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Biomedical subjects

R Brauner

Publications and source records attributed to R Brauner.

At least 19 recordsLinked to original sources
PubMed2006

Final height and gonad function after total body irradiation during childhood.

Short stature and gonad failure can be a side effect of total body irradiation (TBI). The purpose of the study was to evaluate the factors influencing final height and gonad function after TBI. Fifty young adults given TBI during childhood were included. Twenty-seven had been treated with growth hormone (GH). Those given single 10 Grays (Gy) or fractionated 12 Gy TBI had similar characteristics, GH peaks, final heights and gonad function. After the end of GH treatment, 11/20 patients evaluated had GH peak >10 microg/l. Final height was <-2s.d. in 29 (58%). The height loss between TBI and final height (2.4+/-1.1 s.d.) was greater in those who were younger when irradiated (P<0.0001). When the GH-treated and -untreated patients were analyzed separately, this loss was correlated with the age at TBI at 4-8 years for the GH-treated and at 6-8 years for the untreated. Boys showed negative correlations between testicular volume and plasma follicle-stimulating hormone (FSH, P=0.0008) and between plasma FSH and inhibin B (P=0.005) concentrations. We concluded that the indications for GH treatment should be mainly based on the age at irradiation, taking into account the GH peak. The plasma FSH and inhibin B concentrations may predict sperm function.

Adolescent↗
PubMed2005

[Central precocious puberty in girls: prediction of the etiology].

Precocious puberty (PP) is defined in girls by the occurrence of pubertal development before the age of 8. This development raises 3 questions: 1) Is it abnormal puberty or variant of the normal? 2) If abnormal puberty, is it of central, hypothalamic-pituitary, or peripheral, ovarian or adrenal origin? 3) If central, is it idiopathic or due to a lesion, and is there indication to treat it? The PP in a girl with no previous medical history is usually of central and idiopathic origin. However, isolated central PP may reveal a CNS lesion, particularly an optic glioma with its risk of blindness. Two independent predictors of CNS lesion are the age at PP onset of less than 6 years old, and increased plasma estradiol concentration. The selection of the girls for neuroradiological imaging should be based on these two parameters. However, neuroradiological imaging remains necessary until the prospective confirmation of their predictive value.

Adolescent↗
PubMed2005

Social and psycho-intellectual outcome following radical removal of craniopharyngiomas in childhood. A prospective series.

BACKGROUND: A prospective study on childhood craniopharyngiomas (CPs) was conducted from 1994 to 1998 to appreciate the pre- and postoperative clinical, endocrine, mental, and intellectual status of the patients and to determine the incidence and severity of the postoperative hypothalamic syndrome. METHODS: The series included 14 consecutive CPs. Twelve were retrochiasmatic and intraventricular, and two were partly prechiasmatic and extraventricular. All were treated with the aim of "total" removal. The removal was "total" in nine cases but incomplete in the other five. Immediate postoperative follow-up was uncomplicated in all cases. CONCLUSION: At 2-year follow-up, the two children with an extraventricular CP and a "total" tumor removal were intellectually normal, had no hypothalamic syndrome, and attended normal school with good results. The 12 others, although still intellectually normal, were more or less severely affected by a hypothalamic syndrome which altered their social insertion and caused academic failure. The authors conclude from this study that radical surgery should be reserved to extraventricular CPs only.

Adolescent↗
PubMed2005

A nationwide study of granulosa cell tumors in pre- and postpubertal girls: missed diagnosis of endocrine manifestations worsens prognosis.

