A canine model of septic shock: balancing animal welfare and scientific relevance

2007 ◽  
Vol 293 (4) ◽  
pp. H2487-H2500 ◽  
Author(s):  
Peter C. Minneci ◽  
Katherine J. Deans ◽  
Bernie Hansen ◽  
Chantal Parent ◽  
Chris Romines ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Liver Enzymes ◽  
Survival Rates ◽  
Canine Model ◽  
Cell Counts ◽  
Control Regimen ◽  
Oxygen Gradients ◽  
Colony Forming Units ◽  
Alveolar Oxygen ◽  
Renal Abnormalities

A shock canine pneumonia model that permitted relief of discomfort with the use of objective criteria was developed and validated. After intrabronchial Staphylococcus aureus challenge, mechanical ventilation, antibiotics, fluids, vasopressors, sedatives, and analgesics were titrated based on algorithms for 96 h. Increasing S. aureus (1 to 8 × 109 colony-forming units/kg) produced decreasing survival rates ( P = 0.04). From 4 to 96 h, changes in arterial-alveolar oxygen gradients, mean pulmonary artery pressure, IL-1, serum sodium levels, mechanical ventilation, and vasopressor support were ordered based on survival time [acute nonsurvivors (≤24 h until death, n = 8) ≥ subacute nonsurvivors (>24 to 96 h until death, n = 8) ≥ survivors (≥96 h until death, n = 22) (all P < 0.05)]. In the first 12 h, increases in lactate and renal abnormalities were greatest in acute nonsurvivors (all P < 0.05). Compared with survivors, subacute nonsurvivors had greater rises in cytokines and liver enzymes and greater falls in platelets, white cell counts, pH, and urine output from 24 to 96 h (all P < 0.05). Importantly, these changes were not attributable to dosages of sedation, which decreased in nonsurvivors [survivors vs. nonsurvivors: 5.0 ± 1.0 vs. 3.8 ± 0.7 ml·h−1·(fentanyl/midazolam/ medetomidine)−1; P = 0.02]. In this model, the pain control regimen did not mask changes in metabolic function and lung injury or the need for more hemodynamic and pulmonary support related to increasing severity of sepsis. The integration into this model of both specific and supportive titrated therapies routinely used in septic patients may provide a more realistic setting to evaluate therapies for sepsis.

Abstract 15338: Comparison of Treatment Strategies for Neonates With Tetralogy of Fallot and Pulmonary Atresia: A Report From the Congenital Catheterization Research Collaborative

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Holly Bauser Heaton ◽  
Bryan H Goldstein ◽  
Christopher Petit ◽  
Athar M Qureshi ◽  
Courtney McCracken ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Tetralogy Of Fallot ◽  
Primary Repair ◽  
Ductus Arteriosus ◽  
Survival Rates ◽  
Pulmonary Atresia ◽  
Treatment Strategies ◽  
Hospital Length Of Stay ◽  
Complete Repair ◽  
Mechanical Ventilation Duration

Introduction: Neonates with tetralogy of Fallot and pulmonary atresia (TOF/PA) with pulmonary blood flow supplied by the ductus arteriosus require early intervention. This may be accomplished by: initial palliation (IP) followed by complete repair (CR) or initial primary repair (PR). The optimal approach for patients with TOF/PA has not been established. Methods: Neonates with TOF/PA who underwent IP or PR from 2005-17 were retrospectively reviewed from the Congenital Catheterization Research Collaborative. The primary outcome was mortality. Outcomes were compared as IP vs PR and IP+CR vs PR. Secondary outcomes included hospital and procedural complications and are listed in table 1. Propensity scoring was used to adjust for baseline differences between strategies. Results: Of 282 neonates with TOF/PA, 106 underwent PR and 176 underwent IP (144 surgical, 32 transcatheter). Prior to initial intervention, IP patients had higher rates of mechanical ventilation (83.9% vs 72.2%, p=0.023) and DiGeorge syndrome (14.77% vs 4.72%, p=0.009). Mortality was greater in the IP cohort (HR 2.7, 95% CI 1.02 - 7.1, p = 0.046), with no mortality in the PR cohort after 6 months post-repair. After adjustment, differences in survival were no longer significant (HR 1.4, 95% CI 0.7 - 3.1, p=0.39). Both cohorts had similar mechanical ventilation duration and inotrope use as well as procedural and hospital complications. Intensive care and hospital length of stay, cardiac bypass (CPB) and anesthesia time favored PR when compared to IP+CR (p=<0.001). Early reintervention was more common in patients undergoing IP (rate ratio 1.42, p 0.003), but post-complete repair rates were similar (p=0.837). Conclusions: In neonates with TOF/PA, the IP approach is more often utilized in higher-risk patients. Accounting for this difference, IP and PR strategies have similar adjusted survival rates. Perioperative morbidities and lower risk for reintervention generally favor PR.

