Soluble VEGF receptor-2 may be a predictive marker of anti-angiogenic therapy with clinically available safe agents

The identification of biomarkers of anti-angiogenic therapy that predict clinical benefit is of vital importance. We previously reported that a combination treatment with clinically available safe agents, specifically angiotensin-converting enzyme inhibitor (ACE-I) and vitamin K (VK), inhibited the cumulative recurrence of hepatocellular carcinoma (HCC) via suppression of the vascular endothelial growth factor (VEGF). The present study aimed to identify non-invasive biological markers that predict the clinically beneficial effect of this combination regimen. A combination of ACE-I (perindopril; 4 mg/day) and VK (menatetrenone; 45 mg/day) was administered for 54 months following curative therapy for HCC. The cumulative recurrence and several indices, which are reportedly considered as biological markers of anti-angiogenic therapies, were analyzed. The combined treatment of ACE-I and VK markedly inhibited the cumulative recurrence of HCC during the 54-month follow-up. The serum VEGF and soluble VEGF receptor (sVEGFR)-2 were significantly suppressed with this combination regimen, whereas sVEGFR-1 was not. In HCC patients without recurrence, a significant suppression of VEGF and sVEGFR-2 was achieved within 6 and 3 months after treatment, respectively. In conclusion, the combination treatment of ACE-I and VK is a potentially novel anti-angiogenic strategy for secondary chemoprevention against HCC since the two agents are widely used in clinical practice without serious side effects. Furthermore, sVEGFR-2 may become a useful clinical predictive marker of this combination treatment.     

Bone tissue engineering with premineralized silk scaffolds

Silk fibroin biomaterials are being explored as novel protein-based systems for cell and tissue culture. In the present study, biomimetic growth of calcium phosphate on porous silk fibroin polymeric scaffolds was explored to generate organic/inorganic composites as scaffolds for bone tissue engineering. Aqueous-derived silk fibroin scaffolds were prepared with the addition of polyaspartic acid during processing, followed by the controlled deposition of calcium phosphate by exposure to CaCl(2) and Na(2)HPO(4). These mineralized protein-composite scaffolds were subsequently seeded with human bone marrow stem cells (hMSC) and cultured in vitro for 6 weeks under osteogenic conditions with or without BMP-2. The extent of osteoconductivity was assessed by cell numbers, alkaline phosphatase and calcium deposition, along with immunohistochemistry for bone-related outcomes. The results suggest increased osteoconductive outcomes with an increase in initial content of apatite and BMP-2 in the silk fibroin porous scaffolds. The premineralization of these highly porous silk fibroin protein scaffolds provided enhanced outcomes for the bone tissue engineering.     

Variant and invariant patterns embedded in human locomotion through whole body kinematic coordination

Step length, cadence and joint flexion all increase in response to increases in gradient and walking speed. However, the tuning strategy leading to these changes has not been elucidated. One characteristic of joint variation that occurs during walking is the close relationship among the joints. This property reduces the number of degrees of freedom and seems to be a key issue in discussing the tuning strategy. This correlation has been analyzed for the lower limbs, but the relation between the trunk and lower body is generally ignored. Two questions about posture during walking are discussed in this paper: (1) whether there is a low-dimensional restriction that determines walking posture, which depends not just on the lower limbs but on the whole body, including the trunk and (2) whether some simple rules appear in different walking conditions. To investigate the correlation, singular value decomposition was applied to a measured walking pattern. This showed that the whole movement can be described by a closed loop on a two-dimensional plane in joint space. Furthermore, by investigating the effect of the walking condition on the decomposed patterns, the position and the tilt of the constraint plane was found to change significantly, while the loop pattern on the constraint plane was shown to be robust. This result indicates that humans select only certain kinematic characteristics for adapting to various walking conditions.     

Ethical Issues in Psychotherapy

Abstract: The goal of psychotherapy is not only the dissolution of the symptoms, but also to attempt to bring about an improvement in adaptability and deepening the achievement of self-understanding. The nature of psychotherapy is based on the relationship between the therapist and patient. Such a goal and nature mean that some kinds of psychotherapy are beyond the medical model. In this paper ethical issues in psychotherapy are discussed as follows. 1) some complicated matters in informed-consent, 2) the hit or miss techniques of the poorly trained therapist, 3) the protection of privacy, 4) the sexual misconduct of therapists with patients, 5) special consideration for child-adolescent patients.     

Is It Safe to Initiate Selective Cerebral Perfusion with Normothermia?

OBJECTIVE: Preceding selective cerebral perfusion (P-SCP) is a method whereby SCP and systemic perfusion start simultaneously, and the arch vessels are clamped. Cerebral circulation is isolated from systemic circulation to avoid cerebral embolization due to detachment of atherosclerotic material from the aorta, caused by the "sandblasting" effect of high-velocity jets of blood exiting the aortic cannula. However, neither the safety of SCP at normothermia nor the influence of extended SCP time has been sufficiently clarified. To clarify the safety of P-SCP, the comparison study of P-SCP and conventional SCP (C-SCP) was performed retrospectively. METHODS: Fifty-seven patients (C-SCP group: 29 patients; P-SCP: 28 patients) underwent surgery between 1992 and 2002. RESULTS: Nine (15.8%) in-hospital death occurred; 4 in the C-SCP group (13.8%) and 5 in the P-SCP group (17.9%) (NS). The SCP time was 136.6 +/- 68.5 minutes in the C-SCP group and 195.8 +/- 30.7 minutes in the P-SCP group (p < 0.05). One patient in each group exhibited postoperative neurological dysfunction. CONCLUSION: It may be little dangerous to initiate the SCP with normothermia. P-SCP may be useful in cases in which there is pedunculated atherosclerotic material, or mural thrombus in the ascending and arch aorta.     

