Change in body image of patients with alcohol dependence during treatment process]

In order to find useful information for the establishment of new treatment method to alcohol dependence, we investigated the change of the body image of patients with alcohol dependence before and after the treatment. HABIT (Haga Body Image Test), a questionnaire about body image developed in department of psychiatry in Kyoto Prefectural University of Medicine, was used to examine the change of body image between pre- and post-3-month conventional treatment program in 46 patients with alcohol dependence hospitalized into special institutions for treatment of the disease in Kyoto. Patients with poor outcome of the treatment showed improvement of body image on visceral function, feeling of appetite and outward appearance, while patients with good outcome indicated no significant change in these aspects. This finding likely suggests that the treatment would result in good outcome in patients having stable feeling of physical health, and the cognitive treatment approach about these aspects of body image should be performed on the patients with poor treatment outcome. On the other hand, the body image about motor function showed significantly higher score in the patients approach for the patients with poor outcome to become aware of their physical activity would be effective.     

Lamivudine and IFN-beta sequential therapy in HBe antigen-positive patients with chronic hepatitis B virus genotype C infection.

Sequential treatment with lamivudine and interferon (IFN) has induced sustained biochemical and virologic responses in the majority of patients with chronic hepatitis B in France. However, the efficacy of sequential treatment in patients with chronic hepatitis B virus (HBV) genotype C infection has not been evaluated. Twenty-four HBe antigen-positive patients were treated with 100 mg lamivudine alone for 16-32 weeks, then with both 6 MU IFN-beta and lamivudine for 4 weeks, and lastly with IFN-beta alone for 20 weeks. Sustained response was achieved in 7 (29%) patients 24 weeks after the end of therapy. No lamivudine-resistant variants emerged in any patient. Hepatitis flare occurred in 3 patients after the withdrawal of lamivudine, but none had decompensation. The patients with sustained response were significantly younger at baseline (p = 0.033) and had a significantly lower HBV DNA level at the start of IFN (p = 0.020) than those without sustained response. In conclusion, the rate of response to sequential therapy with lamivudine and IFN in HBe antigen-positive patients with HBV genotype C infection was lower than the rate reported previously. Patients who were young or who had a favorable virologic response to lamivudine were more likely to have a sustained response.     

Association of HLA alleles with response (especially biochemical response) to interferon therapy in Japanese patients with chronic hepatitis C.

The response of chronic hepatitis C to interferon (IFN) treatment is classified as complete response (CR), biochemical response (BR), or no response (NR). Several studies have found no difference in prevention of hepatocellular carcinoma by IFN therapy between patients with CR and those with BR. We investigated whether specific human leukocyte antigen (HLA) alleles were associated with response to IFN, especially BR, in 138 patients with chronic hepatitis C. Comparing patients with and without CR, male, a low viral titer, genotype 2a or 2b, HLA-B55, and HLA-DRB1-0803 were more common in the group with CR. Multivariate analysis showed that age (adjusted odds ratio [OR], 0.95 by every year [95% confidence interval [CI] 0.90 - 0.99], p = 0.028), genotype 2a or 2b (5.21 [95% CI 1.63 - 16.6], p = 0.005), and low viral titer (8.58 (2.66 - 27.7), p < 0.001) were associated with CR. Comparing patients with BR and NR, the pretreatment alanine aminotransferase (ALT) level was lower in the BR group (p < 0.001). Both HLA-B7 and HLA-DRB1-0101 were more common in this group (p = 0.002). As the alleles HLA-B7 and HLA-DRB1-0101 were in linkage disequilibrium, the HLA-B7-DRB1-0101 haplotype may be associated with BR. Multivariate analysis indicated that a low ALT level (0.98 by every 1 IU/L [95% CI 0.98 - 0.99], p = 0.001) and HLA-B7-DRB1-0101 haplotype (32.3 [95% CI 1.50 - 693.1], p = 0.026) contributed significantly to BR. This study suggested that host HLA expression, but not viral factors, can influence BR.     

