Erdheim-Chester's disease of the heart: a diagnostic conundrum and collision with the same mass in the orbit

Erdheim-Chester's disease is a rare multisystem xanthogranulomatosis, afflicting the skeletal system with the occasional involvement of soft tissues. We delineate an unusual case of a cardiac variant of Erdheim-Chester's disease presenting with pericardial effusion and as a collision with a synchronous orbital manifestation. We describe our diagnostic pathway and propose a novel treatment option involving nonsteroidal anti-inflammatory drugs. The role of cyclo-oxygenase in the disease process and inhibition thereof by NSAIDs is hypothesized and discussed.     

Long-term prognosis of Salter-Harris type 2 injuries of the distal femoral physis

The objective of this study was to assess long-term sequelae of Salter-Harris type 2 injuries on growth of the distal femoral physis. A retrospective study of 20 patients with Salter-Harris type 2 distal femoral injuries, who were managed between 1994 and 2003, was carried out. The average period of follow-up was 4 years and 2 months. Mean age of fracture was 11 years (range 8-15 years). We classified radiologically these fractures into three types according to initial displacement on anteroposterior and lateral radiographs (type 1=less than 2 mm; type 2=more than 2 mm, contact between fragments; type 3=no contact). Further subdivision into A and B was made according to the absence or presence of metaphyseal comminution. Clinical and radiological outcomes were evaluated at latest follow-up. Two patients with type 1 injuries were treated conservatively, with no complication. All type 2 and 3 fractures (18) were reduced under general anesthesia. At latest follow-up, 14 patients (70%) sustained a complication due to either epiphysiodesis (12), femoral over-lengthening (1) or associated loss of knee motion (5). Seven out of the 12 epiphysiodeses were initial type B injuries. All type 3 fractures ended with complications. The prognosis of these fractures, often caused by a high-energy trauma, can be severe. Additional subdivision of Salter-Harris type 2 distal femoral physeal injuries is proposed to warn the clinician on specific fracture patterns with higher complication risk. Greater awareness of the numerous growth problems that may occur is needed in type 2B, in which the germinal layer of the physeal cells is damaged.     

Surgery for large vestibular schwannomas: how patients and surgeons perceive quality of life

OBJECT: The aim of this study was to assess the consequences of total removal of a large vestibular schwannoma on the patient's symptoms and quality of life (QOL). METHODS: A questionnaire regarding preoperative and postoperative symptoms with measures of both daily and global QOL and a modified 36-Item Short Form Health Survey (SF-36) QOL instrument were sent to 103 patients who had undergone surgery via a retrosigmoid approach for total removal of a Grade III or IV vestibular schwannoma. In addition, 48 patients underwent follow-up clinical examinations to assess their conditions. Seventy-two of the 103 patients completed and returned the questionnaire. Forty-six (64%) of the schwannomas were Grade IV and 26 (36%) were Grade III. The patients' pre- and postoperative symptoms were similar to those reported in other studies. The patients' perceptions of facial movement were likely to be worse than the clinicians' estimation based on the House-Brackmann classification. All scores in the QOL categories were significantly reduced when compared with normative data. Patients with large vestibular schwannomas had lower scores in all SF-36 categories except pain compared with data from other studies. Psychological problems were the preponderant symptoms, and their presence was the most powerful predictive variable for global and daily QOL. CONCLUSIONS: Surgery for a large vestibular schwannoma has a significant impact on the patient's QOL. To improve QOL postoperatively, the patient should be prepared and well informed of the consequences of such a surgery on QOL. Clinicians must be aware that early involvement of a clinical psychologist may be very helpful.     

Adaptation of methotrexate determination in serum with Unicel DxC600(®)

High-dose methotrexate treatment requires pharmacological monitoring in order to tailor administration of folinic acid to reduce side effects. The aim of the study was to validate the adaptation of the EMIT reagent on the l'Unicel DxC 600? Beckman Coulter. The establishment of two assays was necessary to obtain a quantification limit as low as possible (0.05 μmol/L). The linearity of the adapted methods extends from 0.05 to 0.25 μmol/L on the one hand, and from 0.25 to 1 μmol/L on the other hand. For each method, fidelity and accuracy were studied and the limits of detection and quantification were quantified. The correlation with the FPIA method was performed on the Abbott TDX(?). The results of all tests are satisfactory with coefficients of variation (CV) of repeatability and reproducibility of less than 6%. However the daily assays are heavy as 66% of blood samples require at least two dosages and 30% a manual dilution.     

