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: GH , 0.1 IU/kg/day 6 days/week , was given to 30 early pubertal short patients for 3 years . There were 16 males , aged 14.4 + /- 0.8 years , and 14 females , aged 12.2 + /- 1.2 years , at pubertal stage 2 or 3 with slow growth ( 4.2 + /- 1.2 cm/year ) and no detected GH insufficiency or other cause for short stature . They were r and omized in 2 groups : group A with GH alone , and group B with GH and a gonadotropin-releasing hormone agonist during the first 2 years . 28 of the 30 patients completed 3 years of treatment . The annual growth rate increased during the 1st year in both groups and sexes , the increase being significant ( p < 0.01 ) in group A only . Patients of group A kept an improved growth velocity in the 2nd year , then returned to pretreatment growth rate in the 3rd year , while completing their sexual development and bone maturation . Their height , expressed as st and ard deviation score ( SDS ) for bone age , improved in the first 2 years , but decreased thereafter . Group B patients returned to pretreatment growth velocity in the 2nd year , and had no significant improvement in growth rate in the 3rd year with GH alone . Their bone maturation , slow when on the GnRH agonist , accelerated when sexual development resumed . At the end of the 3 years , height , expressed as SDS for age , improved in group A from -2.5 + /- 0.6 to -1.5 + /- 0.4 in males ( p < 0.05 ) and from -2.8 + /- 0.5 to -2.1 + /- 0.9 in females ( NS ) . ( ABSTRACT TRUNCATED AT 250 WORDS Short-term administration of human growth hormone to children with idiopathic short stature can improve mean growth rate and predicted adult height . It is yet unknown whether therapy would alter pubertal development or affect final height . Three-year treatment results in a group of children with idiopathic short stature are reported . For year 1 of the study , 121 prepubertal children were r and omly selected to receive somatotropin , 0.3 mg/kg per week , administered subcutaneously three times weekly ( n = 63 ) , or to be nontreatment control subjects ( n = 58 ) . After 1 year , all subjects were again r and omly selected to receive either three-times-weekly or daily dosing at the same total dose . For the 92 subjects who completed 36 months of treatment , mean growth rate increased from a mean of 4.6 cm/yr before treatment to a mean of 8.0 cm/yr in the first year of treatment . Daily dosing result ed in a significantly faster mean growth rate ( 9.0 cm/yr ) than three-times-weekly dosing ( 7.8 cm/yr ) ( p = 0.0005 ) . Mean growth rates were 7.6 and 7.2 cm/yr during years 2 and 3 , respectively , and did not differ by dosing group . Mean st and ardized height for all subjects improved from -2.7 to -1.6 after 3 years . When the growth rate was st and ardized for bone age , however , subjects who remained prepubertal had a significantly greater gain in mean height SD score than subjects who became pubertal during that 3-year period ( p < 0.02 ) . Mean st and ardized Bayley-Pinneau predicted adult height SD score increased from -2.7 to -1.6 and was independent of the timing of pubertal onset , but for individuals this score was more variable . Year-1 growth response , expressed as growth rate or change in height SD score , was the best predictor of growth in subsequent years . Responses to therapy could not be reliably predicted from baseline anthropometric variables , plasma insulin-like growth factor I SD score , growth hormone levels . Final height assessment will be needed to determine the ultimate benefit of therapy GH is often used to treat children with idiopathic short stature despite the lack of definitive , long-term studies of efficacy . We performed a r and omized , double-blind , placebo-controlled trial to determine the effect of GH on adult height in peripubertal children . Subjects ( n = 68 ; 53 males and 15 females ) , 9 - 16 yr old , with marked , idiopathic short stature [ height or predicted height < or = -2.5 sd score ( SDS ) ] received either GH ( 0.074 mg/kg ) or placebo sc three times per week until they were near adult height . At study termination , adult height measurements were available for 33 patients after mean treatment duration of 4.4 yr . Adult height was greater in the GH-treated group ( -1.81 + /- 0.11 SDS , least squares mean + /- sem ) than in the placebo-treated group ( -2.32 + /- 0.17 SDS ) by 0.51 SDS ( 3.7 cm ; P < 0.02 ; 95 % confidence interval , 0.10 - 0.92 SDS ) . A similar GH effect was demonstrated in terms of adult height SDS minus baseline height SDS and adult height SDS minus baseline predicted height SDS . Modified intent-to-treat analysis in 62 patients treated for at least 6 months indicated a similar GH effect on last observed height SDS ( 0.52 SDS ; 3.8 cm ; P < 0.001 ; 95 % confidence interval , 0.22 - 0.82 SDS ) and no important dropout bias . In conclusion , GH treatment increases adult height in