Effects of different barley and oat varieties on methane production, digestibility, and fermentation pattern in vitro.

The objective of this in vitro study was to determine the effects of different barley and oat varieties on CH4 production, digestibility, and rumen fermentation patterns in dairy cows. Our hypothesis was that oat-based diets would decrease CH4 production compared with barley-based diets, and that CH4 production would differ between varieties within grain species. To evaluate this hypothesis, we conducted an in vitro experiment using a fully automated gas production technique, in which the total gas volume was automatically recorded by the system. The experiment consisted of triplicate 48-h incubations with 16 treatments, including 8 different varieties of each grain. The grain varieties were investigated as a mix with an early-cut grass silage (1:1 ratio of grain to silage on a dry matter basis) and mixed with buffered rumen fluid. We estimated predicted in vivo total gas production and CH4 production by applying a set of models to the gas production data obtained by the in vitro system. We also evaluated in vitro digestibility and fermentation characteristics. The variety of grain species did not affect total gas production, CH4 production, or fermentation patterns in vitro. However, in vitro-determined digestibility and pH were affected by variety of grain species. Grain species affected total gas and CH4 production: compared with barley-based diets, oat-based diets decreased total gas production and CH4 production by 8.2 and 8.9%, respectively, relative to dry matter intake. Grain species did not affect CH4 production relative to in vitro true dry matter digestibility. Oat-based diets decreased digestibility and total volatile fatty acid production, and maintained a higher pH at 48 h of incubation compared with barley-based diets. Grain species did not affect fermentation patterns, except for decreased molar proportions of valerate with oat-based diets. These results suggest that replacing barley with oats in dairy cow diets could decrease enteric CH4 production.

GH safety workshop position paper: a critical appraisal of recombinant human GH therapy in children and adults.

Recombinant human GH (rhGH) has been in use for 30 years, and over that time its safety and efficacy in children and adults has been subject to considerable scrutiny. In 2001, a statement from the GH Research Society (GRS) concluded that 'for approved indications, GH is safe'; however, the statement highlighted a number of areas for on-going surveillance of long-term safety, including cancer risk, impact on glucose homeostasis, and use of high dose pharmacological rhGH treatment. Over the intervening years, there have been a number of publications addressing the safety of rhGH with regard to mortality, cancer and cardiovascular risk, and the need for long-term surveillance of the increasing number of adults who were treated with rhGH in childhood. Against this backdrop of interest in safety, the European Society of Paediatric Endocrinology (ESPE), the GRS, and the Pediatric Endocrine Society (PES) convened a meeting to reappraise the safety of rhGH. The ouput of the meeting is a concise position statement.

Guidelines for Growth Hormone and Insulin-Like Growth Factor-I Treatment in Children and Adolescents: Growth Hormone Deficiency, Idiopathic Short Stature, and Primary Insulin-Like Growth Factor-I Deficiency

BACKGROUND/AIMS: On behalf of the Drug and Therapeutics, and Ethics Committees of the Pediatric Endocrine Society, we sought to update the guidelines published in 2003 on the use of growth hormone (GH). Because idiopathic short stature (ISS) remains a controversial indication, and diagnostic challenges often blur the distinction between ISS, GH deficiency (GHD), and primary IGF-I deficiency (PIGFD), we focused on these three diagnoses, thereby adding recombinant IGF-I therapy to the GH guidelines for the first time. METHODS: This guideline was developed following the GRADE approach (Grading of Recommendations, Assessment, Development, and Evaluation). RESULTS: This guideline provides recommendations for the clinical management of children and adolescents with growth failure from GHD, ISS, or PIGFD using the best available evidence. CONCLUSION: The taskforce suggests that the recommendations be applied in clinical practice with consideration of the evolving literature and the risks and benefits to each individual patient. In many instances, careful review highlights areas that need further research

Serial GH Measurement After Intravenous Catheter Placement Alone Can Detect Levels Above Stimulation Test Thresholds in Children.

