Activation of bone morphogenetic protein/Smad signaling in bronchial epithelial cells during airway inflammation

Bone morphogenetic proteins (BMPs) are pleiotropic secreted proteins, structurally related to transforming growth factor (TGF)-beta and activins. BMPs play pivotal roles in the regulation of embryonic lung development and branching of airways and have recently been considered to influence inflammatory processes in adults due to their chemotactic activity on fibroblasts, myocytes, and inflammatory cells. In this study, we have investigated the possible involvement of BMPs in a model of experimental allergic-airway inflammation in situ using antibodies that detect activated Smad proteins, and have monitored the modulation of BMP ligands during the inflammatory response. Inflamed bronchial epithelial cells and a few scattered alveolar cells expressed levels of phosphorylated Smad1 (pSmad1/5), indicative of active BMP/Smad signaling. This was in contrast to healthy epithelium, which was devoid of immunoreactivity. A mechanistic explanation for increased pSmad1/5 staining during inflammation was provided by the upregulated expression of all the BMP type I receptors, i.e., activin receptor-like kinase (ALK)2, ALK3, and ALK6, in the inflamed bronchial epithelial cells. Furthermore, the mRNA and protein profiles for BMP ligands were significantly altered during airway inflammation with induction of BMP2, BMP4, and BMP6, and downregulation of BMP5 and BMP7. Collectively, our data demonstrate for the first time active BMP/Smad signaling during airway inflammation in bronchial epithelial cells and thus raise the possibility that BMPs could play a determining role in respiratory pathophysiology.     

Liver transplantation for acute liver failure in a SARS-CoV-2 PCR-positive patient

Current guidelines recommend deferring liver transplantation (LT) in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection until clinical improvement occurs and two PCR tests collected at least 24 hours apart are negative. We report a case of an 18-year-old, previously healthy African-American woman diagnosed with COVID-19, who presents with acute liver failure (ALF) requiring urgent LT in the context of SARS-CoV-2 polymerase chain reaction (PCR) positivity. The patient was thought to have acute Wilsonian crisis on the basis of hemolytic anemia, alkaline phosphatase:bilirubin ratio <4, AST:ALT ratio >2.2, elevated serum copper, and low uric acid, although an unusual presentation of COVID-19 causing ALF could not be excluded. After meeting criteria for status 1a listing, the patient underwent successful LT, despite ongoing SARS-CoV-2 PCR positivity. Remdesivir was given immediately posttransplant, and mycophenolate mofetil was withheld initially and the SARS-CoV-2 PCR test eventually became negative. Three months following transplantation, the patient has made a near-complete recovery. This case highlights that COVID-19 with SARS-CoV-2 PCR positivity may not be an absolute contraindication for transplantation in ALF. Criteria for patient selection and timing of LT amid the COVID-19 pandemic need to be validated in future studies.     

Community mental health--the mouse that roared or marketing a public agency

As the market place becomes increasingly competitive, marketing has been more aggressively undertaken by private business, and more recently, by proprietary and not for profit hospitals and other human service organizations. This article describes the efforts of an urban, publicly supported, multi-provider mental health system to develop an assertive, positive marketing stance. Following a brief historical development, the authors describe the current public relations campaign and some of the specific techniques used.     

Electrolyte metabolism in patients with periodic affective disorders during treatment with rubidium

Five patients suffering from periodic affective disorders with short mood-cycles were treated with rubidium chloride, producing peak erythrocyte concentrations between 9 and 13 mmol/l. Loading with rubidium was associated with decreased total body potassium, but red-cell potassium was unchanged. Regular mood-cycling was disturbed, together with the associated body-weight changes. There was a slight extracellular "metabolic" acidosis. Electrolyte concentrations fluctuate abnormally in these patients, and two muscle biopsy specimens had very low potassium contents.     

Lung Function in Gypsies in Greece

The relationship between lung function and smoking and dietary habits was examined in 121 Gypsies (62 males, 59 females) who were 14-70 y of age and who lived in Greece. All were examined clinically, after which they all participated in spirometry tests. Half of the study group had abnormal (< 80% of predicted) forced vital capacity, 36.4% had abnormal (< 80% of predicted) forced expiratory volume in 1 sec, and 5% had serious lung function disturbances (forced vital capacity < 50% of predicted). Approximately 70% of subjects were smokers, and their diets were rich in alcohol and meat; they ate very few salads and oranges. Consequently, decreased lung function might be a major health problem in Gypsies in Greece. Organization of preventive health strategies should improve the overall health of this study group.     