BACKGROUND: There are very few data on the natural history of ovarian granulosa cell tumors (OGCT) in children. The aim of this study was to determine whether early recognition and diagnosis of the initial endocrine signs could improve the outcome of these tumors. METHODS: In a nationwide study from 1990 to 2004, we analyzed the clinical, biological and pathologic data from 40 pre- and postpubertal girls presenting an OGCT. RESULTS: 1. Among the prepubertal girls (n = 29), 17 OGCTs were diagnosed on the basis of precocious pseudopuberty. None of the 17 girls had a peritoneal spread of the tumor (100% FIGO stage Ia). Diagnosis based on a tumoral or acute abdomen (12 cases) was associated with frequent intraperitoneal ruptures of the tumor (50%) and a risk of relapse (2 cases). Of the eight girls who had had a misdiagnosed precocious pseudopuberty, five had a pre- or perioperative tumoral rupture. 2. Among the postpubertal girls (n = 11), endocrine manifestations such as secondary amenorrhea or virilization had been underevaluated in three of them and the diagnosis was established from a tumoral abdomen. This clinical presentation was associated with frequent ruptures of the mass in the peritoneum (80%) and a higher risk of recurrence (30%). 3. A delayed diagnosis of OGCT despite previous endocrine signs (11 cases; 8 pre- and 3 postpubertal) was associated with a high risk of pre- or peri-operative peritoneal tumor spreading (70% FIGO stage Ic or IIc, p <0.05). The mean delay for diagnosis ranged from 3 to 11 months. CONCLUSION: This study highlights the critical role of early diagnosis of OGCT in pre- and postpubertal girls, particularly at the first seemingly banal signs of endocrine disorder. Peritoneal spread of the tumor may thereby be prevented, which improves the prognosis.

Abdominal Pain↗
PubMed2005

Idiopathic male pseudohermaphroditism: variations in presentation and management.

UNLABELLED: Male pseudohermaphroditism (MPH) is the abnormal development of genitalia in an individual with a 46,XY chromosome complement and testicular tissue. The etiology of MPH is unknown in most cases, which are defined as idiopathic. OBJECTIVE: To analyze the data for cases of idiopathic MPH. PATIENTS AND METHODS: A retrospective study of 29 patients with idiopathic MPH and no uterus. RESULTS: Four patients had a family history of abnormal sexual development and five had low birth weight. The initial manifestations were sexual ambiguity (26), microphallus and hypospadias (2), and primary amenorrhea (1). Basal and/or stimulated testosterone concentrations showed insufficient testosterone secretion in three patients. Genitography showed a vagina in 13 patients. Male genitoplasties were performed on 21 out of the 24 patients reared as males and female genitoplasties on five patients. Histological studies of the gonads of these showed streak gonads in one, normal gonads in one and signs of testicular dysgenesis in three others. Molecular studies on the SRY gene (17) showed no mutation. CONCLUSIONS: Idiopathic male pseudohermaphroditism is a heterogeneous condition, even within families with a history of this condition. We propose a set of guidelines for the management of these patients.

Adolescent↗
PubMed2005

Management of boys with short stature and delayed puberty.

OBJECTIVE: To review the management of boys with short stature and delayed puberty and the testosterone priming protocol. METHODS: In 148 boys aged > 14 years seen for height < -2 SDS and constitutional delayed puberty we evaluated growth hormone (GH) secretion and final height (80 boys). RESULTS: The GH peak was < 10 microg/l after arginine-insulin tests performed with testosterone heptylate priming in 8/32 (25%) and without in 62/153 (41%), including first and second evaluations. It was low in 7/11 boys given 2 x 100 mg testosterone (14.7 +/- 1.7 microg/l) and in 1/21 given 4 x 100 mg (21.3 +/- 2.0 microg/l, p = 0.04). It was low during sleep in 4/29 (14%) boys, all having basal plasma testosterone below 3.5 nmol/l. The basal insulin-like growth factor (IGF)-I concentration was below -2 SDS in 22% of the boys evaluated. Final height was -0.8 +/- 0.1 SDS. It was similar in those with low (n = 9) and normal (n = 71) GH peak, and in those treated (n = 22) or untreated (n = 58) with testosterone. It was over 1 SDS lower than the target height in 20% and than the predicted height at the initial evaluation in 14% of the boys. Pubertal growth was not correlated with the GH peak or plasma IGF-I. CONCLUSIONS: The GH peak during the sleep is more frequently normal than the peak after stimulation. The number of testosterone doses influences the quality of priming. The medical problems involved in treating boys with delayed puberty are excluding disease and deciding on testosterone treatment.