Large cell neuroendocrine carcinoma of the uterine cervix with cytogenetic analysis by comparative genomic hybridization: a case study

Large cell neuroendocrine carcinoma (LCNEC) of the uterine cervix is a newly introduced category of the revised World Health Organization classification. We reported a case of cervical LCNEC with cytogenetic analysis by comparative genomic hybridization (CGH). The cervical tumor showed moderately increased mitotic activity (8-14 mitotic figures per 10 high-power fields) and focal necrosis, which made it problematic to differentiate from atypical carcinoid. CGH analysis failed to detect chromosome 11q loss that has been reported to be characteristic of pulmonary atypical carcinoids. Furthermore, chromosome 3q amplification, which has been detected frequently in pulmonary small cell carcinomas and LCNECs but not in pulmonary typical and atypical carcinoids, was the most remarkable chromosomal aberration. Although CGH reports are extremely rare in neuroendocrine tumors of the uterine cervix, specific chromosomal aberrations may be useful in their distinction.     

Habitual Dietary Intake Affects the Altered Pattern of Gut Microbiome by Acarbose in Patients with Type 2 Diabetes

The aim of this research was to reveal the characteristics of gut microbiome altered by acarbose intervention in Japanese patients with type 2 diabetes (T2D) and its possible association with habitual dietary intake. Eighteen patients with T2D were administered acarbose for four weeks. The abundances of two major phyla, namely Actinobacteria and Bacteroidetes, were reciprocally changed accompanied by the acarbose intervention. There were also significant changes in the abundances of ten genera, including the greater abundance of Bifidobacterium, Eubacterium, and Lactobacillus and the lower abundance of Bacteroides in the group after the intervention than that before the intervention. Hierarchical clustering of habitual dietary intake was performed based on the pattern of changes in the gut microbiota and were classified into distinct three clusters. Cluster I consisted of sucrose, cluster II mainly included fat intake, and cluster III mainly included carbohydrate intake. Moreover, the amount of change in Faecalibacterium was positively correlated with the intake of rice, but negatively correlated with the intake of bread. The intake of potato was negatively correlated with the amount of change in Akkermansia and Subdoligranulum. Acarbose altered the composition of gut microbiome in Japanese patients with T2D, which might be linked to the habitual dietary intake.     

Lysosomal enzyme activities are decreased in the retina and their circadian rhythms are different from those in the pineal gland of rats fed an alpha-linolenic acid-restricted diet

The retinal rod outer segment (ROS) is shed and digested daily by phagosomes in retinal pigment epithelial (RPE) cells. We previously observed significantly fewer large phagosomes in rats fed an alpha-linolenic acid (ALNA)-deficient diet. Rats fed a safflower oil diet (ALNA-restricted) or a perilla oil diet (ALNA-sufficient) through two generations were adapted to a 24-h cycle with light from 0700 to 1900 h. They were killed at 0500, 0900, 1300 and 1700 h to determine the activities of four lysosomal enzymes in retina, including beta-glucosidase, beta-glucuronidase, hexosaminidase and acid phosphatase. The enzyme activities at 0500 h were the lowest and then increased gradually until 1700 h, exhibiting similar circadian rhythms in the two dietary groups. However, the activities at each time point were significantly lower in the safflower group. In the pineal gland, the activities were maximum at 1300 h, except for beta-glucosidase, and were not different between groups. These diets had qualitatively similar but quantitatively different effects on the fatty acid compositions of the retina and the pineal gland. These results indicate that decreased amplitudes in electroretinogram and altered size distribution of phagosomes, as induced by a restricted intake of ALNA, are associated with decreased lysosomal enzyme activities in the retina but not in the pineal gland.     

Pharmacokinetic interaction between sorafenib and prednisolone in a patient with hepatocellular carcinoma

Purpose

Sorafenib is primarily metabolized in the liver, by CYP3A4-mediated oxidation and UGT1A9-mediated glucuronidation. However, there is little information about the pharmacokinetic interaction of sorafenib. Here, we report a pharmacokinetic interaction between sorafenib and the CYP3A4 inducer prednisolone in a patient with hepatocellular carcinoma (HCC).

