Testicular function in males with infantile nephropathic cystinosis.

STUDY QUESTION: Do males with the rare lysosomal storage disease infantile nephropathic cystinosis (INC) have a chance of biological fatherhood? SUMMARY ANSWER: Cryostorage of semen could be an option for approximately 20% of young males with INC, with surgical sperm retrieval from the centre of the testes providing additional opportunities for fatherhood. WHAT IS KNOWN ALREADY: Biallelic mutations in the cystinosin (CTNS) gene in INC cause dysfunction in cystine transport across lysosomal membranes and cystine accumulation throughout the body. Spontaneous paternity in cystinosis has not been described, despite the availability of cysteamine treatment. Azoospermia has been diagnosed in small case series of males with INC. ART using ICSI requires few spermatozoa, either from semen or extracted surgically from the testes of azoospermic men. However, there is limited evidence to suggest this could be successful in INC. STUDY DESIGN, SIZE, DURATION: In this prospective cohort study performed between 2018 and 2019, we performed a cross-sectional investigation of 18 male patients with INC to delineate endocrine and spermatogenic testicular function. PARTICIPANTS/MATERIALS, SETTING, METHODS: Serum hormone levels, semen samples (according to World Health Organization 2010 standards), and testicular ultrasound images were analysed in 18 male patients aged 15.4-40.5 years. Surgical sperm extraction was performed in two, and their testicular biopsies were investigated by light and electron microscopy. Past adherence to cysteamine treatment was assessed from medical record information, using a composite scoring system. MAIN RESULTS AND THE ROLE OF CHANCE: Adherence to cysteamine treatment was high in most patients. Testicular volumes and testosterone levels were in the normal ranges, with the exception of two and three older patients, respectively. Serum LH levels were above the normal range in all subjects aged ≥20 years. FSH levels were elevated in all but four males: three with spermatozoa in semen and one adolescent. Inhibin B levels were shown to be lower in older men. Testicular ultrasound revealed signs of obstruction in 67% of patients. Reduced fructose and zinc seminal markers were found in 33%, including two patients with azoospermia who underwent successful surgical sperm retrieval. Histology identified fully preserved spermatogenesis in the centre of their testes, but also tubular atrophy and lysosomal overload in Sertoli and Leydig cells of the testicular periphery. LIMITATIONS, REASONS FOR CAUTION: Limitations of this study are the small number of assessed patients and the heterogeneity of their dysfunction in cystine transport across lysosomal membranes. WIDER IMPLICATIONS OF THE FINDINGS: This study suggests that testicular degeneration in cystinosis results from the lysosomal overload of Sertoli and Leydig cells of the testicular periphery, and that this can possibly be delayed, but not prevented, by good adherence to cysteamine treatment. Endocrine testicular function in INC may remain compensated until the fourth decade of life; however, azoospermia may occur during adolescence. Cryostorage of semen could be an option for approximately 20% of young males with INC, with surgical sperm retrieval providing additional opportunities for biological fatherhood. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Cystinosis Foundation Germany. The authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: n/a.

Phosphate wasting disorders in adults.

A cause of hypophosphatemia is phosphate wasting disorders. Knowledge concerning mechanisms involved in phosphate wasting disorders has greatly increased in the last decade by the identification of phosphatonins, among them FGF-23. FGF-23 is a primarily bone derived factor decreasing renal tubular reabsorption of phosphate and the synthesis of calcitriol. Currently, pharmacological treatment of these disorders offers limited efficacy and is potentially associated to gastrointestinal, renal, and parathyroid complications; therefore, efforts have been directed toward newer pharmacological strategies that target the FGF-23 pathway. This review focuses on phosphate metabolism, its main regulators, and phosphate wasting disorders in adults, highlighting the main issues related to diagnosis and current and new potential treatments.

Glycaemic variability in paediatric patients with type 1 diabetes on continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI): a cross-sectional cohort study.