Adolescent↗
PubMed2004

Congenital gonadotropin deficiency in boys: management during childhood.

OBJECTIVE: To analyze the features of boys with congenital gonadotropin deficiency (CGD), and to determine the value of plasma inhibin B and anti-Müllerian hormone (AMH) for predicting testicular function and the effect of testosterone treatment. PATIENTS: We followed 19 boys for CGD, including five with Kallmann syndrome. RESULTS: The boys were seen before 14 years of age for micropenis (9 boys) or later for delayed puberty (10 boys). No testis was palpable in the scrotum in 13 patients, bilaterally in seven of them. Luteinizing hormone (LH) peak after a gonadotropin releasing hormone (GnRH) test was between 0.5 and 5.6 U/l. Plasma inhibin B was low in the four patients evaluated at less than 1 year old. AMH was low in one of them and normal in four others. Of the older patients, three lad low plasma inhibin B and four had normal concentrations; plasma AMH was low in three of them and increased in four. Testosterone treatment restored penis length to normal in all patients. CONCLUSIONS: Low plasma inhibin B and AMH concentrations may indicate testicular damage in boys with CGD.

Adolescent↗
PubMed2003

Extreme short stature after intrauterine growth retardation: factors associated with lack of catch-up growth.

UNLABELLED: The factors associated with lack of catch-up growth after intrauterine growth retardation (IUGR) are unknown. OBJECTIVE: To identify these factors by analyzing the clinical features and growth hormone (GH)-insulin-like growth factor I (IGF-I) axis. METHODS: 95 patients with height <-3 SD after IUGR were assigned to group 1 without (n = 50) or group 2 with (n = 45) malformations. Twenty-one in group 1 and 19 in group 2 were treated with GH. RESULTS: They were seen at 5.3 +/- 0.5 and 4 +/- 0.5 year (p = 0.02) with heights at -3.4 +/- 0.1 and -3.9 +/- 0.2 SD (p = 0.03). Group 1 differed from group 2 in having a lower frequency of consanguinity (2 vs. 28.9%, p < 0.001), and higher frequencies of target heights (26.5 vs. 6.7%, p = 0.02) and mothers' heights (34.7 vs. 8.9%, p < 0.01) <-2 SD, multiparity (26 vs. 8.9%, p < 0.05), prematurity (36 vs. 15.5%, p < 0.05) and cesarean section birth (42 vs. 17.8%, p = 0.01). The GH-IGF-I axis data and the height increases after 3 years of GH treatment (1.6 +/- 0.2 in group 1 and 1.1 +/- 0.3 SD in group 2) were similar. CONCLUSION: The short height of the parents, particularly of the mother, is associated with factors limiting the catch-up growth after IUGR of children without malformations, while the high frequency of consanguinity in those with malformations suggests that transmitted fetal factors affect organogenesis or development.

Body Height↗
PubMed2003

[Post-radiotherapy hyperthyroidism: a rare complication of cancer treatment in the child].

UNLABELLED: Abnormalities of thyroid function, specially hypothyroidism, are common complications of head and neck irradiation for childhood cancer. Hyperthyroidism is rare and can be misdiagnosed. We report two observations of this condition. OBSERVATIONS: The first patient received conventional craniospinal irradiation for a localized medulloblastoma. Three years later, he presented with profuse sweating, irritability and paroxysmal tachycardia. Biologic evaluation revealed a peripheral hyperthyroidism. The patient was treated with antithyroidian hormonal treatment. The second patient received an irradiation for an undifferentiated nasopharyngeal carcinoma. Three years later, she developed a progressive thyrotoxicosis which was attributed to hyperthyroidism after six months of evolution. Hormonal treatment improved the clinical state after several weeks. CONCLUSION: Hyperthyroidism is a rare complication of head and neck irradiation. This condition justifies a periodic and prolonged evaluation of thyroid function.

