Metastases of esophageal carcinoma to skeletal muscle: Single center experience

Metastases of esophageal carcinoma to the skeletal muscle are rare, but the incidence may be increasing because of better diagnosis resulting from widespread use of positron emission tomography/computed tomography (PET/CT). A cohort of 205 patients with esophageal carcinoma treated at our center who had PET/CT between 2006 and 2010 was retrospectively evaluated for the presence of skeletal muscle metastases. Four patients had skeletal muscle metastases of esophageal carcinoma, including two patients with squamous cell carcinoma. In another patient with squamous cell carcinoma of the esophagus and synchronous skeletal muscle metastases, muscle metastases were subsequently shown to be related to second primary pancreatic adenocarcinoma. In all cases, skeletal muscle metastases were the first manifestation of systemic disease. In three patients palliation was obtained with the combination of external beam radiation therapy, systemic chemotherapy or surgical resection. Skeletal muscle metastases are a rare complication of esophageal carcinoma.     

Effect of transnasal insufflation on sleep disordered breathing in acute stroke: a preliminary study

Background and Purpose

Sleep disordered breathing (SDB) is frequent in acute stroke patients and is associated with early neurologic worsening and poor outcome. Although continuous positive airway pressure (CPAP) effectively treats SDB, compliance is low. The objective of the present study was to assess the tolerance and the efficacy of a continuous high-flow-rate air administered through an open nasal cannula (transnasal insufflation, TNI), a less-intrusive method, to treat SDB in acute stroke patients.

Methods

Ten patients (age, 56.8?±?10.7?years), with SDB ranging from moderate to severe (apnea?Chypopnea index, AHI, >15/h of sleep) and on a standard sleep study at a mean of 4.8?±?3.7?days after ischemic stroke (range, 1?C15?days), were selected. The night after, they underwent a second sleep study while receiving TNI (18?L/min).

Results

TNI was well tolerated by all patients. For the entire group, TNI decreased the AHI from 40.4?±?25.7 to 30.8?±?25.7/h (p?=?0.001) and the oxygen desaturation index >3% from 40.7?±?28.4 to 31?±?22.5/h (p?=?0.02). All participants except one showed a decrease in AHI. The percentage of slow-wave sleep significantly increased with TNI from 16.7?±?8.2% to 22.3?±?7.4% (p?=?0.01). There was also a trend toward a reduction in markers of sleep disruption (number of awakenings, arousal index).

Conclusions

TNI improves SDB indices, and possibly sleep parameters, in stroke patients. Although these changes are modest, our findings suggest that TNI is a viable treatment alternative to CPAP in patients with SDB in the acute phase of ischemic stroke.     

Quels marqueurs osseux chez les patients hémodialysés : phosphatases alcalines osseuses ou ß-CrossLaps ?

BackgroundBone turnover (BT) abnormalities are frequently observed in patients with chronic kidney disease. Bone biopsy remains the gold standard for diagnosis; however, its invasive nature has led to its decreased utilisation. The serum parathyroid hormone (PTH) level is not a reliable bone marker (BM) for BT assessment. The latest international recommendations suggest the use of total alkaline phosphatase (t-ALP) or bone-specific alkaline phosphatase (b-ALP), but not ß-CrossLaps (CTX). We compared b-ALP, t-ALP, and CTX levels in patients on haemodialysis (HD).MethodsAll HD patients at a single institution following a standard 3 × 4 to 3 × 5 hours schedule were included in the study, provided they were free from liver disease. Serum intact PTH, t-ALP, b-ALP, and CTX values were compared at baseline and after 18 months of treatment. A kinetic study was performed for pre- and postdialysis CTX values over a 2-week period. We described the longitudinal evolution of these BMs in two typical patients.ResultsA total of 98 patients on HD (46% female) were evaluated. The mean age was 69.8 ± 11 years and the mean duration of dialysis was 54.4 ± 61 months. At baseline, CTX (2.1 ± 1 μg/L) correlated well with b-ALP (18 ± 11 μg/L; r = 0.64; P < 0.001) and PTH (221 ± 165 pg/mL; r = 0.62; P < 0.001). The changes in these values at 18 months were also correlated (ΔCTX compared with Δb-ALP: r = 0.51; P < 0.001; Δb-ALP compared with ΔPTH: r = 0.37, P < 0.01). b-ALP and t-ALP (245 ± 132 U/L) were closely correlated (r = 0.78), as was their variation over 18 months (r = 0.67), but t-ALP did not correlate with PTH, and correlated poorly with CTX (r = 0.38). The CTX reduction ratio during standard dialysis was approximately 70 to 75% over each session, although predialysis values remained stable.ConclusionIn HD patients, mean CTX values are five times higher than the normal range. CTX appears to be an alternative to b-ALP for assessing BT. b-ALP remains the standard BM, despite being expensive, infrequently available in many laboratories, and not useful for patients with liver disease.     

