Experimental atherosclerosis in rabbits fed cholesterol-free diets: 4. Investigation into the source of cholesteremia

The metabolism of exogenous and endogenous cholesterol was studied in rabbits fed a normal diet of rabbit chow or an atherogenic, semisynthetic diet (SS) containing 40% carbohydrate, 25% casein, and 14% hydrogenated coconut oil. The SS diet was more cholesteremic, betalipoproteinemic and atherogenic. More cholesterol was absorbed and more synthesized by rabbits on the SS diet and more radioactive cholesterol was recovered from their lesions. The chow-fed rabbits excreted 4 times as much feces over a 3 day period. Biliary cholesterol and total bile acids were 2.2 and 2.6 times higher in the SS group. The biliary cholesterol-specific activity was significantly higher in the SS group but cholanoic acid-specific activities and primary/secondary bile acid ratios were significantly lower. The data suggest that one reason for the cholesteremic effect of the SS diet is a reduced level of degradation of endogenous cholesterol to bile acids.     

An immunocytochemical marker for early type I muscle fibers in the developing rat hindlimb

Muscle fibers develop sequentially from several generations of myotubes that express specific isoforms of myosin heavy chain (MHC). We observed that the chicken-derived monoclonal antibody (mAb) S46 binds to myotubes of the fetal rat hindlimb in a specific temporal and spatial pattern. To determine the type and fate of the S46-reactive myotubes, we immunoreacted sections of fetal, neonatal and postnatal hindlimb muscles to this antibody. The mAb S46 bound to a subpopulation of primary myotubes in the tibialis anterior, and to all primary and slow/fast secondary myotubes in the soleus muscle. The S46-reactive primary myotubes represented the oldest set of myotubes in the muscles. Reactivity to S46 was present from the earliest stages of muscle development, peaked in the late fetal period, and dissipated in the first postnatal week, suggesting that mAb S46 binds to a developmental form of slow myosin. The regional distribution of myotubes that bound S46 in fetal muscles was identical to the distribution of type I (slowtwitch) fibers in the adult, indicating that S46-reactive myotubes ultimately develop into type I extrafusal fibers. Thus, mAb S46 can be used as a marker for prospective type I extrafusal fibers in the rat hindlimb.     

Patients with Van Buchem disease, an osteosclerotic genetic disease, have elevated bone formation markers, higher bone density, and greater derived polar moment of inertia than normal

Van Buchem disease is an autosomal recessive disease characterized by overgrowth of the skeleton. In a group of Dutch patients the disease is thought to be due to a 52-kb deletion that results in decreased expression of the SOST gene. To further characterize the disease, the morphology of the metacarpals of six adult subjects and two juveniles with Van Buchem disease were measured on hand x-rays along with nine normal adults and nine adult carriers of the disease. Serum bone formation markers, alkaline phosphatase, type I procollagen peptide, and osteocalcin, and the urinary bone resorption marker, cross-linked N-telopeptide, were determined. Van Buchem patients had increased metacarpal outer diameter, inner diameter, cortical thickness, and bone mineral density. Calculated bone volume and derived polar moment of inertia were markedly elevated (elevations of 158 +/- 33% and 497 +/- 95%, respectively) consistent with increased bone strength. Serum procollagen peptide and osteocalcin were significantly higher in Van Buchem patients. Urinary cross-linked N-telopeptide was significantly elevated in Van Buchem patients. None of these changes was found in Van Buchem carriers. These observations indicate that decreased expression of the SOST gene can lead to increased bone formation and to stronger bones.     

Differential regulation of IL-13 and IL-4 production by human CD8+ and CD4+ Th0, Th1 and Th2 T cell clones and EBV-transformed B cells

In the present study, the requirements and characteristics forthe production of IL-13 by human T cells, T cell clones andB cells were determined and compared with those of IL-4. IL-13was produced by human CD4⁺ and CD8⁺ T lymphocyte subsets isolatedfrom peripheral blood mononuclear cells and by CD4⁺ and CD8⁺T cell clones. CD4⁺ T cell clones belonging to T_h0, T_h1-likeand T_h2-like subsets produced IL-13 following antigen-specificor polyclonal activation. In addition, EBV-transformed B celllines expressed IL-13 mRNA and produced small amounts of IL-13protein. Expression of IL-13 mRNA and production of IL-13 proteinby peripheral blood T cells and T cell clones was induced rapidlyand was relatively long lasting, whereas IL-4 production bythese cells was transient In addition, IL-13 mRNA expressionwas induced by modes of activation that failed to induce IL-4mRNA expression. IL-13 shares many biological activities withIL-4 which Is compatible with the notion that the IL-13 andIL-4 receptors share a common component required for signaltransduction. However, IL-13 lacks the T cell-activating propertiesof IL-4. Here we have shown that this is related to the factthat T cells fall to bind radiolabeled IL-13 and do not expressthe IL-13-speclflc receptor component Taken together, theseresults indicate that the differences In expression and biologicalactivities of IL-4 and IL-13 on T cells may have consequencesfor the relative roles of these cytokines In the immune response.     

