Double-door laminoplasty using autologous spinous process for the management of cervical myelopathy

We describe a technique of double-door laminoplasty for the management of cervical myelopathy using the autologous spinous process instead of an artificial spacer. The aims in the present study were to determine the fusion rate and the incidence rate of breakage in the autologous spinous process, and to assess its efficacy for cervical laminoplasty. Twenty-three patients of cervical myelopathy were treated with double-door laminoplasty followed by implantation of the autologous spinous process. The spinous process from C3 to C7 was resected, at 8 mm from the basal part of the spinous process. The autologous spinous process was made from the removed spinous process, and was implanted between each expanded laminae. Post-operative CT scanning determined the fusion rate between the expanded laminae and the autologous spinous process as 70.4% at 3 months, and 93.5% at 6 months, after the operation. There was no dissociation and no breakage in the autologous spinous process during the follow-up observation period. There were certain advantages to our technique including the high fusion rate and good stability in the autologous spinous process. In addition, this technique was less expensive than other techniques using an artificial spacer. These findings indicated that this technique was a reliable procedure for effectively treating of cervical myelopathy which are caused by multisegmental cervical canal stenosis.     

Factors affecting ST depression during cardiopulmonary exercise testing in patients with mitral stenosis without significant coronary lesions

Symptom-limited cardiopulmonary exercise testing was performed in 37 patients with mitral stenosis (MS) without significant coronary artery stenosis to evaluate factors affecting ST depression in exercise electrocardiograms. The degree of ST depression was not associated with gender or exercise tolerance. The incidence of significant ST depression was higher in the patients receiving than in those not receiving digitalis (P < 0.05). In addition, the patients with atrial fibrillation and a higher heart rate response were more likely to have a high prevalence of significant ST depression than those with sinus rhythm and a lower response (P < 0.05). We concluded that atrial fibrillation, a higher maximum heart rate, and oral digitalis administration were involved in ST depression during exercise testing in patients with mitral stenosis without coronary heart disease.     

Immunohistochemical Mapping of TRK-Fused Gene Products in the Rat Brainstem

The TRK-fused gene (TFG in human, Tfg in rat) was originally identified in human papillary thyroid cancer as a chimeric form of the NTRK1 gene. It was since reported that the gene product (TFG) plays a role in regulating phosphotyrosine-specific phosphatase-1 activity. As shown in the accompanying paper, we produced an antibody to rat TFG and used it to localize TFG to selected neurons in specific regions. In the present study, we mapped the TFG-positive neurons in the brainstem, cerebellum, and spinal cord of rats. In the brainstem, neurons intensely positive for TFG were distributed in the raphe nuclei, the gigantocellular reticular nucleus, the reticulotegmental nucleus of the pons, and some cranial nerve nuclei such as the trigeminal nuclei, the vestibulocochlear nuclei, and the dorsal motor nucleus of the vagus. Purkinje cells in the cerebellum and motor neurons in the spinal anterior horn were also positive for TFG. These results provide fundamental data for studying the functions of TFG in the brain.     

Enteropathy-associated T-cell lymphoma: clinical and histological findings from the international peripheral T-cell lymphoma project

Few large, international series of enteropathy-associated T-cell lymphoma (EATL) have been reported. We studied a cohort of 62 patients with EATL among 1153 patients with peripheral T-cell or natural killer (NK)-cell lymphoma from 22 centers worldwide. The diagnosis was made by a consensus panel of 4 expert hematopathologists using World Health Organization (WHO) criteria. Clinical correlations and survival analyses were performed. EATL comprised 5.4% of all lymphomas in the study and was most common in Europe (9.1%), followed by North America (5.8%) and Asia (1.9%). EATL type 1 was more common (66%) than type 2 (34%), and was especially frequent in Europe (79%). A clinical diagnosis of celiac sprue was made in 32.2% of the patients and was associated with both EATL type 1 and type 2. The median overall survival was only 10 months, and the median failure-free survival was only 6 months. The International Prognostic Index (IPI) was not as good a predictor of survival as the Prognostic Index for Peripheral T-Cell Lymphoma (PIT). Clinical sprue predicted for adverse survival independently of the PIT. Neither EATL subtype nor other biologic parameters accurately predicted survival. Our study confirms the poor prognosis of patients with EATL and the need for improved treatment options.     

Peripheral T-cell lymphoma, not otherwise specified: a report of 340 cases from the International Peripheral T-cell Lymphoma Project

The International Peripheral T-cell Lymphoma Project is a collaborative effort to better understand peripheral T-cell lymphoma (PTCL). A total of 22 institutions submitted clinical and pathologic material on 1314 cases. One objective was to analyze the clinical and pathologic features of 340 cases of PTCL, not otherwise specified. The median age of the patients was 60 years, and the majority (69%) presented with advanced stage disease. Most patients (87%) presented with nodal disease, but extranodal disease was present in 62%. The 5-year overall survival was 32%, and the 5-year failure-free survival was only 20%. The majority of patients (80%) were treated with combination chemotherapy that included an anthracycline, but there was no survival advantage. The International Prognostic Index (IPI) was predictive of both overall survival and failure-free survival (P < .001). Multivariate analysis of clinical and pathologic prognostic factors, respectively, when controlling for the IPI, identified bulky disease (≥ 10 cm), thrombocytopenia (< 150 × 10(9)/L), and a high number of transformed tumor cells (> 70%) as adverse predictors of survival, but only the latter was significant in final analysis. Thus, the IPI and a single pathologic feature could be used to stratify patients with PTCL-not otherwise specified for novel and risk-adapted therapies.     

