Prognostic factors in dogs with common causes of proteinuria.

INTRODUCTION: Little is known about the prognostic value of increased urine protein to creatinine ratios (UPC) comparing different underlying diseases in dogs. Therefore, between 2014 and 2015, dogs with a UPC of 2,0 or higher measured were retrospectively analysed at least once. They were divided into groups of the most common underlying diseases, namely primary glomerulopathy, Cushing's disease, leishmaniasis and in a group of different diseases. Possible prognostic factors, like UPC at time of diagnosis, creatinine, urine specific gravity, albumin and haematocrit, were assessed. Eighty-nine dogs with severe proteinuria were included in the study. Median time of survival was 42 days. UPC and time of survival did not differ significantly between the groups. Among the dogs with primary glomerulopathy, identified significant risk factors for death included increased UPC (p=0,03), increased creatinine (p.

INTRODUCTION: On sait peu de choses sur la valeur pronostique de l'augmentation du rapport protéines/créatinine urinaires (UPC) en fonction des différentes maladies sous-jacentes chez le chien. Par conséquent, entre 2014 et 2015, les chiens ayant une UPC de 2,0 ou plus ont été étudiés rétrospectivement au moins une fois. Ils ont été divisés en groupes des maladies sous-jacentes les plus courantes, à savoir la glomérulopathie primaire, la maladie de Cushing, la leishmaniose et dans un groupe de maladies diverses. Les facteurs pronostiques possibles, comme l'UPC au moment du diagnostic, la créatinine, le poids spécifique de l'urine, l'albumine et l'hématocrite, ont été évalués. Quatre-vingt-neuf chiens présentant une protéinurie sévère ont été inclus dans l'étude. La durée médiane de survie était de 42 jours. L'UPC et le temps de survie ne différaient pas significativement entre les groupes. Parmi les chiens atteints de glomérulopathie primaire, les facteurs de risque de décès significatifs identifiés comprenaient une UPC élevée (p=0,03), une créatinine élevée (p.

Targeting the Bcl-2-regulated apoptosis pathway by BH3 mimetics: a breakthrough in anticancer therapy?

Induction of apoptosis in tumor cells by direct activation of the Bcl-2-regulated apoptosis pathway by small molecule drugs carries high hopes to overcome the shortcomings of current anticancer therapies. This novel therapy concept builds on emerging insights into how Bcl-2-like molecules maintain mitochondrial integrity and how pro-apoptotic BH3-only proteins lead to its disruption. Means to unleash the pro-apoptotic potential of BH3-only proteins in tumor cells, or to bypass the need for BH3-only proteins by directly blocking possible interactions of Bcl-2-like pro-survival molecules with Bax and/or Bak, constitute interesting options for the design of novel anticancer therapies. For the optimization and clinical implementation of these novel anticancer strategies, a detailed understanding of the role of individual BH3-only proteins in cell death signaling in healthy cells and during tumor suppression is required. In this review, we will touch on the latest findings on BH3-only protein function and attempts to define the molecular properties of the so-called 'BH3 mimetics,' a novel class of anticancer agents, able to prompt apoptosis in tumor cells, regardless of their p53 or Bcl-2 status.

The BH3-only protein BIM contributes to late-stage involution in the mouse mammary gland.

After cessation of lactation, involution of the mouse mammary gland proceeds in two distinct phases, a reversible and an irreversible one, which leads to the death and removal of alveolar cells. Cell death is preceded by the loss of STAT5 activity, which abrogates cell differentiation and gain of STAT3 activity. Despite early observations implicating BCL2 (B cell lymphoma 2) family proteins in this process, recent evidence suggests that STAT3-controlled cathepsin activity is most critical for cell death at the early stage of involution. Somewhat surprisingly, this cell death associates with but does not depend on the activation of pro-apoptotic effector caspases. However, transgenic overexpression of BCL2, that blocks caspase activation, delays involution while conditional deletion of BclX accelerates this process, suggesting that BCL2 family proteins are needed for the effective execution of involution. Here, we report on the transcriptional induction of multiple pro-apoptotic BCL2 family proteins of the 'BH3-only' subgroup during involution and the rate-limiting role of BIM in this process. Loss of Bim delayed epithelial cell clearance during involution after forced weaning in mice, whereas the absence of related Bmf had minor and loss of Bad or Noxa no impact on this process. Consistent with a contribution of BCL2 family proteins to the second wave of cell death during involution, loss of Bim reduced the number of apoptotic cells in this irreversible phase. Notably, the expression changes observed within the BCL2 family did not depend on STAT3 signalling, in line with its initiating role early in the process, but rather appear to result from relief of repression by STAT5. Our findings support the existence of a signalling circuitry regulating the irreversible phase of involution in mice by engaging BH3-only protein-driven mitochondrial apoptosis.

