Chronic Localized Encephalitis (Rasmussen's Syndrome) Preceded by Ipsilateral Uveitis: A Case Report

Summary: Chronic localized encephalitis (Rasmussen's syndrome) developed in an 11-year-old girl 1 month after operation for residual cataract due to chronic uveitis that had appeared at age 9 years ipsilateral to the affected cerebral hemisphere. Although the pathogenesis of Rasmussen's syndrome remains unknown, our case provides additional evidence indicating that a viral ocular infection is a possible cause or part of the disorder.     

The review of seclusion and restraint in psychiatric practice]

In order to create the least restrictive setting in psychiatric practice, we investigated the effects of an assessment by a committee on seclusion and restraint. Using consistent procedures, the committees, which were established in 9 hospitals, reviewed seclusion and restraint maintained for periods of over 2 weeks during a 4-month period. Frequency and duration of seclusion and restraint, staff perceptions of and attitudes to the review system, and patient satisfaction were evaluated before and after the study period. As a result of this review process, the frequency of seclusion decreased slightly in 7 hospitals and 1 of the remaining 2 hospitals showed an increased frequency of seclusion days that were partially interrupted. Frequency of restraint decreased slightly in 5 hospitals, and of the remaining 3, 1 interrupted all periods of restraint, while the other 2 institutions showed an increase in interruption of restraint periods. As there were no common patients in 2 specialist psychiatric emergency hospitals between before and after the study periods, statistical analyses were performed. Only minor variables such as duration of partially interrupted periods of restraint, and duration of periods of restraint that were partially released showed a statistically significant increase. Although patient satisfaction showed a significant increase, staff attitudes to and perceptions of the review system became appreciably more negative. These findings suggest that although the review system had the potential to slightly reduce the use of seclusion and restraint, and to increase patient satisfaction, staff burnout was risked because staff effort was perceived to be disproportionately high in relation to the effect achieved. Furthermore, the possibility remains that the slight decrease of seclusion and restraint demonstrated did not necessarily reflect the appropriate use of these strategies, and were not necessarily lasting effects. However, as differences in opinion existed between the review system committee and treating clinicians regarding continuation of long term seclusion and restraint, the review system could have a role in monitoring the long term use of seclusion and restraint. Further investigation is needed into the long term effectiveness of procedures reviewing the use of seclusion and restraint in the psychiatric setting, taking into account both positive and negative outcomes.     

EFFECT OF ARGON PLASMA COAGULATION IN PATIENTS WITH UPPER GASTROINTESTINAL ACTIVE HEMORRHAGE

Background: Acute upper gastrointestinal hemorrhage is a common and life‐threatening medical emergency. Despite a large number of endoscopic methods for hemostasis, active bleeding lacks an adequate therapeutic remedy. The aim of the present study was to evaluate the hemostatic effect of argon plasma coagulation on upper gastrointestinal active bleeding, especially in comparison with heater probe and pure ethanol injection therapy. Methods: Sixty‐eight patients with 77 lesions presenting active bleeding were treated endoscopically and divided into three groups depending on the procedures, that is, argon plasma coagulation group (27 patients with 32 lesions), heater probe group (20 patients with 22 lesions) and pure ethanol injection group (21 patients with 23 lesions). The three groups were similar with respect to all background variables. Episodes of rebleeding were retreated with the same modality as used previously. Results: The primary hemostatic rate in the argon plasma coagulation group was 81.3%, that in the heater probe group was 77.3%, and that in the pure ethanol injection group was 87.0%. The permanent hemostatic rate in the argon plasma coagulation group was 75.0%, that in the heater probe group was 63.6%, and that in the pure ethanol injection group was 78.3%. When examined in terms of Forrest's criteria, the argon plasma coagulation group in Forrest's type I b and the pure ethanol injection group in type I a showed the highest permanent hemostatic rate. Conclusions: Argon plasma coagulation is most suitable in arresting oozing hemorrhage. If pure ethanol injection therapy is possible, it is more effective than other therapies in the case of spurters.     

Allelic and non-allelic heterogeneities in pyridoxine dependent seizures revealed by ALDH7A1 mutational analysis

Pyridoxine dependent seizure (PDS) is a disorder of neonates or infants with autosomal recessive inheritance characterized by seizures, which responds to pharmacological dose of pyridoxine. Recently, mutations have been identified in the ALDH7A1 gene in Caucasian families with PDS. To elucidate further the genetic background of PDS, we screened for ALDH7A1 mutations in five PDS families (patients 1-5) that included four Orientals. Diagnosis as having PDS was confirmed by pyridoxine-withdrawal test. Exon sequencing analysis of patients 1-4 revealed eight ALDH7A1 mutations in compound heterozygous forms: five missense mutations, one nonsense mutation, one point mutation at the splicing donor site in intron 1, and a 1937-bp genomic deletion. The deletion included the entire exon 17, which was flanked by two Alu elements in introns 16 and 17. None of the mutations was found in 100 control chromosomes. In patient 5, no mutation was found by the exon sequencing analysis. Furthermore, expression level or nucleotide sequences of ALDH7A1 mRNA in lymphoblasts were normal. Plasma pipecolic acid concentration was not elevated in patient 5. These observations suggest that ALDH7A1 mutation is unlikely to be responsible for patient 5. Abnormal metabolism of GABA/glutamate in brain has long been suggested as the underlying pathophysiology of PDS. CSF glutamate concentration was elevated during the off-pyridoxine period in patient 3, but not in patient 2 or 5. These results suggest allelic and non-allelic heterogeneities of PDS, and that the CSF glutamate elevation does not directly correlate with the presence of ALDH7A1 mutations.     

