PDZD4 exon 8. Thus, the absence of ALDP, when combined with defects in the B‐cell antigen receptor associated protein 31 (BAP31) and other factors, severely affects VLCFA metabolism on peroxisomal functions and produces ZS‐like pathology.     

Development of photo-amino acid derivative reactivity assay: a novel in chemico alternative method for predicting photoallergy

Photoallergy test of cosmetics and several types of pharmaceutical substances is often necessary for obtaining approval from authorities. However, there are no official test guidelines for photoallergy evaluation. Therefore, we tried to establish a photoallergy test by utilizing an in chemico alternative sensitization method, amino acid derivative reactivity assay (ADRA). To determine the criteria for judging the photoallergy potential, photo-ADRA with or without photoirradiation was performed using 60 photoallergenic chemicals, and cysteine and lysine derivatives were detected using high-performance liquid chromatography either by absorbance or fluorescence measurement. The accuracy of prediction was 81.4% (48 of 59) and 80.0% (48 of 60) using the absorbance and fluorescence methods, respectively. However, as chemicals can breakdown into multiple chemicals during photoirradiation, the absorbance method often cannot perform accurate detection due to co-elution, whereas the fluorescence method can do this due to lack of co-elution. Moreover, all eight chemicals that were found to be negative or false-positive for photoirritation in the 3T3 neutral red uptake phototoxicity test were confirmed as positive for photoallergy using this method. Furthermore, we prepared three types of pseudo-mixtures where we added one photoallergen along with five nonphotoallergens and performed the photo-ADRA by the ultraviolet and fluorescence methods. The result of the fluorescence method was almost the same as that obtained with the use of a single photoallergen and hence the outcome was not affected by the mixture. Thus, this study not only showed a method of evaluating the photoallergy potential of a single chemical but also a mixture, making it useful as an in chemico photoallergy alternative test.     

Homogeneously enhancing breast lesions on contrast enhanced US: differential diagnosis by conventional and contrast enhanced US findings

Objective

To clarify the details of homogeneously enhancing lesions on contrast-enhanced ultrasonography (CEUS) and also to elucidate whether their differential diagnosis is possible.

Methods

Seventy-three homogeneously enhancing lesions on CEUS were retrospectively selected. Two radiologists first assessed conventional US findings alone in consensus to differentiate malignant vs. benign lesions. Then, qualitative and quantitative CEUS findings were analyzed to determine the useful findings for the differential diagnosis. Determined CEUS findings were applied to the indeterminate lesions based on conventional US findings to see whether CEUS can improve the diagnostic performance.

Results

There were 42 cancers (58 %) out of 73. Sensitivity and specificity using conventional US findings alone were 91 and 55 %, respectively. Among the CEUS findings tested, multivariate analysis revealed only the type 3 enhancement pattern, which indicates a larger enhancing area than the precontrast hypoechoic lesion, was related to malignancy (p < 0.05). By adding this information, however, no improvement was achieved in the diagnostic performance as determined by conventional US findings.

Conclusions

Approximately half of the homogeneously enhancing lesions on CEUS are malignant, and differentiation of malignant from benign lesions may be possible, at least to some extent, by meticulous assessment of the conventional US rather than CEUS findings.