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: Short stature and ovarian failure are the main features in Turner syndrome ( TS ) . To optimize GH and estrogen treatment , we studied 68 previously untreated girls with TS , age 2 - 11 yr , who were r and omly assigned to one of three GH dosage groups : group A , 4 IU/m2 day ( approximately 0.045 mg/kg x day ) ; group B , first yr 4 , thereafter 6 IU/m2 x day ( approximately 0.0675 mg/kg/day ) ; group C , first yr 4 , second yr 6 , thereafter 8 IU/m2 x day ( approximately 0.090 mg/kg x day ) . In the first 4 yr of GH treatment , no estrogens for pubertal induction were given to the girls . Thereafter , girls started with 17beta-estradiol ( 5 microg/kg bw x day , orally ) when they had reached the age of 12 yr . Subjects were followed up until attainment of adult height or until cessation of treatment because of satisfaction with the height achieved . Seven-year data of all girls were evaluated to compare the growth-promoting effects of three GH dosages during childhood . After 7 yr , 85 % of the girls had reached a height within the normal range for healthy Dutch girls . The 7-yr increment in height SD-score was significantly higher in groups B and C than in group A. In addition , we evaluated the data of 32 of the 68 girls who had completed the trial after a mean duration of treatment of 7.3 yr ( range , 5.0 - 8.75 ) . Mean ( SD ) height was 158.8 cm ( 7.1 ) , 161.0 cm ( 6.8 ) , and 162.3 cm ( 6.1 ) in groups A , B , and C , respectively . The mean ( SD ) difference between predicted adult height before treatment and achieved height was 12.5 cm ( 2.1 ) , 14.5 cm ( 4.0 ) , and 16.0 cm ( 4.1 ) for groups A , B , and C , respectively , being significantly different between group A and group C. GH treatment was well tolerated in all three GH dosage groups . In conclusion , GH treatment starting in relatively young girls with TS results in normalization of height during childhood , as well as of adult height , in most of the individuals . With this GH and estrogen treatment regimen , most girls with TS can grow and develop much more in conformity with their healthy peers To assess body proportions in girls with Turner syndrome ( TS ) during long term GH treatment , height , sitting height ( SH ) , h and ( H and ) and foot ( Foot ) lengths , and biacromial ( Biac ) and biiliacal ( Biil ) diameters were measured in 68 girls with TS participating in a GH dose-response trial . These previously untreated girls with TS , aged 2 - 11 yr , were r and omly assigned to 1 of 3 GH dosage groups : group A , 4 IU/m2 x day ; group B , first year 4 and thereafter 6 IU/m2 x day ; group C , first year 4 , second year 6 , and thereafter 8 IU/m2 x day . Seven-year data were evaluated to assess the effect of GH treatment on body proportions during childhood . In addition , data from all girls who had reached adult height were evaluated to determine the effect on the adult body proportions . All results were adjusted for age and sex and expressed as SD scores using reference values of healthy Dutch girls . To describe the proportions of SH , H and , Foot , Biac , and Biil to height , these values were adjusted for the SD score of height and were expressed as shape values , using the formula , e.g. for SH : shape SH = ( SH SD score - height SD score)/square root(2 - 2 x correlation coefficient between SH and height in the reference population ) . Furthermore , SD scores using references of untreated girls with TS were calculated for height and SH . Values less than -2 or more than + 2 were considered outside the normal range . At baseline , the shape values of all measurements were significantly higher than zero , but most mean shape values were still within the normal range . Seven-year data of 64 girls and adult height data of 32 girls showed that an increase in height was accompanied by an even higher increase in Foot , result ing in mean SD scores above zero and shape values of + 2 and higher . The increase in the shape value of Foot was significantly higher in groups B and C compared to that in group A after 7 yr of GH treatment , but there were no significant differences between the GH dosage groups in the girls who had reached adult height . The shape values of SH had decreased to values closer to zero after reaching adult height , especially in group A. A similar pattern in the relationship of SH to height was seen using references of girls with TS . No significant changes in the other proportions were found after reaching