OBJECTIVE: This cross-sectional observational cohort study was designed to investigate i) whether glycaemic variability in paediatric patients with type 1 diabetes is lower in those using an insulin pump (CSII) compared with those using multiple daily insulin injections (MDI) and ii) whether urinary F2 -isoprostanes and/or urinary prostaglandin F2 excretion as surrogate marker of oxidative stress and cyclooxygenase activity are associated with glycaemic variability. METHODS: 48 paediatric patients with type 1 diabetes (22 using an insulin pump) underwent an ambulatory 3-day continuous glucose monitoring. All patients continued with normal daily activities and collected urine for two consecutive 24 h periods. The glucose pentagon was used to calculate the glycaemic risk parameter. RESULTS: Insulin requirements, HDL-cholesterol, the mean of glycaemic excursions (P < 0·01) and the standard deviation of mean glucose concentration (P < 0·05) were significantly lower in patients with CSII compared with those using MDI. By contrast, averaged HbA1c during the last twelve months as well as at the time of sensor insertion did not differ significantly between both groups. Summarizing characteristic parameter of acute and long-term metabolic control into the glucose pentagon revealed a significantly lower glycaemic risk parameter in CSI patients compared with both, healthy subjects and patients using MDI (P < 0·05). CONCLUSIONS: Paediatric patients with type 1 diabetes using an insulin pump presented with lower glycaemic variability and a concomitantly lower glycaemic risk parameter compared with those using MDII. Whether these findings translate into a lower risk of diabetes associated cardiovascular complications remains to be elucidated.

Differential effects of short-term growth hormone therapy on the cardiovascular risk profile in patients with chronic kidney disease: a pilot study.

Chronic kidney disease (CKD) is highly associated with an increased cardiovascular morbidity and mortality and is also a state of growth hormone (GH) resistance. We examined the impact of a short-term treatment with rhGH on circulating markers of cardiovascular risk in nonmalnourished CKD patients in a single-center, nonrandomized pilot study. Patients with stable CKD Stage 3 - 5 and age- and sex-matched healthy controls (n = 15 each) received a 7-day treatment with rhGH (1.33 mg/m2 body surface area per day, approximately 30 microg/kg). Prior to onset of rhGH therapy, at the end of the treatment period and at the end of a 7-day wash-out period blood was drawn to assess changes in circulating markers of cardiovascular risk. At time of enrollment CKD patients showed elevated serum concentrations of phosphate, calcium x phosphate product, PTH, fibroblast growth factor-23 (FGF-23), triglycerides, leptin and homocysteine compared to controls. In patients and controls rhGH treatment induced an increase in circulating insulin-like growth factor I (IGF-I), and the molar ratio of IGF-I/IGF binding protein 3 as well as an elevation of glucose, insulin, and triglycerides, whereas serum urea was decreased. In CKD patients, rhGH treatment raised concentrations of leptin, whereas LDL-cholesterol, homocysteine, phosphate, and 25-hydroxyvitamin D were significantly reduced. In controls, but not in CKD patients, rhGH raised 1,25-dihydroxy-vitamin D3 serum levels, which were even more elevated at the end of the wash-out period. In conclusion, short-term treatment with rhGH in CKD patients affects not only insulin and glucose metabolism but also affects serum lipid profile, i.e., LDL-cholesterol, leptin and homocysteine. Long-term trials are required to evaluate the impact of rhGH on cardiovascular morbidity and mortality.

The metabolic fate of doubly stable isotope labelled heat-killed Lactobacillus johnsonii in humans.

OBJECTIVE: In this study, heat-killed Lactobacillus johnsonii (La1), doubly labelled with (13)C and (15)N (hk-dlLa1), was used to follow the metabolic fate after oral administration in humans. DESIGN: Experimental study. SETTING: University of Rostock, Children's Hospital, Research Laboratory. SUBJECTS: Ten healthy adults aged 23-26 years. INTERVENTION: The subjects received 74.6 mg/kg body weight hk-dlLa1 and 10 g alpha-D-raffinose together with breakfast. A sample of venous blood was taken after 2 h. Expired air samples were taken over 14 h, whereas urine and faeces were collected over a period of 48 h. (13)C- and (15)N-enrichments were measured by isotope ratio mass spectrometry. Hydrogen concentrations were measured by electrochemical detection. RESULTS: The orocaecal transit time (OCTT) was reached after 3.4 h. After 2 h, (13)C- and (15)N-enrichment of fibrinogen amounted to 2 and 25 p.p.m. excess, respectively. The (13)CO(2)-exhalation amounted to 9.2% of the ingested dose. The urinary excretion of (13)C and (15)N was 2.1 and 10.4% of the ingested dose, respectively, whereas the faecal excretion was 47.9 and 43.7% of the ingested dose, respectively. CONCLUSIONS: In comparison to OCTT of 3.4 h, both stable isotopes appear after 30 min in breath and urine, indicating that hk-dlLa1 is rapidly digested in the small bowel before reaching the caecum. This is confirmed by (13)C-and (15)N-enrichments of blood plasma fractions. The ingestion of hk-dlLa1 led to a (13)C- and (15)N-excretion of 59.2 and 54.1% of the ingested dose, respectively, of both stable isotopes.