Functional mapping and single chain construction of the anti-cytokeratin 8 monoclonal antibody TS1

The anti-cytokeratin (CK) 8 monoclonal antibody (mab) TS1 has been shown to efficiently bind to CK8 expressed in carcinomas in vivo. The anti-idiotypic antibody of TS1, alphaTS1, can be used to regulate the tumor:non-tumor ratio of TS1 by clearing non-tumor binding TS1 from the circulation. If the interaction of TS1 to CK8 and alphaTS1 is fully understood, mutations can be used to improve the tumor:non-tumor ratio. A scFv was made of the mab TS1 and residues earlier identified by Erlandsson et al. as important for the interaction with both its antigen CK8 and its anti-idiotype alphaTS1, were mutated to alanine or amides and expressed in E. coli. The effects of the mutations were studied by ELISA and residues important for the interactions to both CK8 and alphaTS1 were identified as mainly tyrosines, charged residues, a serine and a tryptophan. Altogether, nine amino acid residues in TS1 were found to be important in the interaction to alphaTS1 and six residues for the interaction to CK8. Important residues, clustered together in the modelled protein, were identified as residues from CDR 3 of the heavy chain and the unexpected participation of a residue in CDR 2 of the light chain. Some of the important residues are likely to be hotspots. Hotspots constitute a few residues in an interaction that contribute most to the binding, energetically. Amino acid residues in hotspots often cluster together in the center of the interaction interface, but can also be spread out to the periphery. The hotspots are often surrounded by hydrophobic patches, which are seen in the modelled TS1 protein used in this study. Amino acid residues that increased the affinity when mutated were also identified for both interactions. These residues are likely to be located outside the interacting interface. It can from this study be concluded that it is wise to precede the mutational procedure with experiments that can give guidelines for the selection of which amino acid residues to mutate. If the guidelines from the chemical modifications from Erlandsson et al. not had been used, this study would have left some residues unmutated and thereby missed important information.     

Adipocytes derived from PA6 cells reliably promote the differentiation of dopaminergic neurons from human embryonic stem cells

The PA6 stromal cell line comprises a heterogeneous population of cells that can induce both mouse and human embryonic stem cells to differentiate into dopaminergic neurons. This ability of PA6 cells has been termed stromal cell‐derived inducing activity (SDIA). The level of SDIA has been found to vary considerably between and within batches of PA6 cells. Not only are the molecular mechanisms that underlie SDIA unknown but also the cell type(s) within the heterogeneous PA6 cultures that underlie SDIA remain poorly defined. In this study, we reveal that adipocytes, which are present within the heterogeneous PA6 cell population, robustly release the factors mediating SDIA. Furthermore, we report that the coculture of human embryonic stem cells with PA6‐derived adipocytes reliably induces their differentiation into midbrain dopaminergic neurons. © 2014 Wiley Periodicals, Inc.