El tratamiento postnatal con melatonina modula la expresión de agentes prostanoides en pulmón de neonatos de oveja con hipertensión pulmonar / Melatonin modulates the expression of pulmonary prostanoids

Background: Living above 2,500 meters in hypobaric conditions induces pulmonary arterial hypertension of the neonate (PAHN), a syndrome whose main features are: pathological remodeling of the pulmonary vessels, abnormal vascular reactivity and increased oxidative stress. Melatonin could have pulmonary antioxidant, anti-remodeling and vasodilating properties for this condition. Aim: To determine the effect of melatonin at the transcript level of prostanoid pathways in the lung of neonatal lambs gestated and born under hypobaric hypoxia. Material and Methods: Vehicle (1.4% of ethanol, n = 6) or melatonin (1 mg * kg1, n = 5) were administered from the postnatal day 4 to 21 to lambs gestated and born at 3,600 meters above sea level. After one week of treatment completion, lung tissue was obtained, the transcript and protein levels of prostanoid synthases and receptors were assessed by RT-PCR and Western Blot. Results: Melatonin induced the expression of prostacyclin synthase transcript and increased protein expression of the prostacyclin receptor. In addition, the treatment decreased the expression of transcript and protein of cyclooxygenase-2, without changes in the expression of the prostanoid vasoconstrictor (thromboxane) pathway. Conclusions: Postnatal treatment with melatonin increases the expression of the prostacyclin-vasodilator pathway without changing the vasoconstrictor thromboxane pathway. Further, the decreased COX-2 induced by melatonin could be an index of lesser oxidative stress and inflammation in the lung.

Area Triangulation Method for Automatic Detection of Venous Emptying Maneuvers

Abstract Venous refilling time (VRT) can diagnose the presence of venous diseases in lower limbs. In order to calculate VRT it is necessary to determine the End of the Emptying Maneuvers (EEM). First Derivative Method (FDM) can be employed for automatic detection of the EEM, but its sensitivity to artifacts and noise can degrade its performance. In contrast, studies report that Area Triangulation Method (ATM) evinces effectiveness in biosignals point finding. This work compares the exactness of ATM and FDM for recognition of the EEM. The annotations made by 3 trained human observers on 37 photoplethysmography records were used as a reference. Bland-Altman graphics supported the analysis of agreement among human observers and methods, which was complemented with Analysis of variance and Multiple Comparisons statistical tests. Results showed that ATM is more accurate than FDM for automatic detection of the EEM, with statistically significant differences (p-value < 0.01).

Health Related Quality of Life, Disability, and Pain in Alpha Mannosidosis: Long-Term Data of Enzyme Replacement Therapy With Velmanase Alfa (Human Recombinant Alpha Mannosidase)

Abstract Alpha-mannosidosis, a rare lysosomal storage disorder caused by deficiency of the lysosomal enzyme alpha-mannosidase, results in accumulation of mannose-rich glycoproteins in the tissues and sequelae leading to intellectual disability, ataxia, impaired hearing and speech, recurrent infections, skeletal abnormalities, muscular pain, and weakness. This study aimed to investigate disability, pain, and overall health using the Childhood Health Assessment Questionnaire (CHAQ) and the EuroQol 5 Dimension-5 Level Questionnaire (EQ-5D-5L) in patients with alpha-mannosidosis participating in rhLAMAN-10, a phase III open-label, clinical trial of velmanase alfa, a recombinanthumanlysosomalalpha-mannosidase. Long-termprognosesformost patients withuntreatedalpha-mannosidosisarepoor due to progressive neuromuscular, skeletal, and intellectual deterioration, leading to increased dependence in mobility and activities of daily living and increased caregiver and health-care burden. Long-term CHAQ and EQ-5D-5L data highlight improvement trends in health-related quality of life and a reduction in disability and pain in patients receiving up to 48 months of velmanase alfa treatment.

Long-Term Galsulfase Treatment Associated With Improved Survival of Patients With Mucopolysaccharidosis VI (Maroteaux-Lamy Syndrome): 15-Year Follow-Up From the Survey Study

Abstract Mucopolysaccharidosis VI (MPS VI) is a progressive lysosomal storage disorder with multiorgan and multisystemic pathology. Currently, galsulfase enzyme replacement therapy (ERT) is the only approved treatment for MPS VI. A crosssectional survey study of 121 patients with MPS VI conducted in 2001 to 2002 and a 10-year follow-up study of the same patients (resurvey study; ClinicalTrials.gov NCT01387854) found that those receiving galsulfase at any time showed physical improvements and a lower mortality rate (16.5%) versus treatment-naive patients (50%). After *15 years, galsulfasetreated patients (n » 104) continue to have a survival advantage over treatment-naive patients (n » 14), as demonstrated by a 24% versus 57% mortality rate. This survival advantage is further supported by data from the commercial use of galsulfase (2005-2016), which show a 5-year mortality rate for galsulfase-treated patients of 12.5%. Together, these findings suggest that galsulfase ERT can increase life expectancies for patients with MPS VI over a period of at least 15 years.

