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: Influenza A infection may cause severe exacerbations of asthma with increased airway responsiveness and airflow obstruction ( 1 ) . Annual vaccination against influenza is therefore recommended for patients with asthma by the Chief Medical Officer of the Department of Health . However , some patients report exacerbations of their asthma , apparently related to influenza vaccination , and there is reluctance to adhere to the recommended vaccination policy ( 2 ) . We therefore studied the effect of a current subunit vaccine on symptoms , medication use , spirometry and airway responsiveness in patients with stable asthma Abstract In order to evaluate the impact of influenza-like illness and the effectiveness of influenza vaccination  in children with oncohematological disease who have completed cancer therapy , 182 children with a diagnosis of oncohematological disease were divided into two subgroups on the basis of the length of time off therapy ( < 6 months or 6–24 months ) and r and omised 1:1 to receive influenza vaccination or not . The controls were 91 otherwise healthy children unvaccinated against influenza .  The results show that the clinical and socioeconomic impact of influenza-like illnesses and the effectiveness of influenza vaccination  in oncohematological children who have completed cancer therapy are related to the length of the off therapy period , and seem to be significantly greater in those who have been off therapy for less than 6 months in comparison with healthy controls . This suggests that the administration of influenza vaccination should be strongly recommended only among oncohematological children who have been off therapy for less than 6 months BACKGROUND Despite current recommendations , many people with asthma do not receive annual vaccination against influenza , partly because of concern that vaccine may trigger exacerbations . Colds can trigger exacerbations , which may be mistaken for vaccine-related adverse events . We undertook a double-blind placebo-controlled multicentre crossover study to assess the safety of influenza vaccine  in patients with asthma , with allowance for the occurrence of colds . METHODS We studied 262 patients , aged 18 - 75 years , who recorded daily peak expiratory flow ( PEF ) , respiratory symptoms , medication , medical consultations , and hospital admissions for 2 weeks before the first injection and until 2 weeks after the second injection . Order of injection ( vaccine and placebo ) was assigned r and omly . There was an interval of 2 weeks between injections . The main outcome measure was an exacerbation of asthma within 72 h of injection ( defined as a fall in PEF of > 20 % ) . FINDINGS Among 255 participants with paired data , 11 recorded a fall in PEF of more than 20 % after vaccine compared with three after placebo ( McNemar 's test p=0.06 ) ; a fall of more than 30 % was recorded by eight after vaccine compared with none after placebo ( binomial test p=0.008 ) . However , when participants with colds were excluded , there was no significant difference in the numbers with falls of more than 20 % between vaccine and placebo ( six vs three ; binomial test p=0.51 ) , although the difference for PEF decreases of more than 30 % approached significance ( five vs none ; binomial test , p=0.06 ) . This association was confined to first-time vaccinees . INTERPRETATION Our findings indicate that pulmonary-function abnormalities may occur as a complication of influenza vaccination . However , the risk of pulmonary complications is very small and outweighed by the benefits of vaccination Little is known about the factors that govern the level of  HIV-1 replication in infected individuals . Recent studies ( using potent antiviral drugs ) of the kinetics of HIV-1 replication in vivo have demonstrated that steady-state levels of viremia are sustained by continuous rounds of de novo infection and the associated rapid turnover of CD4 + T lymphocytes . However , no information is available concerning the biologic variables that determine the size of the pool of T cells that are susceptible to virus infection or the amount of virus produced from infected cells . Furthermore , it is not known whether all CD4 + T lymphocytes are equally susceptible to HIV-1 infection at a given time or whether the infection is focused on cells of a particular state of activation or antigenic specificity . Although HIV-1 replication in culture is known