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Background: The pressure-time product (PTP) is often used to compare conditions with different breathing patterns. Being the pressure-time product calculated with pressures changes over a minute, mechanical load and inspiration time per minute should be its main determinants. The aim of this study was to investigate if the method of PTP computation is affected by the breathing pattern when mechanical load and inspiratory time per minute are constant. Methods: Respiratory mechanics and the PTP developed by the ventilator were calculated in 10 mechanically ventilated patients at three different respiratory rate/tidal volume combinations, provided that minute ventilation and inspiratory time per minute were constant. Results: The static elastance did not change at different tidal volumes. Despite the constant elastic load over a minute, the elastic PTP showed an increment greater than 200% from the higher to the lower respiratory rate, responsible for approximately 80% of the whole PTP increment. On the contrary a ‘corrected’ elastic PTP (calculated using the square root of the elastic pressure-time area), the elastic double product of the respiratory system and the mean elastic pressure per minute, did not significantly change. Conclusions: Changes in breathing pattern markedly affected the PTP independently by the mechanical load and the inspiratory time per minute. In these conditions it could not correctly estimate the metabolic cost of breathing. The use of a ‘corrected’ PTP, the mean inspiratory pressure per minute or the double product of the respiratory system, could overcome this limitation.

Background: Results of a clinical trial recently completed in the United States indicate that administration of tamoxifen (20 mg/day) to women at risk can reduce breast cancer incidence by approximately 50% but is associated with an increased risk of developing endometrial cancer and venous thromboembolic events. Since these adverse effects may be dose related, we investigated the effect of tamoxifen on several biomarkers when the drug was given at doses lower than those currently in use. Methods: In two sequential experiments, 127 healthy hysterectomized women aged 35-70 years were randomly assigned to one of the following four treatment arms: placebo (n = 31) or tamoxifen at 20 mg/day (n = 30) (first experiment); or tamoxifen at 10 mg/day (n = 34) or tamoxifen at 10 mg/ alternate days (n = 32) (second experiment). Baseline and 2-month measurements of the following parameters were compared: 1) total cholesterol (primary end point) and other surrogate markers of cardiovascular disease, e.g., low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, and lipoprotein(a); 2) blood cell count; 3) fibrinogen; 4) antithrombin III; 5) osteocalcin; and, 6) in a subgroup of 103 women, insulin-like growth factor-I (IGF-I), a possible surrogate marker for breast cancer. Results : After adjustment for the baseline values, there were reductions in circulating levels of total cholesterol and IGF-I of the same magnitude in all three tamoxifen treatment arms. A similar pattern was observed for most of the other parameters. In the placebo arm, fibrinogen level, which showed a decrease, was the only parameter exhibiting change. Conclusions: Up to a 75% reduction in the conventional dose of tamoxifen (i.e., 20 mg/day) does not affect the activity of the drug on a large number of biomarkers, most of which are surrogate markers of cardiovascular disease. This study was hypothesis generating, and larger studies are warranted to assess the efficacy of tamoxifen at low doses.

To determine the activity of combination hormonal therapy for platinum-resistant ovarian carcinoma, we treated 20 patients with leuprolide acetate 7.5 mg intramuscularly once a month and tamoxifen 20 mg orally twice a day. Among the 17 evaluable patients, two patients (12%; 95% CI: 0–27) had a partial response, each lasting 7 months. An additional five patients (29%; 95% CI: 8–51) experienced disease stabilization with a median duration of 5 months. This response rate is not significantly different from previously published studies using either leuprolide acetate or tamoxifen alone. The median survival duration was 14.4 months and this was not significantly different from that of our previous study with high-dose Taxol (P = 0.0668). The treatment was well-tolerated, with minimal toxicity. Combination hormone therapy with leuprolide acetate and tamoxifen does not result in increased activity compared with either drug used alone for platinum-refractory ovarian carcinoma. However, hormonal therapy should remain an important consideration for this disease since it has documented activity with minimal associated toxicity.

Background: The power of breathing (PoB) is used to estimate the mechanical workload of the respiratory system. Aim of this study was to investigate the effect of different tidal volume-respiratory rate combinations on the PoB when the elastic load is constant. In order to assure strict control of the experimental conditions, the PoB was calculated on an airway pressure-volume curve in mechanically ventilated patients. Methods: Ten patients received three different tidal volume-respiratory rate combinations while minute ventilation was constant. Respiratory mechanics, PoB and its elastic and resistive components were calculated. Alternative methods to estimate the elastic workload were assessed: elastic work of breathing per litre per minute, elastic workload index (the square root of elastic work of breathing multiplied by respiratory rate) and elastic double product of the respiratory system (the elastic pressure multiplied by respiratory rate). Results: Despite constant elastance and minute ventilation, the elastic PoB showed an increment greater than 200% from the lower to the greater tidal volume, accounting for approximately 80% of the whole PoB increment. On the contrary, elastic work of breathing per litre per minute, elastic workload index and elastic double product did not change. Conclusion: Changes in breathing pattern markedly affect the PoB despite constant mechanical load. Other indexes could assess the elastic workload without tidal volume dependence. Power of breathing use should be avoided to compare different mechanical loads or efficiencies of the respiratory muscles when tidal volume is variable.