peripubertal children with marked idiopathic short stature ABSTRACT . Overnight physiological  growth hormone ( GH ) secretion was evaluated in 95 short , prepubertal children ( 73 boys , 22 girls ) . All the children were below the 3rd centile for height and achieved CH levels greater than 15 mU/1 following pharmacological stimulation . The mean average GH level was 7.1 mU/l and the mean sum of pulse amplitudes 80.4 mU/l . No relationship was found between age , height or height velocity and any of the parameters of GH secretion . The group was r and omized to receive placebo , GH or remain under observation for the first 6 months and then all patients received GH treatment for a further 6 months . Those treated with GH , 0.27 IU/kg ( 0.1 mg/kg ) three times weekly , in the first phase . demonstrated a mean increase in height velocity SDS of 3.24 . There was no difference in growth response between the placebo or observation groups . In the second 6‐month period . all children received GH according to the same dose regimen : they were then observed for a further 6 months following its discontinuation . In the 6 months following withdrawal of GH , all groups showed a significant fall in height velocity SDS , which returned to pretreatment levels , without demonstrating‘catch‐down’growth . Repeat sampling of overnight GH secretion within 3 days of discontinuing GH showed normal secretory patterns with a small reduction in mean peak amplitude . These results suggest that short children without classic GH insufficiency respond well to exogenous GH in the short term and return to pretreatment height velocities afterwards . Consequently , it may be possible to increase final adult height in such children by GH treatment The aim of this study was to compare the growth response of 22 short pre‐pubertal children without growth hormone deficiency , treated with a single daily growth hormone injection ( group A ) , to the growth response of 27 similar children , treated with the same daily dose divided into 2 subcutaneous injections per day ( group B ) , for 1 y , in a r and omized study . GH treatment significantly promoted growth parameters , height st and ard deviation score and height velocity st and ard deviation score in both groups . Serum insulin‐like growth factor I was also increased . There were no significant differences in growth response , serum IGF‐I levels , or the advance in bone age between the two study groups after 1 y of GH therapy . We conclude that twice daily s.c . growth hormone injections provide no advantages over once daily injection of the same dose in promoting the linear growth of short children without growth hormone deficiency Seventy-seven prepubertal short children with heights below the third centile for age and gender were divided into three groups according to their peak GH response to clonidine and insulin provocation .  Group ( I ) included 30 children with peak GH response < 7 micrograms/l , group ( II ) included 19 children , with GH peak response between 7 and 10 micrograms/l , and group ( III ) included 24 children with GH peak > 10 micrograms/l . Each group was divided into two subgroups , a and b. Subgroups (I)b , (II)a and (III)b were treated daily for 1 year with subcutaneous recombinant human growth hormone ( GH ) 15 U/m2/week , and group (I)a was treated with GH ( 30 U/m2/week ) . Before initiation of treatment , the chronological age , the height st and ard deviation score ( HtSDS ) , and the bone age delay did not differ among the study subgroups . The height growth velocity ( GV ) and insulin-like growth factor-I concentrations were significantly higher in group ( III ) , with normal GH response to provocation , compared to those for group ( I ) with GH deficiency . All the children had normal thyroid function and normal glucose tolerance . CT examination of the hypothalamic-pituitary area revealed a picture of empty sella ( either partial or complete ) in 35 per cent of the children in group ( I ) and 21 per cent of children in group ( II ) . After 1 year of GH therapy , the HtSDS , GV , and IGF-I concentrations increased significantly in the four subgroups treated with GH compared to their pretreatment values and to their controls . All the children in group ( I ) were responders ( increment in GV of 2 cm2/year above the pretreatment GV ) , of the nine subjects treated in group (II)a , one child was a non-responder and of the 12 children in group (III)a three children were non-responders . GV was non-significantly higher in group (I)a ( 30 U/m2/week ) v. group (I)b ( 15 U/m2/week ) . GV of children in groups (I)b , with abnormal GH response to provocation , was significantly higher than GV of children in group (III)a . Bone age advanced by less than 1 year in the treated groups ( 0.84 + /- 0.14 years ) v. the untreated groups ( 0.73 + /- 0.3 years ) . None of the children had impaired glucose tolerance or abnormal thyroid function after 1 