to be greatly facilitated by T cell activation , the ability of specific antigenic stimulation to augment HIV-1 replication in vivo has not been studied . We sought to determine whether vaccination of HIV-1-infected adults leads to activation of virus replication and the targeting of vaccine antigen- responsive T cells for virus infection and destruction . Should T cell activation result ing from exposure to environmental antigens prove to be an important determinant of the steady-state levels of HIV-1 replication in vivo and lead to the preferential loss of specific population s of CD4 + T lymphocytes , it would have significant implication s for our underst and ing of and therapeutic strategies for HIV-1 disease . To begin to address these issues , HIV-1-infected individuals and uninfected controls were studied by measurement of immune responses to influenza antigens and quantitation of virion- associated plasma HIV-1 RNA levels at baseline and at intervals after immunization with the trivalent influenza vaccine . Influenza vaccination result ed in readily demonstrable but transient increases in plasma HIV-1 RNA levels , indicative of activation of viral replication , in HIV-1-infected individuals with preserved ability to immunologically respond to vaccine antigens . Activation of HIV-1 replication by vaccination was more often seen and of greater magnitude in individuals who displayed a T cell proliferative response to vaccine antigens at baseline and in those who mounted a significant serologic response after vaccination . The fold increase in viremia , as well as the rates of increase of HIV-1 in plasma after vaccination and rates of viral decline after peak viremia , were higher in individuals with higher CD4 + T cell counts . ( ABSTRACT TRUNCATED AT 400 WORDS Influenza vaccination is recommended for patients with HIV-1 infection ( 1 ) , but no studies have measured its efficacy in this population . Patients infected with HIV-1 , especially those with low CD4 + cell counts , often have minimal antibody responses to influenza vaccine ( 2 , 3 ) , leading some research ers to conclude that vaccination is not cost-effective ( 4 ) . In addition , vaccination has been associated with transient increases in HIV replication ( 5 - 8 ) and small decreases in percentage of CD4 cells ( 8) ; both of these findings are of undetermined clinical relevance . To better estimate the potential benefit of routine influenza vaccination in persons infected with HIV , we conducted a r and omized , controlled trial of influenza vaccine in a sample of HIV-1-infected patients during one influenza season . Methods Study Design The study site , a hospital-based clinic affiliated with the U.S. military , provides care to 400 to 500 patients infected with HIV-1 . Posters invited patients who visited the clinic from October to December 1995 to refer themselves for enrollment . All HIV-infected patients who had not yet received their annual influenza vaccine were eligible to participate . All patients gave informed consent , and the hospital 's institutional review board approved the study . Blood was drawn for measurement of CD4 + cell counts , influenza antibody titers , and plasma quantitative HIV-1 RNA level . Using a r and om computer-generated sequence , which was kept sealed until the end of the study , pharmacy staff prepared syringes that were filled with saline or with influenza vaccine purchased by the hospital for clinical use ( whole virion containing 15 g each of A/Johannesburg/33/94 [ H3N2 ] , A/Texas/36/91 [ H1N1 ] , and B/Harbin/07/94 [ Pasteur Mrieux Connaught , Lyon , France ] . Clinic staff could not distinguish vaccine from placebo . At 1 and 3 months after vaccination , patients returned for follow-up measurement of CD4 + cell count and HIV-1 RNA level and for serologic examination for influenza . Patients returned for viral cultures only if respiratory symptoms developed . At the conclusion of the study , all patients were interviewed about respiratory illness ( broadly defined as any rhinitis , pharyngitis , or cough ) experienced during the study period . Laboratory Assays Sample s for T-cell subset analysis were processed according to st and ard methods . The variation of percentage of CD4 cells on replicate testing was 1 % . Plasma sample s for measurement of HIV-1 RNA level were drawn in acid citrate-dextrose tubes , separated at 2000 rpm for 15 minutes , and stored at 70 C. Serum sample s were stored similarly . Quantitative HIV