Adolescent↗
PubMed2003

Spectrum of NSD1 mutations in Sotos and Weaver syndromes.

Sotos syndrome is an overgrowth syndrome characterised by pre- and postnatal overgrowth, macrocephaly, advanced bone age, and typical facial features. Weaver syndrome is a closely related condition characterised by a distinctive craniofacial appearance, advanced carpal maturation, widened distal long bones, and camptodactyly. Haploinsufficiency of the NSD1 gene has recently been reported as the major cause of Sotos syndrome while point mutations accounted for a minority of cases. We looked for NSD1 deletions or mutations in 39 patients with childhood overgrowth. The series included typical Sotos patients (23/39), Sotos-like patients (lacking one major criteria, 10/39), and Weaver patients (6/39). We identified NSD1 deletions (6/33) and intragenic mutations (16/33) in Sotos syndrome patients. We also identified NSD1 intragenic mutations in 3/6 Weaver patients. We conclude therefore that NSD1 mutations account for most cases of Sotos syndrome and a significant number of Weaver syndrome cases in our series. Interestingly, mental retardation was consistently more severe in patients with NSD1 deletions. Macrocephaly and facial gestalt but not overgrowth and advanced bone age were consistently observed in Sotos syndrome patients. We suggest therefore considering macrocephaly and facial gestalt as mandatory criteria for the diagnosis of Sotos syndrome and overgrowth and advanced bone age as minor criteria.

Abnormalities, Multiple↗
PubMed2003

Assessing short-statured children for growth hormone deficiency.

AIM: To optimize the workup of short-statured children by defining the most appropriate tools for diagnosing growth hormone (GH) deficiency. METHODS: Patients were assigned to prepubertal (n = 113) or pubertal (n = 112, including 25 boys primed with testosterone) age groups. Mean plasma GH concentration during sleep, GH peak after provocative test, and insulin-like growth factor I (IGF-I) were measured in a single evaluation. RESULTS: The mean GH concentration during sleep was more often normal (n = 155) than the GH peak after provocative tests (n = 105) or the IGF-I concentration (n = 88). Prepubertal patients with a normal body mass index (BMI) had mean GH concentrations during sleep that correlated positively with height, growth rate, GH peak after provocative tests, and IGF-I (p < 0.0005 for all) and negatively with the difference between target and patient heights (p = 0.01) and BMI (p < 0.05). Pubertal patients with a normal BMI had a mean GH concentration during sleep that correlated positively with GH after provocative tests (p < 0.0001) and IGF-I (p < 0.005). Mean GH concentration during sleep and IGF-I concentration for boys primed with testosterone were more often normal (n = 23) than the GH peak after provocative tests (n = 14). All 9 patients with pituitary stalk interruption had low IGF-I concentrations; 1 patient had a normal GH peak after provocative test, and 2 patients had normal mean GH concentrations during sleep. CONCLUSIONS: Measuring the GH concentration during sleep and priming boys with pubertal delay can help to exclude idiopathic GH deficiency. Magnetic resonance imaging is needed to exclude anatomic abnormalities when GH and/or IGF-I concentrations are low.

Adolescent↗
PubMed2003

Extremely short stature: influence of each parent's height on clinical-biological features.

