Hepatosplenic T-cell lymphoma: sinusal/sinusoidal localization of malignant cells expressing the T-cell receptor gamma delta

Peripheral T-cell lymphomas consist of a clinically heterogeneous group of malignant disorders whose immunophenotype usually corresponds to that of normal mature T cells. We describe and correlate the clinical, histopathologic, phenotypic, and genotypic findings in two patients with malignant lymphoma presenting with hepatosplenic disease. The morphologic pattern of lymphoma was that of a sinusal/sinusoidal infiltration in spleen, marrow, and liver. This morphologic characteristic was associated with the presence of a productive clonal rearrangement of the T-cell receptor (TCR) delta gene. Lymphoma cells expressed a CD3-TCR-gamma delta- phenotype. They were also double negative (ie, CD4-CD8-) and lacked the CD5 and CD7 antigens. In one patient, tumor progression was associated with phenotypic changes that resulted in a CD3-TCR-gamma delta- phenotype with the same delta-gene rearrangement as initially. These observations suggest the existence of a new type of peripheral T-cell lymphoma characterized by its hepatosplenic presentation, and by the sinusal/sinusoidal tropism and the TCR-gamma delta phenotype of the malignant cells.     

Recombinant human interleukin-11 stimulates multilineage hematopoietic recovery in mice after a myelosuppressive regimen of sublethal irradiation and carboplatin

Interleukin-11 (IL-11) is a novel multifunctional hematopoietic cytokine capable of stimulating cells of the myeloid, lymphoid, erythroid, and megakaryocytic lineages in vitro. We have tested the pleiotropic properties of this cytokine on the hematopoietic recovery of mice after a combined regimen of sublethal irradiation and carboplatin administration. This regimen results in severe myelosuppression, characterized by a prolonged period of thrombocytopenia and severe anemia. Administration of recombinant human IL-11 (rhIL-11; 250 micrograms/kg/d) had multilineage effects on bone marrow and spleen hematopoietic activity, increasing the number of megakaryocyte, erythroid, granulocyte, and macrophage progenitors compared with the vehicle-treated controls. This was reflected in the peripheral circulation by a reduction of both the platelet and hematocrit nadirs and a significantly reduced period of thrombocytopenia and anemia in the rhIL-11-treated mice. The results from this study support the broad spectrum of biologic activities that have been attributed to rhIL-11 in vitro and suggest that this cytokine may be an effective agent in the treatment of myelosuppression associated with cancer chemotherapy and bone marrow transplantation.     

Ticlopidine-induced aplastic anemia: development of chromosomal abnormalities and response to immunosuppressive therapy

Severe aplastic anemia is a well-recognized complication of ticlopidine therapy that carries a high mortality. Therapy with colony-stimulating factors or corticosteroids has been largely ineffective in this disorder. We report a case of ticlopidine-induced aplastic anemia that was successfully treated with cyclosporine and high-dose dexamethasone. The patient rapidly responded to immunosuppressive therapy and had a normal hemogram after cessation of immunosuppression. On long-term follow-up, the patient developed a progressive macrocytic anemia. Repeat bone marrow evaluation demonstrated myelodysplasia with erythroid hypoplasia. An associated chromosomal abnormality consisting of a t(3;16) (q21; p13.3) translocation was detected. This is the first report of a chromosomal abnormality associated with ticlopidine induced marrow aplastic anemia.     