RNA reverse transcriptase polymerase chain reaction assays ( Amplicor Monitor , Roche , Nutley , New Jersey ) were done in batches by Quest Diagnostics at Nichols Institute , San Juan Capistrano , California ; all specimens from individual patients were tested simultaneously . The lower limits of quantification were 400 RNA copies per mL of plasma , and the intra-assay coefficient of variation of 32.3 % to 45.3 % . Serum sample s taken before and 1 month after vaccination were tested for antibody responses to each of the three individual vaccine components by microtiter hemagglutination inhibition ; egg-grown virus antigens starting at a dilution of 1:4 were used ( 9 ) . Sample s below this threshold were assigned a value of 1:2 . Serum sample s obtained 1 month and 3 months after vaccination were tested against the A/Johannesburg/33/94 and A/Nanchang/33/95 ( H3N2 ) virus strains ; the latter is antigenically similar to the A/Wuhan/95-like viruses that were circulating in the United States in 1995 and 1996 . All of the patients who responded to A/Johannesburg/94 ( those who demonstrated a fourfold or greater increase in titer ) also responded to A/Nanchang/95 . Because both A/Johannesburg-like and A/Wuhan-like viruses circulated in the study sample , an antibody response to A/Nanchang/95 occurring between 1 and 3 months after vaccination was defined as evidence of influenza A infection . Viral cultures were performed by using st and ard laboratory methods . Statistical Analysis Statistical analysis was done by using Statview 4.5 software ( Abacus Concepts , Inc. , Berkeley , California ) . Changes in antibody titer , plasma HIV-1 RNA level , and CD4 + cell count were analyzed by using the unpaired t-test to compare vaccine and placebo recipients . Illness rates were compared by using the chi-square test . The percentage of protective efficacy of vaccination was calculated as 1 ( risk ratio comparing vaccine and placebo recipients ) 100 . Results Characteristics of the Study Group A total of 102 patients enrolled in the study . Fifty-five patients were r and omly assigned to receive vaccine , and 47 patients were r and omly assigned to receive placebo .  Table 1 summarizes the participants ' characteristics . Because the study was conducted in fall 1995 , antiretroviral regimens were limited to single or double reverse transcriptase inhibitor combinations . No patients were taking protease inhibitors .  All patients had received at least one previous influenza vaccination .  Table 1 . Baseline Characteristics of the Study Sample Serologic Response to Vaccination Prevaccination and postvaccination paired serum sample s from 49 vaccine recipients and 43 placebo recipients were tested against the three vaccine constituents ( Table 2 ) . Although the aggregate responses to vaccination were statistically significant , only 12 % , 29 % , and 36 % of vaccine recipients had a fourfold or greater response to the A/H1N1 , A/H3N2 , and B components , respectively . Table 2 . Antibody Response to Influenza Vaccination  Protective Efficacy of Influenza Vaccination Peak influenza activity in San Diego County in 1995 and 1996 occurred from mid-January through early February and was predominately caused by the A/Johannesburg ( H3N2 ) virus strain ; some A/Wuhan ( H3N2 ) virus was also present ( San Diego Public Health Department . Personal communication ) . Sixteen of 55 vaccine recipients ( 29 % ) , compared with 23 of 47 placebo recipients ( 49 % ) , reported symptoms of respiratory illness during the fall and winter of 1995 and 1996 ( P=0.04 ) . No patients were hospitalized or treated for pneumonia during the study period . Twenty of 39 patients ( 12 placebo recipients and 8 vaccine recipients ) who reported respiratory illness returned to the clinic for viral respiratory culture . Influenza A ( H3N2 ) virus was isolated from 3 patients , and influenza B virus was isolated from 2 patients , all of whom received placebo . Serum sample s taken 1 and 3 months after vaccination were available for 86 patients ( 43 vaccine recipients and 43 placebo recipients ) . One vaccine recipient and 10 placebo recipients had serologic evidence of influenza A infection ( P=0.004 ) . During the 1995 - 1996 influenza season , 13 of 47 placebo recipients had laboratory-documented influenza A infection ( by culture or serologic examination ) compared with only 1 of 55 vaccine recipients ( P<0.001 ) ( calculated protective efficacy , 93 % [ CI , 69 % to 100 % ] 