Metabolic clearance of recombinant human growth hormone in health and chronic renal failure.

Despite the increasing therapeutic use of recombinant human growth hormone (rhGH), its metabolic clearance has not been investigated in detail. To evaluate the kinetics of rhGH as a possible function of GH plasma concentration and glomerular filtration rate (GFR), we investigated the steady state metabolic clearance rate (MCR), disappearance half-life, and apparent volume of distribution of rhGH at low and high physiological as well as supraphysiological plasma GH levels during pharmacological suppression of endogenous GH secretion in human subjects with normal and reduced renal function. GH in plasma and urine was determined by an immunoradiometric assay, and GFR by inulin clearance. In all subjects MCR decreased and plasma half-life increased with increasing plasma GH concentrations (P < 0.001). MCR of rhGH was approximately half in patients with chronic renal failure at each GH level and plasma half-life was increased by 25-50%. Allowing for the linear dependence of MCR on GFR and assuming single-compartment distribution, the estimated renal fraction of total MCR was 25-53 and 4-15% in controls and patients, respectively. Saturation of extrarenal disposal of GH was suggested by an inverse hyperbolic relationship between extrarenal MCR and plasma GH concentrations in all subjects. Fractional GH excretion was up to 1,000-fold higher in patients than in controls. We conclude that MCR of hGH is a function of plasma GH concentrations and GFR. Extrarenal elimination is saturable in the upper physiological range of GH concentrations, whereas renal MCR is independent of plasma GH levels. The kidney handles GH like a microprotein involving glomerular filtration, tubular reabsorption, and urinary excretion.

Impaired postprandial regulation of insulin-like growth factor binding protein-1 in children with chronic renal failure.

Patients with chronic renal failure (CRF) have elevated plasma levels of insulin-like growth factor-1 (IGFBP-1). We sought to determine the dynamics of plasma IGFBP-1 in response to an endogenous insulin pulse during an oral glucose tolerance test (oGTT) in 12 prepubertal children with advanced CRF [glomerular filtration rate (GFR) 12.5 +/- 4 mL/min/1.73 m2] and in 9 age-, gender-, and body size-matched controls with normal renal function. Glucose and insulin responses to oGTT were significantly elevated in CRF (P < 0.01), indicating decreased sensitivity to the hypoglycemic action of insulin. Fasting plasma IGFBP-1 levels in CRF (235 +/- 40 ng/mL) were 2.5-fold increased compared with controls (94 +/- 11.6 ng/mL, P < 0.0001). In controls, plasma IGFBP-1 levels rapidly decreased with time by 52%, to a level of 45 +/- 6.7 ng/mL 180 min after the oral glucose load. In contrast, plasma IGFBP-1 levels in CRF patients slowly decreased with time by 25%, to a level of 176 +/- 28 ng/mL (P < 0.001 vs. controls) 180 min after the oral glucose load. For the group as a whole, the percent decrease in IGFBP-1 at 180 min was positively correlated with GFR (r = 0.85, P < 0.0001). Plasma GH concentrations were not statistically different at baseline, but showed a paradoxical increase in CRF patients thereafter. Plasma IGF-I concentrations at baseline were comparable in CRF patients and controls and similarly decreased by about 10% (P < 0.01) after the oral glucose load. In summary, our study shows that the decline of plasma IGFBP-1 in response to an oral glucose load is impaired in children with CRF despite increased insulin levels. This impaired postprandial decline of plasma IGFBP-1 might interfere with glucose homeostasis by blocking insulin-like activity of free IGFs in vivo and thereby contribute to glucose intolerance in uremia.

