Objectives The use of steroid therapy in cardiac surgical patients remains controversial. The aim of this clinical investigation was to determine the effect of small-dose dexamethasone therapy on ...patient-perceived quality of recovery (QoR) scores in elective cardiac surgical patients. In addition, the authors assessed the impact of dexamethasone on the incidence of common adverse events after cardiopulmonary bypass (CPB). Design A prospective, randomized study. Setting University hospitals. Participants One hundred seventeen patients undergoing cardiac surgery with CPB and anticipated early tracheal extubation. Interventions Subjects were randomized to receive either dexamethasone (dexamethasone group, 8 mg at the induction of anesthesia and at the initiation of CPB) or placebo (control group, saline). Measurements and Main Results The QoR was assessed using the QoR-40 scoring system preoperatively and on postoperative days (PODs) 1 and 2. Secondary outcome measures assessed in the postoperative period included nausea, vomiting, fatigue, febrile responses, shivering, pulmonary gas exchange, and analgesic requirements. Global QoR-40 scores (median range) were higher in the dexamethasone group compared with the control group on POD 1 (167 133-192 v 157 108-195; p < 0.0001) and POD 2 (173 140-196 v 166 122-196; p = 0.001). In the dexamethasone group, improved QoR was observed in the QoR-40 dimensions of emotional state ( p = 0.002), physical comfort ( p = 0.0001-0.006), and pain ( p < 0.0001). The incidences or severity of postoperative fatigue ( p < 0.0001), febrile responses ( p < 0.0001), and shivering ( p = 0.001) were reduced in the dexamethasone group. Conclusions Patient-perceived postoperative QoR in cardiac surgical patients is enhanced significantly by small-dose dexamethasone treatment.
Background Epoprostenol sodium with arginine-mannitol excipients (epoprostenol AM; Veletri Actelion Pharmaceuticals Ltd, Allschwil, Switzerland) and epoprostenol sodium with glycine-mannitol ...excipients (epoprostenol GM; Flolan GlaxoSmithKline, Triangle Park, NC) are intravenous treatments for pulmonary arterial hypertension (PAH). Epoprostenol AM contains different inactive excipients, resulting in greater stability at room temperature compared with epoprostenol GM. Methods In this prospective, multicenter, open-label, randomized, phase IV exploratory study, epoprostenol-naïve patients in need of injectable prostanoid therapy were randomized 2:1 to open-label epoprostenol AM or epoprostenol GM. The study period was 28 days, followed by a 30-day safety follow-up. Study aims were to descriptively compare the safety, tolerability, drug metabolite levels, and treatment effects of epoprostenol AM and epoprostenol GM in PAH. Statistical analysis was descriptive only because of the exploratory nature of the study. Results Thirty patients with PAH (18-70 years, 24 women, 20 idiopathic PAH) were randomized to epoprostenol AM (n = 20) or epoprostenol GM (n = 10). Most frequently reported adverse events included jaw pain, headache, nausea, and flushing. Two deaths occurred during the study period, and 1 death occurred during the 30-day safety follow-up period, all in patients receiving epoprostenol AM. All deaths were classified by the treating physician as unrelated to epoprostenol AM. The median (range) change from baseline to day 28 in 6-minute walk distance was 36 m (−127 to 210 m) and 49 m (−44 to 110 m) for the epoprostenol AM and epoprostenol GM groups, respectively. Conclusions In this randomized clinical study of epoprostenol AM in PAH, use of this novel preparation with greater room temperature stability was well tolerated.
Abstract ▪704▪This icon denotes a clinically relevant abstract
Neurofibromatosis type 1 predisposes individuals to the development of juvenile myelomonocytic leukemia, a fatal myeloproliferative ...disease (MPD). In genetically engineered murine models, nullizygosity of Nf1, a tumor suppressor gene which encodes a Ras GTPase activating protein, results in hyperactivity of Raf-Mek-Erk in hematopoietic stem and progenitor cells (HSPCs). Activated Erk1/2 phosphorylate kinases and transcription factors with plethoric mitogenic roles in diverse cell types. However, genetic studies examining Erk1/2’s differential and/or combined control of normal and Nf1-deficient myelopoiesis are lacking. Moreover, prior studies relying on chemical Mek-Erk inhibitors have reached conflicting conclusions in normal and Nf1-deficient mice. Here, we show that while single Erk1 or Erk2 disruption does not grossly compromise myelopoiesis, dual Erk1/2 ablation rapidly ablates granulocyte and monocyte production, diminishes progenitor cell number, and prevents HSPC proliferation. Intriguingly, genetic disruption of Erk1/2 in the context of Nf1 nullizygosity (Mx1Cre+Nf1flox/floxErk1−/−Erk2flox/flox) fully protects against the genesis of MPD. Collectively, we identify a fundamental requirement for Erk1/2 signaling in normal and Nf1-deficient hematopoiesis, elucidating a critical hematopoietic function for Erk1/2 while genetically validating highly-selective Mek-Erk inhibitors for the attenuation of a leukemia that is otherwise resistant to traditional therapy.
