Aging-related Decrease of Human ASC Angiogenic Potential Is Reversed by Hypoxia Preconditioning Through ROS Production

Adipose stroma/stem cells (ASC) represent an ideal source of autologous cells for cell-based therapy. Their transplantation enhances neovascularization after experimental ischemic injury. Aging is associated with a progressive decrease in the regenerative potential of mesenchymal stem cells (MSCs) from bone marrow. This work aims to determine the aging effect on human ASC capacities. First, we show that aging impairs angiogenic capacities of human ASC (hASC) in a mouse ischemic hindlimb model. Although no change in hASC number, phenotype, and proliferation was observed with aging, several mechanisms involved in the adverse effects of aging have been identified in vitro combining a concomitant decrease in (i) ASC ability to differentiate towards endothelial cells, (ii) secretion of proangiogenic and pro-survival factors, and (iii) oxidative stress. These effects were counteracted by a hypoxic preconditioning that improved in vivo angiogenic capacities of hASC from older donors, while hASC from young donors that have a strong ability to manage hypoxic stress were not. Finally, we identified reactive oxygen species (ROS) generation as a key signal of hypoxia on hASC angiogenic capacities. This study demonstrates for the first time that age of donor impaired angiogenic capacities of hASC in ischemic muscle and change in ROS generation by hypoxic preconditioning reverse the adverse effect of aging.     

Regional coronary vasoconstriction after combined beta-adrenergic and calcium channel blockade in patients with coronary artery disease

The beta-adrenergic and calcium channel blocking drugs, which individually and combined have proven efficacious in the treatment of angina pectoris, appear to have opposing effects on coronary artery vasomotion. Previous studies have shown that beta-adrenergic blockade may potentiate and calcium channel blockade reverse coronary vasoconstriction during adrenergic cold stimulation in patients with coronary artery disease. To assess the coronary hemodynamic effects of combined drug therapy, thermodilution coronary sinus and great cardiac vein flow and mean arterial pressure were measured during serial cold pressor testing, both before and after 0.1 mg/kg of intravenous propranolol and again after the addition of 10 mg of sublingual nifedipine in 21 patients (9 without [group A1] and 12 with [group A2] greater than 50% narrowing of the left anterior descending coronary artery). In an additional 15 patients (6 patients without [group B1] and 9 with [group B2] left anterior descending artery stenosis), serial cold pressor testing was performed reversing the drug order. Despite significant increases in mean arterial pressure (p less than 0.01) during cold pressor testing, coronary sinus resistance responses after propranolol plus nifedipine were not statistically significant for any group. However, regional coronary resistance responses differed between patients with and without left anterior descending artery stenosis. In group A1, great cardiac vein resistance was unchanged after propranolol plus nifedipine. In group A2, great cardiac vein flow decreased significantly after propranolol plus nifedipine from 8 +/- 17 to -4 +/- 12% (p less than 0.01 versus control), and great cardiac vein resistance increased from 4 +/- 21 to 15 +/- 19% (p less than 0.01 versus control). A similar significant response was observed for groups B1 and B2. Regional coronary vasoconstriction during adrenergic stimulation after combined drug therapy was only observed in patients with significant left anterior descending artery stenosis. These data suggest that in some patients with severe coronary artery disease, combined beta-adrenergic and calcium channel blockade modified regional coronary responses to adrenergic stimulation with an inhomogeneous distribution of blood flow to potentially ischemic regions without affecting total coronary blood flow. These data also imply that an improvement in anginal symptoms after combined drug therapy may be due primarily to mechanisms that reduce myocardial oxygen demand rather than to improved myocardial oxygen supply.     

Laparoscopic cholecystectomy after age 75]

AIM OF THE STUDY: The aim of this prospective study was to determine the feasibility, complications and benefits of laparoscopic cholecystectomy in the patients over 75 years of age. METHODS: From January 1992 to July 1998, among the 863 patients who underwent laparoscopic cholecystectomy, 102 patients over 75 years (group I) were compared to 761 younger patients (group II). RESULTS: The conversion rate was 22% in group I versus 13% in group II (P = 0.017). Mortality and morbidity rates were respectively 1% and 13.7% in elderly patients versus 0 and 6.6% in younger patients (P = 0.009). Mean length of hospital stay was higher in group I: 6.9 versus 4.5 d in group II (P < 10(-6)). CONCLUSIONS: Laparoscopic cholecystectomy is feasible in patients above 75 for the treatment of symptomatic gallstones and acute cholecystitis with a low morbidity rate.     

