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R Brauner

Publications and source records attributed to R Brauner.

At least 19 recordsLinked to original sources
PubMed2000

Adult height after growth hormone (GH) treatment for GH deficiency due to cranial irradiation.

BACKGROUND: The indications and factors affecting the growth in response to treatment with growth hormone (GH) of patients with cranial irradiation-induced GH deficiency remain unclear. PROCEDURE: The adult heights of 56 patients treated with GH (0.4-0.6 U/kg/week) as daily sc injections were analysed. They had been given 18 or 24 Grays (Gy) cranial irradiation for leukemia (group 1, 26 cases), 50 +/- 1 Gy for various tumors (group 2, 13 cases), 46 +/- 1 Gy for retinoblastoma (group 3, 8 cases), or 34 +/- 2 Gy with spinal irradiation for medulloblastoma (group 4, 9 cases). Twenty- five of these 56 patients had early puberty and were also treated with gonadotropin-releasing hormone (GnRH) analog. RESULTS: The standing (-1.0 +/- 0.2 in group 1, -0.7 +/- 0.3 in group 2, -1.1 +/- 0.3 in group 3, and -2.0 +/- 0.4 SD in group 4) and sitting (-1.8 +/- 0.2 in group 1, -0.4 +/- 0.4 in group 2, -1.2 +/- 0.4 in group 3, and -3. 4 +/-0.4 SD in group 4) adult heights were shor ter (P < 0.05 for standing and P < 0.001 for sitting heights) for group 4 than for each of the other groups. Of the 47 patients given cranial (and not craniospinal) irradiation, sitting adult height was shorter (P = 0. 02) and the difference between standing adult and target heights greater (P = 0.03) in those patients in whom puberty occurred at a normal age than in those treated with GnRH analog. Conclusion. The incomplete catch-up of growth seems to be mainly due to the reduction in sitting height of patients given spinal irradiation and in whom puberty occurred at a normal age. This suggests that GnRH analog treatment should be more widely used to treat children with early and/or rapidly progressing puberty after cranial irradiation.

Adolescent↗
PubMed2000

Growth, puberty and hypothalamic-pituitary function in children with suprasellar arachnoid cyst.

UNLABELLED: A suprasellar arachnoid cyst may cause disorders of growth, puberty and hypothalamic-pituitary function, due to the proximity of the cyst to the hypothalamic-pituitary area. A total of 30 patients (17 boys) with cyst diagnosed at 4.3 +/- 1 years were routinely evaluated at 5.4 +/- 1 years; 24 of them had one or multiple cyst derivations. Some 23 cases had an abnormal height, weight or puberty: short (< -2SD, 5 cases) or tall ( > 2SD, 10 cases) stature, overweight (body mass index, BMI, > 2SD, 6 cases), central precocious puberty (10 cases) and/or no progression of pubertal development (3 cases). The growth hormone (GH) peaks after pharmacological stimulation test were low (< 10 MICROg/L) in 16 patients, confirmed by a second evaluation in 8/11 of them. The plasma free thyroxine was low in five patients, prolactin was high in two and the cortisol and concomitant plasma and urinary osmolalities were normal. BMI was correlated negatively with the GH peaks (r = -0.37, P < 0.01) and positively with the plasma leptin concentrations (r = 0.55, P < 0.01). The plasma fasting insulin concentrations were also correlated negatively with the GH peaks (r = -0.55, P < 0.02) and positively with the plasma insulin-like growth factor I concentrations (r = 0.64, P < 0.002). The adult height (12 cases) was at 4SD in 1 and < -2SD in 4 patients, two of whom had precocious puberty untreated with gonadotropin releasing hormone (GnRH) analogue, and two had untreated GH deficiency. The adult height of those treated was normal. One girl had primary amenorrhoea and two boys had low plasma testosterone, despite a normal gonadotropin response to a GnRH test. CONCLUSION: Suprasellar arachnoid cysts may cause deficiencies of growth hormone and thyrotropin, stimulation of the hypothalamic-pituitary-gonadal axis, tall stature and/or overweight. These last two disorders may be due to hyperinsulinism, itself due to suprasellar arachnoid cyst.

