In vitro activity and beta-lactamase stability of the new oral cephalosporin Bay v 3522

The activity of the new oral cephalosporin Bay v 3522 was compared to that of six other beta-lactam agents. Bay v 3522 inhibited methicillin-susceptibleStaphylococcus aureus andStaphylococcus epidermidis at 2 µg/ml, compared to MICs of 8 µg/ml for the other cephalosporins tested. It was more active againstStreptococcus pyogenes (MIC 0.06 µg/ml) than cefuroxime, cefixime, cephalexin and cefaclor. Groups B, C and G streptococci were inhibited at 0.12 µg/ml, while the MIC90 forStreptococcus bovis and viridans streptococci was 0.5 and 2 µg/ml, respectively. The MIC90 for enterococci andListeria monocytogenes was 8 µg/ml.Clostridium perfringens was inhibited by 0.12 µg/ml, but mostBacteroides spp. were resistant. The MIC90 for beta-lactamase positiveEscherichia coli (producing primarily TEM-1) was >64 µg/ml and for beta-lactamase negative strains 16 µg/ml. The MIC90 for high-level beta-lactamase producingKlebsiella pneumoniae was >64 µg/ml versus 4 µg/ml for other isolates. The MIC90 forMoraxella catarrhalis was 2 µg/ml, forHaemophilus influenzae 1 µg/ml, and forNeisseria gonorrhoeae 4 µg/ml.Enterobacter cloacae, Citrobacter freundii, Proteus mirabilis, Providencia spp. andPseudomonas aeruginosa were resistant. Bay v 3522 was destroyed by TEM-1, SHV-1, TEM-3 and P99 beta-lactamases.     

APC I1307K and the E1317Q variants are not present in Chinese colorectal cancer patients.

PURPOSE: The APC I1307K and E1317Q variants predispose to colorectal adenomas and carcinomas in Caucasians, but data are lacking in Asians. METHODS AND RESULTS: We sequenced the APC gene from codons 1261 to 1409 and found none of 147 Chinese, 20 Malay, and 11 Indian colorectal cancer patients in Singapore to carry the APC I1307K or E1317Q variants. CONCLUSION: These variants are rare in these Asian populations, and play little role in colorectal cancer causation in Chinese.     

The plasminogen activation system reduces fibrosis in the lung by a hepatocyte growth factor-dependent mechanism

Mice deficient in the plasminogen activator inhibitor-1 gene (PAI-1-/- mice) are relatively protected from developing pulmonary fibrosis from bleomycin administration. We hypothesized that one of the protective mechanisms may be the ability of the plasminogen system to enhance hepatocyte growth factor (HGF) effects, which have been reported to be anti-fibrotic in the lung. HGF is known to be sequestered in tissues by binding to extracellular matrix components. Following bleomycin administration, we found that HGF protein levels were higher in bronchoalveolar lavage fluid from PAI-1-/- mice compared to wild-type (PAI-1+/+) mice. This increase could be suppressed by administering tranexamic acid, which inhibits plasmin activity. Conversely, intratracheal instillation of urokinase into bleomycin-injured PAI-1+/+ mice to activate plasminogen caused a significant increase in HGF within bronchoalveolar lavage and caused less collagen accumulation in the lungs. Administration of an anti-HGF neutralizing antibody markedly increased collagen accumulation in the lungs of bleomycin-injured PAI-1-/- mice. These results support the hypothesis that increasing the availability of HGF, possibly by enhancing its release from extracellular matrix by a plasmin-dependent mechanism, is an important means by which activation of the plasminogen system can limit pulmonary fibrosis.     

Cytokine responses in mice infected with<Emphasis Type="Italic"> Clonorchis sinensis</Emphasis>

FVB and BALB/c mice show different morbidity, development of Clonorchis sinensis, and pathological changes following C. sinensis infection. FVB mice are susceptible and BALB/c mice are relatively more resistant to C. sinensis infection. To investigate the relationship between cytokine reaction and susceptibility to C. sinensis infection in FVB and BALB/c mice, we described both the patterns and kinetics of Th1 cytokines and Th2 cytokines in spleen cell culture. Interleukin (IL)-4 and IL-10 cytokine production in the culture supernatants of the concanavalin-A-stimulated spleen cells increased at 2–3 weeks post-infection in both strains. IL-5 production increased between 2 and 5 weeks post-infection in both strains, and reached a peak level at 2 weeks post-infection in BALB/c mice and 4 weeks post-infection in FVB mice. In contrast, gamma interferon (IFN-) production decreased between 2 and 4 weeks in both strains. IL-2 production increased slightly in BALB/c mice following infection, but was unchanged in FVB mice. IL-4 production over preinfection levels was significantly higher in FVB mice, whereas IFN-, IL-2, and IL-10 production were significantly higher in BALB/c mice. The levels of serum immunoglobulin E (IgE) and blood eosinophils in both mouse strains significantly increased between 3 and 6 weeks postinfection. Serum IgE levels were significantly higher in FVB mice than in BALB/c mice. The results of this study suggest that susceptibility to C. sinensis infection is associated with Th2 cytokine production, especially IL-4 which is predominant in relatively susceptible FVB mice.     

