Impaired chemoreflex sensitivity in adult patients with multiple organ dysfunction syndrome—the potential role of disease severity

Objective The cardiac chemoreflex sensitivity is a powerful predictor of autonomic dysfunction in chronic heart failure and after myocardial infarction. The objective of the present study was to characterize cardiac chemoreflex sensitivity in patients with multiple organ dysfunction syndrome (MODS). We also aimed to elucidate the effect of the severity of MODS on the assessment of cardiac chemoreflex sensitivity.Design Prospective cohort study.Setting Twelve-bed medical intensive care unit in a university center.Patients Forty consecutively admitted patients with MODS during a 7-month period. Patients with MODS were identified by an APACHE II score of 20 or more. Sepsis was defined as a Sepsis Score, according to Elebute and Stoner, of 12 or more.Interventions The cardiac chemoreflex sensitivity was assessed using the regression of heart interval (ms) versus arterial oxygen pressure (mmHg).Measurements and results First, we established a new method to assess cardiac chemoreflex sensitivity and applied it to healthy controls and patients. Second, we found that cardiac chemoreflex sensitivity correlated with the severity of MODS as calculated by the APACHE II score (r²=0.34, p=0.001). This relation was best fitted by a model including minimum heart rate and standard bicarbonate in 24 h (r²=0.5, p<0.001) and Glasgow Coma Scale (r²=0.5, p=0.005). Age, however, did not significantly contribute (r²=0.001, p=0.8).Conclusions The calculation of cardiac chemoreflex sensitivity enabled us to quantify an important component of the cardiorespiratory interactions in patients with MODS. Severity of illness was a more pronounced determinant of impaired cardiac chemoreflex sensitivity than age. The quantification of the cardiorespiratory interactions by measuring the cardiac chemoreflex sensitivity has potential to identify a subgroup of patients with worse prognosis.     

Adjuvant pretreatment with alum protects neonatal mice in sepsis through myeloid cell activation

The high mortality in neonatal sepsis has been related to both quantitative and qualitative differences in host protective immunity. Pretreatment strategies to prevent sepsis have received inadequate consideration, especially in the premature neonate, where outcomes from sepsis are so dismal. Aluminium salts‐based adjuvants (alum) are used currently in many paediatric vaccines, but their use as an innate immune stimulant alone has not been well studied. We asked whether pretreatment with alum adjuvant alone could improve outcome and host innate immunity in neonatal mice given polymicrobial sepsis. Subcutaneous alum pretreatment improves survival to polymicrobial sepsis in both wild‐type and T and B cell‐deficient neonatal mice, but not in caspase‐1/11 null mice. Moreover, alum increases peritoneal macrophage and neutrophil phagocytosis, and decreases bacterial colonization in the peritoneum. Bone marrow‐derived neutrophils from alum‐pretreated neonates produce more neutrophil extracellular traps (NETs) and exhibit increased expression of neutrophil elastase (NE) after in‐vitro stimulation with phorbol esters. In addition, alum pretreatment increases bone marrow and splenic haematopoietic stem cell expansion following sepsis. Pretreatment of neonatal mice with an alum‐based adjuvant can stimulate multiple innate immune cell functions and improve survival. These novel findings suggest a therapeutic pathway for the use of existing alum‐based adjuvants for preventing sepsis in premature infants.     

How chromosomal deletions can unmask recessive mutations? Deletions in 10q11.2 associated with CHAT or SLC18A3 mutations lead to congenital myasthenic syndrome

A congenital myasthenia was suspected in two unrelated children with very similar phenotypes including several episodes of severe dyspnea. Both children had a 10q11.2 deletion revealed by Single Nucleotide Polymorphisms array or by Next Generation Sequencing analysis. The deletion was inherited from the healthy mother in the first case. These deletions unmasked a recessive mutation at the same locus in both cases, but in two different genes: CHAT and SLC18A3.     

Intermittent PTH administration and mechanical loading are anabolic for periprosthetic cancellous bone

The purpose of this study was to determine the individual and combined effects on periprosthetic cancellous bone of intermittent parathyroid hormone administration (iPTH) and mechanical loading at the cellular, molecular, and tissue levels. Porous titanium implants were inserted bilaterally on the cancellous bone of adult rabbits beneath a loading device attached to the distal lateral femur. The left femur received a sham loading device. The right femur was loaded daily, and half of the rabbits received daily PTH. Periprosthetic bone was evaluated up to 28 days for gene expression, histology, and µCT analysis. Loading and iPTH increased bone mass by a combination of two mechanisms: (1) Altering cell populations in a pro‐osteoblastic/anti‐adipocytic direction, and (2) controlling bone turnover by modulating the RANKL‐OPG ratio. At the tissue level, BV/TV increased with both loading (+53%, p < 0.05) and iPTH (+54%, p < 0.05). Combined treatment showed only small additional effects at the cellular and molecular levels that corresponded to a small additive effect on bone volume (+13% compared to iPTH alone, p > 0.05). This study suggests that iPTH and loading are potential therapies for enhancing periprosthetic bone formation. The elucidation of the cellular and molecular response may help further enhance the combined therapy and related targeted treatment strategies. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:163–173, 2015.

     

Immunoradiometric assay of carcinoembryonic antigen with use of avidin-biotin labeling

In evaluating an enzyme-linked immunoassay of carcinoembryonic antigen (CEA) we found that the IgG fraction of polyclonal anti-CEA antibodies (DAKO) bound very well to the walls of polypropylene test tubes. We therefore developed an immunoradiometric CEA assay based on this binding of polyclonal anti-CEA antibody. We biotinylated a commercially available monoclonal antibody (Hybritech) and bound this to the CEA-anti-CEA bound to the tube wall. For detection we used 125I-labeled streptavidin. In comparison with several immunoassays for CEA this system offered several advantages such as greater linearity of the standard curve (from 0 to 74 micrograms/L), a steeper dose-response curve, and smaller coefficients of variation in the clinically useful range. This assay system may be used for other large molecules, so that only one tracer, the 125I-labeled streptavidin, has to be labeled; thus the technique seems suited for several different assays.     

Accessory mitral valve tissue: Appearance on cardiac computed tomography

Accessory mitral valve tissue is an uncommon congenital malformation and a rare cause of left ventricular outflow tract obstruction. Although echocardiography provides a "gold standard" for evaluation of valves, the high temporal and spatial resolutions of computed tomography technology makes it useful in the assessment of valvular structure and function.     

Ricinoleic acid effect on the electrical activity of the small intestine in rabbits.

Using myoelectric recording techniques, we examined the myoelectric effects of castor oil; ricinoleic acid (cis isomer), the active ingredient of castor oil; and ricinelaidic acid (trans isomer) in the small intestine of New Zealand white rabbits. Ricinoleic acid, 2 microgram/kg per min (6mM), was perfused into a distal 12-cm ileal loop. An abnormal myoelectric pattern developed that was similar to the alteration in the electrical activity that has previously been reported for cholera enterotoxin. Castor oil, 0.85 ml/kg, had a similar effect. Ricinelaidic acid, 2 microgram/kg per min, induced no activity. A second preparation consisted of an intraluminal perfusion of ricinoleic acid, 2 microgram/kg per min, into the first section of the duodenum. The abnormal myoelectric pattern was observed in the jejunum and the ileum but not the duodenum. The mean onset time for the development of this altered myoelectric state for all experiments was 3.5 h. These studies suggest that an active motility component in addition to the secretory state exists throughout the small intestine that is exposed to castor oil or ricinoleic acid.