Reduced concentration of serum growth hormone (GH)-binding protein in children with chronic renal failure: correlation with GH insensitivity. The European Study Group for Nutritional Treatment of Chronic Renal Failure in Childhood. The German Study Group for Growth Hormone Treatment in Chronic Renal Failure.

Growth retardation in children with chronic renal failure (CRF) despite normal or elevated GH levels indicates a peripheral insensitivity to the action of GH. One possible molecular mechanism is a reduced density of GH receptors in GH target organs. In humans, the circulating high affinity GH binding protein (GHBP) is thought to reflect GH receptor expression, because it is derived from the extra-cellular domain of the GH receptor by proteolytic cleavage. We, therefore, analyzed serum GHBP levels by ligand-mediated immunofunctional assay in 126 children with CRF compared to reference values obtained by analysis of 773 healthy children. In 77% of CRF patients, serum GHBP concentrations were below the mean for age- and gender-matched controls. The decrease in serum GHBP levels was related to the degree of renal dysfunction. In advanced CRF (glomerular filtration rate, < 35 mL/min.1.73 m2), mean age- and gender-adjusted GHBP levels were -1.40 +/- 0.18 SD score; 36% of patients had GHBP levels below the normal range (< -2 SD score). Children with end-stage renal disease (n = 26) had the lowest GHBP levels (-2.25 +/- 0.22 SD score). Multiple linear regression analysis revealed that body mass index, rather than glomerular filtration rate, is the prevailing determinant of serum GHBP levels in CRF. GHBP levels correlated with both the spontaneous growth rate ( r = 0.44; P < 0.0001) and the growth response to GH therapy (r = 0.48; P < 0.005), indicating decreased sensitivity to both endogenous and exogenous GH. Subcutaneous GH therapy did not consistently affect serum GHBP levels after 3 months of treatment. It is suggested that low GHBP levels in children with CRF represent a quantitative tissue GH receptor deficiency as one of the molecular mechanisms of GH insensitivity.

Multifactorial control of the elimination kinetics of unbound (free) growth hormone (GH) in the human: regulation by age, adiposity, renal function, and steady state concentrations of GH in plasma.

To evaluate the principal determinants of the MCR and plasma t1/2 of unbound (free) GH in man, we performed steady state infusions of 3 doses of recombinant human GH during pharmacological suppression (iv octreotide) of endogenous GH secretion in 24 healthy adults and 12 patients (6 adults and 6 children) with chronic renal failure (CRF). Free plasma GH was calculated from total plasma GH (measured by immunoradiometric assay) and GH-binding protein activity (radioligand assay). The MCR of free GH was determined from free plasma GH and the rate of recombinant human GH infusion. The t1/2 of free plasma GH, and the concentration and the in vivo dissociation constant (Kd) of GH-binding protein (GHBP) were estimated by dynamic modeling of the postinfusion total plasma GH concentration decay curves. The MCR of free GH decreased and the plasma GH t1/2 increased significantly with increasing plasma GH concentrations. The MCR of free GH over its physiological concentration range was positively correlated with the body mass index as a measure of relative obesity and negatively related to age, but only at supraphysiological GH concentrations. In the adult patients with CRF, the MCR of free GH was decreased at each infusion rate by 25-38%, and the t1/2 was increased by 80-170%. Children with CRF showed a significantly lower MCR and higher t1/2 of plasma free GH than adult patients. Modeling and direct measurements of the off-rate of GH from its high affinity GHBP indicated normal dissociation rate constants but decreased molar concentrations of the GHBP in uremic plasma. We conclude that the rate of elimination of free GH from plasma in man is controlled by 1) plasma total free GH concentrations, 2) relative obesity, and 3) renal function within the physiological GH concentration range, whereas 4) age is a negative predictor of MCR only at supraphysiological GH concentrations.

Does recombinant growth hormone improve adult height in children with chronic renal failure?