adult height . In conclusion , on the average , untreated girls with TS have relatively large trunk , h and s , and feet , and broad shoulders and pelvis compared to height . The increase in height after long term GH treatment is accompanied by an even higher increase in Foot and a moderate improvement of the disproportion between height and SH . Recently published reference data from untreated adults with TS and the results of a different patient group receiving a comparable GH dosage suggest that the disproportionate growth of feet has to be considered a part of the natural development in TS , but might be influenced by higher GH dosages . The development of large feet can play a role in the decision of the girl to discontinue GH treatment in the last phase of growth Seventy girls with Turner syndrome , verified by karyotype , were r and omly assigned to observation or treatment with human growth hormone ( hGH ) , ox and rolone , or a combination of hGH plus ox and rolone for a period of 12 to 24 months , to assess the effect of treatment on growth velocity and adult height . Subsequently , all subjects received either hGH alone or hGH plus ox and rolone . Data are presented for 62 subjects treated for a period of 3 to 6 years . When compared with the anticipated growth rate in untreated patients , the growth rate after treatment with hGH , both alone and in combination with ox and rolone , showed a sustained increase for at least 6 years . Treatment is continuing in over half of the subjects ; at present , 14 ( 82 % ) of 17 girls receiving hGH alone and 41 ( 91 % ) of 45 girls receiving combination therapy exceeded their expected adult heights .  Thirty girls have completed treatment ; mean height for these 30 patients is 151.9 cm , compared with their mean original projected adult height of 143.8 cm . We conclude that therapy with hGH , alone and in combination with ox and rolone , can result in a sustained increase in growth rate and a significant increase in adult height for most prepubertal girls with Turner syndrome To optimize the growth promoting effect of growth hormone ( GH ) , 65 previously untreated girls with Turner syndrome ( TS ) , chronological age ( CA ) 2 - 11 yr , were r and omized into 3 dosage regimen groups : A , B , and C , with a daily recombinant-human GH dose during 4 study years of 4 - 4 - 4 - 4 , 4 - 6 - 6 - 6 , and 4 - 6 - 8 - 8 IU/m2 b.s . The first GH dosage increase in groups B and C result ed in a significantly higher mean height velocity ( HV ) compared with constant dose group A. During the third year , when the dose was raised again only in group C , mean HV was significantly higher in groups B and C than in group A , and in group C compared with group B. In year 4 only group C mean HV remained significantly higher than group A. The pattern of change in HSDSCA ( Dutch-Swedish-Danish Turner references ) was identical ; however , in year 4 mean delta HSDSCA in group B also remained significantly higher than group A. After 4 yr GH treatment , the following was determined . 1 ) The mean delta HSDSCA was significantly higher for groups B and C compared with group A , but not significantly different between groups B and C. 2 ) Although significantly higher compared with estimated values for untreated Dutch girls with TS , bone maturation of the GH treated girls was not significantly different between groups . 3 ) It was positively related with the degree of bone age ( BA ) retardation at start of study and negatively with baseline CA . 4 ) Both the modified Index of Potential Height ( mIPHRUS ) and a recently developed Turner-specific final height ( FH ) prediction method ( PTSRUS ) , based on regression coefficients for H , CA , and bone age , showed significant increases in mean FH prediction , without significant differences between groups . PTSRUS values were markedly higher than the mIPHRUS values . Dose dependency could be shown for the area under the curve ( AUC ) for GH , but delta HSDSCA was not linearly related with AUC . Baseline GH binding protein ( BP ) levels were in 84 % of the cases within the normal age range ; the decrease in mean levels after 6 months GH was not significant . Mean insulin-like growth factor I ( IGF-I ) and IGFBP-3 plasma levels increased significantly , without significant differences between groups . delta HSDSCA during GH was dependent on IGF-I plasma levels at baseline and during the study period , beta-0.002 and beta-0.0004 . Thus , a stepwise GH-dosing approach reduced the " waning " effect