scholarly journals A shorter equilibration period in the VitTrans in-straw bovine embryo vitrification method improves post-warming outcomes

2020 ◽  
Author(s):  
Iris Martínez-Rodero ◽  
Tania García-Martínez ◽  
Erika Alina Ordóñez-León ◽  
Meritxell Vendrell-Flotats ◽  
Carlos Olegario-Hidalgo ◽  
...  
Keyword(s):  
Inner Cell Mass ◽  
Cell Mass ◽  
Survival Rates ◽  
Field Conditions ◽  
Bovine Embryo ◽  
Direct Transfer ◽  
Treatment Groups ◽  
Cell Counts ◽  
Hatching Rates

Abstract Background VitTrans is a device that enables the vitrification and warming/dilution of in vitro produced bovine embryos followed by their direct transfer to recipient females in field conditions. This study sought to improve the VitTrans method by comparing two equilibration times: short (SE: 3 min) and long (LE: 12 min). Outcome measures recorded in vitrified D7 and D8 expanded blastocysts were survival and hatching rates, differential cell counts, apoptosis rate and gene expression. Results While survival rates at 3 h and 24 h post-warming were reduced (P < 0.05) after vitrification, hatching rates of D7 embryos vitrified after SE were similar to those obtained in fresh non-vitrified blastocysts. Hatching rates of vitrified D8 blastocysts were lower (P < 0.05) than of fresh controls, regardless of treatment. Total cell counts, and inner cell mass and trophectoderm cell numbers were similar in hatched blastocysts derived from D7 blastocysts vitrified after SE and fresh blastocysts, while vitrified D8 blastocysts yielded lower values, regardless of treatment. The rate of apoptotic cells was significantly higher in both treatment groups when compared to fresh controls, although apoptosis rates were lower using the SE than LE protocol. No differences emerged in expression of the genes BAX, AQP3, CX43 and IFNτ between blastocysts vitrified after SE or LE, whereas a significantly higher abundance of BCL2L1 and SOD1 transcripts was observed in blastocysts vitrified after SE compared to LE. Conclusions The VitTrans device combined with a shorter exposure to the equilibration medium improves vitrification/warming outcomes facilitating the direct transfer of vitrified embryos under field conditions.

scholarly journals Redox Balance and Cellular Inflammation in the Diaphragm, Limb Muscles, and Lungs of Mechanically Ventilated Rats

2010 ◽  
Vol 112 (2) ◽  
pp. 384-394 ◽  
Author(s):  
Judith Marín-Corral ◽  
Leticia Martínez-Caro ◽  
José A. Lorente ◽  
Marta de Paula ◽  
Lara Pijuan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mechanical Ventilation ◽  
Lung Injury ◽  
Protein Adducts ◽  
Organ Injury ◽  
Mechanically Ventilated ◽  
Ventilator Induced Lung Injury ◽  
Cellular Inflammation ◽  
Cell Counts ◽  
Limb Muscles

Background High tidal volume (VT) mechanical ventilation was shown to induce organ injury other than lung injury and systemic inflammation in animal models of ventilator-induced lung injury. The authors aimed to explore whether high VT mechanical ventilation per se induces early oxidative stress and inflammation in the diaphragm, limb muscles, and lungs of healthy rats exposed to ventilator-induced lung injury. Methods Protein carbonylation and nitration, antioxidants (immunoblotting), and inflammation (immunohistochemistry) were evaluated in the diaphragm, gastrocnemius, soleus, tibialis anterior, and lungs of mechanically ventilated healthy rats and in nonventilated control animals (n = 8/group) for 1 h, using two different strategies (moderate VT [VT = 9 ml/kg] and high VT [VT = 35 ml/kg]). Results The main findings are summarized as follows: compared with controls, (1) the diaphragms and gastrocnemius of high-VT rats exhibited a decrease in reactive carbonyls, (2) the soleus and tibialis of high- and moderate-VT rodents showed a reduction in reactive carbonyls and malondialdehyde-protein adducts, (3) the lungs of high-VT rats exhibited a significant rise in malondialdehyde-protein adducts, (4) the soleus and tibialis of both high- and moderate-VT rats showed a reduction in protein nitration, (5) the lungs of high- and moderate-VT rats showed a reduction in antioxidant enzyme levels, but not in the muscles, and (6) the diaphragms and gastrocnemius of all groups exhibited very low inflammatory cell counts, whereas the lungs of high-VT rats exhibited a significant increase in inflammatory infiltrates. Conclusions Although oxidative stress and inflammation increased in the lungs of rats exposed to high VT, the diaphragm and limb muscles exhibited a decline in oxidative stress markers and very low levels of cellular inflammation.