year of GH therapy . In all the treated children , GV after 1 year of GH treatment was correlated significantly with the pretreatment GV ( r = -0.63 , P < 0.01 ) , peak GH response to provocation ( r = -0.59 , P < 0.01 ) , IGF-I concentration ( r = -0.54 , P < 0.01 ) , and positively with the GH dose ( r = 0.589 , P < 0.01 ) . In group ( III ) children , with normal GH reserve , GV correlated significantly with the pretreatment GV ( r = -0.48 , P < 0.01 ) and negatively with the GH peak response to provocation ( r = -0.25 , P < 0.05 ) . In conclusion , GH therapy improved GV of children growing along or parallel to the 3rd centile , irrespective of their GH response to provocation , without untoward effect on skeletal maturation , thyroid function or glucose tolerance Two hundred and thirty-six patients with idiopathic short stature ( ISS ) ( 184 m , 52 f ) who presented at a mean age of 12.2 ( range 2.8 - 17.5 ) years , a mean height of -2.16 st and ard deviation score ( SDS ) , a mean target height ( THT ) of -0.27 SDS ( m = f ) , were reinvestigated at a mean age of 20.5 ( range 18 - 24 ) years . 182(142 m , 37 f ) ( 67 % ) had reached  normal adult height ( AHT ) while 54 ( 39 m , 15 f ) ( 23 % ) had not . However , only 23 ( 17 m , 6 f ) did not reach a height within their familial target . Patients were subdivided into 2 groups according to deviation from familial height target : 60(44 m , 16 f ) were considered adequate for their families ( group 1 ) , while 176 ( 140 m , 39 f ) were smaller ( group 2 ) . Children in group 1 were younger and bone age ( BA ) was less retarded . Patients in group 1 reached their THT , this was not the case in group 2 . Young age , low THT and low predicted adult height ( PAH ) at presentation were the factors associated with poor stratural outcome , but AHT could not be predicted in individuals . In boys , PAH ( Bayley-Pinneau ) ( 0.0 SDS ) exceeded AHT ( -0.7 SDS ) , in girls , both were almost identical ( -0.79 , -0.77 SDS ) . Since most children with ISS reach an AHT within the normal range , attempts to improve AHT by means of growth-promoting therapies appear to be justified only in a minority of selected patients with ISS . Methods to improve the accuracy of individual height prognoses are needed We evaluated the effect of six-month treatment with growth hormone ( GH ) or low- 
    Output:
    
agent
GH therapy can increase short-term growth and improve ( near ) final height .
Increases in height are such that treated individuals remain relatively short when compared with peers of normal stature .
***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: GH , 0.1 IU/kg/day 6 days/week , was given to 30 early pubertal short patients for 3 years . There were 16 males , aged 14.4 + /- 0.8 years , and 14 females , aged 12.2 + /- 1.2 years , at pubertal stage 2 or 3 with slow growth ( 4.2 + /- 1.2 cm/year ) and no detected GH insufficiency or other cause for short stature . They were r and omized in 2 groups : group A with GH alone , and group B with GH and a gonadotropin-releasing hormone agonist during the first 2 years . 28 of the 30 patients completed 3 years of treatment . The annual growth rate increased during the 1st year in both groups and sexes , the increase being significant ( p < 0.01 ) in group A only . Patients of group A kept an improved growth velocity in the 2nd year , then returned to pretreatment growth rate in the 3rd year , while completing their sexual development and bone maturation . Their height , expressed as st and ard deviation score ( SDS ) for bone age , improved in the first 2 years , but decreased thereafter . Group B patients returned to pretreatment growth velocity in the 2nd year , and had no significant improvement in growth rate in the 3rd year with GH alone . Their bone maturation , slow when on the GnRH agonist , accelerated when sexual development resumed . At the end of the 3 years , height , expressed as SDS for age , improved in group A from -2.5 + /- 0.6 to -1.5 + /- 0.4 in males ( p < 0.05 ) and from -2.8 + /- 0.5 to -2.1 + /- 0.9 in females ( NS ) . ( ABSTRACT TRUNCATED AT 250 WORDS Short-term administration of human growth hormone to children with idiopathic short stature can improve mean growth rate and predicted adult height . It is yet unknown whether therapy would alter pubertal development or affect final height . Three-year treatment results in a group of children with idiopathic short stature are reported . For year 1 of the study , 121 prepubertal children were r and omly selected to receive somatotropin , 0.3 mg/kg per week , administered subcutaneously three times weekly ( n = 63 ) , or to be nontreatment control subjects ( n = 58 ) . After 1 year , all subjects were again r and omly selected to receive either three-times-weekly or daily dosing at the same total dose . For the 92 subjects who completed 36 months of treatment , mean growth rate increased from a mean of 4.6 cm/yr before