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.

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.

[Squatting cast for biomechanical treatment of decentred hip joints]. / Sitz-Hock-Gips zur biomechanischen Behandlung dezentrierter Hüftgelenke.

The so-called "congenital" luxation of the hip joint is endemic in Central Europe and occurs in about 1% of all newborn infants. By the means of ultrasonographic diagnosis according to the Graf method an early detection instantly after birth has become a good clinical routine in the German-speaking countries. Sonography-based conservative treatment has become the gold standard. The cast in squatting ("human") position is a standard procedure in order to retain the originally decentred or unstable hip joints in the reduced position: 100° flexion and 50° abduction are necessary to fix the hip joint in the reduced position without the risk of avascular necrosis. After the fixation in a squatting-cast, a period of functional bracing in flexed position enhances bony maturation. This two-phase functional conservative treatment can avoid later osteotomies or even early total hip replacement.

Minor cell-death defects but reduced tumor latency in mice lacking the BH3-only proteins Bad and Bmf.

Proapoptotic Bcl-2 family members of the Bcl-2 homology (BH)3-only subgroup are critical for the establishment and maintenance of tissue homeostasis and can mediate apoptotic cell death in response to developmental cues or exogenously induced forms of cell stress. On the basis of the biochemical experiments as well as genetic studies in mice, the BH3-only proteins Bad and Bmf have been implicated in different proapoptotic events such as those triggered by glucose- or trophic factor-deprivation, glucocorticoids, or histone deacetylase inhibition, as well as suppression of B-cell lymphomagenesis upon aberrant expression of c-Myc. To address possible redundancies in cell death regulation and tumor suppression, we generated compound mutant mice lacking both genes. Our studies revealed lack of redundancy in most paradigms of lymphocyte apoptosis tested in tissue culture. Only spontaneous cell death of thymocytes kept in low glucose or that of pre-B cells deprived of cytokines was significantly delayed when both genes were lacking. Of note, despite these minor apoptosis defects we observed compromised lymphocyte homeostasis in vivo that affected mainly the B-cell lineage. Long-term follow-up revealed significantly reduced latency to spontaneous tumor formation in aged mice when both genes were lacking. Together our study suggests that Bad and Bmf co-regulate lymphocyte homeostasis and limit spontaneous transformation by mechanisms that may not exclusively be linked to the induction of lymphocyte apoptosis.

Measured and modelled tritium concentrations in freshwater Barnes mussels (Elliptio complanata) exposed to an abrupt increase in ambient tritium levels.

To improve understanding of environmental tritium behaviour, the International Atomic Energy Agency (IAEA) included a Tritium and C-14 Working Group (WG) in its EMRAS (Environmental Modelling for Radiation Safety) program. One scenario considered by the WG involved the prediction of time-dependent tritium concentrations in freshwater mussels that were subjected to an abrupt increase in ambient tritium levels. The experimental data used in the scenario were obtained from a study in which freshwater Barnes mussels (Elliptio complanata) were transplanted from an area with background tritium concentrations to a small Canadian Shield lake that contains elevated tritium. The mussels were then sampled over 88 days, and concentrations of free-water tritium (HTO) and organically-bound tritium (OBT) were measured in the soft tissues to follow the build-up of tritium in the mussels over time. The HTO concentration in the mussels reached steady state with the concentration in lake water within one or two hours. Most models predicted a longer time (up to a few days) to equilibrium. All models under-predicted the OBT concentration in the mussels one hour after transplantation, but over-predicted the rate of OBT formation over the next 24h. Subsequent dynamics were not well modelled, although all participants predicted OBT concentrations that were within a factor of three of the observation at the end of the study period. The concentration at the final time point was over-predicted by all but one of the models. The relatively low observed concentration at this time was likely due to the loss of OBT by mussels during reproduction.

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.

Non-exchangeable organically bound tritium (OBT): its real nature.

