Novel insight into the detailed myocardial motion and deformation of the rodent heart using high-resolution phase contrast cardiovascular magnetic resonance

Background

Phase contrast velocimetry cardiovascular magnetic resonance (PC-CMR) is a powerful and versatile tool allowing assessment of in vivo motion of the myocardium. However, PC-CMR is sensitive to motion related artifacts causing errors that are geometrically systematic, rendering regional analysis of myocardial function challenging. The objective of this study was to establish an optimized PC-CMR method able to provide novel insight in the complex regional motion and strain of the rodent myocardium, and provide a proof-of-concept in normal and diseased rat hearts with higher temporal and spatial resolution than previously reported.

Methods

A PC-CMR protocol optimized for assessing the motion and deformation of the myocardium in rats with high spatiotemporal resolution was established, and ten animals with different degree of cardiac dysfunction underwent examination and served as proof-of-concept. Global and regional myocardial velocities and circumferential strain were calculated, and the results were compared to five control animals. Furthermore, the global strain measurements were validated against speckle-tracking echocardiography, and inter- and intrastudy variability of the protocol were evaluated.

Results

The presented method allows assessment of regional myocardial function in rats with high level of detail; temporal resolution was 3.2 ms, and analysis was done using 32 circumferential segments. In the dysfunctional hearts, global and regional function were distinctly altered, including reduced global peak values, increased regional heterogeneity and increased index of dyssynchrony. Strain derived from the PC-CMR data was in excellent agreement with echocardiography (r = 0.95, p < 0.001; limits-of-agreement −0.02 ± 3.92%strain), and intra- and interstudy variability were low for both velocity and strain (limits-of-agreement, radial motion: 0.01 ± 0.32 cm/s and −0.06 ± 0.75 cm/s; circumferential strain: -0.16 ± 0.89%strain and −0.71 ± 1.67%strain, for intra- and interstudy, respectively).

Conclusion

We demonstrate, for the first time, that PC-CMR enables high-resolution evaluation of in vivo circumferential strain in addition to myocardial motion of the rat heart. In combination with the superior geometric robustness of CMR, this ultimately provides a tool for longitudinal studies of regional function in rodents with high level of detail.     

Cervical lymph node metastasis in squamous cell carcinoma of the buccal mucosa: a retrospective study on pattern of involvement and clinical analysis

Background The study was performed with an aim to map the pattern of metastasis of squamous cell carcinomas of buccal mucosa to various cervical lymph node levels and analyze its correlation with primary tumor size and histo-pathological grading. Material and Methods 254 patients with squamous cell carcinoma of the buccal mucosa treated with surgery first approach were analyzed retrospectively. The tumor size was noted from pre-operative CT Scans and were divided into early and advanced tumors. The resected specimen was studied to note the histo-pathological grading of the squamous cell carcinoma and the metastatic deposits at various lymph node levels. Results Out of 254 patients (149 females, 105 males), 145 patients showed histo-pathologically proven metastatic deposits in one or more lymph nodes out of which there were 56 patients showing occult metastasis. 78/145 patients showed metastatic involvement of level IB and/or IA lymph nodes, 31 showed involvement of level II and/or I lymph nodes, 27 showed involvement of level III with or without involvement of level I and II and 9 showed metastasis to level IV and V lymph nodes with or without level I, II or III lymph nodes. Cervical lymph node metastasis had statistically significant association with tumor size with advanced tumors showing worse pattern of metastatic spread beyond level I and II lymph nodes. As the degree of differentiation of squamous cell carcinoma reduced, they were more prone for cervical metastasis with moderately and poorly differentiated squamous cell carcinoma showing higher involvement of level III, IV and V lymph nodes. Conclusions The majority of buccal mucosa cases showed metastasis to level I, II and III lymph nodes out of which level IB and/or IA was most frequently involved. Metastasis to level IV and V lymph nodes was rare and was seen especially in patients with advanced primary tumor and poor histo-pathologic differentiation. Key words:Oral squamous cell carcinoma (OSCC), cervical lymph node metastasis, histologic differentiation, locally advanced disease.     

Eosinophils stimulate fibroblast DNA synthesis

Fibrosis complicates a number of chronic inflammatory diseases and occurs in some conditions following chronic hypereosinophilic syndromes. We assessed whether eosinophils might be a source of fibrogenic factors. Extracts of human and guinea pig cell populations enriched for eosinophils contained substances that stimulated tritiated thymidine incorporation by human fibroblasts. Supernatants derived from resting eosinophils and extracts prepared from eosinophil granules also contained fibrogenic factors. Our findings demonstrate a new potential role for eosinophils and suggest a causal relationship between tissue eosinophilia and scar formation in certain parasitic conditions.     