Quantitative comparison of spontaneous and paced 12-lead electrocardiogram during right ventricular outflow tract ventricular tachycardia

OBJECTIVES: The purpose of this study was to objectively quantify the similarity of 12-lead electrocardiogram (ECG) waveforms using two quantitative metrics, the correlation coefficient (CORR) and the mean absolute deviation (MAD). BACKGROUND: Comparison of the 12-lead ECG morphology between ventricular tachycardia (VT) and a pace-map is frequently performed; however, there are no objective criteria for quantifying the similarity between two waveform morphologies. METHODS: During ablation of right ventricular outflow tract (RVOT) VT, 12-lead ECG pace-maps were acquired from three superior septal sites, three superior free wall sites, and before each ablation attempt in 15 patients. The 12-lead ECG waveforms of the clinical tachycardia and pace-maps were compared using both MAD and CORR at each site. RESULTS: The MAD scores were lower (i.e., more closely matched) for septal compared with free wall sites (15.9 +/- 5.3% vs. 25.3 +/- 10.2%; p < 0.001). Successful ablation sites had a significantly lower MAD score compared with unsuccessful sites (9.5 +/- 2.8% vs. 13.3 +/- 5.6%; p = 0.01), whereas there was only a trend toward a higher CORR for successful ablation sites (98.2 +/- 1.2% vs. 96 +/- 4.7%; p = 0.07). A MAD score < or =12% was 93% sensitive and 75% specific for identifying a successful ablation site. There was an inverse correlation between MAD score and distance from the site of VT origin (r = 0.63, p < 0.001). CONCLUSIONS: A MAD score >12% between RVOT VT and a pace-map at any site suggests sufficient dissimilarity to dissuade ablation at that site. The MAD score can be used to standardize 12-lead ECG waveform morphology comparisons among different laboratories, and may be useful for guiding ablation of VT.     

High-dose chemoradiotherapy and autologous blood stem cell transplantation in multiple myeloma: results of a phase II trial involving 63 patients

Sixty-three patients with high tumor mass multiple myeloma were treated with high-dose chemotherapy and total body irradiation supported by autologous blood stem cell transplantation. After high-dose therapy, they were monitored for a median of 44 months. Seven patients died early from toxicity. All the other patients, including those whose disease was resistant to previous therapies, showed a tumor mass reduction. At 6 months postengraftment, 40 (71%) of the surviving patients had minimal residual disease and 11 (20%) were in apparent complete remission. During follow-up, 25 out of the 63 (39%) patients relapsed and 16 of these died; 31 (49%) had a sustained remission. The median overall and event-free survival times after transplantation were 59 and 43 months, respectively. The initial serum beta 2-microglobulin value (> or < 2.8 mg/L) and length of previous therapy (> or < 6 courses of chemotherapy) were the only significant prognostic factors. In all surviving patients, blood stem cell autograft provided satisfactory and sustained haematopoietic reconstitution most often within 15 days. High dose chemoradiotherapy followed by autologous blood stem cell transplantation is thus an important therapeutic option for young patients with aggressive multiple myeloma.     

Detection of genomic deletions of PKP2 in arrhythmogenic right ventricular cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited myocardial disease that predominantly affects the right ventricle and is associated with ventricular arrhythmias that may lead to sudden cardiac death. Mutations within at least seven separate genes have been identified to cause ARVC, however a genetic culprit remains elusive in approximately 50% of cases. Although negative genetic testing may be secondary to pathogenic mutations within undiscovered genes, an alternative explanation may be the presence of large deletions or duplications involving known genes. These large copy number variants may not be detected with standard clinical genetic testing which is presently limited to direct DNA sequencing. We describe two cases of ARVC possessing large deletions involving plakophilin‐2 (PKP2) identified with microarray analysis and/or multiplex ligation‐dependent probe amplification (MLPA) that would have been classified as genotype negative with standard clinical genetic testing. A deletion of the entire coding region of PKP2 excluding exon 1 was identified in patient 1 and his son. In patient 2, MLPA analysis of PKP2 revealed deletion of the entire gene with subsequent microarray analysis demonstrating a de novo 7.9 Mb deletion of chromosome 12p12.1p11.1. These findings support screening for large copy number variants in clinically suspected ARVC cases without clear disease causing mutations following initial sequencing analysis.     

