A case of Turner syndrome complicated with brain infarction]

A 21 year-old female college student with a history of Turner syndrome at age 9, and 6-year growth hormone replacement therapy noticed weakness of right extremities when she got up on March 26, 2001. On admission, she showed right hemiparesis (4+/5) and hypesthesia on the right of body. The hemiparesis progressed (3-/5) in spite of antithrombotic therapy. Brain MRI revealed a high intensity lesion with a diameter of 1.5 cm in the posterior limb of the left internal capsule and putamen on DWI and T2WI. MR angiography and TC-CFI revealed no stenosis in her left middle cerebral artery, but > 50% stenosis in the horizontal portion (M1) of her right middle cerebral artery. Branch lesions were presumed to exist in the left M1. Non-atherosclerotic angiopathy, coagulopathy, and other conventional risk factors of brain infarction were not found. Pathogenesis of Turner syndrome might have played a role in the development of brain infarction in this patient.     

Evaluation and treatment for spinal cord tethering in patients with anorectal malformations.

BACKGROUND: It has recently been recognized that there is a close relationship between spinal cord tethering (SCT) and congenital anorectal malformation (ARM). PATIENTS AND METHODS: We evaluated spinal MRI examinations of 28 patients with ARM (14 boys and 14 girls) aged 5 months to 9 years. All patients diagnosed with SCT subsequently underwent operation. Patients were divided into high and low type ARM groups. We reviewed the relationship between SCT and ARM, and evaluated the untethering surgery. RESULTS: We evaluated 14 boys (high, 9; low, 5) and 14 girls (high, 4; low, 10). Of these 28 patients, 13 had SCT on MRI. Five out of 13 patients with high type ARM and 8 out of 15 patients with low type ARM had SCT. Seven out of 10 girls with low type ARM had SCT. Ten of these 13 patients with SCT experienced bowel/urological/orthopedic symptoms. SCT symptoms progressed prior to operation in the 2 patients who underwent untethering surgery a few years after their initial MRI examination. Postoperatively, orthopedic symptoms disappeared completely in all patients, but other symptoms did not. CONCLUSIONS: Based on the results of this study, we recommend routine MRI examination of patients with ARM and early untethering surgery in cases with SCT.     

Antiganglioside antibodies in motor neuron disease and motor dominant neuropathies

Serum antiganglioside antibodies were investigated in motor neuron disease (MND) and in chronic or acute immune-mediated motor-dominant neuropathies. IgM antibody binding to GM1 and GA1, reacting with Gal beta 1-3GalNAc epitope, was seen in 5 out of 26 cases of MND. IgM antibody binding to Gal beta 1-3GalNAc epitope was also detected in 3 out of 3 cases with motor dominant neuropathy with multifocal conduction block (MNMCB). The IgM M-protein in a case with motor dominant neuropathy bound to GM1, GD1b, GM2 but not to GA1. This M-protein may recognize carbohydrate epitope including sialic acid. Antiganglioside antibodies were detected in 11 out of 16 cases with Guillain-Barré syndrome (GBS). Among them, anti-GM1 antibodies were detected in 6 cases. Gal beta 1-3GalNAc epitope was recognized in 3 cases, and GM1 was monospecifically recognized in 3 cases. Thus the binding specificities of anti-GM1 antibody in motor dominant neuropathies were varied. The titers of anti-GM1 antibodies in 1 case with MNMCB and in 6 cases with GBS were more than 1:160, whereas those in MND were less than 1:80. The high titers of antibody in MNMCB and GBS decreased in association with clinical improvement, suggesting that they are closely related with the disease process. Although the titers are low, anti-GM1 antibody in MND may give us a clue to elucidate the pathogenetic mechanisms of this intractable disease.     

