Work of breathing indices in infants with respiratory insufficiency receiving high-flow nasal cannula and nasal continuous positive airway pressure.

OBJECTIVE: To compare work of breathing (WOB) indices between two nCPAP settings and two levels of HFNC in a crossover study. STUDY DESIGN: Infants with a CGA 28-40 weeks, baseline of HFNC 3-5 lpm or nCPAP 5-6 cmH2O and fraction of inspired oxygen ≤40% were eligible. WOB was analyzed using respiratory inductive plethysmography (RIP) for each of the four modalities: HFNC 3 and 5 lpm, nCPAP 5 and 6 cmH2O. N=20; Study weight 1516 g (±40 g). RESULT: Approximately 12,000 breaths were analyzed indicating a high degree of asynchronous breathing and elevated WOB indices at all four levels of support. Phase angle values (means) (P<0.01): HFNC 3 lpm (114.7°), HFNC 5 lpm (96.7°), nCPAP 5 cmH2O (87.2°), nCPAP 6 cmH2O (80.5°). The mean phase relation of total breath (PhRTB) (means) (P<0.01): HFNC 3 lpm (63.2%), HFNC 5 lpm (55.3%), nCPAP 5 cmH2O (49.3%), nCPAP 6 cmH2O (48.0%). The relative labored breathing index (LBI) (means) (P≤0.001): HFNC 3 lpm (1.39), HFNC 5 lpm (1.31), nCPAP 5 cmH2O (1.29), nCPAP 6 cmH2O (1.26). Eighty-two percent of the study subjects-respiratory mode combinations displayed clustering, in which a proportion of breaths either occurred predominantly out-of-phase (relative asynchrony) or in-phase (relative synchrony). CONCLUSION: In this study, WOB indices were statistically different, yet clinically similar in that they were elevated with respect to normal values. These infants with mild-to-moderate respiratory insufficiency demonstrate a meaningful elevation in WOB indices and continue to require non-invasive respiratory support. Patient variability exists with regard to biphasic clustered breathing patterns and the level of supplemental fraction of inspired oxygen ≤40% alone does not provide guidance to the optimal matching of WOB indices and non-invasive respiratory support.

The gut-brain peptide cyclo(His-Pro) is secreted in a pulsatile fashion in fasting humans.

Histidyl-proline diketopiperazine (CHP) is a cyclic dipeptide that is found in many animal tissues, most notably brain and gut. It has been found to have a variety of biologic actions and has been postulated to play a role in appetitive behavior and energy metabolism. This study was conducted in order to characterize the secretory pattern of CHP during a 24 h fast. Four subjects (2 obese and 2 lean) were studied during the latter 24 h of a 36 h fast. Blood was sampled every 10-15 min and assayed for CHP concentration using a specific radioimmunoassay. Analysis revealed that circulating CHP oscillates in humans and that diurnal variation occurred but only in the obese subjects.

Sindbis virus infection decreases intracellular pH: alkaline medium inhibits processing of Sindbis virus polyproteins.

Infection of baby hamster kidney cells by Sindbis virus, an alphavirus, resulted in a decrease in the intracellular pH of approximately 0.5 units within the first 1-2 hr after infection as measured either by equilibrium labeling with [14C]benzoic acid or by use of a pH-sensitive fluorescent probe, 2,7-bis-carboxyethyl-5,6-carboxyfluorescein-acetooxymethyl ester. In contrast, intralysosomal pH, as measured using an endocytized pH-sensitive probe, fluorescein isothiocyanate-labeled dextran, was not altered by Sindbis virus infection. Production of Sindbis virus was reduced by more than 90% and post-translational processing of Sindbis virus envelope precursors was inhibited in infected cells incubated in alkaline medium.

Cell surface effects of human immunodeficiency virus.

Cell killing by human immunodeficiency virus (HIV) is thought to contribute to many of the defects of the acquired immunodeficiency syndrome (AIDS). Two types of cytopathology are observed in HIV-infected cultured cells: cell-cell fusion and killing of single cells. Both killing processes appear to involve cell surface effects of HIV. A model is proposed for the HIV-mediated cell surface processes which could result in cell-cell fusion and single cell killing. The purpose of this model is to define the potential roles of individual viral envelope and cell surface molecules in cell killing processes and to identify alternative routes to the establishment of persistently-infected cells. Elucidation of HIV-induced cell surface effects may provide the basis for a rational approach to the design of antiviral agents which are selective for HIV-infected cells.

Induction of the stress response: alterations in membrane-associated transport systems and protein modification in heat shocked or Sindbis virus-infected cells.

Heat shock or Sindbis virus infection of chick embryo (CE) or baby hamster kidney (BHK) cells resulted in a decrease in the uptake of 86Rubidium+, a K+ tracer. Both stressful treatments decreased 86Rb+ uptake by inhibition of the ouabain-sensitive Na+/K+ ATPase. Alterations in the intracellular levels of monovalent ions may be involved in translational or transcriptional control of the stress response. Heat shock or Sindbis virus infection also resulted in an increase in rate of uptake of [3H]deoxy-D-glucose and a decrease in the incorporation of [3H]glucosamine or [3H]mannose into most cellular proteins. These results suggested that heat shock or Sindbis virus infection alter hexose metabolism and that abnormally glycosylated proteins may accumulate in stressed cells. Exposure of uninfected chick embryo cells to elevated temperature had little effect on the overall rate of incorporation of [32P]orthophosphate into cellular proteins. However, one protein (Mr 31,000; pp31) displayed increased incorporation of [32P]orthophosphate and two other proteins (Mr 33,000 and 20,000; pp33 and pp20) displayed decreased incorporation. Sindbis virus infection failed to mimic or to modify these heat shock induced alterations in protein phosphorylation.