Impact of Elosulfase Alfa on Pain in Patients with Morquio A Syndrome over 52 Weeks: MOR-008: A Randomized, Double-Blind, Pilot Study

Abstract Patients with mucopolysaccharidosis (MPS), and Morquio A syndrome (MPS IVA) in particular, often report substantial pain burden. MOR-008 was a randomized, double-blind, pilot study assessing the safety and efficacy, including impact on patient-reported pain, of 52 weeks of treatment with elosulfase alfa (at a dose of 2.0 or 4.0 mg/kg/week) in patients with Morquio A syndrome (?7 years old). Assessment of pain at baseline revealed that patients (N = 25) had a mean number of pain locations of 5.7, mean pain intensity score of 4.6 (indicative of medium pain), and a mean number of selected pain descriptors of 7.4 words. Treatment with elosulfase alfa improved subjective pain score (reduced to 3.2), pain locations (reduced by a mean of 1 location), and pain descriptor words (reduced to 4.9 words) over 1 year (52 weeks), suggesting that elosulfase alfa can reduce pain in some patients with Morquio A.

Obstructive Sleep Apnea in MPS: A Systematic Review of Pretreatment and Posttreatment Prevalence and Severity

Abstract The mucopolysaccharidoses (MPSs) are a group of inherited, metabolic disorders characterized by progressive multisystem accumulation of partially degraded glycosaminoglycans. This manifests with multilevel airway obstruction, presenting with obstructive sleep apnea (OSA). We systematically reviewed the literature to determine the severity and prevalence of OSA in MPS based on polysomnography analysis. Fifteen studies with 294 participants met the inclusion criteria for review. The pretreatment prevalence of OSA in MPS was 81% with a mean apnea-hypopnea index (AHI) of 10.4. Patients with MPS I are most significantly affected, with 75% suffering with moderate to severe OSA (mean AHI, 16.6). Enzyme replacement therapy (ERT) results in an almost significant reduction in OSA in MPS I (P = .06), while adenotonsillar surgery significantly improves AHI (P = .002). Obstructive sleep apnea least affects MPS III. There is a lack of long-term post-ERT and hematopoietic stem cell transplant data relating to OSA outcomes in this population, with further prospective studies required to determine the ongoing response to treatment.

Comparison of efficacy of atropine versus atropine with pralidoxime in organophosphorus poisoning.

Background: Comparison of the efficacy of atropine alone against atropine with pralidoxime in the treatment of organophosphorus (OP) poisoning. Methods: Forty two patients between the age group of 18 to 65 years, treated for OP poisoning and matched for baseline characteristics, were included in two groupsbased on treatment received as “Atropine only” or “Atropine plus pralidoxime(PAM)”.Main outcomes of the study were ICU stay, total hospital stay and mortality. ICU and hospital stay were compared using ‘t’ test while mortality was compared using Fisher’s exact test. Results: Total hospital stay was not significantly different between the treatment groups (95% CI of difference: -4.227, 0.784). Length of stay was also not significantly different between patients who received atropine plus PAM within 6 hours of consumption of poison and those who received 6 hours later (95% CI of difference: -4.154, 0.954; p value: 0.2). Conclusion: Our data supports the use of only atropine over atropine plus PAM in patients with OP poisoning on account of no significant difference /reduction of hospital/ICU stay and mortality in the latter group. However, a study with a larger sample needs to be conducted, to be able to draw a definitive conclusion.

Altered DNA repair, oxidative stress and antioxidant status in coronary artery disease.

Coronary artery disease (CAD) is a multifactorial disease caused by the interplay of environmental risk factors with multiple predisposing genes. The present study was undertaken to evaluate the role of DNA repair efficiency and oxidative stress and antioxidant status in CAD patients. Malonaldehyde (MDA), which is an indicator of oxidative stress, and mean break per cell (b/c) values, which is an indicator of decreased DNA repair efficiency, were found to be significantly increased in patients compared to normal controls (P<0.05) whereas ascorbic acid and GSH were found to be lower among patients than the control group. It has been found that elevated oxidative stress decreased antioxidant level and decreased DNA repair efficiency can contribute to the development of CAD. This study also showed that high MDA, low ascorbic acid and GSH were significantly associated with high b/c value.