CONTEXT: GH stimulation testing is limited by poor specificity and reproducibility in identifying GH deficiency. Intravenous line placement (IVP) in pediatrics may be a stimulus for GH secretion. OBJECTIVE: The objective of the study was to determine whether the measurement of GH at baseline as well as 15 and 30 minutes after IVP detects additional patients with sufficient peak GH concentrations who are not identified by a subsequent insulin tolerance test (ITT). METHODS: The ITT protocol was modified to include GH measurement at the time of IVP (t = 0) and 15 (t = 15) and 30 (t = 30) minutes later. Insulin was administered at t = 30, and an ITT was performed as per standard protocols. Children were grouped according to the indication for ITT: initial evaluation of GH deficiency (group 1); and GH deficiency at transition to adulthood (group 2). RESULTS: Ninety-seven patients were included (76 in group 1, 21 in group 2). Of these, 27 (28%) had a peak GH concentration of 7 ng/mL or greater (19 in group 1, eight in group 2) either after IVP or ITT. Thirteen subjects (11 in group 1, two in group 2) had GH concentrations of 7 ng/mL or greater after IVP, without exceeding this on a subsequent ITT. Among the 11 group 1 patients, three of these GH peaks of 7 ng/mL or greater occurred at t = 0, 5 at t = 15, and 5 at t = 30, including one patient who had a peak GH of 7 ng/mL or greater at all three time points. CONCLUSION: Some children will not have a sufficient GH response to pharmacological stimuli but will have a robust response to IVP. We recommend GH measurement after IVP in children undergoing GH stimulation testing, particularly when there is a delay between IVP and the administration of the pharmacological stimulus.

Long-term non-surgical therapy of severe persistent congenital hyperinsulinism with glucagon.

BACKGROUND: Congenital hyperinsulinism (CHI) is characterized by severe hypoglycemia caused by dysregulated insulin secretion. The long-term outcome is dependent on prevention of hypoglycemic episodes to avoid the high risk of permanent brain damage. Severe cases are usually resistant to diazoxide or nifedipine. In addition, somatostatin analogues are ineffective in a subgroup of patients to achieve stable euglycemia. In these infants the only remaining long-term option has been subtotal pancreatectomy with high risk of diabetes mellitus. Intravenous infusions of glucagon are used as immediate treatment to stabilize euglycemia in affected newborns. The rationale of this treatment comes from the observation of an increased glycogen content of the liver when glycogenolysis is inhibited by insulin. OBJECTIVE: To review the efficacy and safety of long-term subcutaneous glucagon infusion as a potential therapeutic option for blood glucose stabilization in infants with severe CHI without the need of additional intravenous glucose or immediate surgical intervention. METHOD: Retrospective review of 9 children with CHI who received continuous subcutaneous infusion of glucagon for weeks or months. Glucagon was added to octreotide to replace octreotide-induced suppression of endogenous glucagon secretion, thereby liberating glucose by stimulation of hepatic glycogenolysis. In 3 cases, a stabilized formulation of glucagon was used to prevent glucagon crystallization that frequently occurs in smaller volumes. RESULTS: Introduction of glucagon allowed the reduction or discontinuation of central glucose infusion in all children studied. In 2 patients, glucagon was introduced due to recurrent hypoglycemia despite subtotal pancreatectomy. Six out of 9 children were discharged home on this treatment, which their parents were able to continue without further symptomatic hypoglycemia, convulsions or unconsciousness. In 3 children, subcutaneous glucagon was continuously administered for 1-4 years leading to stable euglycemia. However, 2 children with diffuse type still required subtotal pancreatectomy. As a possible side effect, 2 children developed erythema necrolyticum, which resolved after discontinuation of the glucagon infusion. This has been described before in glucagonoma. CONCLUSION: In this retrospective series, combination therapy of low-dose octreotide and subcutaneous glucagon infusion has been effective in preventing hypoglycemic episodes in severe CHI. We propose this may serve as a therapeutic option in place of high rates of glucose infusion through a central venous catheter and as an alternative to subtotal pancreatectomy in diffuse type of CHI.

