Intravenous immunoglobulin therapy for Guillain-Barré syndrome in Japan: changes in treatment after its inclusion in health insurance coverage]

In December 2000, health insurance in Japan was instituted for the use of intravenous immunoglobulin (IVIg) therapy for the acute phase of Guillain-Barré syndrome (GBS) that required aid to walk or worse. A nation-wide questionnaire survey was made to investigate the changes in treatment. In September 2002, a letter of inquiry was sent to experienced physicians in 620 teaching hospitals associated with the Societas Neurologica Japonica and 417 associated with the Societas Paediatrica Japonica. Totally, 356 neurologists (57%) and 223 pediatricians (53%) responded. After the introduction of IVIg health insurance coverage, more than 90% thought that GBS patients should be hospitalized and given treatment. The frequency of hospitals with an intensive care unit, however, was 70%. Before IVIg therapy's inclusion in health insurance coverage, many neurologists selected plasmapheresis (88%) rather than IVIg (4%) therapy, whereas pediatricians preferred IVIg (49%) to plasmapheresis (12%). After its inclusion, 75% of neurologists selected IVIg rather than plasmapheresis (21%), whereas pediatricians selected IVIg (86%) over plasmapheresis (5%). In March 2003, new payment system based on Diagnosis Procedure Combination was introduced into 82 large hospitals, and leads to difficulties to select IVIg in the hospitals. The payment system should be revised.     

Cross-cultural validation of the Japanese version of the lung cancer subscale on the functional assessment of cancer therapy-lung.

BACKGROUND: The Functional Assessment of Cancer Therapy-Lung (FACT-L) questionnaire, which consists of a core questionnaire (the General Measure of FACT [FACT-G]) and a 9-item Additional Concerns comprised of a 7-item Lung Cancer Subscale (LCS), was developed in an English-speaking culture. The validation of the Japanese FACT-G was reported previously, and this report describes the cross-cultural validation of the LCS. METHODS: The Japanese version of the LCS was developed through an iterative forward-backward translation sequence used throughout the FACT Multilingual Translation Project. In evaluating psychometric performance, its construct validity was investigated with Cronbach's alpha coefficient and factor analysis. Clinical validities of a known-groups comparison and longitudinal validity were also investigated. RESULTS: The FACT-L was administered twice to 180 patients with lung cancer within 2 weeks. The Japanese LCS had borderline values for Cronbachs alpha coefficients (0.62-0.67). Factor analysis indicated that the LCS had the three dimensions of respiratory symptoms, appetite plus body weight, and clear thinking. For clinical validity, a known-groups comparison showed that the LCS could differentiate patients according to truth disclosure, as Japanese doctors sometimes do not fully inform terminally ill patients. However, responsiveness was not proved when performance status was used as an anchor, probably owing to the short interval between the administration of the two measures. CONCLUSION: The Japanese version of the LCS asked questions about multiple symptoms of patients with lung cancer, as did the original English LCS. The longitudinal clinical validity of the Japanese version should be investigated in future clinical trials.     

Choroidal dye filling velocity in patients with Vogt–Koyanagi–Harada disease

Purpose To evaluate quantitative choroidal dye filling velocity in patients with Vogt-Koyanagi-Harada disease (VKH) before and after corticosteroid treatment using indocyanine green (ICG) angiography.Methods ICG angiography was performed in seven VKH patients before and after systemic corticosteroid treatment. Choroidal dye curves were obtained by image analysis software and analyzed using an exponential model. The model’s time constant (τ) was used to evaluate choroidal dye filling velocity.Results Compared with controls, acute phase choroidal τ values in VKH patients were significantly longer, suggesting choroidal circulation disturbance. During the recovery phase, choroidal τ values were significantly shortened, suggesting choroidal circulatory disturbance improvement.Conclusion Choroidal dye filling velocity may be useful for VKH diagnosis and verification of corticosteroid treatment effectiveness.     

Assessment of on-pump beating coronary artery bypass surgery performed after introduction of off-pump approach.

OBJECTIVE: To clarify the position of on-pump beating coronary artery bypass (CAB) and to define preoperative indicators of intentional conversion to the procedure in the era of advancement of off-pump CAB (OPCAB), we assessed on-pump beating CAB performed after the introduction of OPCAB. SUBJECTS AND METHODS: We assessed 130 patients who underwent single CAB [117 (90%) with OPCAB and 13 (10%) with on-pump beating CAB] between August 1999 (when OPCAB was selected as the first-line surgical procedure) and December 2004. RESULTS: No significant differences were seen between the groups in the number of coronary lesions or the prevalence of left main trunk (LMT) lesion. Reduced left cardiac function, cardiac dilatation, and mitral regurgitation (MR) were more remarkable in the on-pump beating CAB group. Preoperative ischemic condition was generally unstable in the both groups. A conversion to on-pump beating CAB occurred at anastomosis for the left anterior descending (LAD) branch in 61% and for the left circumflex (LCX) branch in 15%. LAD patients had more severe left cardiac dysfunction and cardiac dilatation than LCX patients. CONCLUSION: To perform safe and reliable CAB surgery, cardiovascular surgeons should define preoperative indicators of difficult OPCAB and convert OPCAB to on-pump beating CAB intentionally without hesitation when unstable hemodynamics is detected.     

