Angiosarcoma of the breast: Report of a case and its findings of MRI

A 67-year-old woman with angiosarcoma of the left breast is presented. Physical findings showed a hard mass in the left breast with skin discoloration and erythema. Mammography showed a high density shadow in the mass without microcalcification and spicula. On ultrasonography, a hypoechoic mass with an ill-defined boundary was detected. On MRI, the tumor had low signal intensity on T1-weighted images, and higher signal intensity on T2-weighted images. MRI with Gd-DTPA images showed higher signal intensity on T1-weighted images with relatively lower intensity in the central area of the tumor. The artery supplying the tumor derived from the left inner thoracic artery and was visualized on three-dimensional dynamic MRI angiography. Initially misdiagnosed as inflammatory breast cancer, an arterial injection of CPA (100 mg) and 5-FU (500 mg) had been performed preoperatively. The definitive diagnosis of angiosarcoma was established by intraoperative frozen section examination. She underwent modified radical mastectomy and is now free of recurrence. This case emphasizes the difficulties in the clinical diagnosis of angiosarcoma of the breast.     

Low back load reduction using mechanical lift during transfer of patients]

In Japanese care-work sites, care-workers (CWs) have lacked basic health risk awareness for transferring patients. Knowledge of lifting equipment and skills for transfer of patients have not been disseminated and many CWs have suffered from work-related musculoskeletal disorders, especially low back pain (LBP). In order to find better ways of patient transfer which reduce and prevent LBP, we conducted a study of low back loads and operation time during the transfer of a simulated patient, who was totally dependent from bed to wheelchair, using a mechanical lift (Lift) and manual handling (handling). Moreover we examined the levels of skill which CWs had acquired in transfer by Lift and the effects of acquired skill on low back loads and operation time. We explored low back load using surface electromyography (EMG) of the lumbar paraspinals between L3 and L4 and the trunk inclination angle (TIA) measurement method. The subjects were 5 caregivers who performed the task of transferring a simulated patient from lying on the bed to sitting in a wheelchair using the Lift and by handling. Handling transfer was assisted by two-persons at the head and foot. A 'simulated' patient (a 70 kg healthy male; instructed to keep whole body relaxed) was used in all transfer tasks. When subjects used the Lift, we made an ergonomics checklist for reduction of low back load of caregivers. Subjects performed the task 4 times and were evaluated with the checklist. The level of acquired skill was significantly improved by the guidance of the checklist. TIA was observed to be significantly lower in Lift than in handling, but with EMG no significant differences were seen between Lift and handling. The effects of acquired skill on low back loads showed that TIA was statistically reduced at high skill as compared to low skill. However, there were no significant differences between both skills in Lift and handling by EMG. Operation time of Lift showed significant shortening of operation time with high skill as compared to low skill. Operation time of Lift was about 10 times longer than handling. Thus, we suggest that transfer by Lift is a valid way of reducing the burden on CWs low back. Additionally, this study found that for reduction of LBP risk for CWs, it will be important not only to use the Lift but also to observe proper procedure and raise CW skill levels in patient transfer.     

Three Cases with Cavitary Lesions in a Twin Gestation Complicated by a Single Intrauterine Fetal Demise

Three cases with cavitary lesions on the cerebral convexities in twin gestation complicated by a single intrauterine fetal demise were investigated clinicopathologically. They all exhibited profound mental retardation and severe motor disturbance due to rigidospastic tetraplegia. The co-twins were macerated. Neuropathologically, malformed lesions and destructive lesions coexisted in varying degrees according to the time in fetal life, at which insults probably occurred. The cavitary lesions were located bilaterally and symmetrically on the central, parietal and occipital region of the cerebral hemispheres, in some cases, including the frontal region. Case 1 showed an incomplete gyral pattern and porencephaly with polymicrogyria bordering the defect, thus allowing us to date the insult before the 5th fetal month. In case 2, multicystic encephalomalacia was disclosed with cortical dysgenesis exhibiting status marmoratus of the cortex. Case 3 displayed sclerotic cavitary lesions with sclerosis of the insula and a few instances of cortical dysgenesis. Based on the clinical data and pathological findings, the cavitary lesions of case3 may be dated in the third trimester of gestation. Case 2 can be considered to have sustained injuries between the times estimated for cases 1 and 3. As the pathogenesis of the congenital cavitary lesions, several concepts have been proposed: intrauterine DIC (Moore et al. 1969;Romero et al. 1984), vascular disruption (Hoyme et al. 1981;Jung et al. 1984), intrauterine infection such as cytomegalic inclusion disease (Friede et al. 1976), and hypoxia due to CO intoxication of the mother (Bank1 et al. 1967) or other cause. Though the pathological observation of our cases revealed no evidence of intrauterine DIC, renal cortic necrosis, intrauterine infection or occlusion of the intracranial vessels, long-term exposure to the dead twin might have contributed to the lesions of the liveborn co-twin.     

Protein binding of valproic acid in Japanese pediatric and adult patients with epilepsy.