[Sex influence in lipodystrophy of HIV-infected patients and its association with cardiovascular risk factors]. / Impacto del sexo en el síndrome de lipodistrofia en pacientes con infección por el VIH y su asociación con factores de riesgo cardiovascular.

OBJECTIVE: To evaluate the influence of sex in human immunodeficiency virus (HIV)-infected patients with lipodystrophy and its association with cardiovascular risk factors. PATIENTS AND METHOD: A cross-sectional study was conducted in HIV-infected patients aged 20 or over managed at the outpatient Infectious Disease Unit in 2003. Clinical and epidemiological characteristics of HIV infection, lipodystrophy and cardiovascular risk factors were evaluated. RESULTS: Of the 760 patients included in the study, women comprised 28%. Men with lipodystrophy had a higher prevalence of hypertension, hypercholesterolemia, hypoalphalipoproteinemia and hypertriglyceridemia than those without lipodystrophy. Women with lipodystrophy had a higher prevalence of central obesity and hypertriglyceridemia compared with those without lipodystrophy (22.8 vs. 11.2%, p = 0.000; 20.6 vs. 9.3%, p = 0.001; 39.7 vs. 30%, p = 0.03 y 56.6 vs. 40.9%, p = 0.0001, respectively). The lipoatrophy pattern was predominant in men (24.9 vs. 12.6%, p = 0.0001) and lipoaccumulation forms in women (12.3 vs. 22.6%, p = 0.0001). Furthermore, women were younger, had a higher prevalence of smoking, family history of premature coronary heart disease and central obesity, and a lower prevalence of hypertension and hypoalphalipoproteinemia than men with lipodystrophy (42.1 +/- 8 years vs. 44.8 +/- 9.9 years, p = 0.03; 77.5 vs. 64%, p = 0.04; 22.5 vs. 9%, p = 0.003; 31 vs. 8.5%, p = 0.0001; 9.9 vs. 22.8%, p = 0.01; 25.4 vs. 39.7%, p = 0.03). CONCLUSIONS: This study demonstrated that the influence of sex in lipodystrophy in HIV-infected patients affects not only the lipodystrophy pattern, but also the cardiovascular risk profile.

Impacto del sexo en el síndrome de lipodistrofia en pacientes con infección por el VIH y su asociación con factores de riesgo cardiovascular / Sex influence in lipodystrophy of HIV-infected patients and its association with cardiovascular risk factors

Objetivo: Evaluar el impacto del sexo en la presencia del síndrome de lipodistrofia en una población de pacientes infectados por el VIH y su asociación con los factores de riesgo cardiovascular. Pacientes y método: Estudio transversal que incluyó a los pacientes de 20 años de edad o mayores, con infección por el VIH atendidos en la consulta externa del Servicio de Medicina Interna y Enfermedades Infecciosas del Hospital del Mar de Barcelona durante el año 2.003. Se evaluaron las características clínico-epidemiológicas de la infección por el VIH, la presencia de lipodistrofía y los factores de riesgo cardiovascular. Resultados: De los 710 pacientes incluidos en el estudio, las mujeres representaban el 28% de la serie. Los varones con lipodistrofia presentaron una mayor prevalencia de hipertensión arterial, hipercolesterolemia, hipoalfalipoproteinemia e hipertrigliceridemia comparado con los que no presentaban lipodistrofia (22,8 vs. 11,2%, p = 0,000; 20,6 vs. 9,3%, p = 0,001; 39,7 vs. 30%, p = 0,03 y 56,6 vs. 40,9%, p = 0,0001, respectivamente). En las mujeres, la presencia de lipodistrofia se acompañó de una mayor prevalencia de obesidad central e hipertrigliceridemia con respecto a la ausencia de lipodistrofia. En los varones predominó el patrón de lipoatrofia (24,9 vs. 12,6%, p = 0,0001), y en las mujeres el lipoacúmulo (12,3 vs. 22,6%, p = 0,0001). Además, las mujeres eran más jóvenes, tenían una mayor prevalencia de tabaquismo, antecedentes familiares de cardiopatía isquémica prematura y de obesidad central, y una menor prevalencia de hipertensión arterial y de hipoalfalipoproteinemia que los varones con lipodistrofia (42,1 ± 8 años vs. 44,8 ± 9,9 años, p = 0,03; 77,5 vs. 64%, p = 0,04; 22,5 vs. 9%, p = 0,003; 31 vs. 8,5%, p = 0,0001; 9,9 vs. 22,8%, p = 0,01; 25,4 vs. 39,7%, p = 0,03, respectivamente). Conclusiones: El presente estudio demuestra que el impacto del sexo en la lipodistrofia de los pacientes con infección por el VIH no sólo afecta al patrón de lipodistrofia, sino también al perfil de riesgo cardiovascular

