A novel immune competent murine hypertrophic scar contracture model: A tool to elucidate disease mechanism and develop new therapies

Hypertrophic scar (HSc) contraction following burn injury causes contractures. Contractures are painful and disfiguring. Current therapies are marginally effective. To study pathogenesis and develop new therapies, a murine model is needed. We have created a validated immune‐competent murine HSc model. A third‐degree burn was created on dorsum of C57BL/6 mice. Three days postburn, tissue was excised and grafted with ear skin. Graft contraction was analyzed and tissue harvested on different time points. Outcomes were compared with human condition to validate the model. To confirm graft survival, green fluorescent protein (GFP) mice were used, and histologic analysis was performed to differentiate between ear and back skin. Role of panniculus carnosus in contraction was analyzed. Cellularity was assessed with 4′,6‐diamidino‐2‐phenylindole. Collagen maturation was assessed with Picro‐sirius red. Mast cells were stained with Toluidine blue. Macrophages were detected with F4/80 immune. Vascularity was assessed with CD31 immune. RNA for contractile proteins was detected by quantitative real‐time polymerase chain reaction (qRT‐PCR). Elastic moduli of skin and scar tissue were analyzed using a microstrain analyzer. Grafts contracted to ～45% of their original size by day 14 and maintained their size. Grafting of GFP mouse skin onto wild‐type mice, and analysis of dermal thickness and hair follicle density, confirmed graft survival. Interestingly, hair follicles disappeared after grafting and regenerated in ear skin configuration by day 30. Radiological analysis revealed that panniculus carnosus doesn't contribute to contraction. Microscopic analyses showed that grafts show increase in cellularity. Granulation tissue formed after day 3. Collagen analysis revealed increases in collagen maturation over time. CD31 stain revealed increased vascularity. Macrophages and mast cells were increased. qRT‐PCR showed up‐regulation of transforming growth factor beta, alpha smooth muscle actin, and rho‐associated protein kinase 2 in HSc. Tensile testing revealed that human skin and scar tissues are tougher than mouse skin and scar tissues.     

Electrode catheter ablation for ventricular tachycardia: efficacy of a single cathodal shock.

Electrode catheter ablation was used to treat 11 distinct types of sustained ventricular tachycardias in eight patients. Rigid electrophysiological criteria were used to identify five left and five right ventricular arrhythmogenic sites; one of them gave rise to tachycardia with two distinct configurations. A single R-wave-synchronised 250 or 150 J cathodal shock was delivered at each site. One patient had mildly symptomatic episodes of sustained ventricular tachycardia during the first four days after the shock--there were no other complications. At discharge none of the patients was taking antiarrhythmic drugs. They were followed for 8-20 months (mean 14). Ablation abolished five of the 11 ventricular tachycardias. There was no recurrence in three of the eight patients. In two patients identical ventricular tachycardias recurred because the identification of the arrhythmogenic site was incorrect.     

Distinction between the Preneoplastic and Neoplastic State of Murine Mammary Glands

We have, using nuclear magnetic resonance spectroscopy, measured the relaxation times and diffusion coefficient of water protons in primary mammary adenocarcinomas of mice. In our biological model, three morphological stages were defined: (a) mammary gland tissue from pregnant mice, (b) preneoplastic nodules, and (c) neoplastic tissue. It was found that neoplastic tissues could be distinguished from normal and prenoeplastic tissue. Spin-spin and spin-lattice relaxation times and the diffusion coefficient of water protons are increased in the neoplastic tissue relative to mammary gland tissue from pregnant mice and preneoplastic nodule tissue.     

Genomes, phylogeny, and evolutionary systems biology

With the completion of the human genome and the growing number of diverse genomes being sequenced, a new age of evolutionary research is currently taking shape. The myriad of technological breakthroughs in biology that are leading to the unification of broad scientific fields such as molecular biology, biochemistry, physics, mathematics, and computer science are now known as systems biology. Here, I present an overview, with an emphasis on eukaryotes, of how the postgenomics era is adopting comparative approaches that go beyond comparisons among model organisms to shape the nascent field of evolutionary systems biology.     

Giant retroperitoneal leiomyosarcoma. Multiorgan block removal

INTRODUCTION

Retroperitoneal tumors are rare, mostly malignant. Locally aggressive, and more frequent in women in their 5th decade of life. Its symptoms are nonspecific, including abdominal pain and palpable mass. To diagnosis is helpful computed tomography and biopsy. It needs surgery for absolute healing.

PRESENTATION OF CASE

67 years old man was admitted with back pain and fever. Abdominal imaging tests showed a 15 cm abdominal mass without clear organodependencia. Endoscopy with biopsies evidenced mesenchymal neoplasia of undetermined origin. In surgery we confirm its resecability and was necessary multiorgan resection. Pathologic diagnosis: well differentiated retroperitoneal leiomyosarcoma. Started adjuvant radiotherapy. In subsequent tests showed the presence of liver metastases.

DISCUSSION

Retroperitoneal tumors are developed from nerve, vascular, muscular, connective, supportive and fibroareolar tissue from this space. Its size does not modificate survival or resectability. We used TC and biopsy for its diagnose. Adjuvant therapy does not affect survival or quality of life, surgery remains the only curative option. Locoregional recurrence is the most influential figure in the prognosis. A large percentage of patients required a second surgery (between 45 and 82%).

CONCLUSION

The only curative option of retroperitoneal sarcomas is surgery, which usually requires multiple organ resection. Chemotherapy and radiotherapy are mostly a surgical supplement. Chemotherapy has not shown significant increase in survival.     

Bochdalek hernia and repetitive pancreatitis in a 33 year old woman

INTRODUCTION

Bochdalek hernia presentation in adulthood is rare. The presentation in newborns is the most common, manifesting with data from respiratory failure secondary to pulmonary hypoplasia, requiring urgent surgical intervention with high morbidity and mortality.

PRESENTATION OF CASE

We present the case of a 33 year old woman admitted in the emergency room with severe abdominal pain in the left upper quadrant and disnea. After physical examination and laboratory test we diagnose mild acute pancreatitis. The patient haven’t colelitiasis by ulstrasound or any risk factor for pancreatitis. Initially she received medical treatment and was discharged after one week. After four weeks she presented the same symptoms in two different occasions, with severe and mild pancreatitis respectively. A computed tomography report a left posterolateral diafragmatic hernia. In spite of the rare association of pancreatitis and Bochdalek hernia, we realized it as the etiology until the second event and planned his surgery. We made a posterolateral torachotomy and diafragmatic plasty with a politetrafluoroetileno mesh and after a 6 months follow up she has coursed asymptomatic.

DISCUSSION

The high rate of complications in this type of hernia requires us to perform surgical treatment as the hernia is detected. In this case it is prudent medical treatment prior to surgical correction despite this being the origin of the pancreatitis, because the systemic inflammatory response added by the surgical act could result in a higher rate of complications if not performed at the appropriate time. There is no precise rule to determine the type of approach of choice in this type of hernia which thoracotomy or laparotomy may be used.

CONCLUSION

Bochdalek hernia is a rare find in adults who require treatment immediately after diagnosis because of the high risk of complications. When presented with data from pancreatitis is recommended to complete the medical treatment of pancreatitis before surgery to obtain the best results, unless it exist another abdominal complication.