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Rationale: Autoimmunity is believed to play a role in idiopathic pulmonary arterial hypertension (IPAH). It is not clear whether this is causative or a bystander of disease and if it carries any prognostic or treatment significance. Objectives: To study autoimmunity in IPAH using a large cross-sectional cohort. Methods: Assessment of the circulating immune cell phenotype was undertaken using flow cytometry, and the profile of serum immunoglobulins was generated using a standardized multiplex array of 19 clinically validated autoantibodies in 473 cases and 946 control subjects. Additional glutathione S-transferase fusion array and ELISA data were used to identify a serum autoantibody to BMPR2 (bone morphogenetic protein receptor type 2). Clustering analyses and clinical correlations were used to determine associations between immunogenicity and clinical outcomes. Measurements and Main Results: Flow cytometric immune profiling demonstrates that IPAH is associated with an altered humoral immune response in addition to raised IgG3. Multiplexed autoantibodies were significantly raised in IPAH, and clustering demonstrated three distinct clusters: "high autoantibody," "low autoantibody," and a small "intermediate" cluster exhibiting high concentrations of ribonucleic protein complex. The high-autoantibody cluster had worse hemodynamics but improved survival. A small subset of patients demonstrated immunoglobulin reactivity to BMPR2. Conclusions: This study establishes aberrant immune regulation and presence of autoantibodies as key features in the profile of a significant proportion of patients with IPAH and is associated with clinical outcomes. [ABSTRACT FROM AUTHOR]

Exercise training as treatment has become well established in many cardiorespiratory conditions. This is also increasingly the case in pulmonary arterial hypertension, where several studies have demonstrated improvements in symptoms, exercise capacity and quality of life. There remains, however, much potential for development. Current research is focused on clarifying the mechanism of benefit in pulmonary hypertension and exploring strategies for both optimizing the treatment effect and widening access to this intervention. [ABSTRACT FROM AUTHOR]

Daily physical activity is reduced in precapillary pulmonary hypertension (PH), but the underlying mechanisms are inadequately explored. We sought to investigate clinical and physiological relations of daily physical activity and profile differences between less and more active patients with precapillary PH. A prospective, cross-sectional study of 20 patients with precapillary PH who undertook 1) a comprehensive clinical assessment, 2) a preliminary treadmill test, 3) 7-day monitoring of daily walking intensity with triaxial accelerometry, and 4) a personalized treadmill test corresponding to the individual patient mean daily walking intensity with real-time physiological measurements. Significant clinical correlations with individual patient mean walking intensity [1.71 ± 0.27 (SD) m/s²] were observed for log-transformed N-terminal probrain natriuretic peptide (log NT-proBNP; r = −0.75, P = <.001), age (r = −0.70, P = 0.001), transfer factor for carbon monoxide %predicted (r = 0.51, P = 0.022), and 6-min walk distance (r = 0.50, P = 0.026). Significant physiological correlations were obtained for heart rate reserve (r = 0.68, P = 0.001), quadriceps tissue oxygenation index (Q-StO2; r = 0.58, P = 0.008), change in Q-StO2 from rest (r = 0.60, P = 0.006), and ventilatory equivalent for oxygen uptake (r = −0.56, P = 0.013). Stepwise multiple regression analyses retained log NT-proBNP (R² = 0.55), heart rate reserve (R² = 0.44), and Q-StO2 (R² = 0.13) accounting for a significant variance in individual walking intensity. Less active patients had greater physical activity-induced cardiopulmonary impairment, worse quadriceps oxygenation profile, and compromised health-related quality of life compared with more active patients. These preliminary findings suggest a significant relation between right ventricular and peripheral muscle oxygenation status and reduced daily physical activity in precapillary PH. Further research is warranted to unravel the physiological determinants, establish clinical predictors, and identify beneficial interventions. NEW & NOTEWORTHY Daily physical activity holds promise to be a meaningful, patient-related outcome measure in pulmonary hypertension. In this study, novel findings in a representative sample of patients with precapillary pulmonary hypertension link reduced daily walking activity, as measured by triaxial accelerometry, with compromised right ventricular and pulmonary vascular status, peripheral muscle oxygenation, and health-related quality of life, providing a preliminary insight into the physiological mechanisms and clinical predictors of daily physical activity in precapillary pulmonary hypertension. [ABSTRACT FROM AUTHOR]

AbstractPoisoning by organophosphorus pesticides results from inhibition of acetylcholinesterase. The outcome and optimum treatment depend on properties which differ among individual compounds. Treatment consists of supportive care, especially aimed at respiratory complications, and specific antidotal treatment. Treatment with atropine and diazepam is well established, but there is controversy concerning treatment with oximes capable of forcing reactivation of inhibited acetylcholinesterase. Although all parameters have not been fully established, initial bolus doses followed by continuous intravenous infusion to achieve plasma concentrations of 85–170 μmol/L of pralidoxime or 10–20 μmol/L of obidoxime have been recommended. These are well above concentrations that were likely to have been achieved by many of the ineffective regimens reported in the literature. Several independent reasons for failure of attempts at oxime therapy are discussed in this overview. If nothing else, it is likely that maintenance of adequate levels of oxime will shorten the period that a patient requires assisted ventilation with its associated risks. Topics for further laboratory and clinical research are listed. It is important to seek further understanding and the introduction of better practice because death rates from this type of poisoning remain significant. [ABSTRACT FROM AUTHOR]

Can Soman Cause Delayed Neuropathy? JOHNSON, M. K., WILLEMS, J. L., DE BISSCHOP, H. C., READ, D. J., AND BENSCHOP, H. P. (1985). . 5, S180–S181. [ABSTRACT FROM PUBLISHER]