Adolescent↗
PubMed2000

Linkage disequilibrium in inbred North African families allows fine genetic and physical mapping of triple A syndrome.

Triple A syndrome (Allgrove syndrome, MIM No. 231550) is a rare autosomal recessive disorder characterised by ACTH-resistant adrenal insufficiency, achalasia of the cardia, and alacrimia. The triple A gene has been previously mapped to chromosome 12q13 in a maximum interval of 6 cM between loci D12S1629 and D12S312. Using linkage analysis in 12 triple A families, mostly originating from North Africa, we confirm that the disease locus maps to the 12q13 region (Zmax = 10.89 at theta = 0 for D12S1604) and suggest that triple A is a genetically homogeneous disorder. Recombination events as well as homozygosity for polymorphic markers enabled us to reduce the genetic interval to a 3.9 cM region. Moreover, total linkage disequilibrium was found at the D12S1604 locus between a rare allele and the mutant chromosomes in North African patients. Analysis of markers at five contiguous loci showed that most of the triple A chromosomes are derived from a single founder chromosome. As all markers are located in a 0 cM genetic interval and only allele 5 at the D12S1604 locus was conserved in mutant chromosomes, we speculate that the triple A mutation is due to an ancient Arabian founder effect that occurred before migration to North Africa. Since we also found linkage disequilibrium at D12S1604 in two patients from Southern Europe (France and Spain), the founder effect might well extend to other Mediterranean countries. Taking advantage of a YAC contig encompassing the triple A minimal physical region, the triple A gene was mapped to a 1.7 Mb DNA fragment accessible to gene cloning.

Adrenal Insufficiency↗
PubMed2000

The use of insulin-like growth factor 1 reference values for the diagnosis of growth hormone deficiency in prepubertal children.

OBJECTIVE: This study was done to determine whether the use of reference values obtained in children with idiopathic short stature (ISS) improved the clinical value of serum insulin-like growth factor I (IGF-1) as a tool for diagnosing GH deficiency (GHD) in prepubertal children. PATIENTS AND METHODS: Serum IGF-1 was measured with a new IRMA kit (IGFI-RIA CT, Cis Bio, Gif sur Yvette, France) in 168 prepubertal normal children and in prepubertal children with ISS (n = 68), organic GHD due to a craniopharyngioma (oGHD, n = 15) and permanent idiopathic GHD (iGHD, n = 28). RESULTS: IGF-1 was lower (P < 0.001) in iGHD than in either ISS or oGHD and was below the fifth percentile of the normal range in 29/68 ISS (43%), 8/15 oGHD (53%) and 28/28 (100%) iGHD patients. Three oGHD (20%) and two iGHD (7%) patients had a serum IGF-1 below the fifth percentile of the normal group but above the fifth percentile of the ISS group. Thus, a serum IGF-1 below the fifth percentile of the normal group distinguished between normal children and iGHD with 100% sensitivity, between normal and oGHD with 53% sensitivity and between normal and all GHD (idiopathic + organic) with 84% sensitivity; the overall specificity was only 57%. Conversely, a serum IGF-1 below the fifth percentile of the ISS population distinguished between ISS and iGHD with 93% sensitivity, between ISS and oGHD with 33% sensitivity and between ISS and all GHD with 72% sensitivity; the overall specificity was then 95%. CONCLUSIONS: A serum IGF-1 within the normal range virtually excludes idiopathic GHD but does not rule out organic GHD, whereas an IGF-1 below the ISS range is strongly in favour of GHD, after exclusion of poor nutritional status and/or liver disease. An IGF-1 below the normal range but in the idiopathic short stature range gives no definitive conclusion even when it is associated with a low GH peak. Thus, whereas reference values obtained in normal children must be used to interpret serum IGF-1 in short prepubertal children, reference data obtained in idiopathic short stature children should also be taken into account.

Child↗
PubMed1999

Hypothalamic-pituitary function and growth in children with intracranial lesions.