UNLABELLED: Idiopathic extremely short stature probably has several causes. OBJECTIVE: To evaluate the influence of each parent's height on clinical-biological features. METHODS: 57 patients without intrauterine growth retardation seen at 7.9 +/- 0.4 years for height < or = -3 SD were classified according to the difference between their target height and actual height: < 2 SD in familial short stature (FSS, n = 28) and >2 SD in non-FSS (n = 29). RESULTS: Height decreased from -0.5 +/- 0.1 SD at birth to -2 +/- 0.2 SD at 1 year and -2.7 +/- 0.1 SD at 3 years, but the changes in the two groups were similar. FSS children were shorter than non-FSS children both at birth (p = 0.03) and as adults after growth hormone (GH) treatment (p < 0.05), but their plasma insulin-like growth factor I concentrations and GH peaks were similar. The FSS children fathers' heights were more frequently below -2 SD (64%) than the mothers' heights (35%) and were correlated with height at first evaluation (p < 0.05). For the whole population, the mothers' heights were correlated with birth weight (p < 0.05) and with height at first evaluation (p < 0.03). CONCLUSION: This study confirms the influence of the mother's height on birth weight and shows how of the father's height influences idiopathic extremely short stature.

Adolescent↗
PubMed2003

Follow-up of 68 children with congenital adrenal hyperplasia due to 21-hydroxylase deficiency: relevance of genotype for management.

The phenotype of congenital adrenal hyperplasia (CAH) varies greatly. The purpose of this study was to optimize diagnosis and follow-up by comparing phenotype with genotype. Sixty-eight patients with CAH due to 21-hydroxylase deficiency were studied by clinical, hormonal, and molecular genetic methods. Patients were classified according to predicted mutation severity: group 0, null mutation (17.6%); group A, homozygous for IVS2 splice mutation or compound heterozygous for IVS2 and null mutations (33.8%); group B, homozygous or compound heterozygous for I172N mutation (14.7%); group C, homozygous or compound heterozygous for V281L or P30L mutations (26.5%); and group D, mutations with unknown enzyme activity (7.4%). All group 0 and A patients had the salt-wasting form, and group C had nonclassical forms. Group B included five salt-wasting and five simple virilizing forms. Groups 0 and A were younger at diagnosis (P < 0.02), and females were more virilized than those in group B. Group B had higher basal plasma 17-hydroxyprogesterone (564 +/- 162 nmol/liter) and testosterone (11 +/- 3 nmol/liter) levels than group C [59 +/- 13 nmol/liter (P < 0.001) and 1.4 +/- 0.2 nmol/liter (P < 0.005), respectively]. Hydrocortisone doses given to groups 0, A, and B were similar at all ages, but lower in group C (P < 0.01). Final height was below target height in classical (n = 16; -2 +/- 0.2 SD score; P < 0.02) and nonclassical (n = 11; -1.2 +/- 0.4 SD score; P < 0.03) forms. The severity of the genetic defects and the clinical-laboratory features are well correlated. Genotyping, combined with neonatal screening and optimal medical and surgical treatment, can help in the management of CAH.

Adolescent↗
PubMed2002

Factors influencing the growth hormone response to growth hormone-releasing hormone in children with idiopathic growth hormone deficiency.

OBJECTIVE: To evaluate the factors influencing the growth hormone (GH) response to GH-releasing hormone (GHRH) test in idiopathic GH deficiency. METHODS: 28 patients aged 4.9 +/- 0.7 years with certain GH deficiency were given GHRH (2 microg/kg). RESULTS: The GH peak after GHRH was correlated negatively with age at evaluation (r = -0.37, p < 0.05) and body mass index (r = -0.44, p = 0.02), and positively with anterior pituitary height (r = 0.47, p = 0.02), GH peak after non-GHRH stimulation (r = 0.78, p < 0.0001) and spontaneous GH peak (r = 0.82, p = 0.007). It was lower in the patients aged >5 years than in the youngest (p = 0.04), but it was similar in the patients with and without features suggesting a hypothalamic origin. CONCLUSION: The GH response to GHRH test cannot be used to differentiate between hypothalamic and pituitary forms of idiopathic GH deficiency, probably because the GH response decreases after the first 5 years of life, whatever the origin of the deficiency.

Body Height↗
PubMed2002

Growth hormone deficiency: permanence and diagnosis in young adults.