No relevant conflicts of interest to declare.
Background Approximately 5% of combat-related injuries include burns. Previous studies have shown similar mortality rates between military and civilian burn casualties; but causes of death were not ...detailed. Study Design We retrospectively reviewed autopsy reports of patients with burns treated at the US Army Institute of Surgical Research Burn Center from 2004 to 2007. Results Of 1,255 admissions, 100 (8%) died, with autopsies performed on 74 (36 burned during military operations). Causes of death included infection (61%); disorders of the pulmonary (55%), cardiac (36%), renal (27%), gastrointestinal (27%), and central nervous (11%) systems; and multiorgan dysfunction (15%). Patients burned as a result of military operations were younger men with more associated inhalation injuries, greater severity of injury, and longer time from injury to admission and to death. They died more frequently of infection (notably fungus, Pseudomonas , and Klebsiella ) and gastrointestinal complications; and those not burned in military operations had greater numbers of cardiac and renal causes of death. Conclusion Casualties of military operations are clinically different and die from different causes than patients not burned during military operations. The differences are likely reflective of a younger population, with greater severity of illness and longer times from injury to admission. Therapeutic interventions should focus on prevention of infection and gastrointestinal catastrophes in military burn casualties, which are similar to younger burn patients in the US, and minimizing cardiac complications in civilian burn casualties, who are typically older patients and possibly reflective of patients with more comorbidities.
Analysis of cytokine production by CD3+CD4+CD27-CD45RO+ effector memory T cells following stimulation with phorbol 12-myristate 13-acetate (PMA)/ionomycin demonstrated a trend toward an increased ...frequency of IFN-γ-producing cells and a trend toward a decreased frequency of IL-4- and IL-13-producing cells in patients (GATA3+/-) compared with healthy controls (GATA3wt), although there was wide variability and this did not reach statistical significance (Fig 1). Because previous reports have suggested a TH1 bias with a concomitant impairment in TH2 cytokine production,1 we next sought to determine whether there was a defect in TH2 differentiation.
Abstract Background Muscle loss is a sequela of severe burn and critical illness with bed rest contributing significantly to atrophy. We hypothesize that exercise will mitigate muscle loss after burn ...with bed rest. Materials and methods Male rats were assigned to sham ambulatory (S/A), burn ambulatory (B/A), sham hindlimb unloading (S/H), or burn hindlimb unloading (B/H). Rats received a 40% scald burn or sham and were ambulatory or placed in hindlimb unloading, a model of bed rest. Half from each group performed twice daily resistance climbing. Hindlimb isometric forces were measured on day 14. Results Soleus mass and muscle function were not affected by burn alone. Mass was significantly lower in hindlimb unloading (79 versus 139 mg, P < 0.001) and no exercise (103 versus 115 mg, P < 0.01). Exercise significantly increased soleus mass in B/H (86 versus 77 mg, P < 0.01). Hindlimb unloading significantly decreased muscle force in the twitch (12 versus 31 g, P < 0.001), tetanic (55 versus 148 g, P < 0.001), and specific tetanic measurements (12 versus 22 N/cm2 , P < 0.001). Effects of exercise on force depended on other factors. In B/H, exercise significantly increased twitch (14 versus 8 g, P < 0.05) and specific tetanic force (14 versus 7 N/cm2 , P < 0.01). Fatigue index was lower in ambulatory (55%) and exercise (52%) versus hindlimb (69%, P = 0.03) and no exercise (73%, P = 0.002). Conclusions Hindlimb unloading is a significant factor in muscle atrophy. Exercise increased the soleus muscle mass, twitch, and specific force in this model. However, the fatigue index decreased with exercise in all groups. This suggests exercise contributes to functional muscle change in this model of disuse and critical illness.
Mate choice decisions by searchers Wiegmann, Daniel D.; Angeloni, Lisa M.; Seubert, Steven M. ...
Current zoology,
04/2013, Letnik:
59, Številka:
2
Journal Article
Recenzirano
Odprti dostop
For more than two decades rudimentary versions of the fixed sample and sequential search strategies have provided the primary theoretical foundation for the study of mate choice decisions by ...searchers. The theory that surrounds these models has expanded markedly over this time period. In this paper, we review and extend results derived from these models, with a focus on the empirical analysis of searcher behavior. The basic models are impractical for empirical purposes because they rely on the as- sumption that searchers--and, for applied purposes, researchers--assess prospective mates based on their quality, the fitness consequences of mate choice decisions. Here we expound versions of the models that are more empirically useful, reformulated to reflect decisions based on male phenotypic characters. For some organisms, it may be possible to use preference functions to de- rive predictions from the reformulated models and thereby avoid difficulties associated with the measurement of male quality per se. But predictions derived from the two models are difficult to differentiate empirically, regardless of how the models are formu- lated. Here we develop ideas that illustrate how this goal might be accomplished. In addition, we clarify how the variability of male quality should be evaluated and we extend what is known about how this variability influences searcher behavior under each model. More general difficulties associated with the empirical study of mate choice decisions by searchers are also discussed Current Zoology 59 （2）： 184-199, 2013.