The binding of valproic acid to serum proteins in pediatric and adult patients was studied. Serum samples were obtained from 48 Japanese pediatric patients with epilepsy (group A) and 48 Japanese adult patients with epilepsy (group B) receiving valproic acid monotherapy. The patients' age ranged from 1 to 15 years for the pediatric patients and from 18 to 44 years (group B--younger) and 45 to 63 years (group B--older) for the adult patients. The serum concentrations of total and unbound valproic acid were measured by fluorescence polarization immunoassay, and the unbound serum fraction of valproic acid was analyzed by ultrafiltration. The mean association constant, K, and total concentration of binding sites, n(P), were as follows: group A, K = 0.016 L/mumol, n(P) = 1077 microM; group B, K = 0.011 L/mumol, n(P) = 1365 microM; group B--younger, K = 0.013 L/mumol, n(P) = 1291 microM; and group B--older, K = 0.006 L/mumol, n(P) = 1827 microM. Significant differences between groups A and B were observed in the serum free fatty acid concentration and the serum concentration ratio of free fatty acids to albumin. However, no significant differences between the two groups were observed in the binding of valproic acid to serum proteins. Group A's serum concentration ratio of free fatty acids to albumin was significantly lower than in group B--older and was lower than in group B--younger. However, there were no significant differences in binding between group A and groups B--younger and B--older. The serum concentration of albumin was significantly higher in group B--younger than in group B--older. Consequently, there was a significant difference in binding between groups B--younger and B--older. The serum protein binding of valproic acid was similar in pediatric and adult patients with epilepsy, but binding characteristics differed between younger and older adults.     

Symmetrical hemispheric porencephalic cysts due to twin embolization syndrome: a case report]

Twin embolization syndrome (TES) is a complication of monozygotic twining following in utero demise of the co-twin. Passage of thromboplastic materials into the circulation of the surviving fetus results in ischemic structural defects of various systemic organs including the central nervous system (CNS). In our case of monozygotic twining prenatal sonography at the 18th week of gestation revealed intracranial abnormality and demise of the co-twin. Postnatal MRI demonstrates localized cerebral parenchymal defects (porencephalic cysts) in the bilateral hemispheres, which probably were the sequelae to the occlusion of the peripheral branches of the bilateral middle cerebral arteries. She developed physio-mental retardation and subsequently West syndrome. At the 6th months, right porencephalic cyst-peritoneal shunt was performed for progressive enlargement of the head. While the enlargement of the head was well controlled, no changes in her epileptic symptoms were noted. The development of generalized epilepsy in our case may indicate that the involvement of the CNS with TES in our case is not restricted to the porencephalic cysts and their surrounding areas.     

Relationship of periodontal infection to serum antibody levels to periodontopathic bacteria and inflammatory markers in periodontitis patients with coronary heart disease

Several reports have demonstrated a possible association of periodontal infections with coronary heart disease (CHD) by elevated antibody titre to periodontopathic bacteria in CHD patients compared with non-diseased controls. Although each periodontopathic bacterium may vary in virulence for periodontitis and atherosclerosis, antibody response to multiple bacteria in CHD patients has not been understood fully. Therefore, serum levels of antibody to 12 periodontopathic bacteria together with other atherosclerotic risk markers were compared among 51 patients with CHD, 55 patients with moderate to severe chronic periodontitis and 37 healthy individuals. The antibody response was the most prevalent for Porphyromonas gingivalis, a major causative organism, in CHD as well as periodontitis patients. However, antibody positivity was different between CHD and periodontitis if the response was analysed for two different strains of P. gingivalis, namely FDC381 and Su63. While periodontitis patients were positive for both P. gingivalis FDC381 and Su63, a high frequency of antibody positivity for P. gingivalis Su63 but not for FDC381 was observed in CHD patients. The results indicate that the presence of particular periodontopathic bacteria with high virulence may affect atherogenesis. Identifying the virulence factors of P. gingivalis Su63 may gain insight into the new therapeutic modality for infection-induced deterioration of atherosclerosis.     

In vitro activities of oral cephem and telithromycin against clinical isolates of major respiratory pathogens in Japan

The in vitro antibacterial activities of oral cephem antibiotics and ketolide telithromycin against major respiratory pathogens possessing beta-lactam-resistant mutations (within the pbp gene) and/or macrolide-resistant genes (erm and mef) were examined in clinical isolates collected at 66 institutes in all over the Japan between 2002 and 2003. Telithromycin showed the strongest antibacterial activity against methicillinsusceptible Staphylococcus aureus strains with and without macrolide-resistant genes, such as ermA or ermC gene. All the cephem antibiotics showed potent antibacterial activity against Streptococcus pyogenes, with minimum inhibitory concentrations (MICs) of 0.015 mg/L or lower. Cefdinir had a much higher MIC90 against genotypic penicillin-resistant Streptococcus pneumoniae (gPRSP) than cefditoren and cefcapene (8 mg/L cefdinir vs. 1 mg/L cefditoren and cefcapene). The majority of gPRSP harbored either ermB or mefA, and the antibacterial activity of telithromycin against these strains was decreased however some susceptibility was still sustained. Cefditoren exerted the strongest antibacterial activity against beta-lactamase-negative ampicillin-resistant Haemophilus influenzae, with an MIC90 of 0.5 mg/L. These results underline the importance of checking the susceptibility and selecting an appropriate antibiotic against target pathogens.     

