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Growth hormone treatment in adults with liver cirrhosis
ABSTRACTS
576
FROM
THE
20TH
ANNUAL
MILK GROWTH WHEY PARTIALLY GUT MUCOSmS
GROW-lH HORMONE USING THERMAL
IMPROVED WOUND HEALING IN RATS INJURY AS A MODEL OF TRALJhjA Maumon A HOLLYOAK’ D&d N HERNDGN l ‘RoyalBrisbaecIiospltal,B~,Awlnlla ’ Shinus Bores butitote, Galvcstoo, U.S.A.
METHOD: Spnguc-Dawley male rats, weight 3 IO-320 &qns. were @en a 3O%bodysu&ccanavu1tralscaldorshambtuqa6andorsaliocisiiruaued;aad2x225an’foUthickacssdorsalcxcisiocu. Animalswefepairfed. Recombinaathumangrowthbonnollc,2m&/dorplac&owasgivcnby suW injection. Jkisional wouod sk was awsurod by plaaktry each third day. After 14 days, aaimak were sac&i& wound strips aad gastmcs muscle harmted. Hcalitq was asscsscd io a tcnsiometcr.
NoeBura I: Noa Bw +GH 13 Bum 8
0.036 (.013) 0.054 (.023) -
265 (7) 275 (5)
Bura+GH IS Date pM
as mean f (SD).
Significaot groups; VP Noa Burn awl Noa Bum + GH. compakmProcaiure. CONCLUSION: si@cantdiffcrcncctop
1.60 (.06)’ 1.80 (.OS)’
HORMONE
JENNIFFB
D. WALLACE,
TREATMENT
IN ADULTS
WITE
HOSPITAL,
LIVER
CIRRHOSIS.
AND ROSS C CUNEO.
METABOLIC RESEARCHUNIT,DEPARTMENI ALEXANDRA
’ Au other Multiple
GH improved incisional wound healing, but made no nsuvatonofbodywcightormusclemass.
GROWTH
OF MBDICW, BRISBANE AUSTRAL.IA.
PRlNCESS
Normal serum insulin-like m t&x-l (IGF-I) levels arc imponaat for aoabolism in adult homaos. In cirrhosii the growth hormone (GH)-IGF-I axis is demqd with low serum IGF-1 possibly dot to GH rcsistaacc. The catabolic stale can compmmisc swccssful liver transplantation. This pilot study cxamiacd the ability of pharmacolo8kal doses of GH IO overcome GH rcsistaacc induced by &ho&, by assessing dose-mspoasc 8ed safely aspcds. 2 adults with biopsypmvca cirrhoric (45 yr old male, cthaaol-iedeced cirrhosis, Chthi’s clam B; 32 yr old fcmalc, sclmwiq chelqills, child’s clam A). wac studied for 7 days. 3 doses of mcombiaant human OH (0.0s. 0. I and 0.2 U/KS/Day) wcm adminislend sobcomnmosly. coewaainly for 2 ai@ts eecb. Testleg was pufotmcd
ticranovemtgbt&t,bcforcGHandaftcracbd. ScrumwssaaalyscdforGH (mu/l), IGF-I (amoM),and glucorc(ma&l). Basalmetabolicralc(BMR k&day) was measuredby indirectcalorimetryaad RQwsscalculated.Supinebloodpraswc was rmnded. .
PatientI
IGF-1 Dose .......-.........-...“.. GH ..“....“.....” “..“” .“..“...- Gluoz ““.-.-.--.-.1--.-.-..-BP
BMR ...I.-..“..“....”
RQ ...”
