Studies of the renal effects of angiotensin II receptor blockade: the confounding factor of acute water loading on the action of vasoactive systems.

The acute renal tubular effects of two pharmacologically distinct angiotensin II receptor antagonists have been evaluated in normotensive volunteers on various salt diets. In the first study, the renal response to a single oral dose of losartan (100 mg) was assessed in subjects on a low (50 mmol Na/d) and on a high (200 mmol Na/d) salt intake. In a second protocol, the renal effects of 50 mg irbesartan were investigated in subjects receiving a 100 mmol Na/d diet. Both angiotensin II antagonists induced a significant increase in urinary sodium excretion. With losartan, a modest, transient increase in urinary potassium and a significant increase in uric acid excretion were found. In contrast, no change in potassium and uric acid excretions were observed with irbesartan, suggesting that the effects of losartan on potassium and uric acid are due to the intrinsic pharmacologic properties of losartan rather than to the specific blockade of renal angiotensin II receptors. Assessment of segmental sodium reabsorption using lithium as a marker of proximal tubular reabsorption demonstrated a decreased distal reabsorption of sodium with both antagonists. A direct proximal tubular natriuretic effect of the angiotensin II antagonist could be demonstrated only with irbesartan. This apparent discrepancy allowed us to reveal the importance of acute water loading as a possible confounding factor in renal studies. The results of the present analysis show that acute water loading per se may enhance renal sodium excretion and hence modify the level of activity of the renin-angiotensin system expected from a given sodium diet. Since acute water loading is a common practice in clinical renal studies, this confounding factor should be taken into account when investigating the renal effects of vasoactive systems.

Endovascular aortic repair versus open surgical repair for descending thoracic aortic disease a systematic review and meta-analysis of comparative studies.

OBJECTIVES: The purpose of this study was to determine whether thoracic endovascular aortic repair (TEVAR) reduces death and morbidity compared with open surgical repair for descending thoracic aortic disease. BACKGROUND: The role of TEVAR versus open surgery remains unclear. Metaregression can be used to maximally inform adoption of new technologies by utilizing evidence from existing trials. METHODS: Data from comparative studies of TEVAR versus open repair of the descending aorta were combined through meta-analysis. Metaregression was performed to account for baseline risk factor imbalances, study design, and thoracic pathology. Due to significant heterogeneity, registry data were analyzed separately from comparative studies. RESULTS: Forty-two nonrandomized studies involving 5,888 patients were included (38 comparative studies, 4 registries). Patient characteristics were balanced except for age, as TEVAR patients were usually older than open surgery patients (p = 0.001). Registry data suggested overall perioperative complications were reduced. In comparative studies, all-cause mortality at 30 days (odds ratio [OR]: 0.44, 95% confidence interval [CI]: 0.33 to 0.59) and paraplegia (OR: 0.42, 95% CI: 0.28 to 0.63) were reduced for TEVAR versus open surgery. In addition, cardiac complications, transfusions, reoperation for bleeding, renal dysfunction, pneumonia, and length of stay were reduced. There was no significant difference in stroke, myocardial infarction, aortic reintervention, and mortality beyond 1 year. Metaregression to adjust for age imbalance, study design, and pathology did not materially change the results. CONCLUSIONS: Current data from nonrandomized studies suggest that TEVAR may reduce early death, paraplegia, renal insufficiency, transfusions, reoperation for bleeding, cardiac complications, pneumonia, and length of stay compared with open surgery. Sustained benefits on survival have not been proven.

Open elbow arthrolysis for posttraumatic elbow stiffness.

OBJECTIVES: The elbow joint is vulnerable to stiffness, especially after trauma. The aim of this study was to evaluate the results of open arthrolysis for posttraumatic elbow stiffness. DESIGN: Cohort retrospective study. PATIENTS: Eighteen consecutive patients were evaluated by an independent observer at an average of 16 months (6 to 43) after open elbow arthrolysis was performed for posttraumatic stiffness. Initial traumas were: isolated fractures (11) or dislocation (1) and complex fracture-dislocations (6). Initial treatments were: nonoperative (3), radial head resection (1), and ORIF (14). Patients presented predominantly with mixed contractures (combined extrinsic and intrinsic contractures). INTERVENTION: Open elbow arthrolysis. MAIN OUTCOME MEASUREMENTS: Elbow function and patient satisfaction were the principal outcome measures. At follow-up European Society for Shoulder and Elbow Surgery (SECEC) elbow scores were calculated. RESULTS AND CONCLUSIONS: Three patients had minor postoperative complications: 1 partial wound dehiscence, 1 subcutaneous infection, and one seroma. None of these complications influenced the final result clinically. The mean total increase in range of motion was 40 degrees (13 to 112 degrees), with a mean gain in flexion of 14 degrees (0 to 45 degrees) and 26 degrees in extension (5 to 67 degrees). No patient showed signs of elbow instability. There was no radiographic evidence of osteoarthritis progression at follow-up. We did not find any correlations between the type of stiffness, the approaches used, and the results. However, patients with the greatest preoperative stiffness had significantly better improvement of mobility (P<0.001). The best results were obtained in patients who had arthrolysis done within 1 year after the initial trauma (P=0.008). The mean SECEC scores were 88 (52 to 100) for the injured elbows, and 96 (88 to 100) for the contralateral elbows. CONCLUSION: Open elbow arthrolysis for patients with posttraumatic stiffness improves joint function and provides patient satisfaction. The best results, in terms of gain of motion and patient satisfaction, were obtained in patients with severe stiffness who had operations within the first year after initial trauma.

