human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: The more important known pathogenetic mechanisms apparently responsible for the development of adult respiratory distress syndrome ( ARDS ) are briefly discussed . Reactions in the development of ARDS for which corticosteroids are possibly beneficial are pointed out . A prospect i ve study involving 92 patients was design ed to determine the prophylactic value of methylprednisolone sodium succinate ( MPSS ) ( Solu-Medrol ; Upjohn ) in preventing ARDS .  MPSS was administered to 47 seriously injured patients and omitted from the management regimen of 45 patients comparable as regards age and severity of injury . The percentage of patients who developed ARDS was significantly lower in the group that received MPSS than in the control group We investigated the effect of octreotide in the treatment of  severe acute pancreatitis  in a case – control study . Experimental and clinical studies on the effect of octreotide in the treatment of acute pancreatitis have shown controversial results . Since January 1992 , we have been conducting a prospect i ve r and omized study on the effect of octreotide in severe acute pancreatitis , in three hospitals in Israel . The entering criteria included three or more of the Ranson prognostic signs and CT findings of severe pancreatitis . Patients were r and omly assigned to conservative treatment either with or without octreotide ( 0.1 mg subcutaneously three times a day ) . The end points of the study included : complication rate ( ARDS , sepsis , renal failure , pseudocyst , fistula , and abscess ) , length of hospital stay , and mortality .  From January 1992 to December 1996 , 60 patients entered the study . After evaluating the files , 10 patients were excluded due to failure to meet the entering criteria , incomplete data , or incorrect diagnosis . Of the remaining 50 patients , 25 were assigned to octreotide ( treatment group ) and 25 to conservative treatment only ( control group ) . The two groups matched with regard to age , sex , etiology , and severity of the disease . The complication rate was lower in the treatment group with regard to sepsis ( 24 % vs 76 % , P = 0.0002 ) and ARDS ( 28 % vs 56 % , P = 0.04 ) . The hospital stay was shorter in the treatment group ( 20.6 vs 33.1 days , P = 0.04 ) . Two patients died in the treatment group and eight in the control group ( P < 0.019 ) . These results suggest that octreotide may have a beneficial effect in the treatment of severe acute pancreatitis OBJECTIVE To determine the effects of intravenous N-acetylcysteine ( NAC ) on the development of severe adult respiratory distress syndrome ( ARDS )  and mortality rate  in patients with mild-to-moderate acute lung injury and to analyze the duration of ventilatory support and FIO2 required as well as the evolution of the lung injury score . SETTING Three university hospital ICUs and one regional ICU in Switzerl and . PATIENTS Sixty-one adult patients presenting with mild-to-moderate acute lung injury and various predisposing factors for ARDS received either NAC , 40 mg/kg/d , or placebo intravenously for 3 days . MEASUREMENTS Respiratory dysfunction was assessed daily according to the need for mechanical ventilation and FIO2 , the evolution of the lung injury score , and the PaO2/FIO2 ratio . The cardiovascular state , liver function , and kidney function were also monitored . Data were collected at admission ( day 0 ) , during the first 3 days , and on the day of discharge from the ICU . RESULTS The NAC and placebo groups ( 32 and 29 patients , respectively ) were comparable at ICU admission for severity of illness assessed by the simplified acute physiology score ( SAPS ) ( 10.8 + /- 4.6 vs 10.9 + /- 4.8 ) and lung injury score ( LIS ) ( 1.39 + /- 0.95 vs 1.11 + /- 1.08 ) ( mean + /- SD ) . Three patients in each group developed ARDS . The 1-month mortality rate was 22 percent for the NAC group and 35 percent for the placebo group ( difference not statistically significant ) . At admission , 22 of 32 patients ( 69 percent ) in the NAC group were mechanically ventilated compared with 22 of 29 ( 76 percent ) in the placebo group . At the end of the treatment period ( day 3 ) , 5 of 29 ( 17 percent ) in the NAC group and 12 of 25 ( 48 percent ) in the placebo group were still receiving