Hemolysis parameters of St. Jude Medical: Hemodynamic Plus and Regent valves in aortic position

BACKGROUND: Elevated plasma lactate dehydrogenase (LDH) concentration may reflect hemolysis due to mechanical heart valve dysfunction. Thus, knowledge of LDH levels in patients with properly working prostheses is required. Because hemolysis parameters for the SJM Hemodynamic Plus (HP) and Regent series are currently not available, the purpose of our study was to determine these data. METHODS: At 12-19 months follow-up after isolated aortic valve replacement with SJM HP(R) or Regent prostheses, we examined 102 patients by transthoracic echocardiography and determined plasma LDH, haptoglobin, bilirubin and hemoglobin. RESULTS: Five patients with properly working prostheses were excluded because of increased LDH due to non-cardiac reasons. In four patients with paravalvular leakage, LDH was 244, 307, 446 and 628 U/l, respectively. In patients with properly working prostheses, LDH was 287+/-52 (range: 163-374) U/l for HP(R) (n=33) and 274+/-48 (151-386) U/l for Regent valves (n=60, p=0.2). Haptoglobin was <1g/l in all patients; in 91% of HP and 75% of Regent valves, haptoglobin was below detection limit. Bilirubin and hemoglobin as well as red blood cell count (RBC) were normal in all patients except for five patients with renal anemia, two patients with paravalvular leakage and four patients with macrocytosis due to alcohol abuse. There was no correlation between LDH and transvalvular gradient (r=-0.02) or valve size (r=0.25). CONCLUSIONS: In patients with SJM HP(R) or Regent valves in aortic position, LDH values > 400 U/l indicate valvular dysfunction or leakage if non-cardiac causes for hemolysis are excluded. However, paravalvular leakage can be present without substantially increased LDH. Haptoglobin has no diagnostic value as it is almost always markedly reduced. Hemolysis does not correlate with transvalvular gradient or prosthesis size.     

Simultaneous versus delayed hepatectomy for synchronous colorectal liver metastases: a systematic review and meta-analysis

Objective

This was a systematic review and meta-analysis to compare outcomes between patients undergoing simultaneous or delayed hepatectomy for synchronous colorectal liver metastases.

Formoterol in the management of chronic obstructive pulmonary disease

Bronchodilators represent the hallmark of symptomatic treatment of Chronic Obstructive Pulmonary Disease (COPD). There are four categories of bronchodilators: anticholinergics, methylxanthines, short-acting β₂-agonists, and long-acting β₂-agonists such as formoterol. Significant research has been performed to investigate the efficacy, safety and tolerability of formoterol in the therapeutic field of COPD. Formoterol exhibits a rapid onset of bronchodilation similar to that observed with salbutamol, yet its long bronchodilatory duration is comparable to salmeterol. In addition, formoterol presents with a clear superiority in lung function improvement compared with either ipratropium bromide or oral theophylline, while its efficacy improves when administered in combination with ipratropium. Formoterol has been shown to better reduce dynamic hyperinflation, which is responsible for exercise intolerance and dyspnea in COPD patients, compared with other bronchodilators, whereas it exerts synergistic effect with tiotropium. Moreover, formoterol reduces exacerbations, increases days free of use of rescue medication and improves patients’ quality of life and disease symptoms. Formoterol has a favorable safety profile and is better tolerated than theophylline. Collectively, data extracted from multicenter clinical trials support formoterol as a valid therapeutic option in the treatment of COPD.     

A fatty meal aggravates apnea and increases sleep in patients with obstructive sleep apnea

Purpose

The purpose of this study was to investigate the role of a fatty meal before bedtime, on sleep characteristics and blood pressure in patients with obstructive sleep apnea (OSA).

Methods

Recently diagnosed, by full polysomnography (PSG), patients with OSA (n?=?19) were included. These underwent PSG for additional two consecutive nights. Two hours before the PSG examination, a ham and cheese sandwich of 360 kcal was served to all patients, at first night, while a fatty meal of 1,800 kcal was served before the second PSG examination. Comparisons were performed between the last two examinations in terms of PSG data and morning and night blood pressure measurements.

Results

After the fatty meal, a significant increase was observed in total sleep time (p?=?0.026) in the Apnea–Hypopnea Index (AHI) (p?=?0.015), as well as in the absolute number of obstructive and central apneas (p?=?0.032 and p?=?0.042, respectively) compared to the previous night. Conversely, distribution of sleep stages and indices of nocturnal hypoxia (average and minimum SpO₂ and sleep time with SpO₂?<?90 %) did not change significantly. Likewise, no significant change was observed in blood pressure measurements.

Conclusions

Fatty meal intake before sleep can increase AHI in OSA patients, although it does not affect sleep architecture or indices of hypoxia.