A systems perspective on the integrative child psychiatry approach. Discussion of paper: "Working here and now with the individual and family system: A case of a traumatized child"

In this discussion, after a few general comments, I will propose a systems reading of the intervention so elegantly described by Kaija Puura. I will draw parallels between the therapeutic and the family groups as framing-developing systems and formalize the steps taken by the family toward healing under the influence of the therapist's team. En esta discusión, después de algunos comentarios generales, propongo una lectura sistemática de la intervención tan elegantemente descrita por Kaija Puura. Buscaré paralelos entre los grupos terapéuticos y de familia como sistemas de desarrollo enmarcado y formalizaré los pasos tomados por la familia hacia la cicatrización bajo la influencia del equipo del terapista. Après quelques commentaires généraux, je proposerai dans cette discussion une lecture systémique de l'intervention si élégamment décrite par Kaija Puura. J'établirai des parallèles entre les groupes thérapeutiques et familiaux en tant que systèmes d'encadrement-développement et je formaliserai les étapes de guérison franchies par la famille grâce à l'influence de l'équipe thérapeutique. In dieser Diskussion, werde ich nach einigen allgemeineren Aussagen, eine systemische Lesart der von Kaija Puura so eingängig beschriebenen Intervention vorschlagen. Ich werde darin Parallelen zwischen der therapeutischen und Rahmengebenden Familiengruppen ziehen, und die Schritte der Familien hin zu einer Heilung unter dem Einfluss des Therapeutenteams formalisieren.

Traumatic recurrent anterior dislocation of the shoulder: two- to four-year follow-up of an anatomic open procedure.

The purpose of this study was to evaluate the results of an anatomic open stabilization procedure. Twenty-three consecutive patients with traumatic, recurrent, anterior glenohumeral instability were managed with a modified open procedure. All had a Bankart lesion. A standardized, true anatomic capsulolabral reconstruction was performed with suture anchors. Two patients were lost to follow-up, and twenty-one were evaluated after 36 months [range, 24-49 months] by an independent observer. Shoulder stability and function were the principal outcome measures. None of the patients had subsequent dislocations. All returned to full working capacity, and 19 reached their previous level of sport activities. The mean loss in active abduction and flexion was 1 degrees, in internal rotation, one vertebral level, and in external rotation, 7 degrees (arm at 90 degrees of abduction). Two patients had a positive anterior apprehension test. No sign of shoulder osteoarthritis was observed. The open anatomic capsulolabral reconstruction provides excellent results and allows the restoration of stability with good function.

The "open" chimney graft technique for juxtarenal aortic aneurysms with discrepant renal arteries.

OBJECTIVES: A straightforward original Chimney Graft (CG) protocol has been developed at our institution in selected cases of juxtarenal aortic aneurysm (JRAA). The aim of this study was to present our clinical experience of consecutive series with use of uncovered self-expanding stent (SES) as "Open Chimney" (OCh) in the endovascular repair (EVAR) of JRAA. METHODS: A standard endograft with suprarenal fixation struts is delivered with its proximal covered edge just below the highest RA in JRAA presenting the ostium of the two renal arteries at a different aortic level and the distance between the highest renal artery and the beginning of the aneurysm (improved landing zone) ≥10 mm. The low-lying renal artery is maintained patent by the OCh graft (standard SES) delivered from left brachial access (6 Fr). All clinical, anatomical, and operative data were prospectively collected and retrieved for the study analysis. RESULTS: From July 2010 to November 2012, OCh EVAR was offered to 22 consecutive patients considered unfit for JRAA open repair. All procedures were technically successful with aneurysm exclusion and patent OCh graft. One small perioperative type Ia endoleak spontaneously disappeared at the 3-month CT control. One patient died because of acute decompensated heart failure. One patient presented a left hemispheric stroke. The median follow-up of 18 months (range 7-35) showed aneurysm exclusion in all patients without type I and III endoleaks, SES stenosis, and/or renal impairment. CONCLUSIONS: OCh-EVAR is a straightforward technique that can be employed in selected cases of JRAA, avoiding the more complex and expensive fenestrated EVAR.

Percutaneous drainage versus emergency cholecystectomy for the treatment of acute cholecystitis in critically ill patients: does it matter?