    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: Influenza A infection may cause severe exacerbations of asthma with increased airway responsiveness and airflow obstruction ( 1 ) . Annual vaccination against influenza is therefore recommended for patients with asthma by the Chief Medical Officer of the Department of Health . However , some patients report exacerbations of their asthma , apparently related to influenza vaccination , and there is reluctance to adhere to the recommended vaccination policy ( 2 ) . We therefore studied the effect of a current subunit vaccine on symptoms , medication use , spirometry and airway responsiveness in patients with stable asthma Abstract In order to evaluate the impact of influenza-like illness and the effectiveness of influenza vaccination  in children with oncohematological disease who have completed cancer therapy , 182 children with a diagnosis of oncohematological disease were divided into two subgroups on the basis of the length of time off therapy ( < 6 months or 6–24 months ) and r and omised 1:1 to receive influenza vaccination or not . The controls were 91 otherwise healthy children unvaccinated against influenza .  The results show that the clinical and socioeconomic impact of influenza-like illnesses and the effectiveness of influenza vaccination  in oncohematological children who have completed cancer therapy are related to the length of the off therapy period , and seem to be significantly greater in those who have been off therapy for less than 6 months in comparison with healthy controls . This suggests that the administration of influenza vaccination should be strongly recommended only among oncohematological children who have been off therapy for less than 6 months BACKGROUND Despite current recommendations , many people with asthma do not receive annual vaccination against influenza , partly because of concern that vaccine may trigger exacerbations . Colds can trigger exacerbations , which may be mistaken for vaccine-related adverse events . We undertook a double-blind placebo-controlled multicentre crossover study to assess the safety of influenza vaccine  in patients with asthma , with allowance for the occurrence of colds . METHODS We studied 262 patients , aged 18 - 75 years , who recorded daily peak expiratory flow ( PEF ) , respiratory symptoms , medication , medical consultations , and hospital admissions for 2 weeks before the first injection and until 2 weeks after the second injection . Order of injection ( vaccine and placebo ) was assigned r and omly . There was an interval of 2 weeks between injections . The main outcome measure was an exacerbation of asthma within 72 h of injection ( defined as a fall in PEF of > 20 % ) . FINDINGS Among 255 participants with paired data , 11 recorded a fall in PEF of more than 20 % after vaccine compared with three after placebo ( McNemar 's test p=0.06 ) ; a fall of more than 30 % was recorded by eight after vaccine compared with none after placebo ( binomial test p=0.008 ) . However , when participants with colds were excluded , there was no significant difference in the numbers with falls of more than 20 % between vaccine and placebo ( six vs three ; binomial test p=0.51 ) , although the difference for PEF decreases of more than 30 % approached significance ( five vs none ; binomial test , p=0.06 ) . This association was confined to first-time vaccinees . INTERPRETATION Our findings indicate that pulmonary-function abnormalities may occur as a complication of influenza vaccination . However , the risk of pulmonary complications is very small and outweighed by the benefits of vaccination Little is known about the factors that govern the level of  HIV-1 replication in infected individuals . Recent studies ( using potent antiviral drugs ) of the kinetics of HIV-1 replication in vivo have demonstrated that steady-state levels of viremia are sustained by continuous rounds of de novo infection and the associated rapid turnover of CD4 + T lymphocytes . However , no information is available concerning the biologic variables that determine the size of the pool of T cells that are susceptible to virus infection or the amount of virus produced from infected cells . Furthermore , it is not known whether all CD4 + T lymphocytes are equally susceptible to HIV-1 infection at a given time or whether the infection is focused on cells of a particular state of activation or antigenic specificity . Although HIV-1 replication in culture is known to