Background Our understanding of the natural history of idiopathic Parkinson's disease (PD) remains limited. In the era of potential disease modifying therapies, there is an urgent need for studies assessing the natural evolution of treated PD from onset so that relevant outcome measures can be identified for clinical trials. No previous studies have charted progression in unselected patients followed from the point of diagnosis. Methods A representative cohort of 132 PD patients was followed from diagnosis for up to 7.9 years (mean 5.2 years). Comprehensive clinical and neuropsychological evaluations were performed every 18 months. Disease progression was evaluated using well validated clinical measures (motor progression and development of dyskinesia on the Unified PD Rating Scale and HoehneYahr scale, dementia onset according to DSM-IV criteria). Multi-level linear modelling was used to chart the nature and rate of progression in parkinsonian symptoms and signs over time. The prognostic importance of baseline demogr'aphic, clinical and genetic variables was evaluated using survival analysis.Results Axial (gait and postural) symptoms evolve more rapidly than other motor features of PD and appear to be the best index of disease progression. Conversely, conventional outcome measures are relatively insensitive to change over time. Earlier onset of postural instability (HoehneYahr stage 3) is strongly associated with increased age at disease onset and has a significant impact on quality of life. Conclusions Dementia risk is associated with increased age, impaired baseline semantic fluency and the MAPT H1/H1 genotype. The efficacy of disease modifying therapies may be more meaningfully assessed in terms of their effects in delaying the major milestones of PD, such as postural instability and dementia, since it is these that have the greatest impact on patients.
From measurements of airway and esophageal pressures and flow, we calculated the elastance and resistance of the total respiratory system (Ers and Rrs), chest wall (Ecw and Rcw), and lungs (EL and RL) in 11 anesthetized-paralyzed patients immediately before cardiac surgery with cardiopulmonary bypass and immediately after chest closure at the end of surgery. Measurements were made during mechanical ventilation in the frequency and tidal volume ranges of normal breathing. Before surgery, frequency and tidal volume dependences of the elastances and resistances were similar to those previously measured in awake seated subjects (Am. Rev. Respir. Dis. 145: 110-113, 1992). After surgery, Ers and Rrs increased as a result of increases in EL and RL (P < 0.05), whereas Ecw and Rcw did not change (P > 0.05). EL and RL exhibited nonlinearities (i.e., decreases with increasing tidal volume) that were not seen before surgery, and RL showed a greater dependence on frequency than before surgery. The changes in RL or EL after surgery were not correlated with the duration of surgery or cardiopulmonary bypass time (P > 0.05). We conclude that 1) frequency and tidal volume dependences of respiratory system properties are not affected by anesthesia, paralysis, and the supine posture, 2) open-chest surgery with cardiopulmonary bypass does not affect the mechanical properties of the chest, and 3) cardiac surgery involving cardiopulmonary bypass causes changes in the mechanical behavior of the lung that are generally consistent with those caused by pulmonary edema induced by oleic acid (J. Appl. Physiol. 73: 1040-1046, 1992) and decreases in lung volume.
Endobronchial insufflation of oxygen offers possible advantages over conventional ventilation modes in some clinical situations in which nonmovement of the chest may be desirable; however, endobronchial insufflation of oxygen has yet to be used during thoracic surgery in humans. Furthermore, the physiologic mechanisms underlying gas exchange during endobronchial insufflation of oxygen are unclear. This study assessed endobronchial insufflation of oxygen at 45 L/min in 11 patients with an open chest during internal mammary artery harvest. Cardiorespiratory function was measured at baseline during conventional mechanical ventilation and at 5-min intervals during the study period of 20-30 min. In all patients, clinically acceptable gas exchange was achieved, although PaCO2 increased from 32 +/- 3.2 to 44 +/- 7.5 mm Hg (mean +/- SD) at 5 min, but thereafter was unchanged (P greater than 0.1). Cardiac output, vascular pressures, and heart rate were unchanged, although pHa decreased. Surgical access for internal mammary artery harvesting was improved. No mucosal damage or complications occurred. During endobronchial insufflation of oxygen, efficacy of gas exchange and body weight were not correlated, but both subject height and age were correlated with high PaO2 and low PaCO2. We conclude that (a) endobronchial insufflation of oxygen can be used in patients with an open chest; (b) the efficacy of endobronchial insufflation of oxygen is probably improved by increased lung size and by collateral ventilation; and (c) cardiogenic gas mixing contributes little to gas exchange during endobronchial insufflation of oxygen.
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