Patients and methods

The patient was a 72-year-old woman diagnosed with HCC. She was treated with sorafenib at 400 mg daily. On day 9, sorafenib was discontinued due to drug eruption. Nine months later, she was rechallenged with sorafenib at 400 mg daily concurrently with oral prednisolone. Prednisolone was started at 20 mg daily and was tapered by 5 mg every 14 days. We assessed the pharmacokinetics of sorafenib and its major metabolite M-2.

Results

The concentration of sorafenib was gradually increased following tapering of prednisolone. On day 56 after rechallenge, she developed G3 oral mucositis. At this time, serum trough concentrations of sorafenib and M-2 were at 5.9 and 1.1 μg/ml, respectively. Consequently, sorafenib dosage was reduced to 200 mg daily, and the oral mucositis was attenuated. The subsequent concentrations of sorafenib and M-2 obtained with a dose of 200 mg daily ranged from 1 to 3 μg/ml and from 0.1 to 0.4 μg/ml, respectively. Computed tomography scan showed a complete response of the liver tumor with no further recurrence of the rash.

Conclusions

We have demonstrated for the first time that prednisolone stimulates the sorafenib metabolism and that therapeutic drug monitoring could be useful during sorafenib therapy.     

Near‐infrared photoimmunotherapy through bone

Near‐infrared photoimmunotherapy (NIR‐PIT) is a molecularly targeted cancer phototherapy that is based on injecting a conjugate of a silicon‐phthalocyanine derivative, IRdye 700DX (IR700), and a monoclonal antibody that targets an expressed antigen on the cancer cell surface. Subsequent local exposure to NIR light results in the rapid and highly selective immunogenic cell death of targeted cancer cells. Because many cancers grow in bones through which light does not penetrate well, the goal of this study was to determine if NIR‐PIT can effectively treat cancers in bone. A bovine rib was used as a bone sample. Because the sample’s NIR light transmittance was shown to be approximately 4.52% in preliminary tests, it was hypothesized that a maximum radiation dosage of 128 and 1500 J/cm² would be sufficient to induce cell death in in vitro target cells and in vivo mouse tumor models, respectively. Cell viability was measured through bioluminescence studies comparing relative luciferase activity, as well as a cytotoxicity assay. In the in vitro model, tumor cell viability was significantly decreased after 64 and 128 J/cm² NIR light irradiation through the bone. An in vivo mouse tumor model also showed that 1500 J/cm² NIR light irradiation through the bone significantly reduced tumor viability at both 24 and 48 hours posttreatment compared to the control group (P = .026 and .040 respectively). Therefore, despite limitations in light transmission, NIR‐PIT nevertheless is capable of effectively treating cancers within bone.     

Response to antitumor agents of murine transplantable tumors implanted onto chorioallantoic membrane of chick embryo

The chorioallantoic membrane of chick embryo was used to examine the chemosensitivity of the murine tumors, B16-F1 melanoma, B16-F10 melanoma, Meth-A fibrosarcoma, and Ehrlich carcinoma. The tumors were grown on the membrane, and the effects of 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride, cyclophosphamide, dacarbazine, 5-fluorouracil, methotrexate, adriamycin, mitomycin C, vincristine, and cisplatin on the growth of the tumors were tested by iv injection into a vein of the chorioallantoic membrane or injection into the yolk sac. The use of chick embryo limits the time for drug exposure to 3 or 4 days, but Ehrlich carcinoma and Meth-A fibrosarcoma needed longer for the test; the use of irradiation from a cobalt source overcame the problem by increasing the growth rate of the grafts of these two tumors. There appeared to be a good correlation between the effects of the drugs on B16 melanomas grown in the eggs and in the original animals. Many compounds, including pro-drugs such as cyclophosphamide and dacarbazine, could be assayed in this way.