Surgical repair of abdominal wall]

Surgical repair of abdominal wall defects following tumour resection only raises real problems when the nature of the tumour required wide, or even transfixing excision, as in the case of sarcomas or very advanced carcinomas. Superficial repair is performed according to the algorithm of the simplest technique: secondary healing, partial suture, total suture, transplant, or flap (pedicled or free). In the case of transfixing resection, the combination of a biomaterial for reconstruction of the deep plane and a superficial flap is necessary. For very large transfixing defects of the abdomen, a free flap may be required and, in this case, delayed insertion after initial transfer may further reduce the operative risk ("apple turnover" technique). The complications observed in a detailed series of 9 cases operated at Saint-Louis Hospital consisted of one intraoperative cardio-circulatory arrest during second-stage surgery and one late infection at three years. The authors believe that the indications for delayed insertion of a free flap are still very topical in cases in which a very large grafted free flap is necessary in conjunction with a prosthesis. Large abdominal defects after cancer resection can be reconstructed by modern reconstructive surgery.     

Abdominal stab wounds: Self-inflicted wounds versus assault wounds

Intentional penetrating wounds, self inflicted or inflicted by others, are increasingly common. As a result, it can be difficult for the forensic examiner to determine whether the cause is self-inflicted or not. This type of trauma has been studied from a psychological perspective and from a surgical perspective but the literature concerning the forensic perspective is poorer. The objective of this study was to compare the epidemiology of abdominal stab wounds so as to distinguish specific features of each type. This could help the forensic scientist to determine the manner of infliction of the wound.We proposed a retrospective monocentric study that included all patients with an abdominal wound who were managed by the visceral surgery department at Angers University Hospital. Demographic criteria, patient history, circumstances and location of the wound were noted and compared. A comparison was drawn between group 1 (self inflicted wound) and group 2 (assault).This study showed that the only significant differences are represented by the patient's prior history and the circumstances surrounding the wound, i.e. the scene and time of day. In our study, neither the site, nor the injuries sustained reveal significant clues as to the origin of the wound. According to our findings, in order to determine the cause, the forensic examiner should thus carefully study the circumstances and any associated injuries.     

Prolonged right ventricular failure after relief of cardiac tamponade

PURPOSE: To report a case of severe and fatal cardiac complication following pericardiotomy to relieve a malignant tamponade. Right ventricular (RV) failure was responsible for major hypoxemia and for a persistent shunt through a patent foramen ovale. In the absence of pulmonary embolism and coronary occlusion, possible pathophysiologic mechanisms are discussed. CLINICAL FEATURES: This 53-yr-old patient presented with oropharyngeal carcinoma previously treated by chemotherapy. One month later, he showed clinical and echocardiographic signs of cardiac tamponade. He had a circumferential pericardial effusion with complete end-diastolic collapse of the right cavities. After an emergent pericardiotomy, he rapidly presented severe hypoxemia. Transesophageal echocardiography showed an akinetic and dilated right ventricle, paradoxical septal wall motion and a normal left ventricular function. A contrast study revealed a right-to-left shunt. No residual pericardial effusion was detectable. Pulmonary angiography excluded a pulmonary embolism and the coronary angiogram was normal. Troponin Ic was elevated postoperatively and peaked on day two (3.78 micro g x L(-1)). The patient died of refractory shock with persistent intracardiac shunt and RV akinesia on day nine. CONCLUSION: Although pulmonary embolism or thrombus of a coronary vessel are the most common causes of prolonged RV failure after pericardiotomy, other mechanisms may be invoked. The possibility is raised that a rapid increase in RV tension may induce the development of muscular injury and impair coronary blood flow, despite a normal coronary angiogram. These could result in a stunned myocardium and opening of a patent foramen ovale. We hypothesize that gradual decompression of a chronic pericardial effusion might be beneficial in patients at risk.     

Increased tubular proliferation as an adaptive response to glomerular albuminuria

Renal tubular atrophy accompanies many proteinuric renal diseases, suggesting that glomerular proteinuria injures the tubules. However, local or systemic inflammation and filtration of abnormal proteins known to directly injure tubules are also present in many of these diseases and animal models; therefore, whether glomerular proteinuria directly causes tubular injury is unknown. Here, we examined the renal response to proteinuria induced by selective podocyte loss. We generated mice that express the diphtheria toxin receptor exclusively in podocytes, allowing reproducible dose-dependent, specific ablation of podocytes by administering diphtheria toxin. Ablation of <20% of podocytes resulted in profound albuminuria that resolved over 1-2 weeks after the re-establishment of normal podocyte morphology. Immediately after the onset of albuminuria, proximal tubule cells underwent a transient burst of proliferation without evidence of tubular damage or increased apoptosis, resulting in an increase in total tubular cell numbers. The proliferative response coincided with detection of the growth factor Gas6 in the urine and phosphorylation of the Gas6 receptor Axl in the apical membrane of renal tubular cells. In contrast, ablation of >40% of podocytes led to progressive glomerulosclerosis, profound tubular injury, and renal failure. These data suggest that glomerular proteinuria in the absence of severe structural glomerular injury activates tubular proliferation, potentially as an adaptive response to minimize the loss of filtered proteins.