be greatly facilitated by T cell activation , the ability of specific antigenic stimulation to augment HIV-1 replication in vivo has not been studied . We sought to determine whether vaccination of HIV-1-infected adults leads to activation of virus replication and the targeting of vaccine antigen- responsive T cells for virus infection and destruction . Should T cell activation result ing from exposure to environmental antigens prove to be an important determinant of the steady-state levels of HIV-1 replication in vivo and lead to the preferential loss of specific population s of CD4 + T lymphocytes , it would have significant implication s for our underst and ing of and therapeutic strategies for HIV-1 disease . To begin to address these issues , HIV-1-infected individuals and uninfected controls were studied by measurement of immune responses to influenza antigens and quantitation of virion- associated plasma HIV-1 RNA levels at baseline and at intervals after immunization with the trivalent influenza vaccine . Influenza vaccination result ed in readily demonstrable but transient increases in plasma HIV-1 RNA levels , indicative of activation of viral replication , in HIV-1-infected individuals with preserved ability to immunologically respond to vaccine antigens . Activation of HIV-1 replication by vaccination was more often seen and of greater magnitude in individuals who displayed a T cell proliferative response to vaccine antigens at baseline and in those who mounted a significant serologic response after vaccination . The fold increase in viremia , as well as the rates of increase of HIV-1 in plasma after vaccination and rates of viral decline after peak viremia , were higher in individuals with higher CD4 + T cell counts . ( ABSTRACT TRUNCATED AT 400 WORDS Influenza vaccination is recommended for patients with HIV-1 infection ( 1 ) , but no studies have measured its efficacy in this population . Patients infected with HIV-1 , especially those with low CD4 + cell counts , often have minimal antibody responses to influenza vaccine ( 2 , 3 ) , leading some research ers to conclude that vaccination is not cost-effective ( 4 ) . In addition , vaccination has been associated with transient increases in HIV replication ( 5 - 8 ) and small decreases in percentage of CD4 cells ( 8) ; both of these findings are of undetermined clinical relevance . To better estimate the potential benefit of routine influenza vaccination in persons infected with HIV , we conducted a r and omized , controlled trial of influenza vaccine in a sample of HIV-1-infected patients during one influenza season . Methods Study Design The study site , a hospital-based clinic affiliated with the U.S. military , provides care to 400 to 500 patients infected with HIV-1 . Posters invited patients who visited the clinic from October to December 1995 to refer themselves for enrollment . All HIV-infected patients who had not yet received their annual influenza vaccine were eligible to participate . All patients gave informed consent , and the hospital 's institutional review board approved the study . Blood was drawn for measurement of CD4 + cell counts , influenza antibody titers , and plasma quantitative HIV-1 RNA level . Using a r and om computer-generated sequence , which was kept sealed until the end of the study , pharmacy staff prepared syringes that were filled with saline or with influenza vaccine purchased by the hospital for clinical use ( whole virion containing 15 g each of A/Johannesburg/33/94 [ H3N2 ] , A/Texas/36/91 [ H1N1 ] , and B/Harbin/07/94 [ Pasteur Mrieux Connaught , Lyon , France ] . Clinic staff could not distinguish vaccine from placebo . At 1 and 3 months after vaccination , patients returned for follow-up measurement of CD4 + cell count and HIV-1 RNA level and for serologic examination for influenza . Patients returned for viral cultures only if respiratory symptoms developed . At the conclusion of the study , all patients were interviewed about respiratory illness ( broadly defined as any rhinitis , pharyngitis , or cough ) experienced during the study period . Laboratory Assays Sample s for T-cell subset analysis were processed according to st and ard methods . The variation of percentage of CD4 cells on replicate testing was 1 % . Plasma sample s for measurement of HIV-1 RNA level were drawn in acid citrate-dextrose tubes , separated at 2000 rpm for 15 minutes , and stored at 70 C. Serum sample s were stored similarly . Quantitative HIV RNA