Erythrocytes, as well as microbubble contrast agents, are important factors in improving thermal and therapeutic effects of high-intensity focused ultrasound

Erythrocytes, as well as microbubble contrast agents, are important factors in improving thermal effect of high-intensity focused ultrasound (US), or HIFU, and increasing the coagulation volume produced by HIFU irradiation. In vitro experiments used human plasma with various concentrations of human erythrocytes in combination with or without Levovist. In vivo experiments used eight Japan white rabbits with three degrees of anemia. Using a 2.17-MHz transducer, HIFU was applied for 60 s, and the temperature rise and the volume of coagulation necrosis was evaluated. There was a significant correlation between the HIFU-induced temperature rise and hematocrit, with a correlation coefficient of 0.998 (p=0.0001). Although the temperature rise was smaller at low hematocrit, it was significantly increased by adding Levovist in the suspension (p<0.01). The mean volume of coagulation necrosis was significantly greater in the rabbits with higher hematocrits (p<0.01), and that in the moderate anemia group was significantly increased by using Levovist (p<0.01).     

Fetal case of congenital cystic adenomatoid malformation of the lung: fetal therapy and a review of the published reports in Japan

We herein report a case of type I congenital cystic adenomatoid malformation of the lung (CCAML) with non-immune hydrops fetalis (NIHF), a mediastinal shift and polyhydramnios diagnosed at 24 weeks' gestation by ultrasonography. The fetus was treated with a cyst-amniotic shunt at 29 weeks' gestation. Following a postnatal whole resection of the right lung, postpneumonectomy syndrome appeared and, as a result, the infant died 13 months after delivery due to respiratory failure. Only 19 cases demonstrating CCAML associated with NIHF have been reported previously in Japan. Four cases showed a spontaneous resolution of NIHF, while 5 cases with type I CCAML, which all underwent fetal intervention, demonstrated an excellent outcome.     

The effect of platelet-rich plasma on the cellular response of rat bone marrow cells in vitro

The aim of this study was to investigate the effect of platelet-rich plasma (PRP) on the proliferation and the differentiation of rat bone marrow cells (RBMCs). PRP, platelet-poor plasma (PPP), and bone marrow cells were derived from the rats (hearts and tibia) and the cells were cultured with or without PRP or PPP (0 [control]), 0.2 approximately 10 microL/mL). The proliferation of RBMCs was measured on days 2 and 4, and alkaline phosphatase (ALP) staining and activity measurement were evaluated to determine the effect of PRP on the differentiation on days 4 and 8. PRP enhanced the proliferation significantly compared to the control group (P < .05). These enhancements were greater than ones induced by the addition of PPP. ALP staining appeared to show that PRP decreased the number of ALP positive cells and ALP activity significantly (P < .05). Our results demonstrate that PRP stimulates the proliferation but suppresses the differentiation of RBMCs.     

Development of the ICH guidelines for immunotoxicology evaluation of pharmaceuticals using a survey of industry practices

An anonymous survey of pharmaceutical industry practices for immunotoxicology evaluation was conducted. This was in support of the development of the guideline on the preclinical evaluation of unintended modulation of the immune system for the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use. The survey was conducted in two phases in 2003 and 2004. A total of 64 responses were received of which 45 were included in the formal evaluation. The remaining compounds were excluded because they were cytotoxic anti-neoplastic drugs (N = 7), or due to insufficient information (N = 12). The purpose of the survey was to gather data on the correlation between routine toxicology studies (RTS) and additional immunotoxicological studies (AIS). The results of the survey were evaluated by the Expert Working Group (EWG) and classified as to positive or negative findings in RTS and AIS. The results of the survey showed that for 27 of 45 compounds (60%), the RTS and AIS endpoints were in agreement. In 12 of 45 cases (27%), the RTS endpoints showed immune modulation not observed in the AIS assays. Finally for 6 of 45 drugs (13%) a response was seen with the AIS methods where no significant effect was observed in the RTS endpoints. Length of dosing and the number of tests evaluated were similar in all groups. The groups where RTS detected signs of immunosuppression were more likely to have been dosed at or above MTD. This data contributed to the consensus in the EWG that routine immune function testing as an initial screen for all new drugs is not required. Instead, a weight-of-evidence approach including RTS and other causes for concern is recommended to identify the need for additional immunotoxicity studies.