treatment to a mean of 8.0 cm/yr in the first year of treatment . Daily dosing result ed in a significantly faster mean growth rate ( 9.0 cm/yr ) than three-times-weekly dosing ( 7.8 cm/yr ) ( p = 0.0005 ) . Mean growth rates were 7.6 and 7.2 cm/yr during years 2 and 3 , respectively , and did not differ by dosing group . Mean st and ardized height for all subjects improved from -2.7 to -1.6 after 3 years . When the growth rate was st and ardized for bone age , however , subjects who remained prepubertal had a significantly greater gain in mean height SD score than subjects who became pubertal during that 3-year period ( p < 0.02 ) . Mean st and ardized Bayley-Pinneau predicted adult height SD score increased from -2.7 to -1.6 and was independent of the timing of pubertal onset , but for individuals this score was more variable . Year-1 growth response , expressed as growth rate or change in height SD score , was the best predictor of growth in subsequent years . Responses to therapy could not be reliably predicted from baseline anthropometric variables , plasma insulin-like growth factor I SD score , growth hormone levels . Final height assessment will be needed to determine the ultimate benefit of therapy GH is often used to treat children with idiopathic short stature despite the lack of definitive , long-term studies of efficacy . We performed a r and omized , double-blind , placebo-controlled trial to determine the effect of GH on adult height in peripubertal children . Subjects ( n = 68 ; 53 males and 15 females ) , 9 - 16 yr old , with marked , idiopathic short stature [ height or predicted height < or = -2.5 sd score ( SDS ) ] received either GH ( 0.074 mg/kg ) or placebo sc three times per week until they were near adult height . At study termination , adult height measurements were available for 33 patients after mean treatment duration of 4.4 yr . Adult height was greater in the GH-treated group ( -1.81 + /- 0.11 SDS , least squares mean + /- sem ) than in the placebo-treated group ( -2.32 + /- 0.17 SDS ) by 0.51 SDS ( 3.7 cm ; P < 0.02 ; 95 % confidence interval , 0.10 - 0.92 SDS ) . A similar GH effect was demonstrated in terms of adult height SDS minus baseline height SDS and adult height SDS minus baseline predicted height SDS . Modified intent-to-treat analysis in 62 patients treated for at least 6 months indicated a similar GH effect on last observed height SDS ( 0.52 SDS ; 3.8 cm ; P < 0.001 ; 95 % confidence interval , 0.22 - 0.82 SDS ) and no important dropout bias . In conclusion , GH treatment increases adult height in peripubertal children with marked idiopathic short stature ABSTRACT . Overnight physiological  growth hormone ( GH ) secretion was evaluated in 95 short , prepubertal children ( 73 boys , 22 girls ) . All the children were below the 3rd centile for height and achieved CH levels greater than 15 mU/1 following pharmacological stimulation . The mean average GH level was 7.1 mU/l and the mean sum of pulse amplitudes 80.4 mU/l . No relationship was found between age , height or height velocity and any of the parameters of GH secretion . The group was r and omized to receive placebo , GH or remain under observation for the first 6 months and then all patients received GH treatment for a further 6 months . Those treated with GH , 0.27 IU/kg ( 0.1 mg/kg ) three times weekly , in the first phase . demonstrated a mean increase in height velocity SDS of 3.24 . There was no difference in growth response between the placebo or observation groups . In the second 6‐month period . all children received GH according to the same dose regimen : they were then observed for a further 6 months following its discontinuation . In the 6 months following withdrawal of GH , all groups showed a significant fall in height velocity SDS , which returned to pretreatment levels , without demonstrating‘catch‐down’growth . Repeat sampling of overnight GH secretion within 3 days of discontinuing GH showed normal secretory patterns with a small reduction in mean peak amplitude . These results suggest that short children without classic GH insufficiency respond well to exogenous GH in the short term and return to pretreatment height velocities afterwards . Consequently , it may be possible to increase final adult height in such children by GH treatment The aim of this study was to compare the growth response of 22 short pre‐pubertal children without growth hormone deficiency , treated with a single daily growth hormone injection ( group A ) , to the growth response of 27 similar children , treated with the same daily dose divided into 2 subcutaneous injections per day ( group B ) , for 1 y , in a r and omized study . GH treatment significantly promoted growth parameters , height st and ard deviation score and height velocity st and ard deviation score in both groups . Serum insulin‐like growth factor I was also increased . There were no significant differences in growth response , serum IGF‐I levels , or the advance in bone age between the two study groups after 1 y of GH therapy . We conclude that twice daily s.c . growth hormone injections provide no advantages over once daily injection of the same dose in promoting the linear growth of short children without growth hormone deficiency Seventy-seven prepubertal short children with heights below the third centile for age and gender were divided into three groups according to their peak GH response to clonidine and insulin provocation .  