Ectopic Meis1 expression in the mouse limb bud alters P-D patterning in a Pbx1-independent manner

During limb development, expression of the TALE homeobox transcription factor Meis1 is activated by retinoic acid in the proximal-most limb bud regions, which give rise to the upper forelimb and hindlimb. Early subdivision of the limb bud into proximal Meis-positive and distal Meis-negative domains is necessary for correct proximo-distal (P-D) limb development in the chick, since ectopic Meis1 overexpression abolishes distal limb structures, produces a proximal shift of limb identities along the P-D axis, and proximalizes distal limb cell affinity properties. To determine whether Meis activity is also required for P-D limb specification in mammals, we generated transgenic mice ectopically expressing Meis1 in the distal limb mesenchyme under the control of the Msx2 promoter. Msx2:Meis1 transgenic mice display altered P-D patterning and shifted P-D Hox gene expression domains, similar to those previously described for the chicken. Meis proteins function in cooperation with PBX factors, another TALE homeodomain subfamily. Meis-Pbx interaction is required for nuclear localization of both proteins in cell culture, and is important for their DNA-binding and transactivation efficiency. During limb development, Pbx1 nuclear expression correlates with the Meis expression domain, and Pbx1 has been proposed as the main Meis partner in this context; however, we found that Pbx1 deficiency did not modify the limb phenotype of Msx2:Meis1 mice. Our results indicate a conserved role of Meis activity in P-D specification of the tetrapod limb and suggest that Pbx function in this context is either not required or is provided by partners other than Pbx1

The value of air plethysmography in predicting clinical outcome after surgical treatment of chronic venous insufficiency

Purpose: The role of air plethysmography (APG) as a predictor of clinical outcome after surgery in venous disease is yet to be defined. The purpose of this study was to investigate the value of APG in predicting clinical outcome after venous surgery for chronic venous insufficiency (CVI). Methods: Seventy-three extremities in 71 patients with Class 3 through 6 CVI were assessed preoperatively with CEAP (c linical, e tiologic, a natomic, p athophysiologic) criteria, standing reflux duplex ultrasound scan, and APG with measurements of preoperative venous filling index (VFI), venous volumes, ejection fraction, and residual volume fraction. After surgical treatment of the affected limbs, repeat APG studies were obtained within 6 weeks. Established venous reporting standards were used for follow-up to calculate clinical symptom scores (CSSs) in each patient. Results: Superficial venous reflux occurred alone in 24 limbs or in conjunction with perforator incompetence in 26 limbs. Deep and superficial reflux, with or without perforator incompetence, was found in 16 limbs, and seven limbs had isolated deep insufficiency. Follow-up was available in 60 of 71 patients (mean period, 44.3 months). Postoperative APG demonstrated significant hemodynamic changes after surgery as measured with VFI, venous volumes, ejection fraction, and residual volume fraction. Mean CSSs decreased from 7.35 ± 0.56 preoperatively to 1.79 ± 0.32 at late follow-up after surgery (P Conclusions: Normalization of the VFI after venous surgery for CVI is predictive of a good clinical outcome. This APG measurement may be a useful parameter to predict adequacy of surgery in patients with venous insufficiency. (J Vasc Surg 2000;32:961-8.