scholarly journals The Bactericidal Activity and Spore Inhibition Effect of Manuka Honey against Clostridioides Difficile

Antibiotics ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 684
Author(s):  
Lillian Yu ◽  
Reynal Palafox-Rosas ◽  
Brian Luna ◽  
Rosemary C. She
Keyword(s):  
Bactericidal Activity ◽  
Viable Cell ◽  
Manuka Honey ◽  
Inhibition Effect ◽  
Natural Substances ◽  
Clostridioides Difficile ◽  
Cell Counts ◽  
Colony Forming Units ◽  
Conventional Antibiotics ◽  
Drug Free

Clostridioides difficile colitis overgrowth occurs when the normal gut microbiome becomes disrupted, often due to antibiotics. Effective treatment remains elusive, due partly to the persistence of its spores in the gut. Natural substances like manuka honey offer an alternative antimicrobial mechanism of action to conventional antibiotics. We investigated the antibiotic activity of manuka honey against 20 C. difficile isolates. The minimum inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBC) of manuka honeys of methylglyoxal (MGO) grades 30+, 100+, 250+, and 400+ were determined based on broth microdilution. Sporicidal activity was assessed in a range of honey concentrations by enumerating total viable cell and spore counts at 0–96 h after organism inoculation. The MICs of C. difficile ranged from 4% to >30% (w/v). MIC50 for the four MGO grades were similar at 10–14%. MBC results for the majority of isolates were distributed bimodally at MBC/MIC ratios ≤4 or MBC >30%. Growth kinetics in honey showed total viable cell counts remaining >105 colony-forming units (CFU)/mL at all time points, whereas spore counts remained within 1-log of baseline (102 CFU/mL) in honey but steadily increased in the drug-free control to >105 CFU/mL by 96 h. Manuka honey demonstrated variable inhibitory and bactericidal activity against C. difficile. MGO grade had no noticeable impact on overall MIC distributions or bactericidal activity. Although manuka honey could inhibit spore proliferation, it did not eradicate spores completely.

scholarly journals Along the Process Chain to Probiotic Tablets: Evaluation of Mechanical Impacts on Microbial Viability

Pharmaceutics ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 66 ◽  
Author(s):  
Karl Vorländer ◽  
Ingo Kampen ◽  
Jan Henrik Finke ◽  
Arno Kwade
Keyword(s):  
Cell Survival ◽  
Survival Rates ◽  
Process Chain ◽  
Rapid Loss ◽  
Process Step ◽  
Colony Forming Units ◽  
Tablet Properties ◽  
Compaction Stress ◽  
Semi Solid ◽  
Initial Process

Today, probiotics are predominantly used in liquid or semi-solid functionalized foods, showing a rapid loss of cell viability. Due to the increasing spread of antibiotic resistance, probiotics are promising in pharmaceutical development because of their antimicrobial effects. This increases the formulation requirements, e.g., the need for an enhanced shelf life that is achieved by drying, mainly by lyophilization. For oral administration, the process chain for production of tablets containing microorganisms is of high interest and, thus, was investigated in this study. Lyophilization as an initial process step showed low cell survival of only 12.8%. However, the addition of cryoprotectants enabled survival rates up to 42.9%. Subsequently, the dried cells were gently milled. This powder was tableted directly or after mixing with excipients microcrystalline cellulose, dicalcium phosphate or lactose. Survival rates during tableting varied between 1.4% and 24.1%, depending on the formulation and the applied compaction stress. More detailed analysis of the tablet properties showed advantages of excipients in respect of cell survival and tablet mechanical strength. Maximum overall survival rate along the complete manufacturing process was >5%, enabling doses of 6   ×   10 8 colony forming units per gram ( CFU   g total − 1 ), including cryoprotectants and excipients.