Non-receptor protein-tyrosine kinases as molecular targets for antiangiogenic therapy (Review)

Antiangiogenic therapy, including blockade of vascular endothelial growth factor (VEGF) signaling, was highly anticipated to improve the prognosis for patients with advanced cancers following the success of preclinical animal models. However, antiangiogenic monotherapy with VEGF antagonists has produced disappointing results in clinical trials to date. One of the reasons for this poor outcome is that angiogenesis is not solely regulated by VEGF. Inhibition of VEGF signaling, therefore, may select for tumor cell populations that stimulate angiogenesis through VEGF-independent pathways. Successful antiangiogenic therapy, therefore, may require simultaneous blockade of signaling downstream from multiple proangiogenic factor receptors. Recently, we found that non-receptor protein-tyrosine kinases, including members of the Src and Fes families, play vital roles in the responses of cultured endothelial cells to several proangiogenic factors. In this review, we summarize the contributions of these kinase families to angiogenic pathways in endothelial cells, and discuss the potential of these kinases as new targets for antiangiogenic drug discovery.     

Regulatory T cells and regulatory natural killer (NK) cells play important roles in feto-maternal tolerance

In the early pregnancy decidua, lymphocytes express some activation markers on their surface, suggesting that maternal lymphocytes are activated and recognize the semiallograftic fetus. Therefore, the immunoregulation system must work to prevent fetus rejection. Recent data showed that parts of the immunoregulation system such as CD4⁺CD25⁺ regulatory T (Treg) cells, Th3 cells, Tr1 cells, regulatory NK cells, and a tryptophan-catabolizing enzyme, indolamine 2,3 deoxygenase, play very important roles in the maintenance of pregnancy. Not only Treg cells but also regulatory NK cells may inhibit maternal T cell or NK cell fetal attack.     

Development of an antigen-presenting cell-targeted DNA vaccine against melanoma by mannosylated liposomes

As part of our research involving the targeted delivery of plasmid DNA (pDNA) to antigen-presenting cells (APCs), we developed mannosylated cationic liposomes: N-[1-(2,3-dioleyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTMA)/cholesten-5-yloxy-N-(4-((1-imino-2-D-thiomannosyl-ethyl)amino)butyl)formamide (Man-C4-Chol)/Chol (Man liposomes). In this study, we used melanoma-associated antigen expressing pDNA; pUb-M and Man liposomes to create a novel APC-targeted DNA vaccine against melanoma and examined its potency by measuring the Ub-M mRNA expression in splenic dendritic cells and macrophages, the cytotoxic T lymphocyte (CTL) activity against melanoma B16BL6 cells and the melanoma B16BL6-specific anti-tumor effect after intraperitoneal (i.p.) administration. We verified that Man lipoplex induces significantly higher pUb-M gene transfection into dendritic cells and macrophages than unmodified lipoplex and naked DNA and it also strongly induces CTL activity against melanoma, inhibits its growth and prolongs the survival after tumor challenge compared with unmodified liposomes and the standard method (naked pDNA, intramuscular (i.m.)). These results demonstrate that Man liposomes are a potent APCs-targeted vector that induce strong immunopotency of DNA vaccine against melanoma.     

Pathology and virus dispersion in cynomolgus monkeys experimentally infected with severe acute respiratory syndrome coronavirus via different inoculation routes

Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) causes SARS. The pathogenic mechanisms of SARS-CoV remain poorly understood. Six cynomolgus monkeys were inoculated with the HKU39849 isolate of SARS-CoV via four routes. After intranasal inoculation, the virus was isolated from respiratory swabs on days 2-7 postinoculation (p.i.) and virus genome was detected in intestinal tissues on day 7 p.i. Virus was not detected after intragastric inoculation. After intravenous inoculation, infectious virus was isolated from rectal swabs, and virus antigen was detected in intestinal cells on day 14 p.i. After intratracheal (i.t.) inoculation, virus antigen-positive alveolar cells and macrophages were found in lung and infectious virus was detected in lymphoid and intestinal tissues. The peribronchial lymph nodes showed evidence of an immune response. Lung tissue and/or fluid and/or the peribronchial lymph node of the intratracheally inoculated animals had high TNF-alpha, IL-8 and IL-12 levels. SARS lung lesions are only generated in monkeys by i.t. inoculation. The virus appears to spread into and perhaps via the intestinal and lymphatic systems. It has been suggested previously that viraemia may cause intestinal infections in SARS patients.     

Glomus tumor beneath the plica synovialis in the knee: a case report

Glomus tumors are rare benign tumors distinguished clinically by their small size and ability to cause extreme pain. These lesions are usually found beneath the fingernails. Atypical locations of the tumor are difficult to diagnose, especially when the lesion is situated in a deep anatomic structure. We describe a 33-year-old man with glomus tumor beneath the plica synovialis in the knee. He had experienced right knee pain for 10 years which increased with movements of the knee. There was a point of tenderness on palpation at the lateral aspect of the knee. CT scan with arthrography showed a small mass on the lateral femoral condyle in the joint space. It was seen retrospectively in MRI. Arthroscopy demonstrated the soft tissue mass beneath the plica synovialis. We made a separate incision and removed it completely. An immediate disappearance of the pain was observed after surgery. Histology was the glomus tumor of the vascular type. The tumor seemed to be stimulated by the plica synovitis or the lateral joint capsule and it caused pain on motion similar to meniscal tear. There has been no recurrence for 3 years after surgery.