(Ca2+ + Mg2+)-ATPase activator: its presence in human red blood cells and rabbit skeletal muscle.

We find that both human red blood cells and rabbit skeletal muscle contain a soluble activator which can stimulate (Ca2+ + Mg2+)-ATPase activity. The activator protein from either source can enhance the (Ca2+ + Mg2+)-ATPase of both the red blood cell membrane and the microsomal fraction from skeletal muscle. The data suggest that they are members of the class of Ca2+-binding modulator proteins. A possible physiological role for the skeletal muscle activator protein in the contractile process is discussed.

L-[4-11C]aspartic acid: enzymatic synthesis, myocardial uptake, and metabolism.

Sterile, pyrogen-free L-[4-11C]aspartic acid was prepared from 11CO2 using phosphoenolpyruvate carboxylase and glutamic/oxaloacetic acid transaminase immobilized on Sepharose supports to determine if it is a useful indicator for in vivo, noninvasive determination of myocardial metabolism. An intracoronary bolus injection of L-[4-11C]aspartic acid into dog myocardium showed a triexponential clearance curve with maximal production of 11CO2 100 s after injection. Inactivation of myocardial transaminase activity modified the tracer clearance and inhibited the production of 11CO2. Positron-computed tomography imaging showed that the 11C activities retained in rhesus monkey myocardium are higher than those observed in dog heart after intravenous injection of L-[4-11C]aspartic acid. These findings demonstrated the rapid incorporation of the carbon skeleton of L-aspartic acid into the tricarboxylic acid cycle after enzymatic transamination in myocardium and suggested that L-[4-11C]aspartic acid could be of value for in vivo, noninvasive assessment of local myocardial metabolism.

13N-labeled L-amino acids for in vivo assessment of local myocardial metabolism.

The hot cell synthesis of sterile, pyrogen-free 13N-labeled L-amino acids was accomplished by employing the appropriate immobilized enzymes on a CNBr-activated Sepharose support and using remote, semiautomated systems. The syntheses were completed 6-12 min after cyclotron production of [13N]ammonia. Myocardial time-activity curves after intracoronary injection of 13N-labeled L-amino acids in dogs were triexponential in both normal and ischemic myocardium. Higher retention of 13N activity was observed in ischemic segments. Positron computed tomography imaging also showed increased uptake of 13N-labeled L-glutamate and L-alanine in ischemic segments compared with normal myocardium when blood flow corrections were made. Myocardial transaminases are primarily responsible for the observed retention fractions. It suggests the participation of the carbon skeletons of these amino acids in the Krebs cycle.

Evaluation of children with possible appendicitis using technetium 99m leukocyte scan.

