Neonatla vestibular stimulation and mating in cerebellar mutants

Two cerebellar mutants, staggerer and reeler, and their congenic nonmutants were used in this experiment. Experimental animals were subjected to intense rotational stimulation on a tilted plane during the first 3 weeks of life, while controls were left nonstimulated. The capacity for mating, as evidenced by vaginal plugs or the occurrence of pregnancy, was assayed during two periods: between 36 and 89 days of age (Experiment A) and between 90 and 120 days of age (Experiment B). During Experiment A the mutants as well as the normals were caged inter se with partners of the opposite sex. During Experiment B the animals were caged with intact, sexually experienced partners. The animals were examined daily for evidence of mating. During Experiment A, only 3 of the 89 couples participating in this study showed evidence of mating. During Experiment B, the number of males of both strains which had mated increased significantly. The staggerer females showed a relatively high level of mating activity, whether stimulated or not. The reeler females, in contrast, rarely mated, although early stimulation significantly increased the level of sexual efficiency. The majority of the normal males and females mated, whether stimulated or not. It was concluded that massive motor-sensory stimulation in infancy, improving gait and body balance in staggerer and reeler mice, may also improve mating efficiency.     

Analysis of Erectile Responses to BAY 41-8543 and Muscarinic Receptor Stimulation in the Rat

IntroductionSoluble guanylate cyclase (sGC) is the receptor for nitric oxide (NO) and in pathophysiologic conditions where NO formation or bioavailability is impaired, erectile dysfunction (ED) occurs.AimThe aim of this study was to investigate erectile responses to the sGC stimulator BAY 41-8543 in physiologic and pathophysiologic conditions.MethodsIncreases in intracavernosal pressure (ICP) in response to intracavernosal (ic) injections of BAY 41-8543 were investigated in the anesthetized rat.Main Outcome MeasuresIncreases in ICP/MAP in response to ic injections of BAY 41-8543 and the interaction of BAY 41-8543 with exogenous and endogenously released NO were investigated and the effect of the sGC stimulator on cavernosal nerve injury was assessed. The mechanism of the increase in ICP/MAP in response to ic injection of acetylcholine was investigated.ResultsThe ic injections of BAY 41-8543 increased ICP/MAP and the duration of the response. BAY 41-8543 was less potent than sodium nitroprusside (SNP) and ic injections of BAY 41-8543 and SNP produced a larger response than the algebraic sum of responses to either agent alone. Simultaneous ic injection of BAY 41-8543 and cavernosal nerve stimulation produced a greater response than either intervention alone. Atropine and cavernosal nerve crush injury decreased the response to nerve stimulation and ic injection of BAY 41-8543 restored the response.ConclusionThese data show that BAY 41-8543 has significant erectile activity and can synergize with exogenous and endogenously released NO. This study shows that atropine and nerve crush attenuate the response to cavernosal nerve stimulation and that BAY 41-8543 can restore the response. The results with atropine, L-NAME and hexamethonium indicate that the response to ic injection of acetylcholine is mediated by muscarinic receptors and the release of NO with no significant role for nicotinic receptors. These results suggest that BAY 41-8543 would be useful in the treatment of ED. Lasker GF, Pankey EA, Allain AV, Dhaliwal JS, Stasch J-P, Murthy SN, and Kadowitz PJ. Analysis of erectile responses to BAY 41-8543 and muscarinic receptor stimulation in the rat. J Sex Med 2013;10:704–718.     

Predicting late-onset growth abnormalities using growth velocity between trimesters

Objectives.?To determine whether growth velocity parameters derived from routine prenatal ultrasound measurements at first, second and third trimester can identify normal growth at term as well as late-onset growth abnormalities.

Material and methods.?Longitudinal study of fetal growth in normal singleton pregnancies with three normal ultrasound examinations and delivered at term. Fetuses were classified into 3 groups (?<?10th percentile, 10–90th percentile, >?90th percentile) based on birth weight. Multiple regression on birth weight classification was used to build up a prediction equation of fetal growth potential (FGP) based on fetal biometry and fetal growth velocity parameters between ultrasound examinations. Best cut-off value for FGP predicting growth restriction and macrosomia were defined.

Results.?356 pregnancies were included. Fetal biometry growth velocities between examinations were calculated for all measurements. Using best cut-off values, the estimated sensitivity, specificity and odds ratio were: 60% [44;74], 91%[89;92] and 14.55 [6.30;33.98] and 53% [36;69], 89%[88;91] and 10 [4.27;23.49] for the prediction of growth restriction and macrosomia, respectively.