Sensitization of TRPA1 by PAR2 contributes to the sensation of inflammatory pain

Proinflammatory agents trypsin and mast cell tryptase cleave and activate PAR2, which is expressed on sensory nerves to cause neurogenic inflammation. Transient receptor potential A1 (TRPA1) is an excitatory ion channel on primary sensory nerves of pain pathway. Here, we show that a functional interaction of PAR2 and TRPA1 in dorsal root ganglion (DRG) neurons could contribute to the sensation of inflammatory pain. Frequent colocalization of TRPA1 with PAR2 was found in rat DRG neurons. PAR2 activation increased the TRPA1 currents evoked by its agonists in HEK293 cells transfected with TRPA1, as well as DRG neurons. Application of phospholipase C (PLC) inhibitors or phosphatidylinositol-4,5-bisphosphate (PIP(2)) suppressed this potentiation. Decrease of plasma membrane PIP(2) levels through antibody sequestration or PLC-mediated hydrolysis mimicked the potentiating effects of PAR2 activation at the cellular level. Thus, the increased TRPA1 sensitivity may have been due to activation of PLC, which releases the inhibition of TRPA1 from plasma membrane PIP(2). These results identify for the first time to our knowledge a sensitization mechanism of TRPA1 and a novel mechanism through which trypsin or tryptase released in response to tissue inflammation might trigger the sensation of pain by TRPA1 activation.     

Preservation of the Characteristics of the Cultured Human Type II Alveolar Epithelial Cells

The human type II alveolar epithelial cells lost their specific characteristics during cultivation. We examined the ultrastructural and biochemical nature of the human type II cells cultured by two culture systems. To make a physiological alveoli model, the epithelial cells were seeded onto the cell culture insert and allowed contact with the air directly. The cells exposed to the air expressed polarity and immature lamellar bodies in their cytoplasm. Separately, the alveolar epithelial cells were cultured as spheroids to construct the three-dimensional condition. These cells expressed mature morphological characteristics as epithelial cells and lamellar bodies. The expression of the surfactant apoprotein-A (SP-A) and -C (SP-C) mRNA was compared in the cells cultured as a monolayer, the air exposed and the spheroids. SP-A mRNA was detected in all the cultured epithelial cells, but SP-C mRNA, a specific protein for the type II cells, was expressed only in the cells forming spheroids. The expression of uPA, one of the fibrinolytic enzymes, its receptor (uPAR) and its inhibitor-1 (PAI-1) were also examined. The epithelial cells exposed to the air and formed spheroids expressed a larger amount of uPA mRNA than the monolayer, although the amount of uPAR mRNA were comparable in these cells. The amount of PAI-1 mRNA significantly increased when the epithelial cells were exposed to the air. These results indicate that the type II alveolar epithelial cells induced and preserved their specific characteristics by taking the physiological three-dimensional structure, and these characteristics were partially restored by exposure to the air. Those findings suggest that the alveolar epithelial cells should be cultivated in three-dimensional form with contact to the air to regenerate an appropriate alveolar tissue.     

RhoA/ROCK pathway mediates p38 MAPK activation and morphological changes downstream of P2Y12/13 receptors in spinal microglia in neuropathic pain

Recent studies have indicated an important role of ATP receptors in spinal microglia, such as P2Y12 or P2Y13, in the development of chronic pain. However, intracellular signaling cascade of these receptors have not been clearly elucidated. We found that intrathecal injection of 2‐(methylthio)adenosine 5′‐diphosphate (2Me‐SADP) induced mechanical hypersensitivity and p38 mitogen‐activated protein kinase (MAPK) phosphorylation in the spinal cord. Intrathecal administration of P2Y12/P2Y13 antagonists and Rho‐associated coiled‐coil‐containing protein kinase (ROCK) inhibitor H1152 suppressed not only p38 MAPK phosphorylation, but also mechanical hypersensitivity induced by 2Me‐SADP. In the rat peripheral nerve injury model, intrathecal administration of antagonists for the P2Y12/P2Y13 receptor suppressed activation of p38 MAPK in the spinal cord. In addition, subarachnoidal injection of H1152 also attenuated nerve injury‐induced spinal p38 MAPK phosphorylation and neuropathic pain behavior, suggesting an essential role of ROCK in nerve injury‐induced p38 MAPK activation. We also found that the antagonists of the P2Y12/P2Y13 receptor and H1152 had inhibitory effects on the morphological changes of microglia such as retraction of processes in both 2Me‐SADP and nerve injured rats. In contrast these treatments had no effect on the number of Iba1‐positive cells in the nerve injury model. Collectively, our results have demonstrated roles of ROCK in the spinal microglia that is involved in p38 MAPK activation and the morphological changes. Inhibition of ROCK signaling may offer a novel target for the development of a neuropathic pain treatment. GLIA 2015;63:216–228