ventilatory support ( p = 0.01 ) , The FIO2 was 0.37 less than admission value ( day 0 ) in the NAC group , and 0.20 less in the placebo group ( p < 0.04 ) ; the oxygenation index ( PaO2/FIO2 ) improved significantly ( p < 0.05 ) from day 0 to day 3 only in the NAC-treated group . The LIS showed a significant regression ( p = 0.003 ) in the NAC-treated group during the first 10 days of treatment : no change was observed in the placebo group . No adverse effects were observed during the treatment with NAC . CONCLUSIONS Intravenous NAC treatment during 72 h improved systemic oxygenation and reduced the need for ventilatory support in patients presenting with mild-to-moderate acute lung injury subsequent to a variety of underlying diseases . Development of ARDS and mortality were not reduced significantly by this therapy BACKGROUND Traditional approaches to mechanical ventilation use tidal volumes of 10 to 15 ml per kilogram of body weight and may cause stretch-induced lung injury in patients with acute lung injury and the acute respiratory distress syndrome . We therefore conducted a trial to determine whether ventilation with lower tidal volumes would improve the clinical outcomes in these patients . METHODS Patients with acute lung injury and the acute respiratory distress syndrome were enrolled in a multicenter , r and omized trial . The trial compared traditional ventilation treatment , which involved an initial tidal volume of 12 ml per kilogram of predicted body weight and an airway pressure measured after a 0.5-second pause at the end of inspiration ( plateau pressure ) of 50 cm of water or less , with ventilation with a lower tidal volume , which involved an initial tidal volume of 6 ml per kilogram of predicted body weight and a plateau pressure of 30 cm of water or less . The primary outcomes were death before a patient was discharged home and was breathing without assistance and the number of days without ventilator use from day 1 to day 28 . RESULTS The trial was stopped after the enrollment of 861 patients because  mortality was lower in the group treated with lower tidal volumes than in the group treated with traditional tidal volumes ( 31.0 percent vs. 39.8 percent , P=0.007 ) , and the number of days without ventilator use during the first 28 days after r and omization was greater in this group ( mean [ + /-SD ] , 12+/-11 vs. 10+/-11 ; P=0.007 ) . The mean tidal volumes on days 1 to 3 were 6.2+/-0.8 and 11.8+/-0.8 ml per kilogram of predicted body weight ( P<0.001 ) , respectively , and the mean plateau pressures were 25+/-6 and 33+/-8 cm of water ( P<0.001 ) , respectively . CONCLUSIONS In patients with acute lung injury and the acute respiratory distress syndrome , mechanical ventilation with a lower tidal volume than is traditionally used results in decreased mortality and increases the number of days without ventilator use Objective : To determine if ketoconazole , a thromboxane A2 synthetase inhibitor , given within the first 24 hrs after diagnosis and arrival in the intensive care unit ( ICU ) would decrease the frequency of adult respiratory distress syndrome in the septic patient population . Design : Prospect i ve , r and omized , double-blind , placeocontrolled study . Setting : Twelve-bed , surgical ICU in a university-affiliated hospital . Patients : Fifty-four consecutive patients admitted to the surgical ICU with the diagnosis of sepsis composed the study sample . Sepsis was defined as including two or more of the following signs in a patient with a systolic blood pressure of < 80 mm Hg or a systemic vascular resistance of < 800 dyne-sec/cm5 : a ) temperature ≥39 ° C or ≤35 ° C ; b ) white blood cell count of > 12,000 leukocytes , or ≤4000 leukocytes/μL , or ≥20 % immature cells ; c ) positive blood culture ; d ) known or strongly suspected source of infection from which a known pathogen was cultured . Interventions : Patients were r and omized to receive either ketoconazole ( 400 mg ) or placebo in a double-blind fashion as early as possible and in < 24 hrs after surgical ICU admission or after the diagnosis of sepsis was established . Measurements and Main Results : Adult respiratory distress syndrome ( ARDS ) was diagnosed if the following criteria were met : a ) intrapulmonary shunt of > 20 % , or a PaO2/Fio2 ratio of < 150 requiring