13.0 15.0
II.0 13.4
25.0 70
0.0
03
0.05 0.1 0.2
5.5 11.0 25.0
0.0 0.05 0.1 0.2
Patient2
-
AuSPEN
FROM CHEESE EXPERMENTAL
tested
the efficacy
of a milk
growth
factor
extract
purified
from
cheese whey against experimental intestinal mucositis in rats. contains
a mixture
of growth
factors
with
basic iso-
electric points. Rats were injected on days 1, 2 and 3 with 2.5 mg/kg of the chemotherapy drug, methotrexate, resulting in severe histological damage to the small bowel and bacterial translocation across the gut. Whey extract (15 to 514 mg/day) was given orally for 5-12 days, starting on day 1, while controls received an isonitrogenous diet. Five days’ administration of
Caatmcr wei@ b) 2.08 (.06) 2.22 (Lx)
diffcrcnce p<.OS ANOVA-SCHEFFE
FACTORS ENRICHED PROTECT’S AGAINST
OF
Gut mucositis occurs as a common side-effect of highdose The symptoms chemotherapy and can be dose-limiting. including mouth ulcers, diarrhoea and pain can necessitate several weeks of total parenteral nutrition. Although there are no therapies for gut mucositis, experimental evidence suggests clinical potential for some growth factors. Since milk is rich in growth factors that may be tailored to the needs of the gut, we The extract
REsuLTs
Body Welgbt (rpl) 321 (6) 341 (5)
MEETING
Gordon S. Howarth, Jo C. Cool & Leanna C. Read. CRC for Tissue Growth and Repair, Child Health Research Institute, North Adelaide, South Australia, 5006.
AIM: Examinethcc&ctofGrowtbHonnonc(GH)onwouodhcalingand muscle mass in therdly injured mts.
Tensile Stree8th (lCJOU2) 0.033 (.OZS) 0.039 (.021)
SCIENTIFIC
5.7
131/74
13.6 16.1
6.1 6.3 7.3
133n3 120/73 139/81
1800 1645 1723 1711
0.74 0.71 0.69 0.78
25.8 38.4 56.0 63.7
5.6 5.7 6.2 7.2
109169 m/64 107168 1 I9168
1664 1563 I658 1825
0.78 0.76 0.75 0.73
WecnncludcthatexogenousGHtreatmentin cirrhosis(i) ovummestheGH tiscance of
cirrb&. incmasingserumIGF-I. (ii) dosesof 0.10.2 U/k&lay arcqutrcd 10increase both rrmm GH and IGF-I. (iii) such dcecs do not scrioos!y affect blood gluawe. blood pressure or fluid homcostasih aad (iv) inkaces on chermogmesis am incoesistcm. GH treatmem may provide aoabolic sopPon in cirrhosis.
the extract increased the villus small bowel up to 56% above
surface length index of the that in methotrexate-injected
controls. The crypt area index was also significantly increased 64% in the jejunum. Sucrase activity was significantly higher in the ileum (270%) but not the jejunum. Bacterial translocation was significantly reduced in rats receiving oral whey extract. We conclude that oral administralion of a whey growth factor extract reduces methotrexate damage in the small bowel, suggesting clinical applications in gut mucositis.
HORMONE (GH) THERAPY CAN IMPROVE GROWTH ECONOMY IN MALNOURISHED CIRRHOTIC PROTEIN PATIENTS &&j?onv J. Donaghy. -Richard J. Floss, Claire Wicks, ‘Sian Cwyfan Hughes, ‘Jeffrey Holly,Alexander E. Gimsonand Roger Williams. Institute of Liver Studies, Kings College Hospital and ‘Dept. of Endocrinology, St Ballholorwws Hospital, London, UK. Cirrhosis is associated with protein calorie malnutrition and GH resistance, with low circulating levels of insulin-like growth factor-l (IGF-I) and its major binding protein IGFBP-3. We conducted a double blind, plqcebo controlled trial of GH therapy in 20 cirrhotic patients to assess reversibility of GH resistance, subsequent impact on protein economy and safety. Patients were treated with daily SC injections of either GH (0.25 IU / kg) or placebo for 7 days, after a 3 day baseline period. Levels of GH,
IGF-I and IGFBP-3 were measured by RIA, and urinary nitrogen by the Kjeldahl technique. Serum IGF-I levels rose significantly only in the GH group from mean 69.2fSE 7 @ml on day 1 to 170.6&46 on day 11 (~~0.05) although this response was attenuated in comparison to that seen in normals. IGFBP-3 levels also rose significantly from 1.65f0.3 mg/L to 2.94f0.6 (~~0.005) in the GH group. Cumulative daily nitrogen balance improved significantly from 1.12f1.4 g/day (day 1) to 27.38f12.5 (day 10) in the GH group (~~0.05) but,no significant change was seen in the placebo group -1.76fl.23 (day 1) to 3.95f7.65 (day 10). We conclude that GH therapy was able to partially overcome the GH resistance of cirrhosis, increasing production of IGF-I and IGFBP-3 and effecting significant improvement in nitrogen balance. GH may have an important role in the treatment of malnourished cirrhotics.