Graft infection after endovascular abdominal aortic aneurysm repair

IntroductionAlthough the natural history and management of infected open abdominal aortic aneurysm (AAA) repair is well described, only sporadic case reports have described the fate of patients with infected endografts placed in the abdominal aorta. The present study describes a tertiary referral center's experience with infected endovascular aneurysm repairs (EVARs).MethodsThe medical records of 1302 open and endovascular aortic procedures were queried from January 2000 to January 2010. The cases were reviewed for prior aortic procedures, prosthetic implants, and etiology of current open procedure. Demographics, operative details, and perioperative courses were documented.ResultsNine patients (1 woman) with a mean age of 71 years had an EVAR that later required an open procedure for explantation and surgical revision for suspected infection. All grafts were explanted through a midline transperitoneal approach, with a mean time to explant of 33 months. The explanted endografts included 4 Zenith (Cook, Bloomington, Ind), 2 Ancure (Endovascular Technologies, Menlo Park, Calif), 2 Excluders (Gore, Flagstaff, Ariz), and 1 AneuRx (Medtronic, Minneapolis, Minn). Eight of the nine original EVARs were performed at other hospitals; 1 patient had EVAR and open explant at the University of Michigan. All patients had preoperative computed tomography scans, except one who was transferred in extremis with a gastrointestinal hemorrhage. Three patients also had a tagged leukocyte scan, and two had magnetic resonance imaging to further reinforce the suspicion of infection before explantation and bypass planning. Rifampin-soaked Hemashield (Boston Scientific) in situ grafts were used in four patients, with extra-anatomic (axillary-bifemoral) bypass used in the other five. The in situ group had no positive preoperative or postoperative cultures, with the exception of the unstable patient who died the day of surgery. For the other five patients, positive tissue cultures were found for Bacteroides, Escherichia coli, coagulase-negative Staphylococcus, Streptococcus, and Candida. Three patients were found to have aortic-enteric fistula, two of whom died before discharge from the hospital. The remaining seven survived to discharge. Average length of stay was 22 days, with a median follow-up of 11 months.ConclusionThis series of infected EVARs is the largest group of infected AAA endografts reported to date. Because EVAR of AAAs is presently the most common method of repair, development of endograft infection, while rare, can be managed with acceptable mortality rates. Patients presenting with aortic-enteric fistula after EVAR appear to have a more virulent course

Substantiation of ovarian effects of leptin by challenging a mouse model of obesity/ Type 2 diabetes

The goal of the current was to elucidate if treatment with gonadotrophins and leptin can circumvent infertility in obese mice and to establish whether reproductive effects of leptin are influenced at the hypothalamus-hypophysis or ovarian level by using a leptin deficient mouse model of obesity/type 2 diabetes (ob/ob) treated with leptin. The ovulatory response and the fertilization success were compared with the results obtained in ob/ob dams pretreated with a gonadotrophin-replacement therapy or in two groups (ob/ob and wild-type) of control non-pretreated females. The number of corpora lutea was significantly lower in control ob/ob mice than in wild-type dams. Treatment with gonadotrophin-replacement therapy did not increase significantly the ovulation rate in ob/ob, but the administration of leptin-replacement treatment allowed the authors to obtain a number of corpora lutea and oocytes/zygotes similar to those obtained in wild-type females. Furthermore, the leptin supply succeeded in producing fertilized zygotes, although in a lower number than found in the wild-type control. Thus, the hypogonadotrophic state in obese mice may be circumvented by the administration of a gonadotrophin-replacement therapy combined with a protocol for controlled ovarian stimulation, but fertile ovulations are only obtained after applying leptin-replacement therapy. Current results strongly support the existence of direct local effects of leptin on the ovary. © 2010 Elsevier Inc. All rights reserved

Disruption of the endothelial nitric oxide synthase gene affects ovulation, fertilization and early embryo survival in a knockout mouse model

Two consecutive experiments determined whether disruption of the endothelial nitric oxide synthases (NOS) gene (Nos3) affects ovulation, fertilization, implantation, and embryo development. In the first trial, Nos3-knockout mice (groups Nos3-/-) and wild-type mice (groups Nos3+/+) showed significant differences in mean number of corpora lutea (9.7±1.2 in Nos3-/- versus 14.2±1.2 in Nos3+/+; P<0.01), rate of anovulation (48.3±7.3% in Nos3-/- versus 29.7±6.3 in Nos3+/+; P<0.05), total mean number of recovered oocytes/zygotes (4.0±1.1 in Nos3-/- versus 10.4±1.6 in Nos3+/+; P<0.01), and non-fertilization rate (50.7 in Nos3-/- versus 3.3% in Nos3+/+; P<0.001). Inthe second trial, implantation and early pregnancy losses in Nos3-knockout and wild-type dams were detected by real-time ultrasound imaging. The number of embryos reaching implantation was higher in Nos3+/+ than in Nos3-/- mice (7.5±0.4 vs 4.0±0.4; P<0.005); thereafter, embryo losses were detected between days 8.5 and 13.5, in 62.5% of the Nos3-knockout dams and, at days 10.5 and 11.5, in 16.7% of the control females (P<0.005). Thus, NO and NOS3 deficiencies affect reproductive and developmental features in the Nos3-knockout mouse model. © 2008 Society for Reproduction and Fertility