Group ( I ) included 30 children with peak GH response < 7 micrograms/l , group ( II ) included 19 children , with GH peak response between 7 and 10 micrograms/l , and group ( III ) included 24 children with GH peak > 10 micrograms/l . Each group was divided into two subgroups , a and b. Subgroups (I)b , (II)a and (III)b were treated daily for 1 year with subcutaneous recombinant human growth hormone ( GH ) 15 U/m2/week , and group (I)a was treated with GH ( 30 U/m2/week ) . Before initiation of treatment , the chronological age , the height st and ard deviation score ( HtSDS ) , and the bone age delay did not differ among the study subgroups . The height growth velocity ( GV ) and insulin-like growth factor-I concentrations were significantly higher in group ( III ) , with normal GH response to provocation , compared to those for group ( I ) with GH deficiency . All the children had normal thyroid function and normal glucose tolerance . CT examination of the hypothalamic-pituitary area revealed a picture of empty sella ( either partial or complete ) in 35 per cent of the children in group ( I ) and 21 per cent of children in group ( II ) . After 1 year of GH therapy , the HtSDS , GV , and IGF-I concentrations increased significantly in the four subgroups treated with GH compared to their pretreatment values and to their controls . All the children in group ( I ) were responders ( increment in GV of 2 cm2/year above the pretreatment GV ) , of the nine subjects treated in group (II)a , one child was a non-responder and of the 12 children in group (III)a three children were non-responders . GV was non-significantly higher in group (I)a ( 30 U/m2/week ) v. group (I)b ( 15 U/m2/week ) . GV of children in groups (I)b , with abnormal GH response to provocation , was significantly higher than GV of children in group (III)a . Bone age advanced by less than 1 year in the treated groups ( 0.84 + /- 0.14 years ) v. the untreated groups ( 0.73 + /- 0.3 years ) . None of the children had impaired glucose tolerance or abnormal thyroid function after 1 year of GH therapy . In all the treated children , GV after 1 year of GH treatment was correlated significantly with the pretreatment GV ( r = -0.63 , P < 0.01 ) , peak GH response to provocation ( r = -0.59 , P < 0.01 ) , IGF-I concentration ( r = -0.54 , P < 0.01 ) , and positively with the GH dose ( r = 0.589 , P < 0.01 ) . In group ( III ) children , with normal GH reserve , GV correlated significantly with the pretreatment GV ( r = -0.48 , P < 0.01 ) and negatively with the GH peak response to provocation ( r = -0.25 , P < 0.05 ) . In conclusion , GH therapy improved GV of children growing along or parallel to the 3rd centile , irrespective of their GH response to provocation , without untoward effect on skeletal maturation , thyroid function or glucose tolerance Two hundred and thirty-six patients with idiopathic short stature ( ISS ) ( 184 m , 52 f ) who presented at a mean age of 12.2 ( range 2.8 - 17.5 ) years , a mean height of -2.16 st and ard deviation score ( SDS ) , a mean target height ( THT ) of -0.27 SDS ( m = f ) , were reinvestigated at a mean age of 20.5 ( range 18 - 24 ) years . 182(142 m , 37 f ) ( 67 % ) had reached  normal adult height ( AHT ) while 54 ( 39 m , 15 f ) ( 23 % ) had not . However , only 23 ( 17 m , 6 f ) did not reach a height within their familial target . Patients were subdivided into 2 groups according to deviation from familial height target : 60(44 m , 16 f ) were considered adequate for their families ( group 1 ) , while 176 ( 140 m , 39 f ) were smaller ( group 2 ) . Children in group 1 were younger and bone age ( BA ) was less retarded . Patients in group 1 reached their THT , this was not the case in group 2 . Young age , low THT and low predicted adult height ( PAH ) at presentation were the factors associated with poor stratural outcome , but AHT could not be predicted in individuals . In boys , PAH ( Bayley-Pinneau ) ( 0.0 SDS ) exceeded AHT ( -0.7 SDS ) , in girls , both were almost identical ( -0.79 , -0.77 SDS ) . Since most children with ISS reach an AHT within the normal range , attempts to improve AHT by means of growth-promoting therapies appear to be justified only in a minority of selected patients with ISS . Methods to improve the accuracy of individual height prognoses are needed We evaluated the effect of six-month treatment with growth hormone ( GH ) or low- 
    Output:
    