Gidon Berger

Sepsis impairs alveolar epithelial function by downregulating Na-K-ATPase pump

Widespread vascular endothelial injury is the major mechanism for multiorgan dysfunction in sepsis. Following this process, the permeability of the alveolar capillaries is augmented with subsequent increase in water content and acute respiratory distress syndrome (ARDS). Nevertheless, the role of alveolar epithelium is less known. Therefore, we examined alveolar fluid clearance (AFC) using isolated perfused rat lung model in septic rats without ARDS. Sepsis was induced by ligating and puncturing the cecum with a 21-gauge needle. AFC was examined 24 and 48 h later. The expression of Na-K-ATPase proteins was examined in type II alveolar epithelial cells (ATII) and basolateral membrane (BLM). The rate of AFC in control rats was 0.51 ± 0.02 ml/h (means ± SE) and decreased to 0.3 ± 0.02 and 0.33 ± 0.03 ml/h in 24 and 48 h after sepsis induction, respectively (P < 0.0001). Amiloride, significantly decreased AFC in sepsis; conversely, isoproterenol reversed the inhibitory effect of sepsis. The alveolar-capillary barrier in septic rats was intact; therefore the finding of increased extravascular lung water in early sepsis could be attributed to accumulation of protein-poor fluid. The expression of epithelial sodium channel and Na-K-ATPase proteins in whole ATII cells was not different in both cecal ligation and puncture and control groups; however, the abundance of Na-K-ATPase proteins was significantly decreased in BLMs of ATII cells in sepsis. Early decrease in AFC in remote sepsis is probably related to endocytosis of the Na-K-ATPase proteins from the cell plasma membrane into intracellular pools, with resultant inhibition of active sodium transport in ATII cells.

Clinical and experimental pain perception is attenuated in patients with painless myocardial infarction

Abstract Background. The lack of pain alarm in painless myocardial infarction (MI) leads to increased morbidity and mortality, since patients do not seek medical treatment in a timely manner. We aimed to explore whether reduced systemic pain perception in response to experimental stimuli and pain related personality variables characterizes painless MI patients. Methods. Level of chest pain intensity was assessed by numerical scale, range from 0 (no pain) to 100 (maximal pain). Heat pain threshold, magnitude estimation of supra‐threshold phasic and tonic painful stimuli as well as anxiety and pain catastrophizing scores were assessed in 92 acute MI patients; 67 with and 25 without chest pain, respectively. All experimental stimuli were performed by Thermal Sensory Analysis (TSA) and applied to the right forearm. Results. Greater intensity of chest pain scores was inversely correlated with lower pain threshold (r = −0.417, p < 0.001), and directly associated with higher pain scores in response to the heat pain (r = 0.354, p = 0.002). Patients with painful MI demonstrated lower pain threshold (41.9 ± 3.6 °C vs. 44.9 ± 3.8 °C, p = 0.001) and higher catastrophizing level (10.6 ± 12.0 vs. 5.4 ± 8.8, p = 0.032). Logistic regression analysis revealed that older age and lower pain scores in response to supra‐threshold painful stimuli were associated with greater risk for painless MI. The demographic variables, history of ischemic heart, risk factors for coronary artery disease, ST‐T segment changes on ECG and troponin levels were similar in both groups. Conclusions. This study suggests that reduced systemic pain perception as well as cognitive personality variables play an important role in the etiology of painless MI.

Outcome of Pneumocystis jirovecii pneumonia diagnosed by polymerase chain reaction in patients without human immunodeficiency virus infection

Background and objective:  Pneumonia caused by Pneumocystis jirovecii (PCP) in patients without human immunodeficiency virus (HIV) infection is associated with high mortality. The diagnosis of PCP at our institution is based on detection of DNA using a polymerase chain reaction (PCR) assay. The aim of this study was to describe the clinical manifestations, outcomes and factors associated with mortality due to PCP, as diagnosed by PCR, in patients without HIV infection.

Characterization of Pulmonary Venous Hypertension Patients with Reactive Pulmonary Hypertension as Compared to Proportional Pulmonary Hypertension

Background: Patients with pulmonary venous hypertension (PVH) secondary to left heart disease can be further classified according to their hemodynamic profile: pulmonary hypertension (PH) in proportion to the pulmonary capillary wedge pressure (PCWP) and PH out of proportion to the PCWP or reactive PH. Currently, there are no measures that enable prediction of the development of reactive PH in patients with left heart disease. Objectives: In this study, we aim to characterize PVH patients with reactive PH as compared to proportional PH in an attempt to create a distinct profile for patients with left heart disease carrying a high risk for the development of reactive PH. Methods: Thirty-three PVH patients with reactive PH and 29 PVH patients with proportional PH were analyzed retrospectively over a 6-year period. Clinical, laboratory, echocardiographic and hemodynamic parameters were noted and compared between subgroups. Results: There was no significant difference between PVH patients with reactive and proportional PH with regard to gender, age (65.91 ± 11.9 vs. 66.69 ± 10.5 years) and body surface area (1.89 ± 0.24 vs. 1.9 ± 0.23 m2). Prevalence of the metabolic syndrome components was similar in both groups. Interestingly, PCWP was similar in both groups, as were the structural and functional parameters of the left heart. Conclusions: PVH patients with reactive PH have a similar profile as patients with proportional PH; consequently, the evolution of reactive PH is unpredictable. Therefore, it is imperative that physicians maintain a high index of suspicion for the development of reactive PH even in the early stage of heart disease.