ventilatory support for > 48 hrs ; b ) pulmonary artery occlusion pressure of < 18 nun Hg and no clinical signs of heart failure ; and c ) diffuse infiltrates on chest radiograph . Treatment result ed in significant ( p = .002 ) reduction in the frequency of ARDS compared with the placebo group , 64 % vs. 15 % in the ketoconazole treated group . The mortality rate was also reduced from 39 % in the placebo group to 15 % in the ketoconazole group ( p = .05 ) . A statistically significant reduction in ventilator and ICU days was not achieved . Conclusions : Ketoconazole ( 400 mg through the gastrointestinal tract ) given early in the septic course may prevent ARDS and decrease the mortality rate in high-risk , septic patients . ( Crit Care Med 1993 ; 21:1635–1642 Because the formation of platelet thrombi has been incriminated in the development of the adult respiratory distress syndrome ( ARDS ) , we tested trie hypothesis that early administration of antiplatelet agents might protect the lungs in patients at risk to develop ARDS after circulatory shock . This double-blinded study included 40 patients treated with either 3 mg/kg ± 24 h of dipyridamole or a corresponding dose of placebo after an episode of hemorrhagic , traumatic , or septic shock . Each patient also received 100 mg of aspirin daily . Arterial blood gases and chest x-rays were not significantly different between dipyridamole and placebo groups . Moreover , two patients receiving dipyridamole but none receiving placebo developed ARDS . This pilot study does not support a beneficial effect of dipyridamole in the prevention of ARDS after circulatory shock The possible beneficial effect of aprotinin , a broad protease inhibitor , on the incidence and outcome of ARDS was examined in two complementary studies . In the first study , the effect of aprotinin was assessed in 147 patients admitted with multiple trauma or shock . In the 57 patients who developed ARDS , mortality was significantly less in those who had previously received aprotinin ( 8/20 , 40 % ) than in those who had not ( 26/37 , 70 % ) . Although both treatment groups were well matched , this was a retrospective study and a second prospect i ve , r and omised , controlled study was therefore carried out . In 78 patients at risk of ARDS , there was no significant difference between treated and control patients in the incidence , duration or severity of ARDS , or in mortality or other major complications . It is concluded that aprotinin is not effective in improving any aspect of ARDS or its outcome in seriously ill patients We performed a phase I/II trial in North America of a recombinant surfactant protein C-based surfactant ( Venticute ) as treatment for the acute respiratory distress syndrome . Patients were prospect ively r and omized to receive either st and ard therapy or st and ard therapy plus one of two doses of exogenous surfactant given four times over 24 hours .  Surfactant administration was well tolerated . No significant treatment benefit was associated with surfactant treatment . Bronchoalveolar lavage of treated patients at 48 hours reflected the presence of exogenous surfactant components , did not show evidence of improved surface tension lowering function , and had interleukin-6 concentrations that were significantly lower than control group values , consistent with an antiinflammatory treatment effect . The presence of exogenous surfactant was not detected in lavage fluid obtained at 120 hours . Future studies might rationally employ larger surfactant doses and a more prolonged dosing schedule Objective To evaluate the effects of HA-1A , a human monoclonal antiendotoxin antibody , in septic patients with ARDS . Design Sub study of a multicenter , double-blinded , placebo-controlled trial of HA-1A in septic patients . Patients 63 septic patients with ARDS at the time of study entry . InterventionA single intravenous injection of HA-1A ( 100 mg ) or placebo . Results A quantitative radiographic score , the PaO2/FIO2 ratio and an index of the severity of ARDS did not show a significant difference between the treatment and placebo groups at 3 , 5 and 7 days after treatment . The duration of endotracheal intubation did not differ between the two groups . 15 of 30 HA-1A treated patients ( 50 % ) and 23 of 33 placebo-tre 
    Output:
    