Background Pasireotide (SOM230), a long-acting somatostatin analogue (LAR), has improved agonist activity at somatostatin receptors. We tested the effect of SOM230 on insulin secretion, serum glucose ...concentrations, tumor growth, and survival using an MEN1 transgenic mouse model. Methods Eight 12-month-old conditional Men1 knockout mice with insulinoma were assessed. The treatment ( n = 4) and control groups ( n = 4) received monthly subcutaneous injections of SOM230 or PBS. Serum insulin and glucose levels were determined by enzyme-linked immunosorbent assay and enzymatic colorimetric assay, respectively. Tumor activity, growth, and apoptosis were determined by microPET/CT scan and histologic analysis. Results On day 7, there was a decrease in serum insulin levels from 1.06 ± 0.28 μg/L to 0.37 ± 0.17 μg/L ( P = .0128) and a significant increase in serum glucose from 4.2 ± 0.45 mmol/L to 7.12 ± 1.06 mmol/L ( P = .0075) in the treatment group but no change in the control group. Tumor size was less in the treatment group (2,098 ± 388 μm2 ) compared with the control group (7,067 ± 955 μm2 ; P = .0024). Furthermore, apoptosis was increased in the treatment group (6.9 ± 1.23%) compared with the control group (0.29 ± 0.103%; P = .002). Conclusion SOM230 demonstrates antisecretory, antiproliferative, and proapoptotic activity in our MEN1 model of insulinoma. Further studies of the effects of SOM230 in PNET patients with MEN1 mutations are warranted.
Background
Extramedullary hematopoiesis (EMH) occurs in patients with hematologic disorders, but rarely within the paranasal sinuses. We report a case of EMH in a 17-year-old male with sickle cell ...disease (SCD) who presented with occipital pain and sinusitis. A computed tomography (CT) scan demonstrated heterogeneous opacification of the right maxillary sinus concerning for allergic fungal sinusitis or a fungal ball with bony erosion. He was taken to the operating room for endoscopic biopsy and a limited endoscopic sinus surgery. Grossly, his maxillary sinus was filled with spiculated osseous tissue. Final pathology demonstrated active hematopoietic bone marrow filling the sinus.
Methods
We present a case report and literature review of sinonasal EMH.
Results
We identified 14 articles with 15 patients. EMH was typically associated with SCD or beta thalassemia. The average age of presentation was 30. There was a male sex predilection with a ratio of 11:15. The most common presenting symptom was a headache and nasal obstruction (33% for both). The most common finding on CT was a soft tissue expansile mass (73%). The most commonly affected location was the maxillary sinus (60%).
Conclusions
This case report serves as a reminder to consider EMH as an uncommon cause of sinus opacification, particularly in patients with SCD or beta thalassemia. The expansion of hematopoietic tissue may be identified as a sinus mass on CT. By recognizing the potential manifestations of chronic anemia, an accurate and timely diagnosis can be made.
Candida albicans is a fungal pathogen that causes potentially fatal infections among immune-compromised individuals. The emergence of drug resistant C. albicans strains makes it important to identify ...new antifungal drug targets. Among potential targets are enzymes known as peptidyl-prolyl cis/trans isomerases (PPIases) that catalyze isomerization of peptide bonds preceding proline. We are investigating a PPIase called Ess1, which is conserved in all major human pathogenic fungi. Previously, we reported that C. albicans Ess1 is essential for growth and morphogenetic switching. In the present study, we re-evaluated these findings using more rigorous genetic analyses, including the use of additional CaESS1 mutant alleles, distinct marker genes, and the engineering of suitably-matched isogenic control strains. The results confirm that CaEss1 is essential for growth in C. albicans, but show that reduction of CaESS1 gene dosage by half ( delta /+) does not interfere with morphogenetic switching. However, further reduction of CaEss1 levels using a conditional allele does reduce morphogenetic switching. We also examine the role of the linker alpha -helix that distinguishes C. albicans Ess1 from the human Pin1 enzyme, and present results of a genome-wide transcriptome analysis. The latter analysis indicates that CaEss1 has a conserved role in regulation of RNA polymerase II function, and is required for efficient termination of small nucleolar RNAs and repression of cryptic transcription in C. albicans.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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