Discussion.?Fetal growth potential can be derived and calculated from standard ultrasound measurements. It can improve identification of these fetuses at risk for late-onset growth abnormalities and their related morbidity.     

Proton spectroscopic imaging (Dixon method) of the liver: clinical utility

The contribution of proton spectroscopic (PS) imaging to magnetic resonance (MR) imaging of the liver was assessed at 0.5 T in 55 patients with known or suspected hepatic malignancy. PS images were compared subjectively with T1- and T2-weighted spin-echo (SE) images for hepatic lesion detection and conspicuity. For hepatic metastases (n = 27), PS images were equal to T1-weighted images in lesion detection in 17 patients but showed fewer lesions in five patients and false-negative results in two. When compared with T2-weighted images, PS images depicted more lesions in six patients, an equal number of lesions in 18, and fewer lesions in two. Hepatomas (n = 8) were detected with each sequence in all patients. Hepatomas were often more conspicuous on PS images than on T2-weighted images; they were of equal conspicuity on PS and T1-weighted images in most cases. Whereas fatty infiltration (n = 16) appeared on PS images as areas of low signal intensity similar to that of paraspinal muscle, it produced no detectable abnormality on either T1- or T2-weighted images. PS imaging is inferior to T1-weighted SE imaging in the detection of hepatic metastases. The major role of PS imaging at intermediate field strength is to differentiate focal fatty infiltration from hepatic metastases.     

Percutaneous cholecystostomy: an alternative to surgical cholecystostomy for acute cholecystitis?

Emergency percutaneous cholecystostomy was successfully performed in 39 of 40 attempted procedures in 37 hospitalized patients with possible acute cholecystitis. All cholecystostomies were performed with ultrasound guidance and preferentially with the transhepatic route, and all but four were performed at the patient's bedside. The patients had been hospitalized an average of 27 days before the procedure. Twenty-two of the 37 patients (59%) eventually died during hospitalization because of other medical or surgical problems. Only minor complications related to percutaneous cholecystostomy placement occurred in this series: catheter dislodgment without sequelae (n = 2) and significant abdominal pain (n = 2). Technical problems included guide-wire buckling during catheter insertion (n = 1) and failed attempted cholecystostomy (n = 1). Percutaneous cholecystostomy is a safe alternative to surgical cholecystostomy in the treatment of patients suspected of having acute cholecystitis.     

Supplementation With a New Therapeutic Oxygen Carrier Reduces Chronic Fibrosis and Organ Dysfunction in Kidney Static Preservation

Static preservation is currently the most widely used organ preservation strategy; however, decreased donor organ quality is impacting outcome negatively. M101 is an O₂ carrier with high‐oxygen affinity and the capacity to function at low temperatures. We tested the benefits of M101 both in vitro, on cold preserved LLC‐PK1, as well as in vivo, in a large white pig kidney autotransplantation model. In vitro, M101 supplementation reduced cold storage‐induced cell death. In vivo, early follow‐up demonstrated superiority of M101‐supplemented solutions, lowering the peak of serum creatinine and increasing the speed of function recovery. On the longer term, supplementation with M101 reduced kidney inflammation levels and maintained structural integrity, particularly with University of Wisconsin (UW). At the end of the 3‐month follow‐up, M101 supplementation proved beneficial in terms of survival and function, as well as slowing the advance of interstitial fibrosis. We show that addition of M101 to classic organ preservation protocols with UW and Histidine–Tryptophane–Ketoglutarate, the two most widely used solutions worldwide in kidney preservation, provides significant benefits to grafts, both on early function recovery and outcome. Simple supplementation of the solution with M101 is easily translatable to the clinic and shows promises in terms of outcome.     

Benefits of small volume and small syringe for bone marrow aspirations of mesenchymal stem cells

Purpose

Aspirating bone marrow from the iliac crest using small volumes of 1–4 ml with a 10-ml syringe has been historically proposed for harvesting adult mesenchymal stem cells and described as a standard technique to avoid blood dilution. The disadvantage of repeated small aspirations is that there is a significantly increased time to harvest the bone marrow. However, it is not known if a large volume syringe can improve the rate of bone marrow aspiration without increasing blood dilution, thus reducing the quality of the aspirate. We compared the concentrations of mesenchymal stem cells obtained under normal conditions with two different size syringes.

