Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to evaluate the hemodynamic effects of INPV, eight patients with COPD (FEV1/FVC, 54 +/- 6 percent; mean +/- SD), respiratory failure (PaO2, 52 +/- 6 mm Hg; PaCO2, 56 +/- 4 mm Hg), and clinical signs of inspiratory muscle fatigue underwent right cardiac catheterization while performing 20 minutes of INPV by a cuirass ventilator at a pressure (-20 to -40 cm H2O) able to reduce the diaphragmatic electromyographic activity. Patients showed a mild basal pulmonary artery hypertension. During INPV, no changes in the mean values of HR (from 79 +/- 20 to 80 +/- 18 beats per minute), systolic BP (141 +/- 19 to 139 +/- 16 mm Hg), CO (5.2 +/- 0.8 to 5.1 +/- 1.3 L/min), mean PAP (23.8 +/- 3.8 to 23.9 +/- 4.4 mm Hg), RAP (4.3 +/- 2.6 to 5.5 +/- 2.5 mm Hg), PWP (10.3 +/- 4.5 to 9.4 +/- 2.9 mm Hg), TPR (369 +/- 76 to 392 +/- 124 dynes.s.cm-5), and PVR (199 +/- 51 to 233 +/- 94 dynes.s.cm-5) were observed. Direct systemic BP monitoring could be performed in six patients. During INPV, three patients showed "pulsus paradoxus," as assessed by an inspiratory fall in systolic BP of 11, 13, and 20 mm Hg, respectively. We conclude that INPV by cuirass ventilator does not induce adverse hemodynamic effects in patients with COPD who have pulmonary artery hypertension.
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PMID:Hemodynamic effects of negative-pressure ventilation in patients with COPD. 218 97

Haemodynamic studies at rest and during exercise together with radionuclide ventriculography, pulmonary function and clinical well-being assessment were evaluated in ten patients with COPD and secondary pulmonary hypertension (mean PAP 25 mm Hg), before and after 6 months therapy with pirbuterol 20 mg thrice daily. Despite the continued pharmacological action of pirbuterol on the heart and systemic circulation during peak pirbuterol levels at 6 months, no significant effect on the pulmonary circulation was observed. Seven patients reported an improvement in the level of fatigue, the partial pressure of carbon dioxide fell significantly (6.5 +/- 0.9 to 6.1 +/- 0.9 kPa: P less than 0.01) and there was a slight bronchodilator effect [forced expiratory volume in 1s (FEV1) 0.60 +/- 0.18 to 0.71 +/- 0.2 1s-1: P less than 0.02] after 6 months. The drug was generally well tolerated but three patients with pre-existing biliary tract disease developed obstructive jaundice.
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PMID:Long term haemodynamic, pulmonary function and symptomatic effects of pirbuterol in COPD. 251 10

Sipuleucel-T (Provenge) (Sip-T) is first -in class as a therapeutic autologous vaccine approved for the treatment of men with asymptomatic or minimally symptomatic castrate-resistant metastatic prostate cancer. This product is the culmination of decades of basic immunological and prostate cancer investigations and 13 y of clinical trial investigations. Sip-T represents a paradigm shift in cancer therapeutics and represents the first approved autologous therapeutic cancer vaccine, which has demonstrated a survival benefit. The potential benefit of this product is the excellent risk to benefit ratio, which will allow for the combination of this approach with other more toxic therapies. The favorable risk to benefit will also afford the opportunity for trials investigating this product earlier in the disease state and in combination with local therapies. The ability to target more localized or lower volume disease will maximize the therapeutic benefit over a longer period of time. The novelty of the platform of this approach could be used to treat any cancer with a tumor-specific cell surface target. The main product of Sip-T is the re-infusion of a patient's antigen presenting cells from leukapheresis after ex-vivo exposure to a chimeric protein of human GM-CSF and PAP. In metastatic CRPC patients three infusions of these activated cells over a month lead to statistically significant 4.1 mo increase in median survival and a 22.5% reduction in risk of death. The main side effect from this re-infusion of activated immune cells is a "flu-like" syndrome that includes chills, fatigue, fevers, back pain, nausea, joints aches and headaches in decreasing order of frequency. Immune monitoring during the clinical trials also demonstrated a specific cellular and antibody immune response, suggesting the proposed mechanism of adoptive immunotherapy to PAP was behind this survival benefit. This product also serves as a proof of principle for targeted immunotherapy for others cancers with defined cell surface markers. In summary, the approval of Sip-T based on a survival benefit and very tolerable safety profile will 1) enhance our ability to care for men with advanced prostate cancer, 2) allow for further investigations of this approach in combination with others therapies with different mechanisms of action and non-overlapping toxicities, and 3) allow further investigations earlier in the course of the disease.
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PMID:Sipuleucel-T (Provenge) autologous vaccine approved for treatment of men with asymptomatic or minimally symptomatic castrate-resistant metastatic prostate cancer. 2283 54

Exercise stresses the pulmonary circulation through increases in cardiac output (.Q) and left atrial pressure. Invasive as well as noninvasive studies in healthy volunteers show that the slope of mean pulmonary artery pressure (mPAP)-flow relationships ranges from 0.5 to 3 mm Hg.min.L(-1). The upper limit of normal mPAP at exercise thus approximates 30 mm Hg at a .Q of less than 10 L.min(-1) or a total pulmonary vascular resistance at exercise of less than 3 Wood units. Left atrial pressure increases at exercise with an average upstream transmission to PAP in a close to one-for-one mm Hg fashion. Multipoint PAP-flow relationships are usually described by a linear approximation, but present with a slight curvilinearity, which is explained by resistive vessel distensibility. When mPAP is expressed as a function of oxygen uptake or workload, plateau patterns may be observed in patients with systolic heart failure who cannot further increase .Q at the highest levels of exercise. Exercise has to be dynamic to avoid the increase in systemic vascular resistance and abrupt changes in intrathoracic pressure that occur with resistive exercise and can lead to unpredictable effects on the pulmonary circulation. Postexercise measurements are unreliable because of the rapid return of pulmonary vascular pressures and flows to the baseline resting state. Recent studies suggest that exercise-induced increase in PAP to a mean higher than 30 mm Hg may be associated with dyspnea-fatigue symptomatology.
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PMID:Exercise-induced pulmonary hypertension: physiological basis and methodological concerns. 2334 76