Single center prospective study of tacrolimus efficacy and safety in treatment of rheumatoid arthritis

The aim of this study was to prospectively evaluate the efficacy and safety of tacrolimus for treating rheumatoid arthritis (RA) patients in clinical practice. Fifty-five active RA patients who had been resistant or intolerant to other disease-modifying antirheumatic drugs were enrolled in this open-label trial. Patients were administered tacrolimus at a dosage of 1, 2 or 3 mg once daily, and followed up for 24 weeks. They were divided into three groups according to their dosage. Efficacy and safety were evaluated utilizing clinical and laboratory findings. Eighty percent of the patients had moderate or high disease activity; 55% were elderly and 53% had complications; 65% of the patients were started on tacrolimus as a monotherapy. Moderate or good response rates were achieved as follows: 38.2% (4 weeks); 41.8% (12 weeks); and 45.6% (24 weeks). Adverse events were observed in seven cases (12.7%). Only one case required hospitalization due to severe hyperglycemia caused by a high tacrolimus concentration (24.2 ng/ml); we suspected a drug interaction in this subject. Mean concentrations were dose-dependent in the 1, 2, and 3 mg/day groups (2.96, 4.29, and 8.32 ng/ml, respectively). Four cases of high concentration (over 10 ng/ml), without any signs or symptoms, were observed in the 3 mg/day group; in these cases, doses were decreased and no severe adverse events occurred. Tacrolimus was found to be both effective and safe in treating active RA patients with complicated backgrounds in clinical practice. Blood concentration measurements and dose adjustments should be performed to prevent severe adverse events in a 3 mg/day group. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

TCRzeta mRNA splice variant forms observed in the peripheral blood T cells from systemic lupus erythematosus patients

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease of unknown etiology. Tyrosine phosphorylation and protein expression of the T-cell receptor ζ chain (ζ) have been reported to be significantly decreased in SLE T cells. In addition, ζ mRNA with alternatively spliced 3′ untranslated region (ζmRNA/as-3′UTR) is detected predominantly in SLE T cells, and aberrant ζ mRNA accompanied by the mutations in the open reading frame including ζ mRNA lacking exon7 (ζmRNA/exon7-) is observed in SLE T cells. These ζ mRNA splice variant forms exhibit a reduction in the expression of TCR/CD3 complex and ζ protein on their cell surface due to the instability of ζ mRNA splice variant forms as well as the reduction in interleukin (IL)-2 production after stimulating with anti-CD3 antibody. Data from cDNA microarray showed that 36 genes encoding cytokines and chemokines, including IL-2, IL-15, IL-18, and TGF-β2, were down-regulated in the MA5.8 cells transfected with the ζ mRNA splice variant forms. Another 16 genes were up-regulated and included genes associated with membranous proteins and cell damage granules, including the genes encoding poliovirus-receptor-related 2, syndecan-1, and granzyme A.     

Myeloablative allogeneic hematopoietic stem cell transplantation for non-Hodgkin lymphoma: a nationwide survey in Japan

We retrospectively surveyed the data of 233 patients who underwent myeloablative allogeneic hematopoietic stem cell transplantation (allo-HSCT) for non-Hodgkin lymphoma (NHL). Donors were HLA-matched relatives in 154 patients (66%) or unrelated volunteers in 60 (26%). Ninety patients (39%) were in complete remission. One hundred ninety-three (83%) received a total body irradiation (TBI)-based regimen, and 40 (17%) received a non-TBI-based regimen. Acute graft-versus-host disease (GVHD) occurred in 155 (67%) of the 233 evaluable patients; grade II to IV in 90 (39%), and grade III to IV in 37 (16%). Treatment-related mortality (TRM) was observed in 98 patients (42%), and 68% of them were related to GVHD. In a multivariate analysis, chemoresistance, prior autograft, and chronic GVHD were identified as adverse prognostic factors for TRM. Relapse or progression of lymphoma was observed in 21%. The 2-year overall survival rates of the patients with indolent (n = 38), aggressive (n = 111), and lymphoblastic lymphoma (n = 84) were 57%, 42%, and 41%, respectively. In a multivariate analysis, chemoresistance, prior autograft, and prior radiotherapy were identified as adverse prognostic factors for overall survival. Although myeloablative allo-HSCT represents an effective therapeutic option for patients with NHL, more work is still needed to decrease TRM and relapse.