CD4 and CD8 act as co-receptors during thymic selection of the T cell repertoire

The selection of T cell receptor specificities must logically not only involve the alpha beta-TCR but, also the CD4 and CD8 molecules, as antigen recognition by the alpha beta-TCR on mature T cells is facilitated by the CD4 and CD8 co-receptors. In this review, the studies that provided key advances in our understanding of the possible role of CD4 and CD8 in T cell development will be discussed.     

Conduction tissue in congenital heart surgery

The anatomy of the cardiac conduction system in normal and malformed hearts reconstructed from histological serial sections is reviewed. The sinus node and its arterial supply are located in the right superior cavoatrial junction except in hearts with left-sided juxtaposition of the atrial appendages, mirror-image, and isomeric arrangements of the atria. In the presence of normally positioned atrial and ventricular septal structures, the triangle of Koch is a useful guide to the location of the atrioventricular node and the penetrating bundle. In hearts with isolated ventricular septal defects, it is necessary to distinguish between a perimembranous defect and a muscular inlet defect. The conduction axis runs in the area of fibrous continuity at the posteroinferior edge of a perimembranous defect but in the anterosuperior rim of a muscular inlet defect. In most hearts with tetralogy of Fallot, the danger area is the region of aortic-mitral-tricuspid fibrous continuity where the axis penetrates. In hearts with atrioventricular septal defects, the lack of contiguity between atrial and ventricular septum results in a posterior displacement of the nodal triangle and coronary sinus and an elongation of the nonbranching bundle. Hearts with abnormally located atrioventricular nodes and conduction axes are mainly those with atrioventricular discordance, ambiguous atrioventricular connection in presence of left-hand pattern ventricular topology, hearts with univentricular atrioventricular connection to a morphologically left or indeterminate ventricle, and hearts with a straddling tricuspid valve. The location of the atrioventricular node is governed by the orientation of the ventricular septum and by the pattern of ventricular topology.

---

Resumen Se revisa la anatomía del sistema de conducción cardiaca en los corazones normales y con malformaciones a la luz de la reconstrucción a partir de cortes histológicos seriados. El nódulo sinusal y su irrigación arterial está ubicado en la unión cavoatrial derecha, excepto en corazones con yuxtaposición izquierda de las auriculillas o con alteraciones en imagen en espejo e isoméricas de las aurículas. En presencia de estructuras septales atriales y ventriculares normalmente ubicadas, el tríangulo de Koch es una guía útil para la localización del nódulo atrioventricular y la penetración del haz. En corazones con defectos septales ventriculares aislados es necesario distinguir entre un defecto perimembranoso y un defecto del tracto muscular de entrada. El haz de conducción avanza en el área de continuidad fibrosa sobre el borde posteroinferior de un defecto perimembranoso, en el filo anterosuperior de un defecto del tracto muscular de entrada. En la mayoría de los corazones con tetralogía de Fallot el área de peligro se encuentra en la región del trígono fibroso aórticomitral y tricuspídeo sobre el cual penetra el haz de conducción. En corazones con defectos septales atrioventriculares la falta de continuidad entre el septo atrial y el ventrícular resulta en un desplazamiento posterior del triángulo de Koch y del seno coronario y en una elongación del haz no ramificado. Corazones con nódulos atrioventriculares y haces de conducción anormalmente ubicados son principalmente aquellos con discordancia atrioventricular, con conexión atrioventricular ambigua en presencia de un patrón izquierdo de arquitectura ventricular, corazones con conexión atrioventricular univentricular a un ventrículo morfológicamente izquierdo o indeterminado y corazones con válvula tricuspídea cabalgante. La ubicación del nódulo atrioventricular está determinada por la orientación del septo ventricular y por el patrón de la arquitectura ventricular.