Objective: To evaluate the influence of sex in human immunodeficiency virus (HIV)-infected patients with lipodystrophy and its association with cardiovascular risk factors. Patients and method: A cross-sectional study was conducted in HIVinfected patients aged 20 or over managed at the outpatient Infectious Disease Unit in 2003. Clinical and epidemiological characteristics of HIV infection, lipodystrophy and cardiovascular risk factors were evaluated. Results: Of the 760 patients included in the study, women comprised 28%. Men with lipodystrophy had a higher prevalence of hypertension, hypercholesterolemia, hypoalphalipoproteinemia and hypertriglyceridemia than those without lipodystrophy. Women with lipodystrophy had a higher prevalence of central obesity and hypertriglyceridemia compared with those without lipodystrophy (22.8 vs. 11.2%, p = 0.000; 20.6 vs. 9.3%, p = 0.001; 39.7 vs. 30%, p = 0.03 y 56.6 vs. 40.9%, p = 0.0001, respectively). The lipoatrophy pattern was predominant in men (24.9 vs. 12.6%, p = 0.0001) and lipoaccumulation forms in women (12.3 vs. 22.6%, p = 0.0001). Furthermore, women were younger, had a higher prevalence of smoking, family history of premature coronary heart disease and central obesity, and a lower prevalence of hypertension and hypoalphalipoproteinemia than men with lipodystrophy (42.1 ± 8 years vs. 44.8 ± 9.9 years, p = 0.03; 77.5 vs. 64%, p = 0.04; 22.5 vs. 9%, p = 0.003; 31 vs. 8.5%, p = 0.0001; 9.9 vs. 22.8%, p = 0.01; 25.4 vs. 39.7%, p = 0.03). Conclusions: This study demonstrated that the influence of sex in lipodystrophy in HIV-infected patients affects not only the lipodystrophy pattern, but also the cardiovascular risk profile

Acute insulin responses to leucine in children with the hyperinsulinism/hyperammonemia syndrome.

Mutations of glutamate dehydrogenase cause the hyperinsulinism/hyperammonemia syndrome by desensitizing glutamate dehydrogenase to allosteric inhibition by GTP. Normal allosteric activation of glutamate dehydrogenase by leucine is thus uninhibited, leading us to propose that children with hyperinsulinism/hyperammonemia syndrome will have exaggerated acute insulin responses to leucine in the postabsorptive state. As hyperglycemia increases beta-cell GTP, we also postulated that high glucose concentrations would extinguish abnormal responsiveness to leucine in hyperinsulinism/hyperammonemia syndrome patients. After an overnight fast, seven hyperinsulinism/hyperammonemia syndrome patients (aged 9 months to 29 yr) had acute insulin responses to leucine performed using an iv bolus of L-leucine (15 mg/kg) administered over 1 min and plasma insulin measurements obtained at -10, -5, 0, 1, 3, and 5 min. The acute insulin response to leucine was defined as the mean increase in insulin from baseline at 1 and 3 min after an iv leucine bolus. The hyperinsulinism/hyperammonemia syndrome group had excessively increased insulin responses to leucine (mean +/- SEM, 73 +/- 21 microIU/ml) compared with the control children and adults (n = 17) who had no response to leucine (1.9 +/- 2.7 microU/ml; P < 0.05). Four hyperinsulinism/hyperammonemia syndrome patients then had acute insulin responses to leucine repeated at hyperglycemia (blood glucose, 150-180 mg/dl). High blood glucose suppressed their abnormal baseline acute insulin responses to leucine of 180, 98, 47, and 28 microU/ml to 73, 0, 6, and 19 microU/ml, respectively. This suppression suggests that protein-induced hypoglycemia in hyperinsulinism/hyperammonemia syndrome patients may be prevented by carbohydrate loading before protein consumption.