of the growth response after 4 yr treatment without undue bone maturation . FH prediction was not significantly different between treatment groups . Irrespective of the GH dose used , initiation of GH treatment at a younger age was beneficial after 4 yr GH when expressed as actual cm gained or as gain in FH prediction , but was not statistically significant when expressed as delta HSDSCA over the study period In 1983 , a multicenter , collaborative , prospect i ve study was begun to investigate the efficacy of human growth hormone ( hGH ) , alone and in combination with ox and rolone , in girls with Turner syndrome . While subjects in the control group grew 3.8 cm/yr ( -0.1 SD for untreated Turner patients ) , subjects receiving hGH alone  grew 6.6 , 5.4 and 4.6 cm/yr in years 1 - 3 , respectively ( + 3.1 , + 2.0 , + 1.4 SD ) . Subjects in the combination therapy group grew 9.8 , 7.4 and 6.1 cm/yr ( + 6.6 , + 4.3 , + 3.0 SD ) . Turner subjects in both treatment groups showed increased in Bayley-Pinneau predicted adult heights and in Turner projected adult heights Preliminary results are presented after 2 years of the Canadian long-term multicentre study on the impact of hormone therapy on the final height , sexual development and psychological status of girls with Turner syndrome . Girls entering the study were r and omized either to be treated with recombinant human growth hormone or to act as controls . Both groups received oestrogen replacement therapy in the same dose and format at the age of 13 years . However , for the purpose s of the psychological study at this time , children receiving oestrogen were excluded from analysis . Girls treated with GH for a period of 2 years showed a significant increase in growth rate , which declined with continued treatment , while the growth rate in the control group remained constant throughout . There was a correlation between the higher growth rate and the girls ' perceptions of themselves as more intelligent , more attractive , having more friends , greater popularity and experiencing less teasing than the untreated group . Growth rate was not correlated with family or school functioning STUDY OBJECTIVE To determine the influence of the injection frequency and the initial bone age on the efficacy of treatment with biosynthetic growth hormone in Turner 's syndrome . DESIGN R and omized study . SETTING Referral-based pediatric endocrinology departments of seven university medical centers . PATIENTS Fifty-two patients with Turner 's syndrome confirmed with chromosomal analysis . TREATMENT Somatotropin recombinant DNA ( 24 IU/m2 of body surface area ) subcutaneously administered in three or six injections per week for 2 years . Patients who were older than 12 years at the beginning of the study received low doses of estrogen . RESULTS The following statistically significant findings supported the use of six injections per week compared with three injections per week : the mean ( + /- SD ) increment in height during 2 years was 11.3 cm ( 3.8 cm ) with six injections vs 8.6 cm ( 3.4 cm ) with three injections ; the increment in height st and ard deviation score was 0.9 cm ( 0.5 cm ) vs 0.6 cm ( 0.3 cm ) ; the growth velocity was 6.6 cm/y ( 2.0 cm/y ) vs 5.2 cm/y ( 1.7 cm/y ) in year 1 and 4.7 cm/y ( 2.0 cm/y ) vs 3.4 cm/y ( 1.7 cm/y ) in year 2 ; and the increment in height st and ard deviation score for bone age was 0.8 cm ( 0.5 cm ) vs 0.4 cm ( 0.6 cm ) . For patients whose initial bone age was more than 13 years , growth velocity increased by 1 to 2 cm in year 1 ; in year 2 no increment was observed . We did not observe adverse effects . CONCLUSIONS Biosynthetic growth hormone in a higher-frequency regimen in Turner 's syndrome is more efficient in terms of increment in height , growth velocity , and height st and ard deviation score for bone age than treatment in a lower-frequency regimen . In patients with an initial bone age of more than 13 years , the response was poor . Longer follow-up is necessary to assess the effect on final height OBJECTIVES To study final height in girls with Turner ’s syndrome treated with once or twice daily injections of growth hormone ( GH ) in combination with low dose ethinyl oestradiol . DESIGN Until final height was reached , the effect of fractionated subcutaneous injections given twice daily was compared with once daily injections of a total GH dose of 6 IU/m2/day 
    Output:
    
agent
Skeletal maturity was not accelerated by treatment with recombinant growth hormone ( hGH ) .