Denaturation experiments show that the larger part of organically bound tritium (OBT) consists of "buried tritium" and is not bound to carbon, as has been traditionally assumed. The logistical growth analysis of hydrogen isotopes in dry plant matter reveals a larger rate of increase of OBT than organically bound hydrogen (OBH). This is reflected by tritium accumulation for 1.4 and 2 in the primary hydration shell and in the base-pairing hydrogens of DNA respectively. If tritons and protons are considered as quantum mechanical entities, the accumulative tritium transfer from water to the hydrogen bonds of biopolymers is generally valid. Growth experiments confirm the assumed rapid isotope exchange "in vivo", which is not observed "in vitro" by denaturation.

A point mutation in an unusual Sec7 domain is linked to brefeldin A resistance in a Plasmodium falciparum line generated by drug selection.

The malaria parasite Plasmodium falciparum has an unusual organization of its secretory compartments. As an approach to a functional identification of auxiliary proteins involved in secretion, a parasite line was generated by drug selection that is resistant to brefeldin A, an inhibitor of the secretory pathway. In the resistant line, neither protein secretion nor parasite viability were affected by the drug. The analysis of a sec7 domain, a conserved structure of guanine nucleotide exchange factors (ARF-GEF) required for the activation of ADP-ribosylation factors, revealed a single methionine-isoleucine substitution in the resistant parasite line. ARF-GEFs are key molecules in the formation of transport vesicles and the main targets of brefeldin A. The methionine residue in this position of sec7 domains is highly conserved and confers brefeldin A sensitivity. Unlike other eukaryotes that have multiple ARF-GEFs, the plasmodial genome encodes a single sec7 domain. This domain shows a distinct structural difference to all sec7 domains analysed so far; two conserved subdomains that are essential for protein function are separated in the plasmodial protein by an insertion of 146 amino acids.

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.

Theoretical foundation and experimental proof of the accumulating transfer of tritium from water into DNA and other biomolecules in vitro and in vivo.

Heisenberg's uncertainty principle, which describes a fundamental property of matter, predicts the light hydrogen isotope to prefer the strong hydrogen bridge positions (with large local uncertainty). In contrast, the heavy hydrogen isotope tritium originally localized in water, should finally be found in the exchangeable hydrogen bridge positions of proteins, carbohydrates and nucleotides which are definitely less strong than those of water. The fractionation factor of tritium and protium measured between water and DNA as well as the mixture of biomolecules of liver confirm this conclusion and show in addition, a tritum accumulation also in the hydration sheets of the biomolecules. Furthermore, the larger intrinsic rate of natural increase of tritium than of hydrogen in tissue solids of growing maize and barley confirm the accumulating tritium transfer from water to biomolecules taking place in vivo.

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.

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.

Annular abscesses in surgical endocarditis: anatomic, clinical, and operative features.

BACKGROUND: The aim of this study was to determine patterns of anatomic, clinical, and operative features in surgical endocarditis (SE) with annular abscess (AA). METHODS: The study consisted of a retrospective analysis of SE cases with AA between 1981 and 1997. RESULTS: A total of 41 cases with AA were found in 106 consecutive SE cases. There was a higher incidence of AA in aortic (37 of 71 [52%]) (p<0.01) compared to mitral (6 of 42 [14.3%]) or tricuspid (0 of 12) infections. However, the mitral abscesses had a greater tendency toward fistula or pseudoaneurysm formation (4 of 6 [67%]) than other valve abscess cavities (7 of 46 [15%]) (p<0.01). Severe heart failure (p<0.01), heart block (p<0.05), and fistula/pseudoaneurysm (p<0.001), were more often found in SE with AA than without. There were 46 separate aortic AA in 37 instances of aortic valve SE. Of these, 31 of 46 (67%) were less than 1 cm (group 1), 10 of 46 (22%) were large but confined to a given cusp annulus (group 2), 4 of 46 (8.6%) were large between multiple cusps (group 3), and 1 of 46 (2.2%) was circumferential (group 4). There were four instances of aortoventricular discontinuity. Group 1 abscesses were repaired by local closure without a patch significantly more often than the other groups. The mortality of SE with AA was significantly greater for larger AA (groups 3 and 4, 3 of 5 [60%]) than for smaller AA (groups 1 and 2, 0 of 36) (p<0.001). There were six separate mitral AA in six instances of mitral SE, five requiring patch repair. The 30-day operative mortality for AA cases was 3 of 41 (7.3%) compared to 2 of 65 (3.1%) without AA. All AA mortalities involved large AA in the aortic valve position. Of 35 mechanical valves placed for AA, only one required subsequent removal for prosthetic endocarditis. CONCLUSIONS: Annular abscesses are most frequent in aortic AA, but fistulas/pseudoaneurysms are more frequent in mitral AA. Small to moderate aortic AA can be managed by local closure without an increased mortality compared to SE without AA. Patients with large aortic AA have a higher operative mortality. Mechanical prostheses are safe and effective for the majority of patients with AA.