Intracranial lesions may affect hypothalamic-pituitary (HP) function and growth in several ways, depending on the location of the lesion within this area, the presence or absence of secondary hydrocephalus, and/or treatment of the lesion by surgery and/or radiotherapy. The lesion may cause a deficiency of HP hormones or, conversely, activation of the HP-gonadal axis leading to precocious puberty. Growth hormone (GH) deficiency is the most frequent endocrine abnormality that results from the lesions of the HP area. There has been progress in diagnosis, patterns of replacement therapy and the administration of biosynthetic GH in association with gonadotropin-releasing hormone analogues in precocious puberty. The major problem in these patients is the dramatic increase in their weight, which frequently occurs after surgery and increases their psychosocial and physical disabilities. It may be due to the hyperinsulinism caused by the lesion. This hyperinsulinism may be the factor that replaces GH in stimulating growth factor production and leads to normal growth in some of the patients.

Brain Neoplasms↗
PubMed1999

Effect of short-term testosterone treatment on leptin concentrations in boys with pubertal delay.

Testosterone administration increases growth hormone (GH) secretion and decreases the plasma leptin concentration in men. We evaluated the effect of increased GH secretion due to short-term testosterone treatment on leptin concentrations. Ten boys aged 14.8 +/- 0.2 (mean +/- SE) years with transient GH deficiency caused by pubertal delay were evaluated before and after (3 months) 4 intramuscular injections of 100 mg testosterone heptylate, given at 15-day intervals. The leptin concentration decreased from 5.4 +/- 1.3 to 3. 6 +/- 1.1 microgram/l (p < 0.001), despite a weight gain of 3.4 +/- 0.5 kg. There were significant increases in body mass index (BMI), from -0.2 +/- 0.5 to 0.2 +/- 0.5 SD, p < 0.005, in GH peak after stimulation test, from 6.3 +/- 0.5 to 21.7 +/- 2.9 microgram/l, p < 0. 0003, in plasma testosterone, from 0.6 +/- 0.1 to 6.5 +/- 1.3 microgram/l, p < 0.001, in insulin-like growth factor-I (IGF-I), from 152 +/- 21 to 330 +/- 30 microgram/l, p < 0.0001, and in IGF-binding protein-3 (IGFBP-3), from 4.2 +/- 0.5 to 5.4 +/- 0.4 mg/l, p < 0.01. But there were no changes in blood glucose (4.7 +/- 0.1 and 4.8 +/- 0.1 mmol/l), or plasma fasting insulin (9.0 +/- 1.2 and 8.1 +/- 1.3 mIU/l). The leptin concentrations were positively correlated with the BMI before (p < 0.03) and after (p < 0.04) testosterone, but not with the GH peak after stimulation, or with plasma testosterone, IGF-I or IGFBP-3. The leptin and insulin concentrations after testosterone treatment were positively correlated (p < 0.04). Thus, short-term testosterone treatment of boys with pubertal delay decreases their leptin concentrations. The lack of correlation with GH secretion or with its changes, despite the dramatic increase in GH secretion, and the lack of change in insulin are additional features suggesting that testosterone increases the leptin concentration mainly by an effect on adipose tissue.

Adolescent↗
PubMed1999

Idiopathic growth hormone deficiency: presentation, diagnostic and treatment during childhood.