***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: Short stature and ovarian failure are the main features in Turner syndrome ( TS ) . To optimize GH and estrogen treatment , we studied 68 previously untreated girls with TS , age 2 - 11 yr , who were r and omly assigned to one of three GH dosage groups : group A , 4 IU/m2 day ( approximately 0.045 mg/kg x day ) ; group B , first yr 4 , thereafter 6 IU/m2 x day ( approximately 0.0675 mg/kg/day ) ; group C , first yr 4 , second yr 6 , thereafter 8 IU/m2 x day ( approximately 0.090 mg/kg x day ) . In the first 4 yr of GH treatment , no estrogens for pubertal induction were given to the girls . Thereafter , girls started with 17beta-estradiol ( 5 microg/kg bw x day , orally ) when they had reached the age of 12 yr . Subjects were followed up until attainment of adult height or until cessation of treatment because of satisfaction with the height achieved . Seven-year data of all girls were evaluated to compare the growth-promoting effects of three GH dosages during childhood . After 7 yr , 85 % of the girls had reached a height within the normal range for healthy Dutch girls . The 7-yr increment in height SD-score was significantly higher in groups B and C than in group A. In addition , we evaluated the data of 32 of the 68 girls who had completed the trial after a mean duration of treatment of 7.3 yr ( range , 5.0 - 8.75 ) . Mean ( SD ) height was 158.8 cm ( 7.1 ) , 161.0 cm ( 6.8 ) , and 162.3 cm ( 6.1 ) in groups A , B , and C , respectively . The mean ( SD ) difference between predicted adult height before treatment and achieved height was 12.5 cm ( 2.1 ) , 14.5 cm ( 4.0 ) , and 16.0 cm ( 4.1 ) for groups A , B , and C , respectively , being significantly different between group A and group C. GH treatment was well tolerated in all three GH dosage groups . In conclusion , GH treatment starting in relatively young girls with TS results in normalization of height during childhood , as well as of adult height , in most of the individuals . With this GH and estrogen treatment regimen , most girls with TS can grow and develop much more in conformity with their healthy peers To assess body proportions in girls with Turner syndrome ( TS ) during long term GH treatment , height , sitting height ( SH ) , h and ( H and ) and foot ( Foot ) lengths , and biacromial ( Biac ) and biiliacal ( Biil ) diameters were measured in 68 girls with TS participating in a GH dose-response trial . These previously untreated girls with TS , aged 2 - 11 yr , were r and omly assigned to 1 of 3 GH dosage groups : group A , 4 IU/m2 x day ; group B , first year 4 and thereafter 6 IU/m2 x day ; group C , first year 4 , second year 6 , and thereafter 8 IU/m2 x day . Seven-year data were evaluated to assess the effect of GH treatment on body proportions during childhood . In addition , data from all girls who had reached adult height were evaluated to determine the effect on the adult body proportions . All results were adjusted for age and sex and expressed as SD scores using reference values of healthy Dutch girls . To describe the proportions of SH , H and , Foot , Biac , and Biil to height , these values were adjusted for the SD score of height and were expressed as shape values , using the formula , e.g. for SH : shape SH = ( SH SD score - height SD score)/square root(2 - 2 x correlation coefficient between SH and height in the reference population ) . Furthermore , SD scores using references of untreated girls with TS were calculated for height and SH . Values less than -2 or more than + 2 were considered outside the normal range . At baseline , the shape values of all measurements were significantly higher than zero , but most mean shape values were still within the normal range . Seven-year data of 64 girls and adult height data of 32 girls showed that an increase in height was accompanied by an even higher increase in Foot , result ing in mean SD scores above zero and shape values of + 2 and higher . The increase in the shape value of Foot was significantly higher in groups B and C compared to that in group A after 7 yr of GH treatment , but there were no significant differences between the GH dosage groups in the girls who had reached adult height . The shape values of SH had decreased to values closer to zero after reaching adult height , especially in group A. A similar pattern in the relationship of SH to height was seen using references of girls with TS . No significant changes in the other