scholarly journals A New Phage Lysin Isolated from the Oral Microbiome Targeting Streptococcus pneumoniae

2020 ◽  
Vol 13 (12) ◽  
pp. 478
Author(s):  
Imme van der Kamp ◽  
Lorraine A. Draper ◽  
Muireann K. Smith ◽  
Colin Buttimer ◽  
R. Paul Ross ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Multidrug Resistant ◽  
Oral Microbiome ◽  
Lytic Activity ◽  
Host Strain ◽  
Pneumococcal Infections ◽  
Highly Pathogenic ◽  
Cell Counts ◽  
Colony Forming Units ◽  
Invasive Infections

Streptococcus pneumoniae is highly pathogenic and causes several mucosal and invasive infections. Due to the rising number of multidrug-resistant (MDR) strains of S. pneumoniae, new antimicrobials with alternative mechanisms of action are urgently needed. In this study, we identified two new Streptococcal phages from the oral microbiome, 23TH and SA01. Their lysins, 23TH_48 and SA01_53, were recombinantly expressed, characterized and tested for their lethality. SA01_53 was found to only lyse its host strain of S. anginosus, while 23TH_48 was found to possess a broader lytic activity beyond its host strain of S. infantis, with several S. pneumoniae isolates sensitive to its lytic activity. 23TH_48 at a concentration of five activity units per mL (U/mL) was found to reduce cell counts of S. pneumoniae DSM 24048 by 4 log10 colony forming units per mL (CFU/mL) within 1 h and effectively prevented and destroyed biofilms of S. pneumoniae R6 at concentrations of 228.8 ng/µL and 14.3 ng/µL, respectively. Given its high lytic activity, 23TH_48 could prove to be a promising candidate to help combat pneumococcal infections.

Fulminant and rapidly fatal hemophagocytic lymphohistiocytosis in patients with HIV infection: A report of five cases and a review

2019 ◽  
Vol 30 (12) ◽  
pp. 1224-1228
Author(s):  
Paul Lam ◽  
Zeb Khan ◽  
Isha Bhatt ◽  
John Quale
Keyword(s):  
Hiv Infection ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Hemophagocytic Syndrome ◽  
Ferritin Level ◽  
Survival Rates ◽  
Epstein Barr Virus Infection ◽  
Pneumocystis Jiroveci ◽  
Barr Virus ◽  
Reactive Hemophagocytic Syndrome ◽  
Cell Counts

Hemophagocytic lymphohistiocytosis is a rare entity and diagnosis can be elusive. Commonly recognized inciting causes include autoimmune disorders, malignancies, and a wide variety of infections. With prompt recognition and treatment, survival rates approach 50%. Five cases of reactive hemophagocytic syndrome in patients with underlying HIV infection are reported. All of the patients had CD3/CD4 cell counts of <200 cells/µL. All cases presented with fever and all had marked cytopenias, with platelet counts falling to 10–15,000/µL. Ferritin levels were >5000 ng/mL in all cases. Concomitant inciting conditions included Epstein–Barr virus infection, Pneumocystis jiroveci, multiple myeloma, and Hodgkin’s lymphoma; in one case, no inciting condition was identified. Despite broad-spectrum antimicrobial and immunosuppressive therapy, all five patients died within one month of presentation. The finding of fever and cytopenia in a patient with underlying HIV infection should prompt the clinician to determine a ferritin level. If markedly elevated, an aggressive work-up for hemophagocytic syndrome should be conducted. However, even with prompt recognition, mortality rates may be high in patients with underlying HIV infection.

scholarly journals Selective damage to erythroblasts by 55-Fe

Blood ◽  
1975 ◽  
Vol 45 (6) ◽  
pp. 801-810 ◽  
Author(s):  
U Reincke ◽  
H Burlington ◽  
EP Cronkite ◽  
M Hillman ◽  
J Laissue
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Pluripotent Stem Cells ◽  
Short Range ◽  
Pluripotent Stem Cell ◽  
Bone Marrow Cells ◽  
Marrow Cell ◽  
Auger Electrons ◽  
Cell Counts ◽  
Colony Forming Units

Abstract The low energy and short range of 55-Fe Auger electrons were utilized in mice to deliver lethal intracellular radiation to iron-incorporating erythropoietic precursors with minimal radiation damage to other bone marrow cells. The ensuing intramedullary, selective erythropoietic death was demonstrated by absolute and differential bone marrow cell counts and by decreased blood uptake of 59-Fe. The decreased number of colony-forming units in spleen colony assay and the decreased ability of tranplanted bone marrow to protect fatally irradiated mice shows that the bone marrow was partially depleted of pluripotent stem cells. These data are interpreted to indicate an increased pluripotent stem cell utilization in response to increased demand for differentiation of stem cells along the erythropoietic pathway.