Background The aim if this study was to compare percutaneous drainage (PD) of the gallbladder to emergency cholecystectomy (EC) in a well-defined patient group with sepsis related to acute calculous/acalculous cholecystitis (ACC/AAC).Methods Between 2001 and 2007, all consecutive patients of our ICU treated by either PD or EC were retrospectively analyzed. Cases were collected from a prospective database. Percutaneous drainage was performed by a transhepatic route and EC by open or laparoscopic approach. Patients' general condition and organ dysfunction were assessed by two validated scoring systems (SAPS II and SOFA, respectively). Morbidity, mortality, and long-term outcome were systematically reviewed and analyzed in both groups.Results Forty-two patients [median age = 65.5 years (range = 32-94)] were included; 45% underwent EC (ten laparoscopic, nine open) and 55% PD (n = 23). Both patient groups had similar preoperative characteristics. Percutaneous drainage and EC were successful in 91 and 100% of patients, respectively. Organ dysfunctions were similarly improved by the third postoperative/postdrainage days. Despite undergoing PD, two patients required EC due to gangrenous cholecystitis. The conversion rate after laparoscopy was 20%. Overall morbidity was 8.7% after PD and 47% after EC (P = 0.011). Major morbidity was 0% after PD and 21% after EC (P = 0.034). The mortality rate was not different (13% after PD and 16% after EC, P = 1.0) and the deaths were all related to the patients' preexisting disease. Hospital and ICU stays were not different. Recurrent symptoms (17%) occurred only after ACC in the PD group.Conclusions In high-risk patients, PD and EC are both efficient in the resolution of acute cholecystitis sepsis. However, EC is associated with a higher procedure-related morbidity and the laparoscopic approach is not always possible. Percutaneous drainage represents a valuable intervention, but secondary cholecystectomy is mandatory in cases of acute calculous cholecystitis.

Systems analysis of MVA-C induced immune response reveals its significance as a vaccine candidate against HIV/AIDS of clade C.

Based on the partial efficacy of the HIV/AIDS Thai trial (RV144) with a canarypox vector prime and protein boost, attenuated poxvirus recombinants expressing HIV-1 antigens are increasingly sought as vaccine candidates against HIV/AIDS. Here we describe using systems analysis the biological and immunological characteristics of the attenuated vaccinia virus Ankara strain expressing the HIV-1 antigens Env/Gag-Pol-Nef of HIV-1 of clade C (referred as MVA-C). MVA-C infection of human monocyte derived dendritic cells (moDCs) induced the expression of HIV-1 antigens at high levels from 2 to 8 hpi and triggered moDCs maturation as revealed by enhanced expression of HLA-DR, CD86, CD40, HLA-A2, and CD80 molecules. Infection ex vivo of purified mDC and pDC with MVA-C induced the expression of immunoregulatory pathways associated with antiviral responses, antigen presentation, T cell and B cell responses. Similarly, human whole blood or primary macrophages infected with MVA-C express high levels of proinflammatory cytokines and chemokines involved with T cell activation. The vector MVA-C has the ability to cross-present antigens to HIV-specific CD8 T cells in vitro and to increase CD8 T cell proliferation in a dose-dependent manner. The immunogenic profiling in mice after DNA-C prime/MVA-C boost combination revealed activation of HIV-1-specific CD4 and CD8 T cell memory responses that are polyfunctional and with effector memory phenotype. Env-specific IgG binding antibodies were also produced in animals receiving DNA-C prime/MVA-C boost. Our systems analysis of profiling immune response to MVA-C infection highlights the potential benefit of MVA-C as vaccine candidate against HIV/AIDS for clade C, the prevalent subtype virus in the most affected areas of the world.

Dispositifs de délivrance de principes actifs pour des applications ophtalmologiques [Drug delivery systems for intraocular applications].

Numerous drug delivery systems (DDSs) can be used as intraocular tools to provide a sustained and calibrated release for a specific drug. Great progress has been made on the design, biocompatibility, bioavailability, and efficacy of DDSs. Although several of them are undergoing clinical trials, a few are already on the market and could be of a routine use in clinical practice. Moreover, miniaturization of the implants makes them less and less traumatic for the eye tissues and some DDSs are now able to target certain cells or tissues specifically. An overview of ocular implants with therapeutic application potentials is provided.

Is our heart a well-designed pump? The heart along animal evolution.

A carrier system for gases and nutrients became mandatory when primitive animals grew larger and developed different organs. The first circulatory systems are peristaltic tubes pushing slowly the haemolymph into an open vascular tree without capillaries (worms). Arthropods developed contractile bulges on the abdominal aorta assisted by accessory hearts for wings or legs and by abdominal respiratory motions. Two-chamber heart (atrium and ventricle) appeared among mollusks. Vertebrates have a multi-chamber heart and a closed circulation with capillaries. Their heart has two chambers in fishes, three chambers (two atria and one ventricle) in amphibians and reptiles, and four chambers in birds and mammals. The ventricle of reptiles is partially divided in two cavities by an interventricular septum, leaving only a communication of variable size leading to a variable shunt. Blood pressure increases progressively from 15 mmHg (worms) to 170/70 mmHg (birds) according to the increase in metabolic rate. When systemic pressure exceeds 50 mmHg, a lower pressure system appears for the circulation through gills or lungs in order to improve gas exchange. A four-chamber heart allows a complete separation of systemic and pulmonary circuits. This review describes the circulatory pumping systems used in the different classes of animals, their advantages and failures, and the way they have been modified with evolution.