Dysregulation of insulin secretion in children with congenital hyperinsulinism due to sulfonylurea receptor mutations.

Mutations in the high-affinity sulfonylurea receptor (SUR)-1 cause one of the severe recessively inherited diffuse forms of congenital hyperinsulinism or, when associated with loss of heterozygosity, focal adenomatosis. We hypothesized that SUR1 mutations would render the beta-cell insensitive to sulfonylureas and to glucose. Stimulated insulin responses were compared among eight patients with diffuse hyperinsulinism (two mutations), six carrier parents, and ten normal adults. In the patients with diffuse hyperinsulinism, the acute insulin response to intravenous tolbutamide was absent and did not overlap with the responses seen in either adult group. There was positive, albeit significantly blunted, acute insulin response to intravenous dextrose in the patients with diffuse hyperinsulinism. Graded infusions of glucose, to raise and then lower plasma glucose concentrations over 4 h, caused similar rises in blood glucose but lower peak insulin levels in the hyperinsulinemic patients. Loss of acute insulin response to tolbutamide can identify children with diffuse SUR1 defects. The greater response to glucose than to tolbutamide indicates that ATP-sensitive potassium (KATP) channel-independent pathways are involved in glucose-mediated insulin release in patients with diffuse SUR1 defects. The diminished glucose responsiveness suggests that SUR1 mutations and lack of KATP channel activity may contribute to the late development of diabetes in patients with hyperinsulinism independently of subtotal pancreatectomy.

Calcium-stimulated insulin secretion in diffuse and focal forms of congenital hyperinsulinism.

OBJECTIVES: To identify infants with hyperinsulinism caused by defects of the beta-cell adenosine triphosphate-dependent potassium channel complex and to distinguish focal and diffuse forms of hyperinsulinism caused by these mutations. STUDY DESIGN: The acute insulin response to intravenous calcium stimulation (CaAIR) was determined in 9 patients <20 years with diffuse hyperinsulinism caused by defective beta-cell sulfonylurea receptor (SUR1(-/-)), 3 patients with focal congenital hyperinsulinism (6 weeks to 18 months), a 10-year-old with insulinoma, 5 with hyperinsulinism/hyperammonemia syndrome caused by defective glutamate dehydrogenase (6 months to 28 years), 4 SUR1(+/-) heterozygotes with no symptoms, and 9 normal adults. Three infants with congenital focal disease, 1 with diffuse hyperinsulinism, and the child with insulinoma underwent selective pancreatic intra-arterial calcium stimulation with hepatic venous sampling. RESULTS: Children with diffuse SUR1(-/-) disease and infants with congenital focal hyperinsulinism responded to CaAIR, whereas the normal control group, patients with hyperinsulinism/hyperammonemia syndrome, and SUR1(+/-) carriers did not. Selective arterial calcium stimulation of the pancreas with hepatic venous sampling revealed selective, significant step-ups in insulin secretion that correlated anatomically with the location of solitary lesions confirmed surgically in 2 of 3 infants with congenital focal disease and in the child with insulinoma. Selective arterial calcium stimulation of the pancreas with hepatic venous sampling demonstrated markedly elevated baseline insulin levels throughout the pancreas of the infant with diffuse hyperinsulinism. CONCLUSIONS: The intravenous CaAIR is a safe and simple test for identifying infants with diffuse SUR1(-/-) hyperinsulinism or with focal congenital hyperinsulinism. Preoperative selective arterial calcium stimulation of the pancreas with hepatic venous sampling can localize focal lesions causing hyperinsulinism in children. The combination of these calcium stimulation tests may help distinguish focal lesions suitable for cure by local surgical resection.