During the past decade, the safety and efficacy of long-term treatment with recombinant human growth hormone (rhGH) in children with chronic renal failure before and after renal transplantation has been established. This article reviews the increasing evidence that rhGH treatment also results in a significant improvement of adult height in patients with childhood-onset chronic renal failure. The eventual height benefit of extended rhGH treatment appears to be 1.0 to 1.5 standard deviations on average. Whereas prepubertal rhGH treatment has a beneficial effect on final height, the efficacy of rhGH during puberty is less evident. The cumulative duration of rhGH treatment was found to be the most important positive, and the duration of dialysis treatment periods a negative predictor of rhGH efficacy, stressing the importance of prolonged rhGH treatment starting early in the course of chronic renal failure.

Predictors of growth response to rhGH in short children before and after renal transplantation. German Study Group for Growth Hormone Treatment in Chronic Renal Failure.

Many children with chronic renal failure (CRF) present with a reduced height and a reduced height velocity resulting in diminished final height irrespective of renal replacement therapy. Recombinant human growth hormone (rhGH) has become a new treatment modality for short renal patients, and the response to rhGH varies widely. In order to identify possible predictors of response to rhGH, the influence of sex, chronological age, bone age, pubertal status, height and height velocity at basal, target height, treatment modality for CRF, residual glomerular filtration rate (GFR), and steroid treatment was analyzed by single and multiple regression analysis in 49 children prior to and after renal transplantation. During the first treatment year with 28 to 30 IU rhGH/m2/week given by daily s.c. injections, height velocity was highest in patients on conservative treatment and lowest in patients on dialysis. Height velocity expressed in cm/year was inversely correlated with age (r = -0.63; P < 0.0001) and positively correlated with pretreatment height velocity (r = 0.65; P < 0.0001). The increment in height velocity SDS (chronological age) was significantly negatively correlated with the pretreatment height velocity SDS (chronological age) (r = -0.58, P < 0.001), indicating that at any given age the slowest growing children tended to respond best to rhGH treatment. It is concluded that the response to rhGH is significantly influenced by age, pretreatment height velocity, and treatment modality for CRF, whereas the influence of other variables is less important.

Human bioassays to assess environmental genotoxicity: development of a DNA repair assay in HepG2 cells.

A direct assessment of the effects of environmental chemicals on human health has been hampered by the lack of suitable experimental systems. We have recently employed a human liver cell line (HepG2) to assess the biological effects of pollutants at both cellular and DNA levels. A Neutral Red dye uptake assay was used to assess potential cytotoxic effects of xenobiotics. DNA damage was quantified using an unscheduled DNA synthesis assay that measures repair that is induced following exposure to genotoxic compounds. HepG2 cells responded to the known mutagens, 4-nitroquinoline N-oxide and methylmethane sulfonate, both in the Neutral Red assay for cytotoxicity and two DNA repair assays for genotoxicity (monitored autoradiographically or by liquid scintillation counting). The HepG2 DNA repair and cytotoxicity assays also responded to an extract (containing polycyclic aromatic hydrocarbons) of sediment obtained from a polluted site in the Great Lakes. Results indicate that this system can be deployed further to assess potential cyto- and genotoxicity of pollutants. The development of human cell culture assays is a critical step towards a full assessment of the risk that such pollutants pose to human health.

The acute effect of growth hormone on GFR is obliterated in chronic renal failure.

Recombinant human growth hormone (rhGH) has become available for treatment of growth failure in uremic children. Since GH raises the glomerular filtration rate (GFR) in healthy individuals, there has been concern that treatment with rhGH, by its action on glomerular hemodynamics, may adversely affect the progression of renal failure. To further address this issue, inulin clearance (enzymatic steady-state infusion technique) was measured in 7 healthy normotensive adult volunteers and 7 patients with chronic renal failure from glomerular or non-glomerular causes. Subjects were given 4.5 U bid of rhGH by s.c. injection for 3 days. In volunteers, a significant increase in Cin was noted 72 h after start of rhGH administration from 120 ml/min/1.73 m2 (range 91-158) to 133 (108-167) (p less than 0.02). In contrast, no significant increase in Cin was noted in patients with chronic renal failure (baseline Cin 21 ml/min/1.73 m2, 15-32; after rhGH 22 ml/min/1.73 m2, 15-32) despite pronounced effects of GH on S-cholesterol and urea excretion rate. The results show that stimulation of GFR by short-term administration of rhGH is obliterated in chronic renal failure.