reverse transcriptase polymerase chain reaction assays ( Amplicor Monitor , Roche , Nutley , New Jersey ) were done in batches by Quest Diagnostics at Nichols Institute , San Juan Capistrano , California ; all specimens from individual patients were tested simultaneously . The lower limits of quantification were 400 RNA copies per mL of plasma , and the intra-assay coefficient of variation of 32.3 % to 45.3 % . Serum sample s taken before and 1 month after vaccination were tested for antibody responses to each of the three individual vaccine components by microtiter hemagglutination inhibition ; egg-grown virus antigens starting at a dilution of 1:4 were used ( 9 ) . Sample s below this threshold were assigned a value of 1:2 . Serum sample s obtained 1 month and 3 months after vaccination were tested against the A/Johannesburg/33/94 and A/Nanchang/33/95 ( H3N2 ) virus strains ; the latter is antigenically similar to the A/Wuhan/95-like viruses that were circulating in the United States in 1995 and 1996 . All of the patients who responded to A/Johannesburg/94 ( those who demonstrated a fourfold or greater increase in titer ) also responded to A/Nanchang/95 . Because both A/Johannesburg-like and A/Wuhan-like viruses circulated in the study sample , an antibody response to A/Nanchang/95 occurring between 1 and 3 months after vaccination was defined as evidence of influenza A infection . Viral cultures were performed by using st and ard laboratory methods . Statistical Analysis Statistical analysis was done by using Statview 4.5 software ( Abacus Concepts , Inc. , Berkeley , California ) . Changes in antibody titer , plasma HIV-1 RNA level , and CD4 + cell count were analyzed by using the unpaired t-test to compare vaccine and placebo recipients . Illness rates were compared by using the chi-square test . The percentage of protective efficacy of vaccination was calculated as 1 ( risk ratio comparing vaccine and placebo recipients ) 100 . Results Characteristics of the Study Group A total of 102 patients enrolled in the study . Fifty-five patients were r and omly assigned to receive vaccine , and 47 patients were r and omly assigned to receive placebo .  Table 1 summarizes the participants ' characteristics . Because the study was conducted in fall 1995 , antiretroviral regimens were limited to single or double reverse transcriptase inhibitor combinations . No patients were taking protease inhibitors .  All patients had received at least one previous influenza vaccination .  Table 1 . Baseline Characteristics of the Study Sample Serologic Response to Vaccination Prevaccination and postvaccination paired serum sample s from 49 vaccine recipients and 43 placebo recipients were tested against the three vaccine constituents ( Table 2 ) . Although the aggregate responses to vaccination were statistically significant , only 12 % , 29 % , and 36 % of vaccine recipients had a fourfold or greater response to the A/H1N1 , A/H3N2 , and B components , respectively . Table 2 . Antibody Response to Influenza Vaccination  Protective Efficacy of Influenza Vaccination Peak influenza activity in San Diego County in 1995 and 1996 occurred from mid-January through early February and was predominately caused by the A/Johannesburg ( H3N2 ) virus strain ; some A/Wuhan ( H3N2 ) virus was also present ( San Diego Public Health Department . Personal communication ) . Sixteen of 55 vaccine recipients ( 29 % ) , compared with 23 of 47 placebo recipients ( 49 % ) , reported symptoms of respiratory illness during the fall and winter of 1995 and 1996 ( P=0.04 ) . No patients were hospitalized or treated for pneumonia during the study period . Twenty of 39 patients ( 12 placebo recipients and 8 vaccine recipients ) who reported respiratory illness returned to the clinic for viral respiratory culture . Influenza A ( H3N2 ) virus was isolated from 3 patients , and influenza B virus was isolated from 2 patients , all of whom received placebo . Serum sample s taken 1 and 3 months after vaccination were available for 86 patients ( 43 vaccine recipients and 43 placebo recipients ) . One vaccine recipient and 10 placebo recipients had serologic evidence of influenza A infection ( P=0.004 ) . During the 1995 - 1996 influenza season , 13 of 47 placebo recipients had laboratory-documented influenza A infection ( by culture or serologic examination ) compared with only 1 of 55 vaccine recipients ( P<0.001 ) ( calculated protective efficacy , 93 % [ CI , 69 % to 100 % ] 
    Output:
    