Methods

Thirty adults (16 men and 14 women with a mean age of 49?±?14 years) underwent surgery with aspiration of bone marrow from their iliac crest. Bilateral aspirates were obtained from the iliac crest of the same patients with a 10-ml syringe and a 50-ml syringe. Cell analysis determined the frequencies of mesenchymal stem cells (as determined by the number of colonies) from each size of syringe. The cell count, progenitor cell concentration (colonies/ml marrow) and progenitor cell frequency (per million nucleated cells) were calculated. All bone marrow aspirates were harvested by the same surgeon.

Results

Aspirates of bone marrow demonstrated greater concentrations of mesenchymal stem cells with a 10-ml syringe compared with matched controls using a 50-ml syringe. Progenitor cell concentrations were on average 300 % higher using a 10-ml syringe than matched controls using a 50-ml syringe (p?<?0.01).

Conclusions

In normal human donors, bone marrow aspiration from 30 patients demonstrated a reduced mesenchymal stem cell number in aspirates obtained using a larger volume syringe (50 ml) as compared with a smaller volume syringe (10 ml).     

Hyperbaric oxygen therapy improves angiogenesis and bone formation in critical sized diaphyseal defects

Besides the use of autologous bone grafting several osteoconductive and osteoinductive methods have been reported to improve bone healing. However, persistent non‐union occurs in a considerable number of cases and compromised angiogenesis is suspected to impede bone regeneration. Hyperbaric oxygen therapy (HBO) improves angiogenesis. This study evaluates the effects of HBO on bone defects treated with autologous bone grafting in a bone defect model in rabbits. Twenty‐four New‐Zealand White Rabbits were subjected to a unilateral critical sized diaphyseal radius bone defect and treated with autologous cancellous bone transplantation. The study groups were exposed to an additional HBO treatment regimen. Bone regeneration was evaluated radiologically and histologically at 3 and 6 weeks, angiogenesis was assessed by immunohistochemistry at three and six weeks. The additional administration of HBO resulted in a significantly increased new bone formation and angiogenesis compared to the sole treatment with autologous bone grafting. These results were apparent after three and six weeks of treatment. The addition of HBO therapy to autologous bone grafts leads to significantly improved bone regeneration. The increase in angiogenesis observed could play a crucial role for the results observed. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:513–520, 2015.     

Morbidity of graft harvesting versus bone marrow aspiration in cell regenerative therapy

Purpose

Using bone marrow mesenchymal stem cells (MSCs) with aspiration from the iliac crest is commonly used in reconstructive orthopaedic surgery. Because bone marrow aspiration is a percutaneous technique, the morbidity as compared with the classical bone graft should be decreased.

Method

Therefore in a retrospective review of 523 consecutive cases of bone marrow aspiration performed at the Henri Mondor Hospital from 1990 to 2006 for the treatment of fractures, minor and major complications were identified and compared to the number of complications observed during the same period with 435 classical iliac crest bone graft procedures performed for the same indications of treatment of fractures. Minor complications included superficial infections, superficial seromas, and minor haematomas. Major complications included herniation of abdominal contents through massive bone graft donor sites, vascular injuries, deep infections at the donor site, neurologic injuries, deep haematoma formation requiring surgical intervention or transfusion, and iliac wing fractures.

Result

Bone marrow aspiration decreased significantly the number of complications as compared with harvesting classical iliac crest bone graft that was associated with significant morbidity. Adverse events were significantly lower (p?Conclusion In our series the number of complications with bone marrow aspiration was ten times less than the complications observed with the classical technique of bone piece harvesting from the iliac crest, and the complications were clearly less severe.     

Development and Impact of De Novo Anti‐HLA Antibodies in Pediatric Heart Transplant Recipients

There is increasing evidence that de novo anti‐HLA antibodies, more specifically de novo donor‐specific antibodies (DSA) following solid organ transplantation may be associated with negative outcomes including rejection in the first year and graft loss. Limited data are available in pediatric heart transplant recipients. We sought to prospectively determine the incidence, class and early impact of de novo anti‐HLA antibodies in a cohort of pediatric heart transplant recipients. Serial panel reactive antibody testing posttransplant was performed in 25 patients (14 males) transplanted between January 2008 and June 2010. Five patients were sensitized pretransplant; all patients had negative direct crossmatch. Seventy‐two percent developed de novo anti‐HLA antibodies at a median of 2.6 weeks (IQR 1.2 weeks to 6.2 months) posttransplant; 67% of these were DSA. The majority of recipients in our cohort developed de novo anti‐HLA antibodies within the first year posttransplant, with two‐thirds being donor‐specific. Acute cellular rejection, though frequent, was not different in patients with antibody development regardless of class or specificity, and there was no antibody‐mediated rejection, graft loss or early cardiac allograft vasculopathy.