---

Résumé L'anatomie du système de conduction du coeur normal et du coeur siège de malformations reconstituée à partir de coupes sériées histologiques est exposée. Le sinus nodal et sa vascularisation sont situés au niveau de la partie supérieure de la jonction auriculo-ventriculaire droite sauf dans certains cas: coeur avec juxtaposition des auricules du côté gauche, image en miroir et dispositions isomères des oreillettes. Lorsque les cloisons auriculaire et ventriculaire occupent une situation normale, le triangle de Koch constitue un repère utile pour localiser le noyau auriculo-ventriculaire et le faisceau de His. En cas de défects septaux ventriculaires isolés, il est nécessaire de distinguer les défects périmembraneux et les défects musculaires. L'axe nerveux conducteur chemine dans la zone de continuité fibreuse au bord postéroinférieur du défect périmembraneux mais il chemine au bord antéro-supérieur du défect musculaire. En cas de tétralogie de Fallot, le danger se situe souvent au niveau de la zone fibreuse de continuité aortique-mitrale-tricuspide où pénètre l'axe conducteur. En cas de coeur porteur d'un défect septal auriculo-ventriculaire, le défaut de continuité entre la cloison ventriculaire et la cloison auriculaire entraîne le déplacement postérieur du triangle nodal et du sinus coronaire ainsi que l'élongation du faisceau. Les coeurs qui présentent une anomalie du siège des noyaux auriculo-ventriculaires et des nerfs conducteurs sont principalement ceux qui sont le siège d'une anomalie auriculo-ventriculaire, d'une connexion auriculo-ventriculaire ambiguë en cas d'une disposition ventriculaire de type gauche, d'une connexion auriculo-ventriculaire univentriculaire avec une morphologie ventriculaire gauche ou indeterminée, d'une valve tricuspide en fourche. Le siège du noyau auriculo-ventriculaire est fonction de l'orientation du septum ventriculaire et de l'architecture ventriculaire.

---

---

Supported by the British Heart Foundation.     

Microvascular surgery as an adjunctive tool in renal transplantation

There has been a serious shortage of suitable kidneys for transplantation since this procedure became the treatment of choice for many patients with end-stage renal failure. Some harvested kidneys are discarded due to complicated or injured renal vasculature and some potential living related donors are judged unsuitable because their kidneys have multiple vessels. The authors review the basic microsurgical techniques they have used in such situations to salvage kidneys for transplantation. They emphasize the ex-vivo, "bench", microsurgical method for protecting the kidney from prolonged warm ischemia time (as with multiple complicated in-situ anastomoses). Several illustrative case reports from their recent experience are presented. The authors conclude that microvascular surgery is an important adjunct to the armamentarium of the transplant surgeon.     

Pediatric Femoral Shaft Fracture: An Age-Based Treatment Algorithm

PurposeFractures of the femoral shaft in children are common. The rates of bone growth and remodeling in children vary according to their ages, which affect their respective management. MethodsThis paper evaluates the incidence and patterns of pediatric femoral shaft fracture and the current concepts of treatments available.ResultsThe type of fracture—closed or open; stable or unstable—needs to be taken into account. Child abuse should be suspected in fractures sustained by infants. For younger children, non-surgical management is preferred, which include Pavlik harness (< 6 months old) and early spica casting (6 months to 6 years old). Older children (> 6 years old) usually benefit from surgical treatments as outcomes of non-surgical alternatives are worse and are associated with prolonged recovery times. These operative measures for older children that are 6–12 years old include elastic stable intramedullary nailing and submuscular plating. Factors to be considered when devising an appropriate intervention include body mass, location of injury, and nature of fracture. For adolescent and skeletally mature teenagers (> 12 years old), rigid antegrade entry intramedullary fixation is indicated. In the event of open fractures or polytrauma, external fixation should be considered as a temporary treatment method for initial fracture stabilization.ConclusionAn age-based and evidence-based algorithm has been proposed to guide surgeons in the process of evaluating an appropriate treatment.     

Timing of parathyroidectomy for tertiary hyperparathyroidism with end-stage renal disease: A cost-effectiveness analysis

BackgroundTertiary hyperparathyroidism associated with end-stage renal disease is characterized by progression from secondary hyperparathyroidism to an autonomous overproduction of parathyroid hormone that leads to adverse health outcomes. Rates of parathyroidectomy (PTX) have decreased with the use of calcimimetics. Optimal timing of PTX in relation to kidney transplant remains controversial. We aimed to identify the most cost-effective strategy for patients with tertiary hyperparathyroidism undergoing kidney transplant.MethodsWe constructed a patient level state transition microsimulation to compare 3 management schemes: cinacalcet with kidney transplant, cinacalcet with PTX before kidney transplant, or cinacalcet with PTX after kidney transplant. Our base case was a 55-year-old on dialysis with tertiary hyperparathyroidism awaiting kidney transplant. Outcomes, including quality-adjusted life years, surgical complications, and mortality, were extracted from the literature, and costs were estimated using Medicare reimbursement data.ResultsOur base case analysis demonstrated that cinacalcet with PTX before kidney transplant was dominant, with a lesser cost of $399,287 and greater quality-adjusted life years of 10.3 vs $497,813 for cinacalcet with PTX after kidney transplant (quality-adjusted life years 9.4) and $643,929 for cinacalcet with kidney transplant (quality-adjusted life years 7.4).ConclusionCinacalcet alone with kidney transplant is the least cost-effective strategy. Patients with end-stage renal disease-related tertiary hyperparathyroidism should be referred for PTX, and it is most cost-effective if performed prior to kidney transplant.