The Subset Sum game.

In this work we address a game theoretic variant of the Subset Sum problem, in which two decision makers (agents/players) compete for the usage of a common resource represented by a knapsack capacity. Each agent owns a set of integer weighted items and wants to maximize the total weight of its own items included in the knapsack. The solution is built as follows: Each agent, in turn, selects one of its items (not previously selected) and includes it in the knapsack if there is enough capacity. The process ends when the remaining capacity is too small for including any item left. We look at the problem from a single agent point of view and show that finding an optimal sequence of items to select is an [Formula: see text]-hard problem. Therefore we propose two natural heuristic strategies and analyze their worst-case performance when (1) the opponent is able to play optimally and (2) the opponent adopts a greedy strategy. From a centralized perspective we observe that some known results on the approximation of the classical Subset Sum can be effectively adapted to the multi-agent version of the problem.

The effect of respiratory muscle endurance training in patients with myasthenia gravis.

We tested the effect of a home-based respiratory muscle endurance training in patients with mild to moderate generalized myasthenia gravis (MG) on Besinger score, lung function and respiratory muscle endurance. Ten patients performed respiratory muscle endurance training in form of normocapnic hyperpnea training at 50-60% of their maximal voluntary ventilation over 4-6 weeks. MG score, lung function and respiratory endurance were assessed before and after training period. The training significantly increased respiratory endurance from 8.4+/-0.9 min to 17.1+/-1.3 min (p<0.001) and total ventilatory volume from 555+/-87 L to 1081+/-127 L (p=0.004). About 25% of this gain was lost after 3-5 months of detraining. The remaining 75% gain might result from improved neuromuscular coordination rather than muscular training. MG score and lung function, however, did not change. Patients assessed the training effects on physical fitness and respiration as positive. In conclusion, respiratory muscle endurance training can be useful for MG patients as it is enhancing respiratory muscle endurance.

Bosentan improves exercise tolerance and Tei index in patients with pulmonary hypertension and prostanoid therapy.

STUDY OBJECTIVE: Pulmonary arterial hypertension (PAH) is a progressive disease with a bad prognosis. Prostanoids are well established in the medical treatment of this disease. Treatment of patients with progressive disease despite prostanoids remains a therapeutic challenge. In this study, we examined the effect of adding bosentan, an endothelin antagonist, to existing prostanoid therapy on exercise capacity (6-min walking distance [6MWD]) and right ventricular (RV) function (Tei index) in patients with progressive pulmonary hypertension. DESIGN: Prospective, nonrandomized, open-label study. SETTING: University hospital. PATIENTS: Sixteen patients with pulmonary hypertension (PAH, n = 10; pulmonary hypertension due to other cause, n = 6) with progressive disease receiving either beraprost (n = 3), inhaled iloprost (n = 10), or iloprost IV (n = 3). INTERVENTIONS: Combination therapy with bosentan (final dosage, 125 mg bid) was initiated following an interval of 3-months minimum of unchanged prostanoid therapy. MEASUREMENTS AND RESULTS: Tei index, 6MWD, and New York Heart Association (NYHA) functional class were assessed prior to the initiation of combination therapy (baseline), at 6 months after initiation of combination therapy, and every 3 months thereafter. Two patients were followed up for 6 months only; all remaining patients reached a mean follow-up period (+/- SD) of 13.5 +/- 5.0 months (range, 9 to 22 months). 6MWD increased by 42.5 +/- 66 m at 6 months and 44.6 +/- 66 m at the last follow-up (both time points vs baseline, p < 0.001), and Tei index improved by -0.13 +/- 0.08 at 6 months and - 0.13 +/- 0.11 at the last follow-up (both time points vs baseline, p < 0.001). All patients reported subjective improvements. Nine of 16 patients exhibited improvement in NYHA functional class at 6 months. No side effects occurred that required dose adjustment or discontinuation of the study medication. CONCLUSION: Bosentan administered to patients with progressive pulmonary hypertension receiving prostanoids resulted in an increased exercise capacity and an improved RV function. Bosentan therefore appears to be well suited for combination therapy with prostanoids in selected patients pending results of ongoing randomized trials.

Different mechanisms for changes in glucose uptake of the right and left ventricular myocardium in pulmonary hypertension.