Sindbis virus infection increases hexose transport in quiescent cells.

Sindbis virus infection of baby hamster kidney cells or chick embryo cells resulted in a significant increase in the rate of uptake of [2-3H]deoxy-D-glucose ([3H]dGlu). Stimulation of hexose transport in Sindbis virus-infected cells occurred only if the cells were rendered quiescent by culturing at high density or by serum starvation. In contrast, Sindbis virus-induced inhibition of potassium transport, measured as a decrease in the uptake of 86Rb+, was independent of cell growth state. Stimulation of [3H]dGlu uptake in Sindbis virus-infected cells was the result of an increase in the Vmax of the hexose transporter, but not a change in the Km. The stimulation of [3H]dGlu uptake induced by Sindbis virus was insensitive to the drug actinomycin D, but was blocked by cordycepin. The stimulation was also insensitive to treatment with tunicamycin, which prevented the virally induced inhibition of the plasma membrane-associated Na+/K+ ATPase and termination of host protein synthesis.

Intracellular K+ and the expression of transformation parameters by chick cells transformed with the Bryan strain of Rous sarcoma virus.

As normal chick embryo (CE) cells entered quiescence the intracellular concentrations of both Na+ and K+ declined. Comparable decreases in intracellular concentrations of Na+ and K+ were not observed in CE cells transformed by either the Schmidt-Ruppin (SR) or the Bryan (B) strain of Rous sarcoma virus (RSV). Intracellular concentrations of Na+ were higher in SR-RSV-transformed CE cells than in B-RSV-transformed cells and uninfected CE cells at all times after plating. In contrast, intracellular concentrations of K+ were higher in B-RSV-transformed CE cells than in SR-RSV-transformed cells. Uninfected CE cells incubated in medium containing an elevated concentration of K+ (an increase from 5 to 30 mM) exhibited several, but not all, of the transformation parameters expressed by B-RSV-transformed CE cells.

Effects of indomethacin on systemic and coronary hemodynamics in patients with coronary artery disease.

The effects and possible mechanisms of actions of indomethacin on systemic and coronary hemodynamics were studied in 17 patients with coronary artery disease. Group I patients (12) were given either indomethacin or placebo in the absence of prior cyclooxygenase inhibition and group II (five) were given indomethacin after prior treatment with 2600 mg of aspirin. In group I, systolic blood pressure rose from a baseline of 136 +/- 5 mm Hg to a peak level of 158 +/- 8 mm Hg 5 minutes after drug (p less than 0.01). This was associated with a fall in coronary blood flow and a rise in coronary vascular resistance from a baseline of 1.36 +/- 0.4 mm Hg/ml/min to 1.99 +/- 0.7 mm Hg/ml/min 5 minutes after indomethacin (p less than 0.01). Immunoreactive thromboxane B2 levels fell from 191 to 1.4 ng/ml. No changes were noted in plasma renin activity, angiotensin II, or catecholamine levels. Immunoreactive thromboxane B2 levels were undetectable throughout the study period in group II patients and the blood pressure response to indomethacin was attenuated. Baseline coronary blood flow was significantly higher (p less than 0.01) and baseline coronary vascular resistance significantly lower (p less than 0.01) than in group I. At all time points after indomethacin, the fall in coronary blood flow was greater and the increase in coronary vascular resistance less in group II versus group I (p less than 0.001). These findings suggest a dissociation between the effect of indomethacin on systemic and coronary hemodynamics, the former apparently being more prostaglandin-dependent than the latter.

The ratio of plasma membrane cholesterol to phospholipid and the inhibition of Sindbis virus maturation by low NaCl medium.

Sindbis virus maturation is inhibited by low NaCl medium in chick embryo cells and in one strain of BHK cells, but not in another strain of BHK cells which has a different passage history. The plasma membrane of the cells in which Sindbis virus maturation is resistant to low NaCl medium has a higher ratio of cholesterol to phospholipid than the other cells. Cholesterol-containing liposomes, but not cholesterol-free liposomes, can release Sindbis virus from low NaCl-inhibited cells. These results suggest that low NaCl medium may block Sindbis virus maturation by a mechanism which is influenced by the ratio of plasma membrane cholesterol to phospholipid.

Effect of tyramine on myocardial catecholamine release in coronary heart disease.

The influence of tyramine on myocardial catecholamine release and on coronary blood flow has not previously been determined in man. Therefore, the effect of tyramine was measured on coronary and systemic hemodynamics and on norepinephrine (NE) and epinephrine levels in blood from the aorta and coronary sinus in 9 patients with coronary artery disease. Tyramine produced a striking increase in coronary sinus NE, from a baseline of 344 +/- 56 to a peak level of 1416 +/- 310 pg/ml (p less than 0.01) 2 minutes after tyramine. The increase in aortic NE was less striking, from 265 +/- 32 to 421 +/- 63 pg/ml (difference not significant). Therefore, the net release of NE from the heart was increased by tyramine from 12,007 +/- 393 to 139,357 +/- 46,156 pg/ml/min (p less than 0.03). There was no release of epinephrine across the coronary bed. There was a variable response of coronary blood flow and resistance after tyramine. Thus, the rich innervation of the heart by sympathetic nerve endings can result in marked NE release into the coronary sinus.