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.     

Retrospective review of pemetrexed with or without platinum in malignant mesothelioma: The Australian 'Special Access Scheme' experience

Background: Pemetrexed and cisplatin have recently been shown to significantly improve survival compared with cisplatin alone. However, there are only limited data reflecting teaching hospital experience outside a clinical trial. Pemetrexed has only been available in Australia on a restricted basis since 2002. We reviewed our experience of patients treated on the Australian ‘Special Access Scheme’ at three major thoracic oncology units. Methods: Charts were reviewed for all patients enrolled on the scheme. Data was extracted on age, World Health Organization (WHO) performance status, histology, prior therapy, time from diagnosis to starting pemetrexed, chemotherapy (pemetrexed alone or with a platinum), cycle number, response rate, actuarial progression‐free and overall survival. Doses were cisplatin 75 mg/m² or carboplatin AUC = 5 and pemetrexed 500 mg/m² every 21 days. Results: 52 patients (32 male and 20 female) were reviewed. Median age was 58 years and 88% were WHO 0–1. Histology included 54% epithelial, 17% biphasic (epithelial and sarcomatoid) and 21% undefined. The median time from diagnosis to administration of pemetrexed was 145 days. Sixty‐five percent had minimal surgical intervention with video assisted thoracoscopy, pleurodesis and biopsy, while 19% had received prior palliative radiation. Seventy‐one percent were chemotherapy naïve, the remaining 29% having received previous platinum and/or gemcitabine regimens. Twenty‐three percent had pemetrexed alone, 35% in combination with carboplatin and 42% with cisplatin. The median number of cycles was 4 (range 1–13). The response rate was 33%. No toxicity was observed in 20% grade 3–4 toxicity in 10% (majority nausea/vomiting). The median progression‐free and overall survival times from starting pemetrexed were 184 days and 298 days, respectively. Conclusions: Pemetrexed‐based regimens are safe and effective in a community setting in malignant mesothelioma.     

Magnetic Resonance Cisternography in the Diagnosis of Delayed Iatrogenic Cerebrospinal Fistula: A Case Report

A 52–year–old woman presented with a clinical picture consistent with bacterial meningitis 3 years after functional endoscopic sinus surgery. Diagnosis of a cerebrospinal fluid (CSF) fistula was made clinically, and the site of the fistula was confirmed using magnetic resonance cisternography. The utilization of this technique in the diagnosis of CSF disorders is gaining popularity. Its usefulness in the context of other imaging modalities is discussed.     

Tube feeding in mechanically ventilated critically ill patients: a prospective clinical audit.

BACKGROUND: When and whether early enteral nutrition (EN) benefits critically ill patients is debatable. This prospective clinical audit aimed to evaluate the feasibility of an early EN protocol and to identify factors that may hinder EN delivery in critically ill patients. METHODS: Thirty-six medical patients with severe respiratory failure under invasive ventilation and scheduled to receive early EN, with a length of ICU stay >72 hours, were included. As asserted by the Society of Critical Care Medicine, 8% of patients were priority 1, 72% priority 2, and 20% priority 3 for intensive therapeutic and vital support interventions. RESULTS: Overall, because of gastrointestinal complications, only 39% of the prescribed EN was administered; only 8 (22%) patients did tolerate EN within the first 48 hours after admission and did achieve their minimum nutritional requirements. The most frequent complication (78%) was high volume of gastric residuals followed by abdominal distention (61%), both associated with hemodynamic instability (HI). Gastrointestinal dysfunction was associated with high Acute Physiologic and Chronic Health Evaluation II score (p = .01), total calorie intake (p = .02), total carbohydrate intake (p = .02), HI (p = .03), malnutrition (p = .04), volume of IV saline (p = .04), and concurrent vasoactive drug administration (p = .05). CONCLUSIONS: This audit in extremely severe intensive care patients identified several factors that impair gastrointestinal function and preclude EN at any stage, namely early EN. Nutrition management must take into account concurrent therapies, given their potential interference with nutrition and organ function.