MRI of influenza encephalopathy in children: value of diffusion-weighted imaging

PURPOSE: Our purpose was to describe the MR findings of influenza encephalopathy and assess the value of diffusion-weighted imaging for its diagnosis. METHOD: We examined a total of five patients diagnosed as having influenza encephalopathy or encephalitis by MRI, including diffusion-weighted imaging. We analyzed the conventional images and compared them with diffusion-weighted images. RESULTS: Abnormally hyperintense lesions of varying extent and location were noted on T2-weighted and fluid-attenuated inversion recovery images in the cortex and adjacent white matter in every case. They showed no contrast enhancement. Diffusion-weighted imaging demonstrated the lesions as areas of restricted proton diffusion more clearly than conventional imaging. CONCLUSION: Influenza encephalopathy is depicted as areas of T2 elongation having a rather nonspecific distribution. Diffusion-weighted imaging can demonstrate the lesions sensitively and serve as a valuable adjunct to conventional MRI.     

Reduced anxious behavior in mice lacking the CCK2 receptor gene.

Cholecystokinin 2 (CCK2) receptors have been implicated as mediators of anxiety in standard mouse models such as exploratory behavior both in black and white test boxes and in elevated plus-mazes. We investigated the role of the CCK2 receptor in anxiety by evaluating the behavior of mice lacking the gene for this receptor in these standard anxiety models (i.e., exploratory behavior in a black and white test box and exploratory behavior in an elevated plus-maze). In the black and white test box, mice lacking the CCK2 receptor gene showed significantly increased numbers of transitions between the boxes compared to control mice. In the elevated plus-maze, mice lacking the CCK2 receptor gene displayed significantly more head dips than control mice. These results suggest that mice lacking the CCK2 receptor gene are less anxious than normal mice.     

Clinical features and treatment outcomes of dedifferentiated and grade 3 chondrosarcoma: A multi‐institutional study

Chondrosarcoma is the second most common primary malignant bone tumor. In this multicenter study, we sought to evaluate the disease‐specific survival (DSS) and disease‐free survival (DFS), and prognostic factors in patients with dedifferentiated chondrosarcoma (DDCS) or grade 3 chondrosarcoma (G3CS) in Japan. We retrospectively investigated the treatment outcomes and prognostic factors in 62 patients with DDCS and 19 patients with G3CS at 15 institutions participating in the Japanese Musculoskeletal Oncology Group. We also clarified significant clinicopathological factors for oncological outcomes. In surgery for primary lesions aimed at cure, a histologically negative margin (R0) was obtained in 93% (14/15) of patients with G3CS and 100% (49/49) of patients with DDCS. The 5‐year DSS was 18.5% in patients with DDCS and 41.7% in patients with G3CS (p = 0.13). Local control was obtained in 80% (12/15) and 79.6% (39/49) of patients with G3CS and DDCS in the primary lesion after surgery with a wide surgical margin, respectively. In multivariate analysis, stage and no treatment/palliative treatment for the primary lesion were independent prognostic factors for DSS of DDCS, and age and no treatment/palliative treatment for DSS of G3CS. The 5‐year DFS rate was 22.8% in 26 patients with DDCS who did not receive adjuvant chemotherapy, and 21.4% in 14 patients who received adjuvant chemotherapy. The prognosis of DDCS remains poor, although R0 resection was carried out in most cases. Effective and/or intensive chemotherapeutic regimens or agents should be considered or developed for patients with high‐grade chondrosarcoma, particularly for those with DDCS.     

Phthalates rapidly increase production of reactive oxygen species in vivo: role of Kupffer cells

The role of oxidants in the mechanism of tumor promotion by peroxisome proliferators remains controversial. The idea that induction of acyl-coenzyme A oxidase leads to increased production of H(2)O(2), which damages DNA, seems unlikely; still, free radicals might be important in signaling in specialized cell types such as Kupffer cells, which produce mitogens. Because hard evidence for increased oxidant production in vivo after treatment with peroxisome proliferators is lacking, the spin-trapping technique and electron spin resonance spectroscopy were used. Rats were given di(2-ethylhexyl) phthalate (DEHP) acutely. The spin trapping agent alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone was also given and bile samples were collected for 4 h. Under these conditions, the intensity of the six-line radical adduct signal increased to a maximum value of 2.5-fold 2 h after administration of DEHP, before peroxisomal oxidases were induced. Furthermore, DEHP given with [(13)C(2)]dimethyl sulfoxide produced a 12-line electron spin resonance spectrum, providing evidence that DEHP stimulates (*)OH radical formation in vivo. Furthermore, when rats were pretreated with dietary glycine, which inactivates Kupffer cells, DEHP did not increase radical signals. Moreover, similar treatments were performed in knockout mice deficient in NADPH oxidase (p47(phox) subunit). Importantly, DEHP increased oxidant production in wild-type but not in NADPH oxidase-deficient mice. These data provide evidence for the hypothesis that the molecular source of free radicals induced by peroxisome proliferators is NADPH oxidase in Kupffer cells. On the contrary, radical adduct formation was not affected in peroxisome proliferator-activated receptor alpha knockout mice. These observations represent the first direct, in vivo evidence that phthalates increase free radicals in liver before peroxisomal oxidases are induced.     