agent
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: The more important known pathogenetic mechanisms apparently responsible for the development of adult respiratory distress syndrome ( ARDS ) are briefly discussed . Reactions in the development of ARDS for which corticosteroids are possibly beneficial are pointed out . A prospect i ve study involving 92 patients was design ed to determine the prophylactic value of methylprednisolone sodium succinate ( MPSS ) ( Solu-Medrol ; Upjohn ) in preventing ARDS .  MPSS was administered to 47 seriously injured patients and omitted from the management regimen of 45 patients comparable as regards age and severity of injury . The percentage of patients who developed ARDS was significantly lower in the group that received MPSS than in the control group We investigated the effect of octreotide in the treatment of  severe acute pancreatitis  in a case – control study . Experimental and clinical studies on the effect of octreotide in the treatment of acute pancreatitis have shown controversial results . Since January 1992 , we have been conducting a prospect i ve r and omized study on the effect of octreotide in severe acute pancreatitis , in three hospitals in Israel . The entering criteria included three or more of the Ranson prognostic signs and CT findings of severe pancreatitis . Patients were r and omly assigned to conservative treatment either with or without octreotide ( 0.1 mg subcutaneously three times a day ) . The end points of the study included : complication rate ( ARDS , sepsis , renal failure , pseudocyst , fistula , and abscess ) , length of hospital stay , and mortality .  From January 1992 to December 1996 , 60 patients entered the study . After evaluating the files , 10 patients were excluded due to failure to meet the entering criteria , incomplete data , or incorrect diagnosis . Of the remaining 50 patients , 25 were assigned to octreotide ( treatment group ) and 25 to conservative treatment only ( control group ) . The two groups matched with regard to age , sex , etiology , and severity of the disease . The complication rate was lower in the treatment group with regard to sepsis ( 24 % vs 76 % , P = 0.0002 ) and ARDS ( 28 % vs 56 % , P = 0.04 ) . The hospital stay was shorter in the treatment group ( 20.6 vs 33.1 days , P = 0.04 ) . Two patients died in the treatment group and eight in the control group ( P < 0.019 ) . These results suggest that octreotide may have a beneficial effect in the treatment of severe acute pancreatitis OBJECTIVE To determine the effects of intravenous N-acetylcysteine ( NAC ) on the development of severe adult respiratory distress syndrome ( ARDS )  and mortality rate  in patients with mild-to-moderate acute lung injury and to analyze the duration of ventilatory support and FIO2 required as well as the evolution of the lung injury score . SETTING Three university hospital ICUs and one regional ICU in Switzerl and . PATIENTS Sixty-one adult patients presenting with mild-to-moderate acute lung injury and various predisposing factors for ARDS received either NAC , 40 mg/kg/d , or placebo intravenously for 3 days . MEASUREMENTS Respiratory dysfunction was assessed daily according to the need for mechanical ventilation and FIO2 , the evolution of the lung injury score , and the PaO2/FIO2 ratio . The cardiovascular state , liver function , and kidney function were also monitored . Data were collected at admission ( day 0 ) , during the first 3 days , and on the day of discharge from the ICU . RESULTS The NAC and placebo groups ( 32 and 29 patients , respectively ) were comparable at ICU admission for severity of illness assessed by the simplified acute physiology score ( SAPS ) ( 10.8 + /- 4.6 vs 10.9 + /- 4.8 ) and lung injury score ( LIS ) ( 1.39 + /- 0.95 vs 1.11 + /- 1.08 ) ( mean + /- SD ) . Three patients in each group developed ARDS . The 1-month mortality rate was 22 percent for the NAC group and 35 percent for the placebo group ( difference not statistically significant ) . At admission , 22 of 32 patients ( 69 percent ) in the NAC group were mechanically ventilated compared with 22 of 29 ( 76 percent ) in the placebo group . At the end of the treatment period ( day 3 ) , 5 of 29 ( 17 percent ) in the NAC group and 12 of 25 ( 48 percent ) in the placebo group were still