Attention to Background Strain Is Essential for Metabolic Research: C57BL/6 and the International Knockout Mouse Consortium

The International Knockout Mouse Consortium (IKMC) introduces its targeted constructs into C57BL/6N embryonic stem cells. However, breeding with a Cre-recombinase and/or Flp-recombinase mouse is required for the generation of a null allele with the IKMC cassette. Many recombinase strains are in the C57BL/6J background, resulting in knockout animals on a mixed strain background. This can lead to variability in metabolic data and the use of improper control groups. While C57BL/6N and C57BL/6J are derived from the same parental C57BL/6 strain, there are key genotypic and phenotypic differences between these substrains. Many researchers may not even be aware of these differences, as the shorthand C57BL/6 is often used to describe both substrains. We found that 58% of articles involving genetically modified mouse models did not completely address background strain. This review will describe these two substrains and highlight the importance of separate consideration in mouse model development. Our aim is to increase awareness of this issue in the diabetes research community and to provide practical strategies to enable researchers to avoid mixed strain animals when using IKMC knockout mice.     

Permanent acceptance of both cardiac and skin allografts using a mild conditioning regimen for the induction of stable mixed chimerism in mice

Patients who are receiving an organ transplant nowadays are sentenced to the life-long administration of immunosuppressive drugs, which have serious side effects. The reliable induction of donor-specific tolerance therefore remains a major goal in organ transplantation. Previously, we have developed a sublethal, non-myeloablative murine model in which permanent mixed, multilineage chimerism and donor-specific tolerance are established. Our model involves engraftment of fully allogeneic T cell depleted donor bone marrow cells in low dose irradiated and anti-CD3 treated major histocompatibility complex (MHC)-disparate recipient mice. To investigate whether vascularized organ grafts are accepted in our model, we performed heterotopic heart transplantations in our mixed chimeric mice. Chimeric mice permanently accepted hearts from the bone marrow donor (>130 days) and rapidly rejected third party-type allografts (median survival time 9 days). Untreated control recipient mice rejected both donor- and third party-type allografts. In addition, mice that accepted their cardiac grafts, donor-specific acceptance of skin grafts was observed. In conclusion, the establishment of stable mixed chimerism with this low-toxicity regimen resulted in permanent donor-specific acceptance of vascularized organ as well as skin grafts across a full MHC barrier.     

澳大利亚Danielle Mazza教授全科医疗案例分析——产后抑郁症

1病例简介:我从未觉得我的生活是如此的糟糕Jessica,30岁,妊娠前一直从事专业技术工作,有1个6个月大的孩子。她说,在生完孩子后的最初3个月内,她有持续性的腹痛。几个月前,距离她重返工作岗位大约一半时间的时候,她感觉身体不适,并且在过去1个月里越来越严重。她所描述的早期症状是生理性的:恶心、头晕、极度嗜睡。她去看过几个医生,医生给她检测了血红蛋白水平,解释说这可能是哺乳和重返     

Waiting for elective surgery: effect on physical problems and postoperative recovery

BACKGROUND: Long waiting times for elective surgery pose a threat to the quality of care. Our study aimed to assess (i) the physical symptoms and disabilities patients experience during the wait, (ii) the perceived improvements after surgery and (iii) whether problems increase during the wait or longer waits affect postoperative outcomes. METHODS: A cross-sectional questionnaire study with postoperative follow up was held among patients waiting for surgery of varicose veins (n = 176), inguinal hernia (n = 201) and gallstones (n = 128) in 27 hospitals. RESULTS: During the wait, each group reported increased levels of pain and impaired mobility (Nottingham Health Profile, P < 0.05). However, 15-41% of patients had no or mild symptoms, whereas 5% of inguinal hernia patients had severe pain and 17% of gallstone patients reported >or=1 colic attacks per week. Surgery resolved symptoms in 86-95% of patients. The length of the wait was not associated with problems during the wait or with postoperative outcomes (multilevel regression analysis, P > 0.01). CONCLUSIONS: Waiting for general surgery primarily prolongs the suffering from symptoms, which are relieved by surgery. Although the prioritization of patients with more severe symptoms would reduce the overall burden of waiting, patients with minimal symptoms may be advised to refrain from surgery.     