Animals in a bacterial world,a new imperative for the life sciences

In the last two decades, the widespread application of genetic and genomic approaches has revealed a bacterial world astonishing in its ubiquity and diversity. This review examines how a growing knowledge of the vast range of animal–bacterial interactions, whether in shared ecosystems or intimate symbioses, is fundamentally altering our understanding of animal biology. Specifically, we highlight recent technological and intellectual advances that have changed our thinking about five questions: how have bacteria facilitated the origin and evolution of animals; how do animals and bacteria affect each other’s genomes; how does normal animal development depend on bacterial partners; how is homeostasis maintained between animals and their symbionts; and how can ecological approaches deepen our understanding of the multiple levels of animal–bacterial interaction. As answers to these fundamental questions emerge, all biologists will be challenged to broaden their appreciation of these interactions and to include investigations of the relationships between and among bacteria and their animal partners as we seek a better understanding of the natural world.     

The impact of Rapid Response System on delayed emergency team activation patient characteristics and outcomes—A follow-up study

Objective

To evaluate the impact of Rapid Response System (RRS) maturation on delayed Medical Emergency Team (MET) activation and patient characteristics and outcomes.

Design

Observational study.

Setting

Tertiary hospital.

Patients

Recent cohort of 200 patients receiving a MET review and early control cohort of 400 patients receiving a MET review five years earlier at the start of RRS implementation.

Measurements and results

We obtained information including demographics, clinical triggers for and timing of MET activation in relation to the first documented MET review criterion (activation delay) and patient outcomes. We found that patients in the recent cohort were older, more likely to be surgical and to have Not For Resuscitation (NFR) orders before MET review. Furthermore, fewer patients (22.0% vs. 40.3%, p < 0.001) had delayed MET activation. When delayed activation occurred, there was a non-significant difference in its duration (early cohort: 12.0 [IQR 23.0] h vs. recent cohort: 9.0 [IQR 20.5] h, p = 0.554). Similarly, unplanned ICU admissions decreased from 31.3% to 17.3% (p < 0.001). Delayed MET activation was independently associated with greater risk of unplanned ICU admission and hospital mortality (O.R. 1.79, 95% C.I. 1.33.-2.93, p = 0.003 and O.R. 2.18, 95% C.I. 1.42-3.33, p < 0.001, respectively). Being part of the recent cohort was independently associated with a decreased risk of delayed activation (O.R. 0.45, 95% C.I. 0.30-0.67, p < 0.001) and unplanned ICU admission (O.R. 0.5, 95% C.I. 0.32-0.78, p = 0.003).

Conclusions

Maturation of a RRS is associated with a decrease in the incidence of unplanned ICU admissions and MET activation delay. Assessment of a RRS early in the course of its implementation may underestimate its efficacy.     

Increased survival after EMS witnessed cardiac arrest. Observations from the Resuscitation Outcomes Consortium (ROC) Epistry—Cardiac arrest

Background

Out of hospital cardiac arrest (OHCA) is common and lethal. It has been suggested that OHCA witnessed by EMS providers is a predictor of survival because advanced help is immediately available. We examined EMS witnessed OHCA from the Resuscitation Outcomes Consortium (ROC) to determine the effect of EMS witnessed vs. bystander witnessed and unwitnessed OHCA.

Methods

Data were analyzed from a prospective, population-based cohort study in 10 U.S. and Canadian ROC sites. Individuals with non-traumatic OHCA treated 04/01/06-03/31/07 by EMS providers with defibrillation or chest compressions were included. Cases were grouped into EMS-witnessed, bystander witnessed, and unwitnessed and further stratified for bystander CPR. Multiple logistic regressions evaluated the odds ratio (OR) for survival to discharge relative to the EMS-witnessed group after adjusting for age, sex, public/private location of collapse, ROC site, and initial ECG rhythm. Of 9991 OHCA, 1022 (10.2%) of EMS-witnessed, 3369 (33.7%) bystander witnessed, and 5600 (56.1%) unwitnessed.

Results

The most common initial rhythm in the EMS-witnessed group was PEA which was higher than in the bystander- and unwitnessed groups (p < 0.001). The adjusted OR (95% CI) of survival compared to the EMS-witnessed group was 0.41, (0.36, 0.46) in bystander witnessed with bystander CPR, 0.37 (0.33, 0.43) in bystander witnessed without bystander CPR, 0.17 (0.14, 0.20) in unwitnessed with bystander CPR and 0.21 (0.18, 0.24) in unwitnessed cases without bystander CPR.

Conclusions

Immediate application of prehospital care for OHCA may improve survival. Efforts should be made to educate patients to access 9-1-1 for prodromal symptoms.