Melatonin reduces oxidative stress and improves vascular function in pulmonary hypertensive newborn sheep

Pulmonary hypertension of the newborn (PHN) constitutes a critical condition with severe cardiovascular and neurological consequences. One of its main causes is hypoxia during gestation, and thus, it is a public health concern in populations living above 2500 m. Although some mechanisms are recognized, the pathophysiological facts that lead to PHN are not fully understood, which explains the lack of an effective treatment. Oxidative stress is one of the proposed mechanisms inducing pulmonary vascular dysfunction and PHN. Therefore, we assessed whether melatonin, a potent antioxidant, improves pulmonary vascular function. Twelve newborn sheep were gestated, born, and raised at 3600 meters. At 3 days old, lambs were catheterized and daily cardiovascular measurements were recorded. Lambs were divided into two groups, one received daily vehicle as control and another received daily melatonin (1 mg/kg/d), for 8 days. At 11 days old, lung tissue and small pulmonary arteries (SPA) were collected. Melatonin decreased pulmonary pressure and resistance for the first 3 days of treatment. Further, melatonin significantly improved the vasodilator function of SPA, enhancing the endothelial‐ and muscular‐dependent pathways. This was associated with an enhanced nitric oxide‐dependent and nitric oxide independent vasodilator components and with increased nitric oxide bioavailability in lung tissue. Further, melatonin reduced the pulmonary oxidative stress markers and increased enzymatic and nonenzymatic antioxidant capacity. Finally, these effects were associated with an increase of lumen diameter and a mild decrease in the wall of the pulmonary arteries. These outcomes support the use of melatonin as an adjuvant in the treatment for PHN.     

Riesgo de recurrencia tras retirada de la anticoagulación en pacientes con enfermedad tromboembólica venosa no provocada: validación externa del nomograma de Viena y del modelo predictivo DASH

IntroductionScales for predicting venous thromboembolism (VTE) recurrence are useful for deciding the duration of the anticoagulant treatment. Although there are several scales, the most appropriate for our setting has not been identified. For this reason, we aimed to validate the DASH prediction score and the Vienna nomogram at 12 months.MethodsThis was a retrospective study of unselected consecutive VTE patients seen between 2006 and 2014. We compared the ability of the DASH score and the Vienna nomogram to predict recurrences of VTE. The validation was performed by stratifying patients as low-risk or high-risk, according to each scale (discrimination) and comparing the observed recurrence with the expected rate (calibration).ResultsOf 353 patients evaluated, 195 were analyzed, with an average age of 53.5 ± 19 years. There were 21 recurrences in 1 year (10.8%, 95% CI: 6.8%-16%). According to the DASH score, 42% were classified as low risk, and the rate of VTE recurrence in this group was 4.9% (95% CI: 1.3%-12%) vs. the high-risk group that was 15% (95% CI: 9%-23%) (p <.05). According to the Vienna nomogram, 30% were classified as low risk, and the rate of VTE recurrence in the low risk group vs. the high risk group was 4.2% (95% CI:0.5%-14%) vs. 16.2% (95% CI: 9.9%-24.4%) (p <.05).ConclusionsOur study validates the DASH score and the Vienna nomogram in our population. The DASH prediction score may be the most advisable, both because of its simplicity and its ability to identify more low-risk patients than the Vienna nomogram (42% vs. 30%).     

Molecular study of hypersensitivity to spores in adults and children from Castile & Leon

Introduction and objectivesBiological aerosols play a vital role in the interactions between the atmosphere, biosphere, climate and public health and fungal spores are a component with allergic importance.We constructed a database in Castile & Leon (Spain) and carry out molecular-level component-resolved diagnosis to complete the air quality study carried out since 2006 by our aerobiological network (RACYL) to aid clinical diagnosis and treatment.MethodsWe reviewed a database of 19,774 patients (adults and children) with allergic respiratory disease treated in our unit during the last 12 years. We also made a component-resolved diagnosis of the molecules involved in the pathology in a randomly selected population of 150 patients.ResultsThe dimeric glycoprotein Alt a1 from Alternaria is the most prevalent and most useful allergen in the diagnosis of patients with allergy to fungi in our area (94.4%), followed by enolase Alt a 6 (Alternaria), ribonuclease Asp f 1 of Aspergillus and mannitol dehydrogenase from Cla h 8 (Cladosporium).ConclusionsOur results have helped determine which spore molecules are most-closely associated with allergies. Molecular analysis will be useful to determine more accurate and useful immunotherapy in these patients.     

Outcomes at 3 years of a prospective pilot study of Campath-1H and sirolimus immunosuppression for renal transplantation

Campath-1H (alemtuzumab) induction was used for renal transplantation in combination with sirolimus as immunosuppression. We previously reported a high (28%) rate of early rejection with this regimen, and now report 3-year outcomes. Twenty-nine patients were recipients of either deceased donor or non-HLA (Human Leukocyte Antigen) identical living donor primary renal allografts. Clinical parameters including infection, malignancy, kidney function, and kidney histology were followed prospectively for 3 years. Three-year cumulative graft and patient survival were 96% and 100%, respectively. Twenty patients were maintained on steroid-free immunosuppressive regimens, and 15 patients were maintained on monotherapy for immunosuppression (12 on sirolimus). No serious infectious complications were observed and two patients developed basal cell skin cancer. The 3-year results of our initial pilot study demonstrate good graft (96%) and patient (100%) outcomes. Campath-1H induction has yielded a high proportion of patients maintained on immunosuppressive monotherapy (57%) without serious infectious- and no malignancy-related complications. The reported regimen yielded novel insights into both Campath-1H and sirolimus therapy in renal transplantation. Because of the higher incidence of early rejection, we recommend a modified strategy of immunosuppression including a brief course of a calcineurin inhibitor.     

HCG--A new kid on the block in prematurity prevention.

Human chorionic gonadotropin (HCG) is a molecule with multiple endocrine, paracrine, and immunoregulatory actions. Its importance for the enhancement of fertility, successful implantation, and survival of the conceptus in early gestation is recognized. However, studies conducted worldwide in recent years indicate that HCG may also play a significant role in maintaining pregnancy well after the first trimester. Emerging evidence suggests that different biomolecular and physiologic effects of HCG are concordantly directed toward inhibition of myometrial contractility to maintain pregnancy. These studies have prompted preliminary animal and human testing of HCG for the prevention of preterm birth. This article reviews the current knowledge as well as the future perspectives on HCG as a useful new tool in prematurity prevention.     

A case of unilateral opercular syndrome associated with a subcortical lesion

Summary A patient who developed a unilateral opercular syndrome following a cerebrovascular accident is described. Computed tomography showed that the lesion did not affect the opercular cortex, but involved deep white matter and the head of the caudate nucleus of the left hemisphere. Persistent hypophonia and transient aphasia were associated. Comparison with previous cases is discussed.     

Emergency treatment of papaverine priapism

We report a case of vasoactive-agent-induced priapism successfully treated in the emergency department with 10 mg of metaraminol injected into the corpora cavernosa.