The clinical and biological presentation of idiopathic growth hormone (GH) deficiency (GHD) varies greatly, demonstrating the variety of its pathogenic features and explaining why it is difficult to diagnose. We examined 48 patients (26 males) with certain idiopathic GHD diagnosed at 4.8 +/- 0.7 yr. The symptoms that led to the diagnosis of GHD were low growth rate (33 cases), hypoglycemia (12 cases), microphallus (1 case) and in 2 cases the GHD was diagnosed from magnetic resonance imaging (MRI) performed for delayed mental development (1 case), or congenital blindness (1 case). The 2 other cases were diagnosed from routine GH evaluation performed at birth because of idiopathic GHD in siblings. Thirteen had congenital malformation. Twenty three cases (48%) had features suggesting that the GHD was of antenatal origin. Six of them were born by breech delivery. Twenty one cases (44%) had features suggesting a hypothalamic origin. The decrease in growth rate occurred before 0.5 year in 21 (55%), before 1 year in 27 (71%) and before 2 years in 30 (79%): 8 patients (21%) maintained a normal growth rate after this age. Among these 8 patients, 5 had signs suggesting an antenatal origin and 4 had severe episodes of hypoglycemia from birth. The mean GH peak after the pharmacological stimulation test was 3.6 +/- 0.5 micrograms/l. The mean plasma insulin-like growth factor 1 (IGFI) was 0.1 +/- 0.02 U/ml. The GH deficiency was associated with deficiencies of thyrotropin in 26 (54%) and of adrenocorticotrophic hormone in 17 (35%) patients. Among the 15 patients of pubertal age, 9 (60%) had gonadotrophin deficiency. No patient had diabetes insipidus. The MRI showed pituitary stalk interruption syndrome in 39 patients and normal pituitary anatomy in 6 patients. GH treatment reduced the difference between target and actual heights from 3.5 SD (before) to I SD (after 3 years) in the 39 more recently seen patients given 0.5-0.6 U/kg/w GH in 6 or 7 weekly injections. Height gain during the first year and cumulative height gain over 3 years (SD) was correlated negatively with height (SD) at the start of treatment (p < 0.01). We conclude that most of the patients with GHD have features suggesting an antenatal origin. Despite this early origin, the decreased growth rate may occur after 2 years.

Body Height↗
PubMed1998

Growth hormone secretion, puberty and adult height after cranial irradiation with 18 Gy for leukaemia.

UNLABELLED: The dose of prophylactic cranial irradiation given to patients for acute lymphoblastic leukaemia has been decreased from 24 to 18 Gy, but the beneficial effect of this decrease on growth is controversial. This study compares the growth hormone (GH) secretion and growth of 35 patients (20 boys) given 18 Gy at 3.7+/-0.3 (SE) years, and routinely evaluated 5.4+/-0.4 years after irradiation to define the indications for GH treatment in these patients. Of these, 63% had a low GH peak (< 10 microg/l) after one (22 cases) or two (17 cases) stimulation tests. The plasma concentrations of insulin-like growth factor I and its GH-dependent binding protein were normal for age in all but two cases. The height changes between irradiation and evaluation were correlated with the GH peaks (P < 0.03) and were concordant, except in patients with early puberty. This occurred in 16 patients including all 12 girls irradiated before 4 years of age. A significant (P < 0.03) reduction in height (SD) between irradiation and adult height occurred in untreated GH-deficient patients (-1+/-0.3, n=6), but not in GH-deficient patients given GH (-0.6+/-0.3, n=8) or in those with normal GH peak (-0.4+/-0.3, n=7). CONCLUSION: In children irradiated for acute lymphoblastic leukaemia, GH deficiency is frequent after 18 Gy but its impact on adult height is smaller than after higher doses. We suggest that the indications for gonadotropin releasing hormone analogue therapy should be broad in patients with early or rapidly progressing puberty and those for GH therapy in those patients with a below average constitutional height before irradiation.

Adolescent↗
PubMed1998

Ovarian function after bone marrow transplantation during childhood.

Ovarian failure is often brought about by the conditioning protocol used for bone marrow transplantation (BMT). We monitored ovarian function in 31 girls conditioned for BMT at 10.3 +/- 0.6 (s.e., 3.2-17.5) years by chemotherapy alone (group 1, n = 8) or chemotherapy plus body irradiation (12 Gy, fractionated in group 2, n = 9, or 10 Gy single total body in group 3, n = 7, and 5 or 6 Gy single thoraco-abdominal in group 4, n = 7, irradiation) at 13.4 +/- 0.4 (11.7-18.6) years. Breast development was normal (n = 11), did not occur (n = 14), or did not progress spontaneously (n = 2) after BMT. The other four girls who menstruated before BMT had permanent amenorrhea. Basal plasma gonadotropin concentrations were measured in 29; follicle-stimulating hormone was increased in them all and luteinizing hormone in 23. At the last clinical evaluation at 16.3 +/- 0.4 (12.1-21.6) years, 23 girls had complete ovarian failure, two had partial ovarian failure, and six had normal ovarian function. Three of these were the youngest group 1 patients and those who had not received busulfan. We conclude that conditioning for BMT given during childhood frequently prevents normal estrogen secretion at puberty. Adequate substitutive treatment may be necessary to induce growth acceleration and sexual development.