Correction to: Paramagnetic Fluorinated Nanoemulsions for In Vivo F-19 MRI

Molecular Imaging and Biology -     

The usefulness of the three-dimensional enhanced T1 high-resolution isotropic volume excitation MR in the evaluation of shoulder pathology: comparison with two-dimensional enhanced T1 fat saturation MR

Objective:

To evaluate the diagnostic accuracy of three-dimensional (3D) enhanced T₁ high-resolution isotropic volume excitation (eTHRIVE) shoulder MR for variable shoulder pathology such as rotator cuff tear, labral injury and synovial pathology in comparison with two-dimensional enhanced fast spin echo T₁ fat saturation (2D T1 FS) sequences MR.

Methods:

This retrospective study included 86 patients who underwent MRI of the shoulder using eTHRIVE technique. Two radiologists evaluated anatomic identification of the supraspinatus, glenoid labrum and acromioclavicular joint (AC joint) on routine MRI sequences (2D T1 FS) and compared them with the reformatted eTHRIVE images. Subjective scoring of the images was performed with a four-point scale that rated the degree of discrimination of the shape of the supraspinatus, glenoid labrum and AC joint. The diagnostic accuracy of eTHRIVE compared with routine MR images was evaluated in terms of rotator cuff pathology, labral pathology and synovial pathology.

Results:

Anatomic identification scores of the supraspinatus tendon and labrum were significantly lower for eTHRIVE than for 2D T1 FS. There were no significant differences between eTHRIVE and 2D T1 FS in anatomic identification of the AC joint. There were no significant differences between eTHRIVE and 2D T1 FS in diagnosing the three disease categories.

Conclusion:

eTHRIVE had comparable diagnostic accuracy to 2D T1 FS imaging in the evaluation of rotator cuff tears, labral injury and synovial pathology, but anatomic identification was inferior to that of 2D T1 FS.

Advances in knowledge:

The accuracy of 3D eTHRIVE imaging is comparable to that of 2D T1 FS for the diagnosis of rotator cuff tears, labral injury and synovial pathology.     

Ultrasound-Guided Percutaneous Removal of Wooden Foreign Bodies in the Extremities with Hydro-Dissection Technique

ObjectiveWe described the technique of ultrasound (US)-guided percutaneous removal of the foreign bodies (FB) with hydro-dissection in the radiologic department and presented video files of several cases.ResultsThe mean time required for the entire procedure was approximately 20 minutes. There were no significant complications during the US-guided removal or long-term complications after the procedure. All 4 FBs were successfully removed from the soft tissue under US guidance.ConclusionUltrasound-guided percutaneous removal of the FBs with hydro-dissection in the radiology department is a less invasive and safe method over surgical removal in the operating room. Additionally, the use of a guide wire and serial dilator may help minimize soft tissue injury and facilitate the introduction of forceps.     

Hyperbaric oxygen therapy improves angiogenesis and bone formation in critical sized diaphyseal defects

Besides the use of autologous bone grafting several osteoconductive and osteoinductive methods have been reported to improve bone healing. However, persistent non‐union occurs in a considerable number of cases and compromised angiogenesis is suspected to impede bone regeneration. Hyperbaric oxygen therapy (HBO) improves angiogenesis. This study evaluates the effects of HBO on bone defects treated with autologous bone grafting in a bone defect model in rabbits. Twenty‐four New‐Zealand White Rabbits were subjected to a unilateral critical sized diaphyseal radius bone defect and treated with autologous cancellous bone transplantation. The study groups were exposed to an additional HBO treatment regimen. Bone regeneration was evaluated radiologically and histologically at 3 and 6 weeks, angiogenesis was assessed by immunohistochemistry at three and six weeks. The additional administration of HBO resulted in a significantly increased new bone formation and angiogenesis compared to the sole treatment with autologous bone grafting. These results were apparent after three and six weeks of treatment. The addition of HBO therapy to autologous bone grafts leads to significantly improved bone regeneration. The increase in angiogenesis observed could play a crucial role for the results observed. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:513–520, 2015.