Case Report: Osteonecrosis of the Femoral Head after Hip Arthroscopy

Background  

Hip arthroscopy is a common orthopaedic procedure used as a diagnostic and therapeutic tool with a multitude of surgical indications. The complication rate is reportedly between 1.3% and 23.3%. Major complications are related to traction, fluid extravasation, and iatrogenic chondral injury. Although osteonecrosis is a concern with any surgical procedure about the hip, this complication has been primarily a theoretical concern with hip arthroscopy.     

Coagulation defects do not predict blood product requirements during liver transplantation

BACKGROUND: In our experience, correction of coagulation defects with plasma transfusion does not decrease the need for intraoperative red blood cell (RBC) transfusions during liver transplantation. On the contrary, it leads to a hypervolemic state that result in increased blood loss. A previous study has shown that plasma transfusion has been associated with a decreased 1-year survival rate. The aim of this prospective study was to evaluate whether anesthesiologists could reduce RBC transfusion requirements during liver transplantation by eliminating plasma transfusion. METHODS: Two hundred consecutive liver transplantations were prospectively studied over a 3-year period. Patients were divided into two groups: low starting international normalized ratio (INR) value <1.5 and high INR > or =1.5. Low central venous pressure was maintained in all patients before the anhepatic phase. Coagulation parameters were not corrected preoperatively or intraoperatively in the absence of uncontrollable bleeding. Phlebotomy and auto transfusion of blood salvaged were used following our protocol. Independent variables were analyzed in both univariate and multivariate fashion to find a link with RBC transfusions or decreased survival rate. RESULTS: The mean number of intraoperative RBC units transfused was 0.3+/-0.8. Plasma, platelet, albumin, and cryoprecipitate were not transfused. In 81.5% of the patients, no blood product was used during their transplantation. The average final hemoglobin (Hb) value was 91.2+/-15.0 g/L. There were no differences in transfusional rate, final Hb, or bleeding between two groups (low or high INR values). The overall 1-year survival rate was 85.6%. Logistic regression showed that avoidance of plasma transfusion, phlebotomy, and starting Hb value were significantly linked to liver transplantation without RBC transfusion. The need for intraoperative RBC transfusion and Pugh's score were linked to the decreased 1-year survival rate. CONCLUSION: The avoidance of plasma transfusion was associated with a decrease in RBC transfusions during liver transplantation. There was no link between coagulation defects and bleeding or RBC or plasma transfusions. Previous reports indicating that it is neither useful nor necessary to correct coagulation defects with plasma transfusion before liver transplantation seem further corroborated by this study. We believe that this work also supports the practice of lowering central venous pressure with phlebotomy to reduce blood loss, during liver dissection, without any deleterious effect.     

Risk factors leading to midurethral sling revision: a multicenter case-control study

Introduction and hypothesis

To determine risk factors for sling revision after midurethral sling (MUS) placement.

Methods

This multicenter case-control study included patients who underwent MUS placement and subsequent revision secondary to voiding dysfunction from January 1999–2007 from nine Urogynecology centers across the USA. Direct logistic regression analysis was used to determine which diagnostic variables predicted sling revision.

Results

Of the patients, 197 met the study criteria. Patient demographics, urodynamic findings, and operative differences did not increase the risk for sling revision. Risk factors for sling revision did include: pre-existing voiding symptoms (OR 2.76, 95% CI 1.32–5.79; p?=?0.004) retropubic sling type (OR?=?2.28, 95% CI 1.08–4.78; p?=?0.04) and concurrent surgery (OR?=?4.88, 95% CI 2.16–11.05; p?<?0.001)

Conclusions

This study determined that pre-existing obstructive voiding symptoms, retropubic sling type, and concurrent surgery at the time of sling placement are risk factors for sling revision.