576
FROM
THE
20TH
ANNUAL
MILK GROWTH WHEY PARTIALLY GUT MUCOSmS
GROW-lH HORMONE USING THERMAL
IMPROVED WOUND HEALING IN RATS INJURY AS A MODEL OF TRALJhjA Maumon A HOLLYOAK’ D&d N HERNDGN l ‘RoyalBrisbaecIiospltal,B~,Awlnlla ’ Shinus Bores butitote, Galvcstoo, U.S.A.
METHOD: Spnguc-Dawley male rats, weight 3 IO-320 &qns. were @en a 3O%bodysu&ccanavu1tralscaldorshambtuqa6andorsaliocisiiruaued;aad2x225an’foUthickacssdorsalcxcisiocu. Animalswefepairfed. Recombinaathumangrowthbonnollc,2m&/dorplac&owasgivcnby suW injection. Jkisional wouod sk was awsurod by plaaktry each third day. After 14 days, aaimak were sac&i& wound strips aad gastmcs muscle harmted. Hcalitq was asscsscd io a tcnsiometcr.
NoeBura I: Noa Bw +GH 13 Bum 8
0.036 (.013) 0.054 (.023) -
265 (7) 275 (5)
Bura+GH IS Date pM
as mean f (SD).
Significaot groups; VP Noa Burn awl Noa Bum + GH. compakmProcaiure. CONCLUSION: si@cantdiffcrcncctop
1.60 (.06)’ 1.80 (.OS)’
HORMONE
JENNIFFB
D. WALLACE,
TREATMENT
IN ADULTS
WITE
HOSPITAL,
LIVER
CIRRHOSIS.
AND ROSS C CUNEO.
METABOLIC RESEARCHUNIT,DEPARTMENI ALEXANDRA
’ Au other Multiple
GH improved incisional wound healing, but made no nsuvatonofbodywcightormusclemass.
GROWTH
OF MBDICW, BRISBANE AUSTRAL.IA.
PRlNCESS
Normal serum insulin-like m t&x-l (IGF-I) levels arc imponaat for aoabolism in adult homaos. In cirrhosii the growth hormone (GH)-IGF-I axis is demqd with low serum IGF-1 possibly dot to GH rcsistaacc. The catabolic stale can compmmisc swccssful liver transplantation. This pilot study cxamiacd the ability of pharmacolo8kal doses of GH IO overcome GH rcsistaacc induced by &ho&, by assessing dose-mspoasc 8ed safely aspcds. 2 adults with biopsypmvca cirrhoric (45 yr old male, cthaaol-iedeced cirrhosis, Chthi’s clam B; 32 yr old fcmalc, sclmwiq chelqills, child’s clam A). wac studied for 7 days. 3 doses of mcombiaant human OH (0.0s. 0. I and 0.2 U/KS/Day) wcm adminislend sobcomnmosly. coewaainly for 2 ai@ts eecb. Testleg was pufotmcd
ticranovemtgbt&t,bcforcGHandaftcracbd. ScrumwssaaalyscdforGH (mu/l), IGF-I (amoM),and glucorc(ma&l). Basalmetabolicralc(BMR k&day) was measuredby indirectcalorimetryaad RQwsscalculated.Supinebloodpraswc was rmnded. .
PatientI
IGF-1 Dose .......-.........-...“.. GH ..“....“.....” “..“” .“..“...- Gluoz ““.-.-.--.-.1--.-.-..-BP
BMR ...I.-..“..“....”
RQ ...”