UNLABELLED: In patients with pulmonary hypertension (PH) the right ventricular (RV)-to-left ventricular (LV) ratio of fatty acid uptake is reduced. In animal studies, such a finding was combined with an increased glucose uptake in RV myocardium. The aim of this study was to measure the metabolic rates of glucose uptake for the RV and LV myocardium in patients in relationship to parameters of RV and LV function. METHODS: Thirty patients with PH underwent PET with (18)F-FDG and SPECT with (99m)Tc-tetrofosmine. The metabolic rate of glucose uptake was determined for RV and LV myocardium using the method of Patlak. A right heart catheter, thermodilution, and Doppler sonography were used to characterize RV and LV function. From these methods, the stroke work of both ventricles and the RV Tei index were calculated. RESULTS: RV-to-LV ratios of (18)F-FDG-uptake increased with rising pulmonary arteriolar resistance (PAR). With increasing PAR, the metabolic rate of glucose uptake of the left ventricle decreased (r = -0.547; P < 0.01) together with LV stroke work (r = -0.838; P < 0.001). The metabolic rate of glucose uptake of the right ventricle, however, correlated neither with RV stroke work (r = 0.124) nor with PAR (r = 0.189) but with the Tei index (r = 0.78; P < 0.001). CONCLUSION: Increasing right-to-left ratios of glucose uptake with an increasing pressure load in the right ventricle in PH are caused mainly by a significant reduction in the LV metabolic rate of glucose uptake. This is obviously due to a reduced energy demand of the LV myocardium caused by reduced stroke work. An increased metabolic rate of glucose uptake in the right ventricle presumably indicates RV impairment, correlating with the Tei index, which is an established prognostic parameter for cardiac dysfunction and poor survival.

Differential diagnosis of pleural effusions by fuzzy-logic-based analysis of cytokines.

Pleural effusions can be caused by highly different underlying diseases and are characterized by complex interactions of various local and circulating cells as well as numerous soluble parameters like interleukins (IL). Knowledge about this complex network could help to indicate underlying disease. Therefore, we have investigated immunoreactive concentrations of IL-4, IL-6, IL-11, IL-15, IL-17, IL-18, and tumor necrosis factor-alpha (TNF-alpha) in pleural effusions and peripheral blood from patients with tuberculosis, bronchial carcinoma and other carcinomas as well as congestive heart failure (CHF) and pneumonias. To determine the value of cytokine measurement for differential diagnosis, statistical and fuzzy-logic methods were applied. Quantitative analysis showed high concentrations of IL-6 and IL-11 only in pleural effusions. IL-15, IL-17, IL-18 and TNF-alpha could be detected also in blood plasma. Lowest amounts were detected in CHF indicating the non-inflammatory origin of effusions. Statistical analysis did not provide evidence for diagnostic relevance of singular cytokines. Fuzzy-logic analysis was able to assign patients to the correct diseases with 80% accuracy using IL-6 and IL-15 measurement. Our results confirm the pathogenetic role of these cytokines in pleural effusions. Fuzzy-logic-based procedures may help to characterize and distinguish effusions of unknown origin even in small patient groups.

Detection of p53 gene mutations in exhaled breath condensate of non-small cell lung cancer patients.

Early diagnosis of lung carcinoma is greatly desired. A potential source of early information regarding the process of cancerisation in the airways is exhaled breath condensate (EBC). The direct approach to detecting cancerisation is examining DNA from the area of chronic damage, i.e. airways and lung parenchyma. We therefore investigated DNA in EBC of patients with NSCLC and healthy volunteers. Human DNA was amplified by PCR in exhaled breath condensate and used to detect p53 mutations. A PCR of the beta-actin gene fragment was used to detect human DNA in each of the EBC samples. In 65.7% of the samples, the beta-actin gene was found. Extracted DNA as well as native EBC were equally suited as starting material for amplification. Mutations of the p53 gene were investigated in all EBC samples of NSCLC patients. p53 exons 5-8 were amplified using nested PCR and subsequently sequenced. Mutations were found in four of the patients (n=11; 36.4%) while no mutation was found in volunteers (n=10). Mutations detected in EBC were also compared with those of corresponding tumor tissue. Different point mutations in EBC and tumor tissue were revealed in all cases. Our findings demonstrate that exhaled breath condensate may be used for analysis of somatic gene mutations in an area of direct tobacco-related DNA damage.

Exhaled breath condensate acidification in acute lung injury.

Lung injury in ventilated lungs may occur due to local or systemic disease and is usually caused by or accompanied by inflammatory processes. Recently, acidification of exhaled breath condensate pH (EBC-pH) has been suggested as marker of inflammation in airway disease. We investigated pH, ammonia, Lactate, pCO2, HCO3-, IL-6 and IL-8 in EBC of 35 ventilated patients (AECC-classification: ARDS: 15, ALI: 12, no lung injury: 8). EBC-pH was decreased in ventilated patients compared to volunteers (5.85 +/- 0.32 vs. 7.46 +/- 0.48; P < 0.0001). NH4+, lactate, HCO3-, pCO2, IL-6 and IL-8 were analyzed in EBC and correlated with EBC-pH. We observed correlations of EBC-pH with markers of local (EBC IL-6: r = -0.71, P < 0.0001, EBC IL-8: r = -0.68, P < 0.0001) but not of systemic inflammation (serum IL-6, serum IL-8) and with indices of severity of lung injury (Murray's Lung Injury Severity Score; r = -0.73, P < 0.0001, paO2/FiO2; r = 0.54, P < 0.001). Among factors potentially contributing to pH of EBC, EBC-lactate and EBC-NH4+ were found to correlate with EBC-pH. Inflammation-induced disturbances of regulatory mechanisms, such as glutaminase systems may result in EBC acidification. EBC-pH is suggested to represent a marker of acute lung injury caused by or accompanied by pulmonary inflammation.