Evolution of the donor T-cell repertoire in recipients in the second decade after allogeneic stem cell transplantation

After allogeneic stem cell transplantation (SCT), T lymphocyte function is reestablished from the donor's postthymic T cells and through thymic T-cell neogenesis. The immune repertoire and its relation to that of the donor have not been characterized in detail in long-term adult SCT survivors. We studied 21 healthy patients in their second decade after a myeloablative SCT for hematologic malignancy (median follow-up, 12 years). Immune profiles were compared with donor samples cryopreserved at transplant and beyond 10 years from SCT. Only one recipient was on continuing immunosuppression. Compared with the donor at transplant, there was no significant difference in CD4, CD8, natural killer, and B-cell blood counts. However, compared with donors, recipients had significantly fewer naive T cells, lower T-cell receptor excision circle levels, fewer CD4 central memory cells, more effector CD8(+) cells, and more regulatory T cells. TCR repertoire analysis showed no significant difference in complexity of TCRVβ spectratype between recipients and donors, although spectratype profiles had diverged with both gain and loss of donor repertoire peaks in the recipient. In conclusion, long-term allogeneic SCT survivors have subtle defects in their immune profile consistent with defective thymic function but compatible with normal health. This study is registered at http://www.clinicaltrials.gov as NCT00106925.     

Robust expansion of viral antigen-specific CD4+ and CD8+ T cells for adoptive T cell therapy using gene-modified activated T cells as antigen presenting cells

Cytomegalovirus (CMV) reactivation after stem cell transplantation can be treated with CMV-specific T cells, but current in vitro techniques using dendritic cells as antigen-presenting cells are time-consuming and expensive. To simplify the production of clinical grade CMV-specific T cells, we evaluated gene-modified activated T cells [antigen presenting T cells (T-APCs)] as a reliable and easily produced source of APCs to boost CD4+ and CD8+ T-cell responses against the immunodominant CMV antigen pp65. T-APCs expressing the full-length immunodominant CMV pp65 gene were used to stimulate the expansion of autologous T cells. After 10 to 14 days, the T cell lines were tested for antigen specificity by using the flow cytometric intracellular detection of interferon-gamma after stimulation for 6 hours with a pp65 peptide library of 15-mers, overlapping by 11 amino acids. Under optimal conditions, this technique induced a median 766-fold and a 652-fold expansion of pp65-specific CD4+ and CD8+ responder cells, respectively, in 15 T cell lines. In 13 of 15 T cell lines, over 10 antigen-specific CD4+ plus CD8+ T cells were generated starting with only 5x10 peripheral blood mononuclear cells, representing an over 3-log increase. These data indicate that T-APCs efficiently boost pp65-specific CD4+ and CD8+ T cell numbers to clinically useful levels. The approach has the advantage of using a single leukocyte collection from the donor to generate large numbers of CMV-specific T cells within a total 3-week culture period using only one stimulation of antigen.     

Enhancement of Oral Bioavailability of E804 by Self-Nanoemulsifying Drug Delivery System (SNEDDS) in Rats

Indirubin and its derivatives have been shown to interrupt the cell cycle by inhibiting cyclin-dependent kinases, explaining their long-time use in traditional Chinese medicine for the treatment of chronic myelocytic leukemia. A potent derivative of indirubin, indirubin-3′-oxime 2,3-dihydroxypropyl ether (E804), has been shown to block the Src-Stat3 and Src-Stat5 signaling pathway in human cancer cells, inducing apoptosis. The anticancer effects of E804, however, cannot be easily examined in vivo because of its poor water solubility and low absorption. The aim of this study was to develop and evaluate a self-nanoemulsifying drug delivery system (SNEDDS) containing E804 for enhancing its solubility and bioavailability. Solubility of E804 was determined in various vehicles, and pseudoternary phase diagram was used to evaluate the self-emulsifying existence area. The SNEDDS composed of Capmul MCM (oil), Solutol HS 15 (surfactant), and polyethylene glycol 400 (cosurfactant) on the ratio of 20.5:62.5:16 loaded 1.5% of E804. The particle size of droplets was found to be 16.8 and 140 nm, and SNEDDS was stable after freeze–thaw cycles and upon dilution in HCl 0.1 N and pH 7.4 HBSS++. The ability of formulation for absorption enhancement was studied in rats in vivo after oral administration. The results showed that the developed SNEDDS increased the E804 bioavailability 984.23% compared with the aqueous suspension. Our studies for the first time show that the developed SNEDDS can be used as a possible formulation for E804 to improve its solubility and oral bioavailability. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:3792–3799, 2013