receiving ventilatory support ( p = 0.01 ) , The FIO2 was 0.37 less than admission value ( day 0 ) in the NAC group , and 0.20 less in the placebo group ( p < 0.04 ) ; the oxygenation index ( PaO2/FIO2 ) improved significantly ( p < 0.05 ) from day 0 to day 3 only in the NAC-treated group . The LIS showed a significant regression ( p = 0.003 ) in the NAC-treated group during the first 10 days of treatment : no change was observed in the placebo group . No adverse effects were observed during the treatment with NAC . CONCLUSIONS Intravenous NAC treatment during 72 h improved systemic oxygenation and reduced the need for ventilatory support in patients presenting with mild-to-moderate acute lung injury subsequent to a variety of underlying diseases . Development of ARDS and mortality were not reduced significantly by this therapy BACKGROUND Traditional approaches to mechanical ventilation use tidal volumes of 10 to 15 ml per kilogram of body weight and may cause stretch-induced lung injury in patients with acute lung injury and the acute respiratory distress syndrome . We therefore conducted a trial to determine whether ventilation with lower tidal volumes would improve the clinical outcomes in these patients . METHODS Patients with acute lung injury and the acute respiratory distress syndrome were enrolled in a multicenter , r and omized trial . The trial compared traditional ventilation treatment , which involved an initial tidal volume of 12 ml per kilogram of predicted body weight and an airway pressure measured after a 0.5-second pause at the end of inspiration ( plateau pressure ) of 50 cm of water or less , with ventilation with a lower tidal volume , which involved an initial tidal volume of 6 ml per kilogram of predicted body weight and a plateau pressure of 30 cm of water or less . The primary outcomes were death before a patient was discharged home and was breathing without assistance and the number of days without ventilator use from day 1 to day 28 . RESULTS The trial was stopped after the enrollment of 861 patients because  mortality was lower in the group treated with lower tidal volumes than in the group treated with traditional tidal volumes ( 31.0 percent vs. 39.8 percent , P=0.007 ) , and the number of days without ventilator use during the first 28 days after r and omization was greater in this group ( mean [ + /-SD ] , 12+/-11 vs. 10+/-11 ; P=0.007 ) . The mean tidal volumes on days 1 to 3 were 6.2+/-0.8 and 11.8+/-0.8 ml per kilogram of predicted body weight ( P<0.001 ) , respectively , and the mean plateau pressures were 25+/-6 and 33+/-8 cm of water ( P<0.001 ) , respectively . CONCLUSIONS In patients with acute lung injury and the acute respiratory distress syndrome , mechanical ventilation with a lower tidal volume than is traditionally used results in decreased mortality and increases the number of days without ventilator use Objective : To determine if ketoconazole , a thromboxane A2 synthetase inhibitor , given within the first 24 hrs after diagnosis and arrival in the intensive care unit ( ICU ) would decrease the frequency of adult respiratory distress syndrome in the septic patient population . Design : Prospect i ve , r and omized , double-blind , placeocontrolled study . Setting : Twelve-bed , surgical ICU in a university-affiliated hospital . Patients : Fifty-four consecutive patients admitted to the surgical ICU with the diagnosis of sepsis composed the study sample . Sepsis was defined as including two or more of the following signs in a patient with a systolic blood pressure of < 80 mm Hg or a systemic vascular resistance of < 800 dyne-sec/cm5 : a ) temperature ≥39 ° C or ≤35 ° C ; b ) white blood cell count of > 12,000 leukocytes , or ≤4000 leukocytes/μL , or ≥20 % immature cells ; c ) positive blood culture ; d ) known or strongly suspected source of infection from which a known pathogen was cultured . Interventions : Patients were r and omized to receive either ketoconazole ( 400 mg ) or placebo in a double-blind fashion as early as possible and in < 24 hrs after surgical ICU admission or after the diagnosis of sepsis was established . Measurements and Main Results : Adult respiratory distress syndrome ( ARDS ) was diagnosed if the following criteria were met : a ) intrapulmonary shunt of > 20 % , or a PaO2/Fio2 ratio of < 150 requiring