We evaluated the use of technetium 99m albumin colloid white blood cell (TAC-WBC) scan in 33 children with possible appendicitis. Ten children had appendicitis, four of whom had perforated their appendix at the time of surgery. Children with appendicitis differed from children without appendicitis in the incidence of right lower quadrant rebound tenderness (60% vs 17.4%), and white blood cell count (X10(3)/mm3) (14.0 + 1.9 vs 10.7 +/- 1.0). TAC-WBC scans were interpreted as either positive, negative, or indeterminate for appendiceal pathology. Twenty-five children had positive or negative scans for appendiceal pathology. There were 7 true positives, 2 false positives, 16 true negatives, and 0 false negatives. This resulted in a sensitivity of 100%, a specificity of 89%, an accuracy of 92%, a positive predictive value of 78%, and a negative predictive value of 100%. The TAC-WBC scan was indeterminate (abnormal but nondiagnostic for appendicitis) in eight children (24%), three of whom had appendicitis. The main values of TAC-WBC scan in our study of children with possible appendicitis were that it could be used emergently, it was abnormal in 100% of children with appendicitis, and it had a high negative predictive value (100%). The main limitation of TAC-WBC scan in our study was that it was indeterminate for appendiceal pathology in 24% of children. We recommend that TAC-WBC scan be used in children with possible appendicitis because it may allow outpatient management of up to 48%.

L-[1-11C]leucine: routine synthesis by enzymatic resolution.

L-[1-11C]leucine, suitable for the determination of cerebral protein synthesis rates in man using positron emission tomography, has been synthesized using a modified Bucherer-Strecker reaction sequence. The isolation of the pure L-amino acid isomer from the enantiomeric mixture, initially obtained using either an open or closed reaction vessel, was achieved using a D-amino acid oxidase/catalase enzyme complex immobilized on a Sepharose support. The O2 required by the D-amino acid oxidase as the hydrogen acceptor was supplied by catalase. The L-[1-11C]leucine was obtained with a radiochemical purity of greater than 99% and with a radiochemical yield of 25%. Using a remote, semiautomated synthesis system, typical production time was 30-40 min after preparation of H11CN. The use of immobilized enzymes for rapid and effective resolution of amino acid enantiomers eliminates the possibility of protein contamination and assures the production of a sterile, pyrogen-free product.

Synthesis and myocardial kinetics of N-13 and C-11 labeled branched-chain L-amino acids.

Glutamate dehydrogenase (GDH), immobilized on CNBr-activated Sepharose supports, was used with N-13 ammonia to aminate alpha-ketoisocaproic acid (KIC), and alpha-ketoisovaleric acid (KIV) to produce N-13-labeled branched-chain L-amino acids with radiochemical yields ranging from 29% to 35%. From kinetic and practical considerations, pH 7.5-8.0 was established to be optimal for the synthesis of N-13-labeled branched-chain-L-amino acids. Myocardial time-activity curves in dogs at control, during low-flow ischemia, reperfusion, and after transaminase inhibition following intracoronary bolus injection of the N-13-labeled amino acids were biexponential. Higher retention of N-13 activity was observed in ischemic segments both during low-flow ischemia (29.2%) and reperfusion (23.2%) when compared with controls (20.0%), (n = 4). On the other hand, transaminase inhibition decreased residue fractions from 21.0% at control to 13.9% (n = 4). The residual activity with L-[1-11C]leucine allows for the calculation of protein synthesis rates.

Effect of off-pump coronary artery bypass grafting on morbidity.

Three hundred three patients who underwent off-pump coronary bypass were compared with 483 patients who underwent standard on-pump coronary bypass. There was a significant reduction in intraoperative blood transfusion requirements, as well as a significant reduction in the incidence of neurologic, renal, and prolonged ventilatory complications in the off-pump group.

Application of ultrafast computed tomography for diagnosis of perivalvular abscesses. Surgical implications.

The presence of a perivalvular abscess is associated with an increased risk of morbidity and mortality with valve replacement and can require extensive debridement and reconstructive procedures. An accurate noninvasive method for preoperative diagnosis may hasten operation and aid in preoperative and surgical management. Two cases are presented in which ultrafast computed tomography accurately identified perivalvular abscesses not detected on two-dimensional transthoracic echocardiography and guided operative intervention.

Tuberculosis of the thymus.

Tuberculosis is increasing in prevalence in North America, mainly due to HIV infection. We describe an unusual case of TB of the thymus in a HIV sero-negative Filipino immigrant who preoperatively was thought to have a thymoma. We describe the clinical, radiologic and pathologic findings and review the literature on TB of the thymus.

The rudimentary first rib. A cause of thoracic outlet syndrome with arterial compromise.