Quercetin-induced PC12 cell death accompanied by caspase-mediated DNA fragmentation

Flavonoids have been reported to be potent antioxidants and beneficial in oxidative stress related diseases. Quercetin, a major flavonoid in food, deserves much attention because of its antioxidative activity. However, the actions of flavonoids including quercetin are complex and paradoxical. Quercetin caused apoptosis and/or cell death in various cells including cancer cells and normal cells. In this study, we investigated the effects of quercetin with or without hydrogen peroxide (H2O2) on cell death of PC12 cells, a neuronal cell line. We showed that quercetin at 10-30 microM alone caused cell death accompanied by caspase-mediated DNA fragmentation in undifferentiated PC12 cells. Quercetin did not inhibit and rather enhanced 0.1 mM H2O2-induced cell death. The toxic effect of quercetin was not inhibited by antioxidants such as N-acetylcysteine and GSH, although H2O2-induced cell death was inhibited by the antioxidants. Quercetin-induced cell death was reduced by 2 h treatment with nerve growth factor and serum. In addition, quercetin caused cell death in differentiated PC12 cells that were cultured with nerve growth factor for 6 d. Genistein, a soy isoflavone that has the pro-apoptotic activity, also caused cell death with DNA fragmentation. Further evaluation of the potential of dietary flavonoids as neuroprotective reagents is needed.     

A case of congenital high airway obstruction syndrome managed by ex utero intrapartum treatment: case report and review of the literature

Congenital high airway obstruction syndrome (CHAOS) has been reported to be fatal. Ten cases of CHAOS that underwent ex utero intrapartum treatment (EXIT) procedure to secure the fetal airway have been reported. A 36-year-old woman (gravida 3, para 2) was referred to our hospital at 22 weeks of gestation. Sonography revealed large echogenic lungs, flattened diaphragm, and marked hydrops. Magnetic resonance imaging confirmed the diagnosis of CHAOS. Polyhydramnios and fetal skin edema were improved and the fetal ascitic fluid was regressed gradually. At 36 weeks of gestation, an EXIT procedure was undertaken. Fetal laryngoscopy and bronchoscopy showed complete laryngeal obstruction, and a tracheostomy was performed immediately. The infant was discharged from hospital at 6 weeks of age. Thereafter, he developed well both physically and mentally. A laryngoplasty was performed at 20 months of age using silicon sheet as a patent airway. The child has a tracheostomy, is able to phonate but does not speak, and is awaiting decannulation. Use of the EXIT procedure in CHAOS cases offers the potential for salvage and excellent long-term outcome of these fetuses that otherwise would not survive. However, management of the airway, particularly with regard to long-term reconstruction in children with CHAOS, remains challenging.     

Association between maternal gestational diabetes mellitus and high‐sensitivity C‐reactive protein levels in 8‐year‐old children: The Yamanashi Adjunct Study of the Japan Environment and Children’s Study (JECS)

Gestational diabetes mellitus (GDM) is one of the most common pregnancy‐related complications; it is associated with adverse pregnancy outcomes and metabolic disorders in offspring, consistent with the concept of the developmental origins of health and disease. This cohort study of women without diabetes (n = 761), who were part of the Yamanashi Adjunct Study of the Japan Environment and Children’s Study, aimed to explore the associations between maternal GDM and their offspring’s level of high‐sensitivity C‐reactive protein (hsCRP), a biomarker of inflammatory and cardiovascular diseases. We analyzed the associations between GDM and the offspring’s hsCRP levels using a multiple logistic regression model. A mother with GDM significantly increased the risk for high hsCRP level by 4.07‐fold (≥2.0 mg/L) in the child. As such, maternal GDM was significantly associated with increased serum hsCRP levels in 8‐year‐old children.     

Diffusion-weighted echo-planar MR imaging: clinical applications and pitfalls -- a pictorial essay

Diffusion-weighted imaging (DWI) provides unique information about various pathological changes of the brain. DWI is sensitive for the detection of hyperacute infarcts, and useful in distinguishing acute or subacute infarcts from chronic infarcts. DWI is useful in differentiating cytotoxic edema from vasogenic or interstitial edema, which may help to determine prognosis. DWI is useful in differentiating cystic or necrotic tumors from abscesses or epidermoids. DWI can discriminate nonenhanced tumor infiltration from vasogenic edema, and differentiate dysmyelination from demyelination.     

Nonfunctional pituitary macroadenoma manifested as muscular symptoms

A 75-year-old man with a large pituitary adenoma presented with general muscular weakness, including difficulty in rising in the morning and forceless defecation and urination, and muscular pain, numbness and atrophy in the shoulder, neck and thigh. Testosterone replacement and subsequent resection of the pituitary tumor resulted in resolution of the symptoms. The value of pituitary imaging tests for men with hypogonadotropic hypogonadism is discussed.