Exhaled breath condensate nitrite and its relation to tidal volume in acute lung injury.

STUDY OBJECTIVE: Mechanical ventilation may damage the lung. Low tidal volume (VT) is protective, but VT is scaled to body weight (BW) and may be high in functionally small ARDS lungs. We hypothesized that exhaled breath condensate (EBC) nitrite (NO(2)(-)) concentration may increase with lung distension. DESIGN: Prospective, noncontrolled study. SETTING: University hospital and medical ICU. PATIENTS: Thirty-five ICU patients requiring mechanical ventilation (severe pneumonia, n = 31; exacerbated COPD, n = 4). Patients were scored according to American and European Consensus Conference on ARDS criteria (AECC) [no lung injury, n = 7; acute lung injury, n = 13; ARDS, n = 15], as well as the Murray lung injury severity score (LISS) [score 0, n = 3; score 0.1 to 2.5, n = 19; score > 2.5, n = 13]. INTERVENTIONS: EBC was collected and analyzed for NO(2)(-), interleukin (IL)-6, and IL-8. Serum was analyzed for IL-6, IL-8, and procalcitonin. RESULTS: and measurements: EBC NO(2)(-) correlated well with VT (milliliters per kilogram of BW; r = 0.79, p < 0.0001) and expiratory minute volume (r = 0.60, p < 0.0001) but not with other ventilatory parameters or parameters of pulmonary (EBC IL-6, EBC IL-8) or systemic (serum IL-6, IL-8, and procalcitonin) inflammation. The ratio of EBC NO(2)(-) and the size of the VT correlated directly with lung injury (AECC, r = 0.66, p < 0.0001; LISS, r = 0.84, p < 0.0001). CONCLUSION: EBC NO(2)(-) increased linearly with VT. The ratio of EBC NO(2)(-) to VT is assumed to reflect NO(2)(-) release at a given VT. An increase in this ratio indicates an inappropriate increase of NO(2)(-) production most likely due to mechanical stress of the remaining open lung units in injured lungs. We conclude that the EBC NO(2)(-)/VT ratio may help to identify situations of critical mechanical stress.

High in comparison with low tidal volume ventilation aggravates oxidative stress-induced lung injury.

Ventilator settings influence the development and outcome of acute lung injury. This study investigates the influence of low versus high tidal volume (V(t)) on oxidative stress-induced lung injury. Isolated rabbit lungs were subjected to one of three ventilation patterns (V(t)-positive end-expiratory pressure, PEEP): LVZP (6 ml/kg-0 cm H(2)O), HVZP (12 ml/kg-0 cm H(2)O), LV5P (6 ml/kg-5 cm H(2)O). These ventilation patterns allowed a comparison between low and high V(t) without dependence on peak inspiratory pressure (PIP). Infusion of hypochlorite (1000 nmol/min) or buffer (control) was started at t=0 min. Pulmonary artery pressure (PAP), PIP and weight were continuously recorded. Capillary filtration coefficient [K(f,c) (10(-4) ml s(-1) cm H(2)O(-1) g(-1))] was gravimetrically determined (-15/30/60/90/120 min).PIP averaged 5.8+/-0.6/13.9+/-0.6/13.9+/-0.4 cm H(2)O in the LVZP, HVZP and LV5P groups. PIP, K(f,c) or PAP did not change in control groups, indicating that none of the ventilation patterns caused lung injury by themselves. Hypochlorite-induced increase in K(f,c) but not hypochlorite-induced increase in PAP, was significantly attenuated in the LVZP-/LV5P- versus the HVZP-group (K(f,c,max.) 1.0+/-0.23/1.4+/-0.40 versus 3.2+/-1.0*). Experiments with hypochlorite were terminated due to excessive edema (>50 g) at 97+/-2.2/94.5+/-4.5 min in the LVZP-/LV5P-group versus 82+/-3.8* min in the HVZP-group (*: P<0.05). Low V(t) attenuated oxidative stress-induced increase in vascular permeability independently from PIP and PEEP.

Successful resection of a re-occurred pulmonary myosarcoma in a patient with turner syndrome mosaic.

We describe a patient who underwent thoracic radiation therapy for biopsy-proven pulmonary spindle cell sarcoma in the left lower lobe, 15 months after birth. At the age of 37 she developed shoulder pain, fatigue, and progressive exertion dyspnoea. Chest X-ray revealed a pulmonary mass in the left lower lobe due to a cytology-proven malignant tumour.The patient underwent left pneumonectomy. Histology revealed a myosarcoma of the lung, similar to the previous sarcoma. Furthermore, the patient was diagnosed to have Turner syndrome mosaic and chromosomal analysis revealed a translocation t(1;13) in 3/50 metaphases. However a germline mutation of the p53 tumour suppressor gene was excluded. After 2 years of follow-up the patient is stable and there are no signs of recurrence of the tumour.We conclude a re-occurrence of this very rare malignant disorder of the lung after a 36-year interval in a patient with Turner syndrome mosaic. Following initial curative radiation therapy, with a remission over 36 years, lung resection was now successfully performed.