Central venous injuries of the subclavian-jugular and innominate-caval confluences.

Injuries to the central venous system can result from penetrating trauma or iatrogenic causes. Injuries to major venous confluences can be particularly problematic, because the clavicle and sternum seriously limit exposure of the injury site. We report our institution's experience with central venous injuries of the subclavian-jugular and innominate-caval venous confluences. Significant injuries of the subclavian-jugular venous confluence frequently result from penetrating trauma, while injuries to the innominate-caval confluence are usually catheter-related. Median sternotomy provides adequate exposure of the innominate-caval confluence, while exposure of the subclavian-jugular venous confluence requires extension of the median sternotomy incision into the neck and resection of the clavicle. The literature is reviewed.

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.

Characteristics of patients less than 45 years of age compared with older patients undergoing coronary artery bypass grafting.

BACKGROUND: Coronary artery disease (CAD) was not recognized as common among young patients until the study by Yater in 1948. Subsequent studies further elucidated the nature of the disease, which had become more apparent in the younger groups. HYPOTHESIS: The study was undertaken to determine the prevalence of risk factors and severity of coronary disease among young patients aged < or = 45 years undergoing coronary artery bypass grafting (CABG) compared with older patients. METHODS: In all, 112 young patients aged < or = 45 years (Group 1) and 798 older patients aged > 45 years (Group 2) were analyzed for trends to hypertension, smoking, diabetes, family history of heart disease, hypercholesterolemia, obesity, and history of previous myocardial infarction (MI). The severity of disease was examined in terms of number of diseased vessels, vessel size, number of grafts performed, performance of endarterectomies, and left ventricular function. RESULTS: Group 1 had a higher incidence of positive family history (68.5 vs. 51.2%, p < 0.05), and lower incidences of hypertension (62.7 vs. 81.5%, p < 0.05), obesity (42.9 vs. 83.9%, p < 0.05), and history of previous MI (54.5 vs. 94.6%, p < 0.05). Group 2 had a higher incidence of left main disease (22.6 vs. 11.4%, p < 0.05). The distribution of the affected vessels of the young patients was most commonly the left anterior descending (90.4%) followed by the right coronary (79.8%) and circumflex arteries (69.2%). Group 2 had more grafts per patient (3.82 vs. 3.37, p < 0.05). The size of the diseased vessels measured intraoperatively was similar (1.56 vs. 1.58 mm, p = NS) in both groups. Endarterectomy was performed almost three times more often in Group 1 patients (8.2 vs. 3.0%, p < 0.05). Operative mortality was less in Group 1 mean (1.8 vs. 6.3%, p < 0.05). Group 2 had a greater mean left ventricular ejection fraction (53.8 vs. 49.7%, p < 0.05). CONCLUSION: Compared with the older population, patients < or = 45 years of age who underwent CABG had (1) a higher incidence of positive family history of CAD, (2) a higher likelihood of requiring an endarterectomy, and (3) lower operative mortality rate despite a slightly poorer ventricular function.

Reversible snaring for proper prosthetic seating during valve replacement.

A method of reversible suture snaring is described for evaluating the final valve seating and positioning before knot tying of valve sutures. This allows for alteration of the operative plan before investing substantial ischemic time in a nonfunctional result. The procedure has been used in 577 consecutive prosthetic valve replacements in the past 5 years. The technique maintains proper seating while the valve is permanently anchored in place.