Adolescent↗
PubMed1998

Three-year data from a comparative study with recombinant human growth hormone in the treatment of short stature in young children with intrauterine growth retardation.

Growth acceleration and bone maturation were studied for 3 y in 69 children with severe short stature and a history of intrauterine growth retardation (IUGR), to determine the effect of treatment with recombinant human growth hormone (r-hGH). The patients were enrolled in an open, multicentre trial and were randomly allocated to either the treated group (Group 1) or the control group (Group 2). The children in Group 1 were treated daily with 0.2 IU/kg/body weight (0.067 mg/kg) s.c., during 3 y and the children in Group 2 started the study with a 1-y observation period followed by a 3-y treatment period. At birth, their mean weight standard deviation score (SDS) was -2.5 and their mean length SDS -3.5. At baseline, the patients were prepubertal, non-GH deficient, with no known dysmorphic features. Mean age was 4.5 y, bone age was 3.3 y, height SDS was -3.4, height velocity (HV) SDS was -1.6, and body mass index SDS was -1.4. After 1 y of treatment, linear HV in Group 1 increased in comparison with the pre-treatment period (from 5.7 +/- 2.0 to 10.1 +/- 1.7 cm/y; p < 0.001) and with the first year of observation in Group 2 (p < 0.001). Increased HV was sustained during the second and third year of treatment and was significantly higher than at baseline. A similar growth pattern was seen during the 3 y of GH treatment in Group 2. Mean height SDS for chronological age increased by 2.0 +/- 0.7 in the two groups after 3 y of treatment. HV after 1 y of treatment was negatively correlated with growth velocity at baseline. Bone age remained retarded but increased with a mean of almost 4 y after 3 y of treatment in both groups. Even at a dose that is three times the replacement dose treatment with r-hGH was well tolerated. From these results, we conclude that r-hGH treatment over 3 y can induce sustained catch-up growth in young children with severe short stature and a history of IUGR. Long-term studies are needed to assess ultimate effects on final height.

Adolescent↗
PubMed1998

Long-term follow up of 69 patients treated for optic pathway tumours before the chemotherapy era.

AIM: To analyse the long-term results of conservative management with radiotherapy in patients with optic pathway tumours. DESIGN: All 69 patients were symptomatic at diagnosis and most neoplasms involved the optic chiasm and hypothalamus. RESULTS: At 10 years, overall survival and progression free survival were 83% and 65.5%, respectively. After radiotherapy, vision improved in 18 patients and remained stable in 29 other patients. Cerebrovascular complications occurred in nine of 53 patients treated with radiotherapy after a median interval of two and a half years. These complications were five times more frequent in patients with neurofibromatosis type 1 (NF1). Severe intellectual disabilities were present in 18 children, most of whom underwent irradiation at a very young age (median age, 4 years). IMPLICATIONS: Radiotherapy is a valuable treatment in terms of tumour response, visual outcome, and progression free survival. However, in young children and in patients with NF1, major sequelae are encountered and new treatment strategies should be proposed for these patients.

Adolescent↗
PubMed1998

Pituitary apoplexy in an adolescent with prolactin-secreting adenoma.

A 14.8-year-old girl was treated with bromocriptine for a prolactin-secreting adenoma. She suddenly developed headaches, vomiting, fever and meningeal syndrome. This was associated with corticotropin, thyrotropin and gonadotropin deficiencies. Magnetic resonance imaging showed peripheral enhancement and a central hyposignal suggesting intra-adenoma hemorrhage and then disappearance of the adenoma. Hydrocortisone was initiated in emergency to prevent any risk to life.

Adolescent↗
PubMed1998

Androgens and fetal growth.

Boys are heavier than girls at term birth. Children with a 46,XY karyotype and androgen insensitivity syndrome (clinically complete form and/or proven mutations in the androgen receptor gene) were found to have a birth weight comparable to that of girls. These findings support the hypothesis that the difference in birth weight between boys and girls is generated by androgen action.

