Bimodal immunoglobulin A gammopathy in a cat with feline myeloma-related disorders.

A 10-year-old female spayed mixed breed cat with a subcutaneous mass on the right hind limb was revealed with bimodal monoclonal gammopathy composed of IgA by immunoelectrophoresis and immunofixation. Approximately 1 month after referral, the cat died due to renal failure. Postmortem immunohistopathologic evaluation of the subcutaneous mass revealed neoplastic cell proliferation of plasma cells and giant myeloma cells. Neoplastic cells were also present in the liver and spleen. These results led to the diagnosis of a rare case of feline myeloma-related disorders with extramedullary plasmacytoma infiltrating in multiple locations. This report emphasizes the necessity to accumulate cases with similar clinicopathologic findings in the future.

Elevation of plasma basic fibroblast growth factor after nocturnal hypoxic events in patients with obstructive sleep apnea syndrome.

Obstructive sleep apnea syndrome (OSAS) is associated with recurrent nocturnal hypoxia during sleep; this hypoxia has been implicated in the pathogenesis of cardiovascular complication. However, a useful soluble factor that is sensitively correlated with OSAS severity for the diagnosis remains unidentified. We hypothesized that systemic levels of basic fibroblast growth factor (bFGF), a hypoxia-induced cytokine, were affected by nocturnal hypoxemia in OSAS patients, and we assessed whether the degree of change in the plasma bFGF concentrations before and after nocturnal hypoxia is correlated with the severity of OSAS. Thirty subjects who had suspected OSAS and had been investigated by nocturnal polysomnography (PSG) were enrolled. Plasma bFGF and vascular endothelial growth factor (VEGF) concentrations the night before PSG and the next morning were measured by sandwich enzyme-linked immunosorbent assay. Correlations between the changes in these factors and hypoxia-associated parameters for OSAS severity were analyzed. Patients with OSAS had significantly elevated levels of plasma bFGF but not VEGF and hemoglobin after rising. The degree of change in bFGF concentrations after nocturnal apnea episodes was significantly correlated with diagnostic parameters for OSAS severity. The change in plasma bFGF levels is associated with the degree of hypoxic state in OSAS patients, implying that bFGF might be a useful soluble factor for evaluating OSAS severity.

Concomitant obstructive sleep apnea increases the recurrence of atrial fibrillation following radiofrequency catheter ablation of atrial fibrillation: clinical impact of continuous positive airway pressure therapy.

BACKGROUND: Recent studies have suggested an emerging link between obstructive sleep apnea (OSA) and atrial fibrillation (AF). Patients with OSA are less likely to remain in sinus rhythm after radiofrequency catheter ablation of AF. OBJECTIVE: To evaluate the efficacy of appropriate treatment with continuous positive airway pressure (CPAP) on recurrences of AF after ablation. METHODS: This study prospectively included 153 patients (128 men; 60 ± 9 years) who underwent extensive encircling pulmonary vein isolation for drug refractory AF. The standard overnight polysomnographic evaluation was performed 1 week after ablation, and the total duration and the number of central or obstructive sleep apnea or hypopnea episodes were examined. RESULTS: Of 153 patients, 116 patients were identified as having OSA. Data regarding the use of CPAP and recurrences of AF were obtained in 82 patients. The remaining 34 patients with OSA were defined as the no-CPAP group. Polysomnography revealed no sleep-disordered breathing in 37 patients. During a mean follow-up period of 18.8 ± 10.3 months, 51 (33%) patients experienced AF recurrences after ablation. A Cox regression analysis revealed that the left atrial volume (hazard ratio [HR] 1.11; 95% confidence interval [CI] 1.01-1.23; P<.05), concomitant OSA (HR 2.61; 95% CI 1.12-6.09; P<.05), and usage of CPAP therapy (HR 0.41; 95% CI 0.22-0.76; P<.01) were associated with AF recurrences during the follow-up period. CONCLUSIONS: Patients with untreated OSA have a higher recurrence of AF after ablation. Appropriate treatment with CPAP in patients with OSA is associated with a lower recurrence of AF.

Radiofrequency catheter ablation of persistent atrial fibrillation decreases a sleep-disordered breathing parameter during a short follow-up period.

BACKGROUND: Obstructive sleep apnea (OSA) is often associated with atrial fibrillation (AF), but the impact of radiofrequency catheter ablation (RFCA) for AF on sleep apnea syndrome is unknown. METHODS AND RESULTS: A total of 25 patients (3 women; 61 ± 6 years) with sleep apnea syndrome who underwent RFCA for drug-refractory, persistent AF were studied. Polysomnography was also performed 1 day before and 1 week after RFCA in all patients. The total number of central or OSA or hypopnea events was analyzed and compared. Among the 25 patients who all predominantly had obstructive apnea, the apnea-hypopnea index (AHI; median, 21, interquartile range [IQR]: 11-38 to median 15, IQR: 7-23; P=0.002) and obstructive type of apnea (median 10, IQR: 6-19 to median 7, IQR: 2-14; P=0.003) decreased after RFCA. In patients in whom sinus rhythm was restored and maintained after RFCA, the AHI decreased after RFCA (median 22, IQR: 15-38 to median 15, IQR: 7-23; P<0.01), but it did not in those who had AF recurrence (median 10, IQR: 9-11 to median 11, IQR: 10-16; P<0.05). There was a significant correlation between the outcome of RFCA and % change in the AHI (rs=0.569, P=0.003). CONCLUSIONS: In patients with sleep apnea syndrome and AF, restoring sinus rhythm by RFCA was significantly associated with a decrease in AHI (Clinical Trial Registration: Trial number, UMIN000005538).

Transactivation of the dopamine receptor 3 gene by a single provirus integration results in development of B-cell lymphoma in transgenic mice generated from retrovirally transduced embryonic stem cells.

Gene transfer vectors based on retroviruses are commonly used in gene therapy applications because of their unique ability to integrate efficiently into host genomes. This ability also forms the basis of a transformation event that can be induced in transduced cells by transactivation of proto-oncogenes near the vector integration sites. Here, we report on the development of lymphoma in mice generated from embryonic stem cells transduced with an enhanced green fluorescent protein. The cells expressed B220, CD5, Mac1, and IgM on their surfaces and expressed transcription factors characteristic of B-cell lymphoma. Importantly, each mouse had a single copy of the provirus in its genome; the copy was integrated into the second intron of the dopamine receptor 3 (D3) gene, and high-level expression of D3 was detected only in the lymphoma cells. Ectopic expression of D3 in murine marrow cells resulted in preferential proliferation of cells at the pre-B-cell stage in response to a D3-specific agonist, but this proliferation was not observed in vivo. Cells cotransduced with D3 and Bcl-x(L) genes had a phenotype similar to that of lymphoma in vivo, suggesting that the leukemogenesis induced by retroviral integration required "second hit" mutations of additional genes.