Etiology of children's spinal injuries at Rancho Los Amigos.

A review of 277 patients under the age of 16 years admitted to the pediatric spinal injury unit at Rancho Los Amigos Medical Center from 1960 to 1989 showed that 70% of the patients were male; complete and incomplete injuries were about equal; and the average age was 8.8 years. The cause of spinal injury by time period revealed that earlier time periods had etiologies similar to those reported in previously published series. Although the incidence of these traditional causes remained constant, violent injuries by gunshot steadily increased with time. In the most recent 5-year period, gunshot wounds equaled motor vehicle injuries as the most frequent cause of a child's spinal injury admitted to this hospital. Gunshot wound victims averaged 12 years old, 80% were male, and most were thoracic level paraplegics. Half of the 50 adolescents (12-16 years old) injured during the last 5 years were gunshot victims.

Peritoneal loss of growth hormone in children on automated peritoneal dialysis.

OBJECTIVE: To provide quantitative data regarding the daily dialytic loss of growth hormone (GH) in children on peritoneal dialysis (PD). DESIGN: Prospective study involving 24-hour dialysate collections on 3 consecutive days in patients with and without recombinant human GH (rhGH) treatment. SETTING: Single-center outpatient PD program. PATIENTS: Twenty-six children undergoing automated PD (APD): 6 with and 20 without daily rhGH. MAIN OUTCOME MEASURES: Daily peritoneal losses of GH, alpha1-, beta2-microglobulin, transferrin, and albumin. RESULTS: The mean (+/-SEM) daily dialytic GH loss was 2.18+/-0.62 microg/1.73 m2 per day in rhGH-treated patients and 0.42+/-0.28 microg/1.73 m2 per day in untreated patients, (p < 0.05). The intraindividual coefficient of variation of daily GH loss was 65%. The peritoneal loss of GH was positively correlated with that of beta2-microglobulin (r = 0.77, p < 0.001) and alpha1-microglobulin (r = 0.51, p < 0.01). The variability in beta2-microglobulin and alpha1-microglobulin elimination, together with the use of rhGH, explained 66% of the total variability of daily GH excretion. In patients without rhGH therapy, the daily peritoneal GH loss was approximately 0.05% of the estimated daily endogenous production rate based on previous estimates in children with end-stage renal failure. In patients on rhGH therapy, less than 0.1% of the injected rhGH dose was eliminated by dialysis. CONCLUSION: Peritoneal losses of GH in children on APD account only for a minute fraction of endogenous metabolic clearance, and do not explain the variability of the rhGH treatment response. The assessment of dialytic GH elimination may be used to estimate time-integrated mean plasma GH concentrations, and to monitor rhGH treatment compliance.

Long-term experience with growth hormone treatment in children with chronic renal failure.

After a decade of experience with recombinant human growth hormone (rhGH) in children with chronic renal failure (CRF), the long-term efficacy and safety of the drug is now established. In prepubertal children, partial catch-up growth is achieved during the first three treatment years, followed by sustained percentile-parallel growth. Discontinuation of rhGH treatment results in catch-down growth in 75% of patients. Treatment efficacy is inversely correlated with age and baseline height velocity, and positively influenced by genetic target height and residual renal function. Skeletal maturation is not accelerated, suggesting a true increase in final height potential. Side effects are limited to a stimulation of insulin secretion, which is not associated with changes in glucose tolerance, and occasional cases of benign intracranial hypertension. In summary, the advent of rhGH has opened a new era in the management of growth failure in CRF. Available evidence suggests that treatment should start in early childhood and early in the course of renal failure, and should be continued at least until renal transplantation. It remains to be seen whether the beneficial effect of rhGH on height observed during the prepubertal period will result in an eventual increase in adult height.

Stimulation of growth by recombinant human growth hormone in children undergoing peritoneal or hemodialysis treatment. German Study Group for Growth Hormone Treatment in Chronic Renal Failure.