Application of a medium-energy collimator for I-131 imaging after ablation treatment of differentiated thyroid cancer

Purpose

High-energy (HE) collimators are usually applied for I-131 imaging after ablation treatment of differentiated thyroid cancer (DTC). However, purchase of HE collimators has been avoided in many nuclear medicine departments because the HE collimators are more expensive than other collimators. In this study, we compared the I-131 imaging using HE- and medium-energy (ME) collimators, which is more versatile than HE collimators.

Materials and methods

To simulate DTC patients with extra-thyroid beds, a phantom of acrylic containers containing I-131 was used. To simulate patients with thyroid beds, four phantoms representing extra-thyroid beds were arranged around the phantom representing normal thyroid tissues. Patients administered 1.11 or 3.70 GBq NaI-131 were also evaluated. Whole-body imaging and SPECT imaging of the phantoms and patients performed using HE-general-purpose (HEGP) and ME-low-penetration (MELP) collimators, and full-width at half maximum (FWHM) and percent coefficient of variation (%CV) were measured.

Results

In the extra-thyroid beds, FWHM and %CV with MELP were negligibly different from those with HEGP in whole-body imaging. Although FWHM with MELP was a little different from that with HEGP in SPECT imaging, %CV with MELP was significantly higher than that with HEGP. In the thyroid beds, only an extra-thyroid bed including higher radioactivity was identified in whole-body imaging with both collimators. Although SPECT images with MELP could not clarify extra-thyroid beds with low radioactivity, HEGP could identify them. In patients, although some whole-body images with MELP could not detect extra-thyroid beds, whole-body imaging with HEGP and SPECT imaging with both collimators could detect them.

Conclusions

Although HEGP is the best collimator for I-131 imaging, MELP is applicable for not only whole-body imaging but also SPECT imaging.     

PSEUDOMEMBRANOUS COLITIS COMPLICATING ULCERATIVE COLITIS

Clostridium difficile toxin (CD toxin) causes antibiotic‐associated colitis, or pseudomembranous colitis (PMC). Although CD toxin is sometimes found in the stools of patients with ulcerative colitis (UC), UC is rarely complicated by PMC. We report herein a case of PMC complicating UC, and present a review of the literature. A 71‐year‐old woman was diagnosed as having UC of the left colon, and treated with prednisolone and mesalazine. Later, however, lumbar spinal stenosis was also detected. After surgery for lumbar spinal stenosis, she suffered postoperative infection of the lumbar region. After 3‐week treatment with antibiotics, she developed diarrhea, bloody stools, and abdominal pain. Colonoscopy revealed PMC of the cecum, ascending colon, sigmoid colon, and rectum. Stools were positive for CD toxin. As cefotiam hydrochloride, levofloxacin hydrate (LVFX), and prednisolone were suspected as the causative agents, she was treated with 1.5 g vancomycin (VCM) daily for 2 weeks without ceasing LVFX. Her symptoms improved, and colonoscopy confirmed resolution of PMC. The possibility of PMC should be considered in UC patients treated with antibiotics, immunosuppressive agents or corticosteroids who complain of gastrointestinal symptoms. These patients should be thoroughly investigated by several modalities, including colonoscopy and CD toxin testing.     

Deletion of the M5 muscarinic acetylcholine receptor attenuates morphine reinforcement and withdrawal but not morphine analgesia

Little is known about the physiological roles of the M5 muscarinic receptor, the last member of the muscarinic receptor family (M1-M5) to be cloned. In the brain, the M5 receptor subtype is preferentially expressed by dopaminergic neurons of the substantia nigra and the ventral tegmental area. Dopaminergic neurons located in the ventral tegmental area are known to play important roles in mediating both the rewarding effects of opiates and other drugs of abuse and the manifestations of opiate/drug withdrawal symptoms. We therefore speculated that acetylcholine-dependent activation of M5 receptors might modulate the manifestations of opiate reward and withdrawal. This hypothesis was tested in a series of behavioral, biochemical, and neurochemical studies using M5 receptor-deficient mice (M5-/- mice) as novel experimental tools. We found that the rewarding effects of morphine, as measured in the conditioned place preference paradigm, were substantially reduced in M5-/- mice. Furthermore, both the somatic and affective components of naloxone-induced morphine withdrawal symptoms were significantly attenuated in M5-/- mice. In contrast, the analgesic efficacy of morphine and the development of tolerance to the analgesic effects of morphine remained unaltered by the lack of M5 receptors. The finding that M5 receptor activity modulates both morphine reward and withdrawal processes suggests that M5 receptors may represent a novel target for the treatment of opiate addiction.     

Primary small-cell carcinoma of the breast: a case report

We report a case of small-cell carcinoma of the breast. The patient was a 54-year-old Japanese woman with a left breast mass. Mammography revealed a 1.2-cm microlobulated mass with partially ill-defined borders. Ultrasonography disclosed a hypoechoic mass measuring 1.8 × 1.2 × 1.2 cm with heterogeneous internal echoes and partially ill-defined borders. The shape of the mass was round and taller than it was wide in the orthogonal section to the longest axis of the mass. These imaging findings suggested a malignant tumor. Fine-needle aspiration cytology of the tumor also suggested a ductal carcinoma. Breast-conserving surgery was performed with axillary sentinel lymph node biopsy. A diagnosis of small-cell carcinoma of the breast was made based on the histologic and immunohistochemical findings. This rare breast tumor has been reported to be aggressive and associated with a poor prognosis; however, our patient is currently well and has had no clinical recurrence of the disease after 5 years of follow-up without radiotherapy or chemotherapy. Therefore, the prognosis may be better if the tumor is detected early and there is an absence of lymph node metastasis.