P53 and IGFBP-3: apoptosis and cancer protection.

p53, perhaps the single most important human tumor suppressor, is commonly mutated in human cancers. Normally genotoxic stress and hypoxia activate p53, which, through DNA-specific transcription activation, transcriptional repression, and protein-protein interactions, triggers cell cycle arrest and apoptosis. One of the genes induced by p53 was identified as that encoding the insulin-like growth factor binding protein (IGFBP)-3. IGFBP-3 was originally defined by the somatomedin hypothesis as the principal carrier of IGF-I in the circulation and the primary regulator of the amount of free IGF-I available to interact with the IGF-1 receptor. However, there is accumulating evidence that IGFBP-3 can also cause apoptosis in an IGF-independent manner. Thus, IGFBP-3 induction by p53 constitutes a new means of cross-talk between the p53 and IGF axes, and suggests that the ultimate function of IGFBP-3 may be to serve a protective role against the potentially carcinogenic effects of growth hormone and IGF-I.

Role of insulin-like growth factors and their binding proteins in growth control and carcinogenesis.

Interest in the role of the insulin-like growth factor (IGF) axis in growth control and carcinogenesis has recently been increased by the finding of elevated serum insulin-like growth factor I (IGF-I) levels in association with three of the most prevalent cancers in the United States: prostate cancer, colorectal cancer, and lung cancer. IGFs serve as endocrine, autocrine, and paracrine stimulators of mitogenesis, survival, and cellular transformation. These actions are mediated through the type 1 IGF-receptor (IGF-1R), a tyrosine kinase that resembles the insulin receptor. The availability of free IGF for interaction with the IGF-1R is modulated by the insulin-like growth factor-binding proteins (IGFBPs). IGFBPs, especially IGFBP-3, also have IGF-independent effects on cell growth. IGF-independent growth inhibition by IGFBP-3 is believed to occur through IGFBP-3-specific cell surface association proteins or receptors and involves nuclear translocation. IGFBP-3-mediated apoptosis is controlled by numerous cell cycle regulators in both normal and disease processes. IGFBP activity is also regulated by IGFBP proteases, which affect the relative affinities of IGFBPs, IGFs and IGF-1R. Perturbations in each level of the IGF axis have been implicated in cancer formation and progression in various cell types.

Growth hormone and prostate cancer: guilty by association?

Recent case-control studies have found a 7-8% increase in the serum levels of insulin-like growth factor (IGF)-I in patients with prostate cancer (CaP), the most frequently diagnosed cancer in men. We hereby review what is currently known about growth hormone (GH) and the IGF axis in CaP, take a closer inspection of the studies published to date reporting IGF-I levels in CaP patients, and derive implications for the future medical management of patients receiving trophic hormone therapies as well as those at risk for developing CaP. The role of GH in controlling prostate growth and carcinogenesis is still unclear from animal studies and human disease patterns. However, multilayered perturbations of the IGF axis, including the autocrine production of IGFs, IGF binding proteins (IGFBPs) and IGFBP proteases, such as prostate-specific antigen, have been identified in CaP cells and tissues. Interestingly, IGFBP-3 is a potent inhibitor of prostatic IGF action and also mediates prostate apoptosis via an IGF-independent mechanism. Serum IGFBP-3 levels have been identified to be negatively correlated to the risk of CaP. Notably, GH therapy raises both IGF-I and IGFBP-3 levels in serum. Conclusions based on the studies of IGF-I levels in CaP patients are affected by both the populations studied and the types of IGF-I assay employed. While the studies do indicate an association between serum IGF-I levels and CaP risk, causality has not been established. Thus, serum IGF-I level may actually be a confounding variable, serving as a marker for local prostatic IGF-I production. Increased GH levels as seen in acromegaly have been associated with benign prostatic hyperplasia but not with CaP. Thus, serum IGF-I may lead to an ascertainment bias among younger men with benign prostatic hyperplasia who are more likely to present with prostatic symptoms and have subclinical CaP diagnosed. Should serum IGF-I levels be proven to play a causal role in the pathogenesis of CaP, interpreting the risk associated with therapies such as GH must take into account both the duration of exposure and the risk magnitude associated with the degree of serum IGF-I elevation. Since GH-deficient patients often have a subnormal IGF-I serum level, which normalizes on therapy, their CaP risk on GH therapy probably does not increase substantially above that of the normal population. Until further research in the area dictates otherwise, ongoing surveillance and routine monitoring of IGF-I and IGFBP-3 levels in GH recipients must become standard of care.