13.0 15.0
II.0 13.4
25.0 70
0.0
03
0.05 0.1 0.2
5.5 11.0 25.0
0.0 0.05 0.1 0.2
Patient2
-
AuSPEN
FROM CHEESE EXPERMENTAL
tested
the efficacy
of a milk
growth
factor
extract
purified
from
cheese whey against experimental intestinal mucositis in rats. contains
a mixture
of growth
factors
with
basic iso-
electric points. Rats were injected on days 1, 2 and 3 with 2.5 mg/kg of the chemotherapy drug, methotrexate, resulting in severe histological damage to the small bowel and bacterial translocation across the gut. Whey extract (15 to 514 mg/day) was given orally for 5-12 days, starting on day 1, while controls received an isonitrogenous diet. Five days’ administration of
Caatmcr wei@ b) 2.08 (.06) 2.22 (Lx)
diffcrcnce p<.OS ANOVA-SCHEFFE
FACTORS ENRICHED PROTECT’S AGAINST
OF
Gut mucositis occurs as a common side-effect of highdose The symptoms chemotherapy and can be dose-limiting. including mouth ulcers, diarrhoea and pain can necessitate several weeks of total parenteral nutrition. Although there are no therapies for gut mucositis, experimental evidence suggests clinical potential for some growth factors. Since milk is rich in growth factors that may be tailored to the needs of the gut, we The extract
REsuLTs
Body Welgbt (rpl) 321 (6) 341 (5)
MEETING
Gordon S. Howarth, Jo C. Cool & Leanna C. Read. CRC for Tissue Growth and Repair, Child Health Research Institute, North Adelaide, South Australia, 5006.
AIM: Examinethcc&ctofGrowtbHonnonc(GH)onwouodhcalingand muscle mass in therdly injured mts.
Tensile Stree8th (lCJOU2) 0.033 (.OZS) 0.039 (.021)
SCIENTIFIC
5.7
131/74
13.6 16.1
6.1 6.3 7.3
133n3 120/73 139/81
1800 1645 1723 1711
0.74 0.71 0.69 0.78
25.8 38.4 56.0 63.7
5.6 5.7 6.2 7.2
109169 m/64 107168 1 I9168
1664 1563 I658 1825
0.78 0.76 0.75 0.73
WecnncludcthatexogenousGHtreatmentin cirrhosis(i) ovummestheGH tiscance of
cirrb&. incmasingserumIGF-I. (ii) dosesof 0.10.2 U/k&lay arcqutrcd 10increase both rrmm GH and IGF-I. (iii) such dcecs do not scrioos!y affect blood gluawe. blood pressure or fluid homcostasih aad (iv) inkaces on chermogmesis am incoesistcm. GH treatmem may provide aoabolic sopPon in cirrhosis.
the extract increased the villus small bowel up to 56% above
surface length index of the that in methotrexate-injected
controls. The crypt area index was also significantly increased 64% in the jejunum. Sucrase activity was significantly higher in the ileum (270%) but not the jejunum. Bacterial translocation was significantly reduced in rats receiving oral whey extract. We conclude that oral administralion of a whey growth factor extract reduces methotrexate damage in the small bowel, suggesting clinical applications in gut mucositis.
HORMONE (GH) THERAPY CAN IMPROVE GROWTH ECONOMY IN MALNOURISHED CIRRHOTIC PROTEIN PATIENTS &&j?onv J. Donaghy. -Richard J. Floss, Claire Wicks, ‘Sian Cwyfan Hughes, ‘Jeffrey Holly,Alexander E. Gimsonand Roger Williams. Institute of Liver Studies, Kings College Hospital and ‘Dept. of Endocrinology, St Ballholorwws Hospital, London, UK. Cirrhosis is associated with protein calorie malnutrition and GH resistance, with low circulating levels of insulin-like growth factor-l (IGF-I) and its major binding protein IGFBP-3. We conducted a double blind, plqcebo controlled trial of GH therapy in 20 cirrhotic patients to assess reversibility of GH resistance, subsequent impact on protein economy and safety. Patients were treated with daily SC injections of either GH (0.25 IU / kg) or placebo for 7 days, after a 3 day baseline period. Levels of GH,
IGF-I and IGFBP-3 were measured by RIA, and urinary nitrogen by the Kjeldahl technique. Serum IGF-I levels rose significantly only in the GH group from mean 69.2fSE 7 @ml on day 1 to 170.6&46 on day 11 (~~0.05) although this response was attenuated in comparison to that seen in normals. IGFBP-3 levels also rose significantly from 1.65f0.3 mg/L to 2.94f0.6 (~~0.005) in the GH group. Cumulative daily nitrogen balance improved significantly from 1.12f1.4 g/day (day 1) to 27.38f12.5 (day 10) in the GH group (~~0.05) but,no significant change was seen in the placebo group -1.76fl.23 (day 1) to 3.95f7.65 (day 10). We conclude that GH therapy was able to partially overcome the GH resistance of cirrhosis, increasing production of IGF-I and IGFBP-3 and effecting significant improvement in nitrogen balance. GH may have an important role in the treatment of malnourished cirrhotics.