Androgen-Insensitivity Syndrome↗
PubMed1998

Femoro-femoral bypass for repeat open-heart surgery.

Repeat open-heart operations are becoming more frequent with a patient population at higher risk. Sternal re-entry poses the risk of possible damage to vital structures. These include laceration of the myocardium, especially the right ventricle, tearing of patent grafts and internal mammary grafts in particular, or dislodgement of emboli from patent vein grafts. To minimize the risk associated with sternal re-entry, we adopted the method of establishing femoral artery-femoral vein cardiopulmonary bypass (CPB) in order to achieve cardiac decompression prior to sternotomy. Between June 1994 and October 1997, 94 patients underwent repeat open-heart operations at our institution. Of these, seven were a second time reoperation. Mean age was 62 years (range 31-80 years), and 65 were male. Fifty-nine patients had coronary bypass, 27 had aortic valve replacement, 45 had mitral valve replacement, and nine had other procedures (these numbers include patients having combined procedures). In patients with no known vascular disease, the femoral vessels were exposed, and if found suitable, were cannulated, and the patients connected to CPB. The sternum was opened with an oscillating saw, and on penetration through the posterior table, the heart was drained to allow for decompression. If the femoral vein cannula did not allow full bypass, ventilation was maintained until the right atrium was exposed and cannulated and full bypass was achieved. Femoro-femoral bypass was established in 75 patients. In 19 patients it was not done for the following reasons: eight patients had a diseased femoral artery, in one patient the femoral vein could not be cannulated, nonuse of CPB altogether occurred in three patients, and it was because of surgeon's preference in seven patients. In one patient a high pressure developed in the arterial line, requiring conversion to aortic cannulation during the course of CPB, without any negative consequences. There were no problems associated with sternal re-entry, no patient had limb ischemia or venous thrombosis. Two patients (2.6%) had complications related with femoral cannulation, with one having trauma to an atherosclerotic femoral artery requiring repair with vein interposition, and the other a tear of iliac vein requiring laparotomy. Groin wound infection occurred in five patients (6.6%), and groin hematoma in four patients (5.3%). All complications were treated successfully with no permanent damage. Operative mortality was 9% (seven patients). Causes of death included myocardial infarction (2), infection (3), respiratory (1), and cirrhosis (1). We conclude that femoro-femoral bypass prior to sternotomy is a safe and easy method to reduce the risk of sternal re-entry by allowing early decompression of the heart, and in unstable patients it offers better myocardial protection by earlier connection to CPB. Proper selection of patients is important in order to minimize related comorbidity. We recommend this method in redo patients in whom femoral cannulation is feasible.

Adult↗
PubMed1997

Deletions of distal 9p associated with 46,XY male to female sex reversal: definition of the breakpoints at 9p23.3-p24.1.

Monosomy of distal 9p is associated in rare cases with abnormalities of testicular determination, which can lead to male to female sex reversal in a 46,XY genetic background. We present two 46,XY individuals partially monosomic for 9p who were raised as females. Definition of the breakpoints using somatic cell hybrids containing only the rearranged chromosome 9 indicated that in the first patient the breakpoint was located between markers D9S256 and D9S144 and in the second patient, the breakpoint was distal to the marker D9S144. In both cases this corresponds to the cytogenetic position 9p23.3-p24.1. Analysis of highly polymorphic microsatellite markers demonstrated a paternal origin of the rearranged chromosome 9 in both patients. These studies define the minimum region associated with male to female sex reversal as 9p24.1-pter.

Child, Preschool↗
PubMed1997

Contribution of growth hormone deficiency to the growth failure that follows bone marrow transplantation.

