Experimental and investigational phosphodiesterase inhibitors in development for asthma

Introduction: Severe, inadequately-controlled asthma remains a clinical challenge. For this reason, clinical trials and preclinical experimental studies on novel agents as an add-on therapies continue emerge. Phosphodiesterases (PDEs) are enzymes that regulate the function of immune cells by hydrolyzing cyclic guanosine monophosphate/cGMP and cyclic adenosine monophosphate/cAMP. PDEs are divided into subfamilies [PDE3, PDE4, PDE5 and PDE7] which are mainly found in the respiratory tract. Inhibitors of PDEs have already been approved for COPD and pulmonary hypertension.

Areas covered: The role of PDE inhibitors in asthma treatment and the possible mechanism of action via their anti-inflammatory and/or bronchodilating effect are discussed.

Expert opinion: Novel PDE inhibitors exhibiting fewer adverse events may have a role as add-on therapies in asthma treatment in the future. More clinical trials are necessary to prove their efficacy and evaluate their safety profile before approval by regulatory bodies is granted.     

Systemic sclerosis associated with generalized vasculitis and hypopituitarism

Systemic sclerosis (SSc) is a progressively evolving multisystemic disorder of unknown etiology. Beyond skin, several other organs can also be affected with a severity of involvement that is often heterogeneous. We describe a 53-year-old female patient who was admitted urgently to the hospital almost collapsed, because of numerous bleeding deep skin ulcers, located all over the body. Clinical findings and autoantibody screening were typical of SSc. Moreover, both histopathology and immunofluorescence findings were compatible with scleroderma and vasculitis as well. In addition, pituitary hormone investigation revealed severely damaged function of the gland. We assume that severe skin ulceration and serious hypopituitarism were both implications of underlying SSc-associated vasculitis. To the best of our knowledge, these peculiar clinical manifestations have not been described in the international literature to date.     

Correction to: “Best Things”: Parents Describe Their Children with Autism Spectrum Disorder Over Time

Journal of Autism and Developmental Disorders -     

Changes in indications for upper gastrointestinal tract endoscopy and endoscopic findings during the last fifteen years in south-western Greece

BACKGROUND: During the past years, major advances in the management of upper gastrointestinal diseases have been achieved. The aim of this study was to determine if changes in indications for upper gastrointestinal endoscopy and endoscopic findings have occurred during the last 15 years in our area. METHODS: Indications for upper gastrointestinal tract endoscopy and endoscopy findings of patients who underwent upper endoscopy in years 1990, 1995, 2000, and 2005 in our department were compared. RESULTS: Over the 15-year period, the number of diagnostic endoscopies performed in our department in years 1990, 1995, 2000, and 2005 increased (953, 1245, 2350, and 2528, respectively). Acute upper gastrointestinal bleeding had become less frequent (40%, 42.8%, 19.7%, 14.3%, P<0.001), but dyspepsia (24.4%, 33.6%, 54.3%, 51.3%, P=0.002) and reflux (1.8%, 1.3%, 5.1%, 10.8%, P=0.005) more frequent indications for upper endoscopy. The endoscopic findings of duodenal ulcer (39.1%, 22.5%, 20.5%, 9.3%, P<0.001), gastric ulcer (15.9%, 8.3%, 5.7%, 4.6%, P=0.036) as well as erosive gastroduodenitis (35.6%, 22.2%, 15.3%, 4.7%, P<0.001) decreased, whereas that of reflux esophagitis (3.1%, 10.1%, 12%, 16%, P=0.034) increased. Moreover, the percentage of patients with negative endoscopy or minimal endoscopic findings (eg, nonerosive gastritis) increased (12.8%, 33.7%, 54.1%, 64.4%, P<0.001). CONCLUSIONS: In south-western Greece, dyspepsia and reflux as an indication for upper endoscopy have been increasing, whereas acute upper gastrointestinal bleeding has been decreasing. The finding of peptic ulcers at the upper gastrointestinal tract endoscopy has become significantly less frequent, while the percentage of patients with negative results of endoscopy seems to have been increasing rapidly.     

Postoperative Expansion is not a Primary Cause of Infection in Immediate Breast Reconstruction with Tissue Expanders

Perioperative infection is the most common and dreaded complication associated with tissue expander (TE) breast reconstruction. Historically, the expansion period was thought to be the time of greatest hazard to the implant. However, recent institutional observations suggest infectious complications occur prior to expansion. This investigation, therefore, was conducted to determine the timing of infectious complications associated with two‐stage TE breast reconstructions. Following IRB approval, a retrospective review of all consecutive two‐stage immediate TE breast reconstructions at a single institution from November 2007 to November 2011 was conducted. Reconstructions were then divided into two cohorts: those suffering infectious complications and those that did not. Infectious complications including minor cellulitis, major cellulitis, abscess drainage, and explantation were identified. Various operative and patient variables were evaluated in comparison. Eight hundred ninety immediate two‐stage TE breast reconstructions met inclusion criteria. Patients suffering infection were older (55.4 years versus 49.3 years; p < 0.001), and more likely to have therapeutic mastectomy (94% versus 61%; p < 0.0001), the use of acellular dermal matrix (ADM; 72.5% versus 54.9%; p = 0.001), and greater initial TE fill (448.6 mL versus 404.7 mL; p = 0.0078). The average time to developing of infectious symptoms was 29.6 days (range 9–142 days), with 94.6% (n = 87) of infections prior to the start of expansion. Perioperative infections in immediate two‐stage TE to implant breast reconstructions are significant and occur mostly prior to the start of expansion. Thus, challenging the conventional wisdom that instrumentation during expander filling as the primary cause of implant infections. Possible etiologic factors include greater age, therapeutic mastectomy versus prophylactic mastectomy, larger initial TE fill, and the use of ADM.     

Criticality Hidden in Acoustic Emissions and in Changing Electrical Resistance during Fracture of Rocks and Cement-Based Materials

Acoustic emissions (AE) due to microcracking in solid materials permit the monitoring of fracture processes and the study of failure dynamics. As an alternative method of integrity assessment, measurements of electrical resistance can be used as well. In the literature, however, many studies connect the notion of criticality with AE originating from the fracture, but not with the changes in the electrical properties of materials. In order to further investigate the possible critical behavior of fracture processes in rocks and cement-based materials, we apply natural time (NT) analysis to the time series of AE and resistance measurements, recorded during fracture experiments on cement mortar (CM) and Luserna stone (LS) specimens. The NT analysis indicates that criticality in terms of electrical resistance changes systematically precedes AE criticality for all investigated specimens. The observed greater unpredictability of the CM fracture behavior with respect to LS could be ascribed to the different degree of material homogeneity, since LS (heterogeneous material) expectedly offers more abundant and more easily identifiable fracture precursors than CM (homogenous material). Non-uniqueness of the critical point by varying the detection threshold of cracking events is apparently due to finite size effects which introduce deviations from the self-similarity.     

Acute Kidney Injury in Adult Idiopathic Nephrotic Syndrome

Kikuchi-Fujimoto disease (KFD) is a benign and self-limited disease of unknown etiology that affects mainly young women. It presents with localized lymphadenopathy, usually cervical, accompanied with fever, night sweats, and leucopenia. KFD has been rarely described in association with autoimmune disorders, mainly systemic lupus erythematosus (SLE). We report the case of a young patient presenting with KFD coinciding with SLE. The association of KFD and SLE is reviewed. Moreover, a possible pathogenetic role of Ebstein-Barr virus linking the two clinical entities is discussed.