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This pilot randomized controlled clinical trial of patients with ARDS was implemented to study the impact of inhaled nitric oxide (inhNO) on lung function, morbidity, and mortality. Thirty patients with ARDS were randomly allocated to usual care or usual care plus inhNO. The optimal dose of inhNO was determined to be between 0.5 and 40 parts-per-million daily. All therapeutic interventions were standardized. ARDS resulted mainly from sepsis (25 of the 30). During the first 24 h, the hypoxia score increased greatly in patients treated with inhNO +70.4 mm Hg (+59%) versus +14.2 mm Hg (+9.3%) for the control group (p = 0.02), venous admixture decreased from 25.7 to 15.2% in the inhNO group, and from only 19.4 to 14.9% in the control group (p = 0.05). After the first day of therapy no further beneficial effect of inhNO was detected. Forty percent of the patients treated with inhNO were alive and weaned from mechanical ventilation within 30 d after randomization compared with 33.3% in the control group (p = 0.83). The 30-d mortality rate was similar in the two groups; most deaths (11 of 17) were due to multiple organ dysfunction syndrome. This study shows that inhNO, in this population, may improve gas exchange but does not affect mortality.

While an increasing amount of evidence demonstrates the homeostatic functions of the cardiac oxytocin (OT) system, less is known about the role of this hormone in the injured heart. The current study examined the effect of OT infusion on cell apoptosis, expression of proliferating cell nuclear antigen (PCNA) and inflammation in the acute and subacute phases of myocardial infarction (MI). Prior MI male Sprague-Dawley rats were infused subcutaneously with OT 25 or 125 ng/(kg h) for 3 or 7 days. Saline-treated MI and sham-operated rats served as controls. Echocardiography and analysis of cardiac sections were used to disclose OT actions. Left ventricular fractional shortening, estimated to be 46.0 +/- 1.8% in sham controls, declined to 21.1 +/- 3.3% in vehicle-treated MI rats and was improved to 34.2 +/- 2.1 and to 30.9 +/- 2.5% after treatment with OT 25 and 125 ng/(kg h), respectively. OT infusion resulted in: (1) increase of cells expressing PCNA in the infarct zone, diminished cell apoptosis and fibrotic deposits in the remote myocardium; (2) suppression of inflammation by reduction of neutrophils, macrophages and T lymphocytes; (3) depression of the expression of proinflammatory cytokines tumor necrosis factor-alpha and interleukin-6 with promotion of transforming growth factor-beta. OT treatment reduced expression of atrial and brain natriuretic peptides in the infarcted ventricle, as well as the concentration of both peptides in the circulation. These results indicate that continuous OT delivery reduces inflammation and apoptosis in infarcted and remote myocardium, thus improving function in the injured heart.

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Objective This study evaluated subcutaneous injections of tetrodotoxin (TTX) for the treatment of moderate to severe, inadequately controlled cancer-related pain. Methods Eligible patients were randomized to receive TTX (30 μg) or placebo subcutaneously twice daily for four consecutive days. Efficacy was assessed using pain and composite endpoints (including pain and quality of life measures), and safety was evaluated using standard measures. Results 165 patients were enrolled at 19 sites in Canada, Australia, and New Zealand, with 149 patients in the primary analysis “intent-to-treat” population. The primary analysis supports a clinical benefit of TTX over placebo based on the pain endpoint alone with a clinically significant estimated effect size of 16.2% (p = 0.0460). The p value was nominally statistically significant after prespecified (Bonferroni Holm) adjustment for the two primary endpoints but not at the prespecified two-sided 5% level. The mean duration of analgesic response was 56.7 days (TTX) and 9.9 days (placebo). Most common adverse events were nausea, dizziness, and oral numbness or tingling and were generally mild to moderate and transient. Conclusions Although underpowered, this study demonstrates a clinically important analgesic signal. TTX may provide clinically meaningful analgesia for patients who have persistent moderate to severe cancer pain despite best analgesic care. This clinical study is registered with ClinicalTrials.gov (NCT00725114).