Impact of Praziquantel Mass Drug Administration Campaign on Prevalence and Intensity of Schistosoma haemamtobium Check for this Species in other Resources among Schoolchildren in Bahi District; Tanzania

As part of the Tanzania National Schistosomiasis Control Programme; Bahi district in central Tanzania; received two annual rounds of praziquantel mass drug administration (MDA) to control urinary schistosomiasis in schoolchildren. The objectives of this study were to assess the impact of the two rounds of MDA on prevalence and intensity of Schistosoma haemamtobium and the impact of MDA campaigns on knowledge of urinary schistosomiasis; safe water use and contact with potentially unsafe water bodies. A quantitative crosssectional study was carried out among schoolchildren in March and April; 2013. A structured questionnaire was used to collect information on MDA uptake; knowledge of schistosomiasis; sources of water for domestic and other uses. Urine samples were collected from each pupil to examine prevalence and intensity of S. haematobium. Transmission of schistosomiasis was assessed by sampling Bulinus spp snails for cercarial shedding. Uptake of MDA was 39.5 in 2011 and 43.6 in 2012. Prevalence of S. haematobium significantly dropped by 50.0 from 26 in 2011 to 15 in 2012 (p = 0.000). Prevalence of S. haematobium was significantly low in MDA participating (3.1) than non-participating (28.5) schoolchildren (p = 0.000). MDA campaigns had significant impact on knowledge of the disease (p = 0.02) and borderline impact on safe water use (p = 0.04) but had no impact on avoidance of contact with unsafe water bodies (p = 0.06). Bulinus spp. snails were found shedding schistosome cercariae indicating environmental contamination with viable S. haematobium eggs. In conclusion; though MDA significantly reduced prevalence of S. haematobium; uptake was below 50.0 and below the World Health Assembly resolution 54.19 target of 75.0 for 2010. Non-participation in MDA was the likely source of S. haematobium eggs in the environment hence the observed 15.0 prevalence of S. haematobium infection; and cercarial shedding Bulinus spp. snails indicating continuity of transmission hence the need for further health promotion campaigns

VIPoma of pancreas in a child.

An eleven-year-old girl had massive watery diarrhea. She was found to have pancreatic VIPoma. It responded favorably to surgical resection of the tumor. There was no tumor recurrence at 18 months of follow-up.

Inhibición beta-adrenérgica en la hipertensión arterial / Beta adrenergic inhibition in arterial hypertension

El tratamiento de la Hipertensión arterial es un tema de interés para el médico, ya que es la enfermedad cardiovascular de mayor prevalencia en el mundo occidental. El manejo adecuado de esta forma de hipertensión, en paciente en actividad laboral normal, sigue siendo un problema no enteramento resuelto. Pero por otra parte, el tratamiento de la hipertensión arterial implica el control de uno de los factores de riesgo de enfermedade vasculares mayor como el infarto agudo de miocardio o las enfermedades cerebro-vasculares. Durante las Jornadas Rioplatenses de Cardiología que tuvieron lugar en Montevideo en noviembre de 1984 se llevó a cabo un Simposio de hipertensión arterial cuyo objetivo fue la consideración de algunos problemas relacionados con las formas más frecuentes de hipertensión: la hipertensión de modo moderado, generalmente asintomática

Síndrome de urticaria, vasculitis e hipocomplementemia: presentación de un caso / Urticaria syndrome, vasculitis and hypocomplementemia: report of a case

Se presenta el caso de un niño urticaria crónica y vasculitis leucocitoclástica, quien tuvo involucro sistémico múltiple manifestado por artralgias, mialgias, glomerulonefritis membranosa y edema laríngeo; el perfil inmunológico para lupus eritematoso sistémico fue negativo. Se observó además hipocomplementemia persistente y depósitos de C'3 e inmunoglobulinas en piel y riñon, lo cual sugiere activación de la vía clásica del complemento hemolítico. Este síndrome ha sido descrito en pacientes adultos y parece corresponder a una enfermedad de la colágena distinta a las conocidas

Insuficiencia renal aguda por malaria / Acute renal failure due to malaria

Em nosso pais, a malaria apresenta elevada incidencia, principalmente nas regioes Norte e Centro-Oeste.O objetivo deste trabalho e relatar a observacao de 20 em 1.272 casos (1.6%) de malaria que apresentaram insuficiencia renal aguda (IRA) necessitando tratamento por dialise peritoneal (DP), no Hospital de Vila Permanente da Usina Hidreletrica de Tucurui (PA), na Amazonia brasileira. Dos 20 pacientes submetidos a DP, 6 (3%) evoluiram para obito, frequencia menor do que a esperada para a IRA de uma maneira geral quando, em media, 50% apresentam mortalidade. Nao houve diferenca significativa da creatinina, ureia, bilirrubinas, transaminases, hemoglobina, eletrolitos ou da contagem de plaquetas entre os pacientes que evoluiram para a alta hospitalar ou para obito. Entretanto, a intensidade da infestacao parasitaria, a leucocitose e a presenca de acidose metabolica sao parametros desfavoraveis na evolucao destes pacientes Os autores concluem que a IRA, associada a malaria, tem menor mortalidade que a IRA em geral, e que a equipe medica deve estar preparada para propiciar atendimento especializado, em particular nas regioes de maior incidencia desta patologia