Generation of CD1+RelB+ dendritic cells and tartrate-resistant acid phosphatase-positive osteoclast-like multinucleated giant cells from human monocytes

We previously showed that granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) stimulate the differentiation of human monocytes into two phenotypically distinct types of macrophages. However, in vivo, not only CSF but also many other cytokines are produced under various conditions. Those cytokines may modulate the differentiation of monocytes by CSFs. In the present study, we showed that CD14+ adherent human monocytes can differentiate into CD1+relB+ dendritic cells (DC) by the combination of GM-CSF plus interleukin-4 (IL-4) and that they differentiate into tartrate-resistant acid phosphatase (TRAP)-positive osteoclast-like multinucleated giant cells (MGC) by the combination of M-CSF plus IL-4. However, the monocyte-derived DC were not terminally differentiated cells; they could still convert to macrophages in response to M-CSF. Tumor necrosis factor-alpha (TNF-alpha) stimulated the terminal differentiation of the DC by downregulating the expression of the M-CSF receptor, cfms mRNA, and aborting the potential to convert to macrophages. In contrast to IL-4, interferon-gamma (IFN-gamma) had no demonstrable effect on the differentiation of monocytes. Rather, IFN- gamma antagonized the effect of IL-4 and suppressed the DC and MGC formation induced by GM-CSF + IL-4 and M-CSF + IL-4, respectively. Taken together, these results provide a new aspect to our knowledge of monocyte differentiation and provide evidence that human monocytes are flexible in their differentiation potential and are precursors not only of macrophages but also of CD1+relB+DC and TRAP-positive MGC. Such a diverse pathway of monocyte differentiation may constitute one of the basic mechanisms of immune regulation.     

The art of gene therapy for glioma： a review of the challenging road to the bedside

Glioblastoma muhiforme （GBM） is a highly invasive brain tumour that is unvaryingly fatal in humans clesplte even aggres- sive therapeutic approaches such as surgical resection followed by chemotherapy and radiotherapy. Unconventional treatment options such as gene therapy provide an intriguing option for curbing glioma related deaths. To date, gene therapy has yielded encouraging results in preclinical animal models as well as promising safety profiles in phase I clinical trials, but has failed to demonstrate significant therapeutic efficacy in phase III clinical trials. The most widely studied antiglioma gene therapy strategies are suicide gene therapy, genetic immuno- therapy and oncolytic virotherapy, and we have attributed the challenging transition of these modalities into the clinic to four major road- blocks ： （ 1 ） anatomical features of the central nervous system, （2） the host immune system, （3） heterogeneity and invasiveness of GBM and （4） limitations in current GBM animal models. In this review, we discuss possible ways to jump these hurdles and develop new gene therapies that may be used alone or in synergy with other modalities to provide a powerful treatment option for patients with GBM.     

The CT guided transoral approach: A biopsy technique for a poorly differentiated chordoma in a 5 year old

Mass lesions presenting at the craniocervical junction often present a unique challenge due to the complex anatomic arrangement limiting access for tissue diagnosis. The transoral approach has predominantly been used for percutaneous vertebroplasty of high cervical vertebrae with limited literature describing image guided biopsy for bony lesions in this region in the pediatric patient. We describe a technique of computed tomography guided transoral biopsy of a poorly differentiated chordoma located at the C1–C2 level in a 5-year-old child, and review this diagnosis.     

Revisional bariatric surgery: perioperative morbidity is determined by type of procedure

Background

Revisional bariatric procedures are on the rise. The higher complexity of these procedures has been reported to lead to increased risk of complications. The objective of our study was to compare the perioperative risk profile of revisional bariatric surgery with primary bariatric surgery in our experience.

Methods

A prospectively maintained database of all patients undergoing bariatric surgery by three fellowship-trained bariatric surgeons from June 2005 to January 2013 at a center of excellence was reviewed. Patient demographics, type of initial and revisional operation, number of prior gastric surgeries, indications for revision, postoperative morbidity and mortality, length of stay, 30-day readmissions, and reoperations were recorded. These outcomes were compared between revisional and primary procedures by the Mann–Whitney or Chi square tests.

Results

Of 1,556 patients undergoing bariatric surgery, 102 patients (6.5 %) underwent revisional procedures during the study period. Indications for revisions included inadequate weight loss in 67, failed fundoplications with recurrent gastroesophageal reflux disease in 29, and other in 6 cases. Revisional bariatric procedures belonged into four categories: band to sleeve gastrectomy (n = 23), band to Roux-en-Y gastric bypass (n = 25), fundoplication to bypass (n = 29), and other (n = 25). Revisional procedures were associated with higher rates of readmissions and overall morbidity but no differences in leak rates and mortality compared with primary procedures. Band revisions had similar length of stay with primary procedures and had fewer complications compared with other revisions. Patients undergoing fundoplication to bypass revisions were older, had a higher number of prior gastric procedures, and the highest morbidity (40 %) and reoperation (20 %) rates.

Conclusions

In experienced hands, many revisional bariatric procedures can be accomplished safely, with excellent perioperative outcomes that are similar to primary procedures. As the complexity of the revisional procedure and number of prior surgeries increases, however, so does the perioperative morbidity, with fundoplication revisions to gastric bypass representing the highest risk group.