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Purpose: Although the analogy of nitric oxide (NO) to Endothelium-derived Relaxing Factor remains controversial, medical use of exogenous NO gas by inhalation has grown exponentially. This review presents the mechanisms of action of inhaled NO in pulmonary hypertension, hypoxaemia, inflammation and oE~iema, as well as its therapeutic and diagnostic indications wi~ emphasis on acute respiratory distress syndrome (ARDS) and toxicology, Source: Two medical databases (Current Contents, Medline) were searched for citations containing the abovementionned key words to December 1996. Moreover, many presentations in congresses such as 4th International Meeting of Biology of Nitric Oxide, 52nd and 53rd Annual Meeting of Canadian Ana~-thetists' Society or 10th Annual Meeting of European Association of Cardiothoradc Anaesthesiologists were used. Principal findings: Inhaled NO is now recognized as an invaluable tool in neonatal and paediatric critical care, and for heart/lung surgery. Other clinical applications in adults, such as chronic obstructive pulmonary disease and ARDS, require a cautious approach, The inhaled NO therapy is fairly inexpensive, but it would seem that it is not indicated for everybody with regards to the paradigm of its efficiency and potential toxicity. The recent discovery of its anti-inflammatory and extrapulmonary effects open new horizons for future applications. Conclusion: Clinical use of inhaled NO was mostly reported in case series, properly designed clinical trials must now be performed to establish its real therapeutic role. These trials would permit adequate selection of the cardiopulmonary disorders, and subsequently the patients that would maximally benefr from inhaled NO therapy.Objectif : M~me si la relation entre le monoxyde d'azote (NO) et I'EDRF (endothelium-derived relaxing factor) n'est pas 6tablie de fa~on absolue, rutilisation m~icale du NO exog~ne ,~ I'~t gazeux a cru de fa~on exponentielle. Ce survol de la litt&ature rappelle les m6canismes d'action du NO inhale dam rhypertension pulmonalre, rhypox~mie, I'inflammation et I'oed~me et jette un regard sur ses indications diagnostiques et ~rapeutiques principalement en rapport avec le syndrome de d(~tresse respirato/re de radulte (SDRA) et la toxicologie du NO. Sources : Deux bases de donn(~es (Current Contents, Medline) induant d~cembre 1996, ont ~ consult~s en faisant appel aux mots-d& mentionn& plus haut. En outre, on a n_avis~ les travaux prL, sent~ ~ des congrc~ comme le 4th International Meeting of Biolo~/ of Nitrous Oxide, les 52" et 53 e congr~s annuels de La Soci&~ canadienne des anestl~sistes et le I 0 ~ congr~s annuel de I'Assoc/at/on europ~nne des anestha_siolo~stes cardiothoraciques. Principales constatations : l'inhalation de NO est maintenant reconnue comme faisant pattie de l'arsenal th&apeutique n~natalogique, p~diatrique et chirurgical cardiopulmonaire. Chez les adultes, les autres indications comme la maladie pulmonalre obstructive chronique et le SDRA sont moins ~videntes. I'inhalation th6rapeutique de NO ne cof...

Chronic pain in patients with Alzheimer's disease or dementia is a complex issue in the medical field; these patients suffer from the common causes of chronic pain, especially in geriatric medicine. To ensure the correct type and level of given treatment, medical care should be taken to avoid the contribution of chronic pain and cognitive impairment in the elderly population. Acetylcholinesterase inhibitors (AChE-Is) have been proven as an efficient therapeutic resource for significant improvement in dementia of Alzheimer's disease and chronic pain due to the fact that cholinergic deficit is considered as an early finding in cognitive impairment and persisting pain. Some AChE-Is are investigated here in terms of treatment of dementia and chronic pain management. Neostigmine has been used as an adjunct analgesic in the postoperative period and in combination with other analgesic medications in an intrathecal approach. Rivastigmine has, over the past ten years, become the approved agent for the management of dementia of mild to moderate Alzheimer's disease and has gained approval for treating different types of non-Alzheimer's dementia. In this review, we will focus on the two types of AChE-Is (rivastigmine and neostigmine) in the development of their clinical use and their respective mechanisms of actions on improving cognitive function and managing chronic pain.