Trans-activation of glutathione transferase P gene during chemical hepatocarcinogenesis of the rat.

Glutathione transferase P (GST-P; glutathione transferase, EC 2.5.1.18) is known to be specifically expressed at high levels in precancerous lesions and in hepatocellular carcinomas from a very early phase of chemically induced hepatocarcinogenesis in the rat. The almost invariable occurrence of this phenotype in these lesions strongly suggests a mechanism by which GST-P gene is activated together with a crucial transforming gene of liver cells. To distinguish the two alternative possibilities--either the GST-P gene is coactivated with a closely located transforming gene by a cis mechanism or it is activated in trans by a common trans-acting factor--we carried out carcinogenesis experiments using transgenic rats harboring the bacterial chloramphenicol acetyltransferase reporter gene ligated to the upstream regulatory sequence of the GST-P gene. In each of three independent lines tested, liver foci and nodules produced by chemical carcinogens (Solt-Farber procedure) were found to express high levels of chloramphenicol acetyltransferase activity, indicating clearly that the GST-P gene is activated by a trans mechanism during hepatocarcinogenesis.     

IgG Anti-GM1 antibody is associated with reversible conduction failure and axonal degeneration in guillain-barré syndrome

To investigate the pathophysiological role of anti-GM1 antibody in Gullain-Barre syndrome (GBS), we reviewed sequential nerve conduction studies of 345 nerves in 34 GBS patients. Statistically significant correlation between IgG anti-GM1 antibodies and electrodiagnoses was found. Sixteen IgG anti-GM1-positive patients were classified as having acute motor sensory axonal neuropathy (AMAN or AMSAN) (12 patients), as having acute inflammatory demyelinating polyneuropathy (AIDP) (3 patientsrpar;, or as undetermined (1 patient) by electrodiagnostic criteria. Besides axonal features, there was rapid resolution of conduction slowing and block. In 3 patients initially diagnosed as having AIDP, conduction slowing was resolved within days, and 1 of them and 3 AMAN patients showed markedly rapid increases in amplitudes of distal compound muscle action potentials that were not accompanied by prolonged duration and polyphasia. The time courses of conduction abnormalities were distinct from those in IgG anti-GM1-negative AIDP patients. Rapid resolution of conduction slowing and block, and the absence of remyelinating slow components, suggest that conduction failure may be caused by impaired physiological conduction at the nodes of Ranvier. Reversible conduction failure as well as axonal degeneration constitutes the pathopsiological mechanisms in IgG anti-GM1)positive GBS. In both cases, immune-mediated attack probably occurs on the axolemma of motor fibers.     

Human leukocyte antigens in Fisher's syundrome

We performed human leukocyte antigens(HLA)typing for class I antigens on 19 Japanese patients with Fisher's syndrome. We demonstrated a statistically significant association between the disease and the HLA-B39 antigen.     

Lipopolysaccharide Induces CD25-Positive, IL-10-Producing Lymphocytes Without Secretion of Proinflammatory Cytokines in the Human Colon: Low MD-2 mRNA Expression in Colonic Macrophages

Despite the huge number of colonized Gram-negative bacteria in the colon, the normal colon maintains its homeostasis without any excessive immune response. To investigate the potential mechanisms involved, human colonic lamina propria mononuclear cells (LPMCs) obtained from uninflamed mucosa were cultured with lipopolysaccharide (LPS) prepared from Bacteroides vulgatus (BV-LPS) or Bacteroides fragilis (BF-LPS), as representatives of indigenous flora, or pathogenic Salmonella minnesota (SM-LPS). Colonic LPMCs failed to produce inflammatory cytokines in response to any type of LPS. Colonic macrophages barely expressed mRNA for MD-2, an essential association molecule for LPS signaling via Toll-like receptor 4. Further, BV-LPS induced CD25 and Foxp3 expression in lymphocytes and CD4(+)CD25(+) cells expressed IL-10 mRNA. Thus, the low expression of functioning LPS receptor molecules and induction of IL-10-producing CD4(+)CD25(+) lymphocytes by indigenous LPS may play a central role in the maintenance of colonic immunological homeostasis.