Conditioning for bone marrow transplantation (BMT) by total body irradiation frequently causes growth failure. The contribution of growth hormone (GH) deficiency to this failure was assessed in 38 patients given three types of body irradiation: group 1 (n = 18) was given 12 Gy total body irradiation as six fractions, group 2 (n = 14) 10 Gy (one dose) total body irradiation, and group 3 (n = 6) 6 Gy (one dose) thoracoabdominal irradiation, which did not involve the hypothalamic-pituitary area. At the first evaluation, 2.9 +/- 0.2 (SE) years after BMT, the values for the plasma insulin-like growth factor I (IGF-I) and its GH-dependent binding protein (IGFBP-3) were similar in groups 1 and 2 but significantly greater in group 3 (p < 0.02 for IGF-I and 0.01 for IGFBP-3). These values were similar in those patients in groups 1 and 2 who had low GH peaks after stimulation (12 patients: IGF-I, 0.8 +/- 0.2 U/ml; IGFBP-3, 1.6 +/- 0.2 mg/L) and in those with normal GH peaks (20 patients: 1 +/- 0.1 U/ml and 1.8 +/- 0.1 mg/L). The decrease in height 2 years after BMT was significantly (p < 0.01) greater in group 2 than in groups 1 and 3, but 5 years after BMT it was similar in groups 1 and 2 (0.9 +/- 0.2 and 1.4 +/- 0.3 SD), significantly (p < 0.05) greater in group 2 than in group 3 (0.7 +/- 0.2 SD). The individual height changes between BMT and the last clinical evaluation before GH therapy were not correlated with the age at BMT, GH peak after stimulation, plasma IGF-I concentration, or IGFBP-3 concentration. Seven patients with GH deficiency were given GH therapy; their growth rate became normal for age (-2.1 +/- 0.9 SDS before and -0.2 +/- 0.4 SDS for the first year; not significant) without any catch-up growth. We conclude that plasma IGF-I and IGFBP-3 values are of no diagnostic value for GH deficiency after TBI. Their normal or high levels, despite low GH peaks, suggest that bone irradiation induces lesions causing resistance to IGF-I.

Body Height↗
PubMed1997

Intracoronary adenovirus-mediated transfer of immunosuppressive cytokine genes prolongs allograft survival.

BACKGROUND: Intracoronary transfer and expression of recombinant genes in the intact heart is now feasible. In the transplant setting, local modulation of host immune responses by a genetically modified allograft may offer an attractive alternative to systemic immunosuppression. METHODS: We tested the efficacy and in vivo effect of intracoronary transfer of two immunosuppressive cytokine genes. First-generation E1-deleted adenoviral vectors expressing the Epstein-Barr virus interleukin-10 (AdSvIL10) or human transforming growth factor--beta 1 (AdCMVTGF-beta) were used. Rabbit cardiac allografts were transduced during cold preservation by slow (1 ml/min) intracoronary infusion of 10(10) pfu/gm diluted viral vectors and then implanted heterotopically. Controls included E1-deleted adenovirus (Ad5dI434) and AdCMVLacZ. Beating allografts were collected on day 4 for analysis of gene transfer efficacy and distribution. Additional grafts were used for evaluation of alloreactivity (n = 34). RESULTS: Mean allograft viral uptake was 81% (up to 91%). Polymerase chain reactions and reverse transcription-polymerase chain reactions confirmed the presence and expression of both genes in the grafts. beta-Galactosidase staining in AdCMVLacZ-infected grafts demonstrated efficient gene expression, which was highest (100%) in subepicardial regions. More homogeneous transmyocardial distribution of the transgene (in 25% to 40% of cells) could be achieved by pulsatile slow delivery. Allograft survival was 6.9 +/- 0.9 days in controls (n = 12), 11.1 +/- 1.7 days in AdCMVTGF-beta-infected grafts (n = 11, p < 10(-4)), and 11.2 +/- 3 days in AdSvIL10-infected grafts (n = 11, p < 10(-4)). Histologic scores (blinded) showed significantly (p < 0.005) higher regression coefficients for rejection in controls compared with both cytokine-transduced groups. Perioperative administration of cyclosporine A (INN: ciclosporin) to recipients had no effect on survival of AdCMVTGF-beta-infected grafts but reduced survival of AdSvIL10-infected grafts. CONCLUSIONS: Intracoronary gene transfer of immunosuppressive cytokines to cardiac allografts is efficient and effectively prolongs graft survival. Vectors that would induce long-term expression of such genes may make this approach clinically applicable.

Adenoviridae↗