ventilatory support for > 48 hrs ; b ) pulmonary artery occlusion pressure of < 18 nun Hg and no clinical signs of heart failure ; and c ) diffuse infiltrates on chest radiograph . Treatment result ed in significant ( p = .002 ) reduction in the frequency of ARDS compared with the placebo group , 64 % vs. 15 % in the ketoconazole treated group . The mortality rate was also reduced from 39 % in the placebo group to 15 % in the ketoconazole group ( p = .05 ) . A statistically significant reduction in ventilator and ICU days was not achieved . Conclusions : Ketoconazole ( 400 mg through the gastrointestinal tract ) given early in the septic course may prevent ARDS and decrease the mortality rate in high-risk , septic patients . ( Crit Care Med 1993 ; 21:1635–1642 Because the formation of platelet thrombi has been incriminated in the development of the adult respiratory distress syndrome ( ARDS ) , we tested trie hypothesis that early administration of antiplatelet agents might protect the lungs in patients at risk to develop ARDS after circulatory shock . This double-blinded study included 40 patients treated with either 3 mg/kg ± 24 h of dipyridamole or a corresponding dose of placebo after an episode of hemorrhagic , traumatic , or septic shock . Each patient also received 100 mg of aspirin daily . Arterial blood gases and chest x-rays were not significantly different between dipyridamole and placebo groups . Moreover , two patients receiving dipyridamole but none receiving placebo developed ARDS . This pilot study does not support a beneficial effect of dipyridamole in the prevention of ARDS after circulatory shock The possible beneficial effect of aprotinin , a broad protease inhibitor , on the incidence and outcome of ARDS was examined in two complementary studies . In the first study , the effect of aprotinin was assessed in 147 patients admitted with multiple trauma or shock . In the 57 patients who developed ARDS , mortality was significantly less in those who had previously received aprotinin ( 8/20 , 40 % ) than in those who had not ( 26/37 , 70 % ) . Although both treatment groups were well matched , this was a retrospective study and a second prospect i ve , r and omised , controlled study was therefore carried out . In 78 patients at risk of ARDS , there was no significant difference between treated and control patients in the incidence , duration or severity of ARDS , or in mortality or other major complications . It is concluded that aprotinin is not effective in improving any aspect of ARDS or its outcome in seriously ill patients We performed a phase I/II trial in North America of a recombinant surfactant protein C-based surfactant ( Venticute ) as treatment for the acute respiratory distress syndrome . Patients were prospect ively r and omized to receive either st and ard therapy or st and ard therapy plus one of two doses of exogenous surfactant given four times over 24 hours .  Surfactant administration was well tolerated . No significant treatment benefit was associated with surfactant treatment . Bronchoalveolar lavage of treated patients at 48 hours reflected the presence of exogenous surfactant components , did not show evidence of improved surface tension lowering function , and had interleukin-6 concentrations that were significantly lower than control group values , consistent with an antiinflammatory treatment effect . The presence of exogenous surfactant was not detected in lavage fluid obtained at 120 hours . Future studies might rationally employ larger surfactant doses and a more prolonged dosing schedule Objective To evaluate the effects of HA-1A , a human monoclonal antiendotoxin antibody , in septic patients with ARDS . Design Sub study of a multicenter , double-blinded , placebo-controlled trial of HA-1A in septic patients . Patients 63 septic patients with ARDS at the time of study entry . InterventionA single intravenous injection of HA-1A ( 100 mg ) or placebo . Results A quantitative radiographic score , the PaO2/FIO2 ratio and an index of the severity of ARDS did not show a significant difference between the treatment and placebo groups at 3 , 5 and 7 days after treatment . The duration of endotracheal intubation did not differ between the two groups . 15 of 30 HA-1A treated patients ( 50 % ) and 23 of 33 placebo-tre 
    Output:
    