proportions were found after reaching adult height . In conclusion , on the average , untreated girls with TS have relatively large trunk , h and s , and feet , and broad shoulders and pelvis compared to height . The increase in height after long term GH treatment is accompanied by an even higher increase in Foot and a moderate improvement of the disproportion between height and SH . Recently published reference data from untreated adults with TS and the results of a different patient group receiving a comparable GH dosage suggest that the disproportionate growth of feet has to be considered a part of the natural development in TS , but might be influenced by higher GH dosages . The development of large feet can play a role in the decision of the girl to discontinue GH treatment in the last phase of growth Seventy girls with Turner syndrome , verified by karyotype , were r and omly assigned to observation or treatment with human growth hormone ( hGH ) , ox and rolone , or a combination of hGH plus ox and rolone for a period of 12 to 24 months , to assess the effect of treatment on growth velocity and adult height . Subsequently , all subjects received either hGH alone or hGH plus ox and rolone . Data are presented for 62 subjects treated for a period of 3 to 6 years . When compared with the anticipated growth rate in untreated patients , the growth rate after treatment with hGH , both alone and in combination with ox and rolone , showed a sustained increase for at least 6 years . Treatment is continuing in over half of the subjects ; at present , 14 ( 82 % ) of 17 girls receiving hGH alone and 41 ( 91 % ) of 45 girls receiving combination therapy exceeded their expected adult heights .  Thirty girls have completed treatment ; mean height for these 30 patients is 151.9 cm , compared with their mean original projected adult height of 143.8 cm . We conclude that therapy with hGH , alone and in combination with ox and rolone , can result in a sustained increase in growth rate and a significant increase in adult height for most prepubertal girls with Turner syndrome To optimize the growth promoting effect of growth hormone ( GH ) , 65 previously untreated girls with Turner syndrome ( TS ) , chronological age ( CA ) 2 - 11 yr , were r and omized into 3 dosage regimen groups : A , B , and C , with a daily recombinant-human GH dose during 4 study years of 4 - 4 - 4 - 4 , 4 - 6 - 6 - 6 , and 4 - 6 - 8 - 8 IU/m2 b.s . The first GH dosage increase in groups B and C result ed in a significantly higher mean height velocity ( HV ) compared with constant dose group A. During the third year , when the dose was raised again only in group C , mean HV was significantly higher in groups B and C than in group A , and in group C compared with group B. In year 4 only group C mean HV remained significantly higher than group A. The pattern of change in HSDSCA ( Dutch-Swedish-Danish Turner references ) was identical ; however , in year 4 mean delta HSDSCA in group B also remained significantly higher than group A. After 4 yr GH treatment , the following was determined . 1 ) The mean delta HSDSCA was significantly higher for groups B and C compared with group A , but not significantly different between groups B and C. 2 ) Although significantly higher compared with estimated values for untreated Dutch girls with TS , bone maturation of the GH treated girls was not significantly different between groups . 3 ) It was positively related with the degree of bone age ( BA ) retardation at start of study and negatively with baseline CA . 4 ) Both the modified Index of Potential Height ( mIPHRUS ) and a recently developed Turner-specific final height ( FH ) prediction method ( PTSRUS ) , based on regression coefficients for H , CA , and bone age , showed significant increases in mean FH prediction , without significant differences between groups . PTSRUS values were markedly higher than the mIPHRUS values . Dose dependency could be shown for the area under the curve ( AUC ) for GH , but delta HSDSCA was not linearly related with AUC . Baseline GH binding protein ( BP ) levels were in 84 % of the cases within the normal age range ; the decrease in mean levels after 6 months GH was not significant . Mean insulin-like growth factor I ( IGF-I ) and IGFBP-3 plasma levels increased significantly , without significant differences between groups . delta HSDSCA during GH was dependent on IGF-I plasma levels at baseline and during the study period , beta-0.002 and beta-0.0004 . Thus , a stepwise GH-dosing approach reduced the " waning " effect of the growth response after 4 yr treatment without undue bone maturation . FH prediction was not significantly different between treatment groups . Irrespective of the GH dose used , initiation of GH treatment at a younger age was beneficial after 4 yr GH when expressed as actual cm gained or as gain in FH prediction , but was not statistically significant when expressed as delta HSDSCA over the study period In 1983 , a multicenter , collaborative , prospect i ve study was begun to investigate the efficacy of human growth hormone ( hGH ) , alone and in combination with ox and rolone , in girls with Turner syndrome . While subjects in the control group grew 3.8 cm/yr ( -0.1 SD for untreated Turner patients ) , subjects receiving hGH alone  grew 6.6 , 5.4 and 4.6 cm/yr in years 1 - 3 , respectively ( + 3.1 , + 2.0 , + 1.4 SD ) . Subjects in the combination therapy group grew 9.8 , 7.4 and 6.1 cm/yr ( + 6.6 , + 4.3 , + 3.0 SD ) . Turner subjects in both treatment groups showed increased in Bayley-Pinneau predicted adult heights and in Turner projected adult heights Preliminary results are presented after 2 years of the Canadian long-term multicentre study on the impact of hormone therapy on the final height , sexual development and psychological status of girls with Turner syndrome . Girls entering the study were r and omized either to be treated with recombinant human growth hormone or to act as controls . Both groups received oestrogen replacement therapy in the same dose and format at the age of 13 years . However , for the purpose s of the psychological study at this time , children receiving oestrogen were excluded from analysis . Girls treated with GH for a period of 2 years showed a significant increase in growth rate , which declined with continued treatment , while the growth rate in the control group remained constant throughout . There was a correlation between the higher growth rate and the girls ' perceptions of themselves as more intelligent , more attractive , having more friends , greater popularity and experiencing less teasing than the untreated group . Growth rate was not correlated with family or school functioning STUDY OBJECTIVE To determine the influence of the injection frequency and the initial bone age on the efficacy of treatment with biosynthetic growth hormone in Turner 's syndrome . DESIGN R and omized study . SETTING Referral-based pediatric endocrinology departments of seven university medical centers . PATIENTS Fifty-two patients with Turner 's syndrome confirmed with chromosomal analysis . TREATMENT Somatotropin recombinant DNA ( 24 IU/m2 of body surface area ) subcutaneously administered in three or six injections per week for 2 years . Patients who were older than 12 years at the beginning of the study received low doses of estrogen . RESULTS The following statistically significant findings supported the use of six injections per week compared with three injections per week : the mean ( + /- SD ) increment in height during 2 years was 11.3 cm ( 3.8 cm ) with six injections vs 8.6 cm ( 3.4 cm ) with three injections ; the increment in height st and ard deviation score was 0.9 cm ( 0.5 cm ) vs 0.6 cm ( 0.3 cm ) ; the growth velocity was 6.6 cm/y ( 2.0 cm/y ) vs 5.2 cm/y ( 1.7 cm/y ) in year 1 and 4.7 cm/y ( 2.0 cm/y ) vs 3.4 cm/y ( 1.7 cm/y ) in year 2 ; and the increment in height st and ard deviation score for bone age was 0.8 cm ( 0.5 cm ) vs 0.4 cm ( 0.6 cm ) . For patients whose initial bone age was more than 13 years , growth velocity increased by 1 to 2 cm in year 1 ; in year 2 no increment was observed . We did not observe adverse effects . CONCLUSIONS Biosynthetic growth hormone in a higher-frequency regimen in Turner 's syndrome is more efficient in terms of increment in height , growth velocity , and height st and ard deviation score for bone age than treatment in a lower-frequency regimen . In patients with an initial bone age of more than 13 years , the response was poor . Longer follow-up is necessary to assess the effect on final height OBJECTIVES To study final height in girls with Turner ’s syndrome treated with once or twice daily injections of growth hormone ( GH ) in combination with low dose ethinyl oestradiol . DESIGN Until final height was reached , the effect of fractionated subcutaneous injections given twice daily was compared with once daily injections of a total GH dose of 6 IU/m2/day 
    Output:
    