Cellular actions of insulin-like growth factor binding proteins.

The insulin-like growth factors (IGFs), insulin-like growth factor binding proteins (IGFBPs), and the IGFBP proteases are involved in the regulation of somatic growth and cellular proliferation both in vivo and in vitro. IGFs are potent mitogenic agents whose actions are determined by the availability of free IGFs to interact with the IGF receptors. IGFBPs comprise a family of proteins that bind IGFs with high affinity and specificity and thereby regulate IGF-dependent actions. IGFBPs have recently emerged as IGF-independent regulators of cell growth. Various IGFBP association proteins as well as cleavage of IGFBPs by specific proteases modulate levels of free IGFs and IGFBPs. The ubiquity and complexity of the IGF axis promise exciting discoveries and applications for the future.

The "two bag system" for variable intravenous dextrose and fluid administration: benefits in diabetic ketoacidosis management.

1 case-controlled retrospective analysis compared the "two bag system," based on the euglycemic clamp technique, versus the traditional "one bag" method for intravenous diabetic ketoacidosis management. The two bag system can provide more cost-effective intravenous dextrose and fluid delivery and enhance quality of care by improving the efficiency, timeliness, and flexibility of overall control.

Optimizing growth hormone therapy in children.

Over 12 years' experience with recombinant human growth hormone (rhGH) treatment has created a powerful and safe therapeutic tool. However, to fully optimize the potential of GH therapy and to provide a guide for future GH research, several key issues must be addressed. These are the identification of specific patients or conditions for whom rhGH provides proven long-term benefit; an understanding of when treatment should be started and stopped; a determination of the best dose and regimen; establishment of the most accurate parameter in measuring success of the treatment plan; and recognition of the therapy's potential adverse effects and their relation to dosing. To date, approved pediatric indications for GH therapy are GH deficiency, chronic renal insufficiency and Turner syndrome. Long-term benefits for other indications have yet to be clearly demonstrated. Although starting GH therapy at the youngest possible age yields better results, the treatment endpoint remains controversial. Data so far has shown that daily injections are superior to thrice weekly dosing. Bedtime administration provides more physiologic GH profiles than morning injections. Subcutaneous administration of GH is as efficacious as intramuscular GH and better tolerated. Published pilot studies and large ongoing pediatric trials suggest that the growth response is dose-dependent between 0.025 and 0.1 mg/kg per day. Studies in adults, however, show efficacy at lower doses. It appears that both auxologic and biochemical parameters are useful in assessing treatment efficacy, but which marker is best suited for indicating appropriate dose adjustments remains unclear. The normalization of serum GH-dependent growth factors may have a role in individualizing the GH dose in a similar way to the approach used in managing other endocrine deficiencies.

The effects of irradiation and chemotherapy on growth.

The effects of cancer therapy on growth are reviewed. The effects of radiation and chemotherapy on growth hormone production and growth hormone responsiveness by peripheral tissues are examined. The effects of radiotherapy and chemotherapy on other endocrine function pertaining to growth also are discussed. An approach to surveillance of pediatric cancer survivors pertaining to growth and development is suggested.