The symptoms of thoracic outlet syndrome are neurologic, not vascular, in more than 95% of cases. Subclavian artery compression is usually related to cervical ribs; however, congenitally abnormal first ribs may also produce vascular compromise. We review our two cases of thoracic outlet syndrome associated with significant subclavian artery compression caused by rudimentary first ribs and the prior literature emphasizing the mechanism of injury, diagnostic features, and treatment. Transaxillary resection of the first and second ribs was curative in both cases. The operative specimens demonstrated fusion of the rudimentary first rib to the second rib, with compression of the subclavian artery by a large first-rib exostosis. Patients with thoracic outlet syndrome and a rudimentary first rib should be examined for substantial vascular compromise, and, if it is found, the abnormal first and second rib complex should be resected early without prolonged conservative measures.

Danger of false intubation after traumatic tracheal transection.

Blunt tracheobronchial injuries may be difficult to diagnosis at presentation but can pose major airway difficulties. We present a patient with a tracheal transection who underwent intubation with the tip of the endotracheal tube exiting the trachea and terminating in the mediastinum adjacent to the distal trachea. He underwent surgical repair of the injury with end-to-end anastomosis. Although intubation over a flexible fiberoptic bronchoscope is desirable in cases of suspected tracheobronchial injury, it may not be feasible. In cases of suspected tracheobronchial injuries with blind endotracheal intubation, the possibility of false intubation should always be entertained.

Primitive neuroectodermal tumor of the pulmonary hilum in an adult.

A rare case of a thoracic primitive neuroectodermal tumor in an adult is presented. In this case, the aggressive, rapid progression characteristic of the disease was evident.

Off-pump versus on-pump coronary bypass in high-risk subgroups.

BACKGROUND: Cardiopulmonary bypass (CPB) has pathophysiologic sequelae that may be more severe in high-risk subsets. We wanted to determine whether off-pump coronary bypass (OPCAB) could optimize outcomes. METHODS: Our database of 242 OPCAB patients undergoing complete revascularization was compared to a base of 483 CABG patients undergoing CPB. Results were compared for the overall series and in the following high-risk subsets: 80 years of age or older, ventricular dysfunction (ejection fraction (EF) < or = 0.25), prior neurologic event or renal failure, chronic obstructive pulmonary disease (COPD), and reoperation. RESULTS: In the overall series, OPCAB significantly reduced the incidence of intraoperative transfusion requirements and showed a trend toward reduced morbidity in terms of postoperative neurologic and renal complications, prolonged ventilator requirement greater than 3 days, and bleeding requiring reexploration. Mortality was less in the OPCAB group (0.4% versus 2.7%, p = not significant). Similar results were achieved in the following high-risk subgroups (n = off-pump/on-pump): 80 years of age or older (n = 28/58), EF less than or equal to 25% (n = 13/26), preoperative neurologic event (n = 25/36), preoperative renal failure (n = 27/46), COPD (n = 33/43), and reoperation (n = 28/76). OPCAB decreased the incidence of prolonged ventilation in COPD patients (0/33 [0%] versus 4/43 [9.3%] p = not significant) and decreased the incidence of renal complications in the elderly (1/28 [3.6%] versus 9/58 [15.5%] p = not significant). Off-pump coronary bypass reduced but did not eliminate neurologic events in the elderly (2/28 [7.1%] versus 8/58 [13.8%] p = not significant). CONCLUSION: Off-pump coronary bypass significantly reduced the incidence of transfusion requirement compared to the CPB counterparts and had a consistent trend in reducing morbidity and mortality overall and in all high-risk subsets. Neurologic events are not eliminated in OPCAB.

Local transverse arch repair for type A aortic dissection.