Fourteen patients on hemodialysis (HD) and 17 patients on continuous peritoneal dialysis (CPD) were treated with 28-30 IU/m2/week of recombinant human growth hormone (rhGH) for at least 12 months. The HD and CPD patient groups were comparable with regard to age, bone age, height standard deviation scores (SDS), and height velocity at start of treatment. During the first year of rhGH treatment, height velocity increased from 2.9 +/- 1.9 to 5.5 +/- 1.7 cm/year in the HD group and from 3.0 +/- 2.2 to 7.2 +/- 3.2 cm/year in the CPD group. The increase in growth rate was significant in both groups (p < 0.001), and tended to be significantly greater in the CPD than in the HD group (p = 0.09). The marked acceleration of growth under rhGH treatment resulted in an increase in relative height by 0.37 +/- 0.38 SDS in the HD group and by 0.47 +/- 0.69 SDS in the CPD group during the first treatment year. Seven HD and 7 CPD patients completed a second year of rhGH treatment. In these patients, height velocity dropped to 3.6 +/- 2.7 cm/year (HD) and 3.6 +/- 2.3 cm/year (CPD), respectively during the second treatment year. We conclude that rhGH treatment accelerates growth in children both on HD and CPD. The treatment response tends to be greater in CPD compared to HD patients. The efficacy of treatment decreases considerably during the second treatment year.

AIDS and adolescents: school health education must begin now.

PIP: Teenagers must be educated about AIDS. Because thousands of teenagers are at risk because of their behaviors, target groups for special programs should include those who are drug users, gay and bisexual, homeless, or into solicitation and prostitution. Educational material should be developed that includes a culturally sensitive approach for minority teenagers. Certain areas with high prevalence rates of AIDS need special attention because they pose greater risks for teenagers, such as Houston, Los Angeles, Miami, New York City, northern New Jersey, San Francisco, and Washington, DC. Studies show that most teenagers are misinformed or lack of basic knowledge about transmitting or protecting against AIDS. Education should be aimed at countering this misinformation and reducing the panic about the disease. Teenagers need this health-related information for sharing with their siblings and parents as well as for learning for themselves. Most existing school-based education programs are inadequate because few exist, most are only for junior and senior high levels, and may do not focus on prevention information. Ideally, AIDS education should be integrated into existing health or sexuality education programs. The programs should emphasize information on how AIDS is transmitted, how AIDS is not transmitted, and how to protect oneself from HIV.^ieng

Three-year growth hormone treatment in short children with X-linked hypophosphatemic rickets: effects on linear growth and body disproportion.

CONTEXT: Children with X-linked hypophosphatemic rickets (XLH) are prone to progressive disproportionate stunting despite oral phosphate and vitamin D treatment. OBJECTIVE: Our objective was to analyze the effects of GH treatment on stature and lengths of linear body segments in short children with XLH. DESIGN, SETTINGS, AND PATIENTS: A 3-yr randomized controlled open-label GH study in short prepubertal children with XLH (n = 16) on phosphate and calcitriol treatment was conducted. A cohort of XLH patients (n = 76) on conservative treatment served as an XLH reference population. MAIN OUTCOME MEASURES: Changes in SD scores (SDS) of stature and linear body segments, i.e. sitting height, leg and arm length, and sitting height index (i.e. ratio between sitting height and stature) were the main outcome measures. RESULTS: XLH patients presented at time of enrollment with significant impairments of stature (-3.3 SDS) and linear body segments compared with healthy children. Leg length (-3.8 SDS) was most impaired, whereas sitting height (-1.7 SDS) was best preserved. The markedly elevated mean sitting height index (+3.3 SDS) reflected severe body disproportion. GH resulted in a sustained increase in linear growth (stature, +1.1 SDS; sitting height, +1.3 SDS; leg length, +0.8 SDS; arm length, +1.1 SDS; each P < 0.05 vs. baseline), whereas no significant changes were observed in controls. Mean height SDS at 3 yr did not significantly differ between groups. Sitting height index remained stable in both the GH-treated patients and in study controls but increased further in the XLH-reference population. CONCLUSIONS: The 3-yr GH treatment improved linear growth without progression of body disproportion in short children with XLH.