Influence of the lactoperoxidase system on susceptibility of the udder toStreptococcus uberisinfection

1986 ◽  
Vol 53 (4) ◽  
pp. 507-514 ◽  
Author(s):  
Valerie M. E. Marshall ◽  
Wendy M. Cole ◽  
A. John Bramley
Keyword(s):  
Mammary Gland ◽  
Somatic Cell ◽  
Inhibitory Activity ◽  
Inhibitory System ◽  
Somatic Cell Counts ◽  
Streptococcus Uberis ◽  
Cell Counts ◽  
Lactoperoxidase System ◽  
Colony Forming Units ◽  
Lactating Mammary Gland

SummaryLactoperoxidase (LP), thiocyanate (SCN-), pH and somatic cell counts (SCC) were measured in mammary secretions from 20 cows collected 14 d before drying-off, 7 and 21 d after drying-off, and 3–18 d postcalving. The inhibitory activity of the secretions onStreptococcus uberiswas determined and the susceptibility of the udder to infection by this organism was tested by intramammary infusion of 250 colony forming units at the above stages. LP, SCN-, pH and SCO increased during involution and fell postcalving. The secretions collected before drying-off, 7 d after drying-off and postcalving inhibited growth ofStr. uberis.; those collected 21 d after drying-off did not. Inhibitory activity in pre-drying-off secretions was destroyed by heating and restored by addition of LP, glucose and glucose oxidase, but addition of these substances to secretion 21 d after drying-off did not provide a full inhibitory system. The growth ofStr. uberisin the secretions was correlated with intramammary susceptibility, since challenges withStr. uberisat 14 d before drying-off, at 7 and 21 d after drying-off and postcalving led to 43·8, 25·0, 81·3 and 37·5% of quarters becoming infected. It is suggested that the LP/SCN-/H2O2system plays a role in protecting the lactating mammary gland from infection withStr. uberisbut becomes ineffective as involution progresses.

Diagnosis of Ventilator-associated Pneumonia 

1997 ◽  
Vol 87 (2) ◽  
pp. 268-276 ◽  
Author(s):  
Laurent Papazian ◽  
Amapola Autillo-Touati ◽  
Pascal Thomas ◽  
Fabienne Bregeon ◽  
Louise Garbe ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Bronchoalveolar Lavage ◽  
Lung Tissue ◽  
Sampling Technique ◽  
Sampling Techniques ◽  
Ventilator Associated Pneumonia ◽  
Direct Examination ◽  
Gram Staining ◽  
Cell Counts ◽  
Sampling Procedures

Background Ventilator-associated pneumonia (VAP) requires early diagnosis and adequate antibiotic therapy. The aim of this prospective postmortem study was to assess the accuracy of direct examination and quantification of intracellular organisms (ICO) for the diagnosis of VAP. Methods Total and differential cell counts were performed on fluids recovered using nonbronchoscopic sampling techniques (blind bronchial sampling [BBS], mini-bronchoalveolar lavage [mini-BAL]) and from bronchoalveolar lavage (BAL) performed during fiberscopy. These 3 sampling techniques were done within 15 min of death without discontinuing mechanical ventilation. Quantification of ICO was performed on each sample recovered from the various sampling procedures. Gram reaction and morphology of bacteria were evaluated on Gram smears. Results The results of each technique were compared with histology and culture of lung tissue specimens obtained by surgical pneumonectomies in 28 patients who died after at least 72 h of mechanical ventilation. Histology was positive in 13 patients and negative in 15 patients. When only VAP with positive lung culture was considered (histologic signs of bronchopneumonia plus positive lung tissue culture), the sensitivity of Gram staining on BAL, mini-BAL, and BBS was 56%, 44%, and 56%, respectively. If all samples were considered, the sensitivity and the specificity of the determination of the percentage of ICO were low (less than 70%) whatever the sampling technique. Conclusions For initial therapeutic guidance, direct examination and presence of ICO do not contribute for establishing the diagnosis of VAP, essentially because of a lack of sensitivity. However, when positive, Gram staining can obviously guide initial antibiotherapy.

Sign in / Sign up

Export Citation Format

Share Document