BACKGROUND: The management of retrograde dissections originating from the transverse arch is controversial. Although replacing the ascending aorta is clearly beneficial, the appropriate approach to the management of the arch tear is not as apparent and ranges from no intervention to total arch replacement. METHODS: Three patients presented with acute (n = 2) or subacute (n = 1) aortic dissection, with tears involving the transverse arch. All underwent local transaortic pledgeted suture repair of the arch tears during hypothermic circulatory arrest, as well as graft replacement of the ascending aorta. RESULTS: Circulatory arrest times ranged from 12 to 15 minutes (transaortic arch repairs alone) to 48 minutes (transaortic arch repair and open distal graft anastomosis). Postoperatively all patients awoke within 12 hours and subsequently did well neurologically. CONCLUSIONS: In the face of a type A dissection with an entry in the transverse arch, local transaortic repair with concomitant ascending aortic replacement represents a viable middle ground between no arch intervention and lengthy arch replacement. Huge entry tears or aneurysmal arch enlargement would preclude such an approach.

Off-pump obtuse marginal grafting with local stabilization: thoracotomy approach in reoperations.

BACKGROUND: Redo coronary surgery in patients with patent internal mammary artery (IMA) grafts may be hazardous. A thoracotomy approach has been used to graft the circumflex branches to avoid injury from sternal re-entry. Combining this approach with off-pump revascularization techniques may be useful. METHODS: Seven consecutive patients who had undergone prior coronary revascularization developed symptoms attributable to lateral wall ischemia. Five of them had patent IMA grafts. These patients underwent off-pump obtuse marginal grafting using local immobilization techniques via a thoracotomy approach. Inflow was from the descending aorta in 6 patients and splenic artery in 1. RESULTS: Obtuse marginal grafting was successfully performed in all cases without need for cardiopulmonary bypass. CONCLUSIONS: Off-pump obtuse marginal grafting via the thoracotomy route may be useful in redo coronary surgery, particularly in instances of patent IMA grafts.

Technical aspects of total revascularization in off-pump coronary bypass via sternotomy approach.

BACKGROUND: Cardiopulmonary bypass and cardioplegic arrest result in known physiologic inflammatory, coagulopathic, and embolic states that may result in end-organ damage. Interest in off-pump complete coronary revascularization using sternotomy exposure is therefore increasing. METHODS: Using specific surgical and anesthetic techniques, we have been able to achieve total revascularization using off-pump coronary artery bypass grafting procedures (OP-CAB) through a sternotomy approach. Exposure techniques and local stabilization are tailored to individual vessels and cardiac regions. Vascular control is achieved with silicone-elastomer loops, occluders, and shunts. Poor ventricular function, advanced age, and other comorbid conditions, in and of themselves, were not considered contraindications to OP-CAB. Cardiomegaly or situations of small, intramyocardial, or heavily calcified vessels were relative contraindications to OP-CAB. RESULTS: Of 141 sternotomy OP-CAB cases, 132 (93.6%) were completely off-pump. The mean number of OP-CAB grafts per patient in the cases that were completely off-pump was 3.3 (range, 1 to 6). The 30-day operative mortality was 0%. There were four instances of intraoperative cardiac arrest, precipitated by vascular occlusion of the right coronary artery or manipulating a cardiomegalic heart. Advanced age (> or = 80 years) or profound ventricular dysfunction (ejection fraction < or = 0.25) was present in a considerable percentage of patients (10.6% and 9.9%, respectively). CONCLUSIONS: Off-pump coronary artery bypass grafting is successful for total revascularization in large numbers of patients. Anatomic factors, including cardiomegaly and small, intramyocardial, or heavily calcified vessels are possible contraindications to OP-CAB. Patients at highest risk for undergoing cardiopulmonary bypass, including those of advanced age and having ventricular dysfunction, are precisely the ones in whom OP-CAB may be the most useful.

Closure of short, wide patent ductus arteriosus with cardiopulmonary bypass and balloon occlusion.

The wide, short patent ductus arteriosus in adults and older adolescents poses an extreme hazard with standard closed ligation techniques. The method of transpulmonary balloon catheter occlusion and repair of pediatric ductus arteriosus is herein reported in older patients using a Foley catheter and normothermic bypass. Transesophageal echocardiography is crucial in assessing the size of the ductus and confirming adequacy of repair. The technique is simple and safe even in the presence of a wide, short ductus.