The Human Microbiota: The Rise of an “Empire”

The human body hosts rich and diverse microbial communities. Our microbiota affects the normal human physiology, and compositional changes might alter host homeostasis and, therefore, disease risk. The microbial community structure may sometimes occupy discrete configurations and under certain circumstances vary continuously. The ability to characterize accurately the ecology of human-associated microbial communities became possible by advances in deep sequencing and bioinformatics analyses.

Nitrofurantoin pulmonary toxicity: neglected threat.

Nitrofurantoin lung toxicity was diagnosed among ten patients receiving 50 mg/day to prevent recurrent urinary tract infection. In six patients a symptomatic period of 3-36 months preceded the diagnosis. All but one patient, with irreversible lung injury at presentation recovered completely, five after drug discontinuation and four after steroids therapy. Large amount of data regarding unexpected, sometimes severe pulmonary toxicity during nitrofurantoin therapy should maintain a high index of suspicion for the drug usage among patients with non-resolving pulmonary symptoms. Alternatively, the use of other anti-microbial agents with a better risk-to-benefit ratio should be considered.

Vasopressin-2 Receptor Antagonist Attenuates the Ability of the Lungs to Clear Edema in an Experimental Model

In the last two decades, the role of the alveolar active sodium transport was extensively studied and was found to play a crucial role in regulating alveolar fluid clearance (AFC), and thus in keeping the airspaces free of edema. The recent development of highly selective nonpeptide vasopressin-receptor antagonists gives us a rare chance to explore the role of vasopressin in the pathogenesis of lung edema. Therefore, the present study examined the involvement of vasopressin in modulating the ability of the lung to clear edema. Vasopressin enhanced the rate of lung edema clearance by 30% as compared with untreated control rats (from 0.49 ± 0.02 to 0.64 ± 0.02 ml/h), whereas V(2) receptor antagonists significantly decreased the ability of the lung to clear water (from 0.64 ± 0.02 to 0.31 ± 0.06 ml/h; P < 0.0001). In contrast, V(1) receptor antagonist did not change the rate of AFC. The administration of ouabain (a Na,K-ATPase inhibitor) and amiloride (a Na(+) channel blocker) inhibited the stimulatory effects of vasopressin (from 0.64 ± 0.02 to 0.22 ± 0.02 ml/h [P < 0.0001] and from 0.64 ± 0.017 to 0.23 ± 0.02 ml/h [P < 0.0001], respectively). Vasopressin significantly increased Na,K-ATPase protein abundance in the basolateral membranes of the alveolar epithelial cells via V(2) receptor activation. We report a novel role of the vasopressin pathway in AFC. This observation indicates a beneficial role of vasopressin in AFC by up-regulating active sodium transport.

Correction: The Role of Angiotensin II and Cyclic AMP in Alveolar Active Sodium Transport.

The images for Figs ​Figs11 and ​and22 are incorrectly switched. The image that appears as Fig 1 should be Fig 2, and the image that appears as Fig 2 should be Fig 1. The figure captions appear in the correct order. Please see the correct Figs ​Figs11 and ​and22 here. Fig 1 Effect of Ang II on AFC. Fig 2 Different interventions effect on AFC.

The incidence of acute pulmonary embolism following syncope in anticoagulant-naïve patients: A retrospective cohort study

Background A recently published, large prospective study showed unexpectedly high prevalence of acute pulmonary embolism (APE) among patients hospitalized for syncope. In such a case, a high incidence of recurrent pulmonary embolism is expected among patients who were discharged without APE workup. Objectives To determine the incidence of symptomatic APE among patients hospitalized for a first episode of syncope and discharged without APE workup or anticoagulation. Methods This retrospective cohort study included patients hospitalized at Rambam Health Care Campus between January 2006 and February 2017 with a primary admission diagnosis of syncope, who were not investigated for APE and were not taking anticoagulants. The patients were followed up for up to three years after discharge. The occurrence of venous thromboembolism (VTE) during the follow-up period was documented. Results The median follow-up duration was 33 months. 1,126 subjects completed a three-year follow-up. During this period, 38 patients (3.38%) developed VTE, 17 (1.51%) of them had APE. The cumulative incidence of VTE and APE was 1.9% (95% CI 1.3%-2.5%) and 0.9% (95% CI 0.4%-1.3%) respectively. Only seven subjects developed APE during the first year of follow-up. The median times from the event of syncope to the development of APE and VTE were 18 and 19 months respectively. Conclusions The cumulative incidence of VTE during a three-year follow-up period after an episode of syncope is low. In the absence of clinical suspicion, a routine diagnostic workup for APE in patients with syncope cannot be recommended.

Contents Vol. 83, 2012

433 Joint Annual Meeting of the Swiss Society of Pneumology Swiss Society of Pediatric Pneumology Swiss Society for Thoracic Surgery Swiss Underwater and Hyperbaric Medical Society Crans-Montana, April 25–27, 2012 479 Congress Calendar