OBJECTIVE: To optimize the tools for diagnosing idiopathic growth hormone (GH) deficiency. METHODS: We compared the data of 43 young adults treated for GH deficiency before and after GH treatment and puberty. Those with organic lesions were assigned to group 1 (n = 9), those with certain GH deficiency (n = 11) to group 2 and those with no criterion of certitude of GH deficiency to group 3 (n = 23). RESULTS: Group 1 patients: the GH peaks at first [1.5 +/- (SE) 0.4 microg/l] and second (1.9 +/- 0.7 microg/l) evaluations before treatment were similar to those at the third evaluation (1.2 +/- 0.8 microg/l) after treatment. Group 2 patients: they had similar peaks (2.6 +/- 0.8, 2.9 +/- 0.5 and 5.5 +/- 1.4 microg/l). Group 3 patients: the peaks increased from 4.9 +/- 0.4 and 4.8 +/- 0.4 to 18.4 +/- 2.3 microg/l (p < 0.0001); 87% had a GH peak >10 microg/l at this evaluation. The plasma insulin-like growth factor 1 was initially below -2 z-score in 12/13 of these patients and similarly low in 4/17 patients at the third evaluation. The growth rates of the three groups before and their increase during the 1st year of treatment were similar. CONCLUSION: Almost all patients with GH deficiency before puberty without criteria of certitude had a normal GH peak after puberty. Some of these patients probably had a transiently low GH secretion.

Adolescent↗
PubMed2002

Adult height in advanced puberty with or without gonadotropin hormone releasing hormone analog treatment.

Advanced puberty is defined as the onset of puberty in girls at 8-10 years of age and in boys at 9-11 years. This study analyzes adult height in 57 children with advanced puberty to evaluate the results of treating children (9 girls and 8 boys) with gonadotropin hormone releasing hormone (GnRH) analog and the impact of advanced puberty on adult height in untreated children (31 girls and 9 boys). For treated girls, adult height predicted at the onset of treatment (151.9+/-1.7 cm) was similar to the final adult height (155.3+/-1.4 cm), but lower than target height (157.2+/-1.6 cm, p = 0.04). For untreated girls, adult height predicted at the initial evaluation (156.7+/-1 cm) was also similar to adult height (157+/-1 cm), but lower than the target height (157.6+/-1 cm, p = 0.03). The adult heights of both treated and untreated girls were similar to their target heights. For treated boys, adult height predicted at the onset of treatment (173.2+/-3.1 cm) was greater than the final adult height (164.1+/-2.1 cm, p = 0.01), which was lower than target height (170.4+/-1.2 cm, p = 0.01). For untreated boys, adult height predicted at the initial evaluation (170.8+/-2.7 cm) was similar to both the adult height (169.1+/-1.9 cm) and target height (170.2+/-1.2 cm). Height gains between the onset of puberty and adult height were similar in treated (29.9+/-2.3 cm in girls and 29.8+/-1.7 cm in boys) and untreated (28.6+/-1 and 33.1+/-2 cm) children. When expressed as SD, the adult height was significantly shorter than that at 4 years in treated girls (difference 1 SD, p = 0.03), in untreated girls (difference 0.9 SD, p = 0.0002) and in treated boys (difference 0.9 SD, p = 0.02), but it was similar to that in untreated boys. Adult height was below target height by >5 cm in seven girls (two of them treated) and five boys (four of them treated). In conclusion, treating advanced puberty did not change the adult height reached by girls, and was associated with reduced growth potential in boys. The adult heights of untreated children were similar to those predicted at the initial evaluation and to target heights, but in girls they were 1 SD lower than the height at 4 years. These data suggest that advanced puberty decreases the growth potential by about 5 cm, and that GnRH analog treatment does not prevent this.

Adult↗
PubMed2001

Local delivery of mithramycin restores vascular reactivity and inhibits neointimal formation in injured arteries and vascular grafts.

Arterial restenosis is responsible for the high failure rates of vascular reconstruction procedures. Local sustained drug delivery has shown promise in the prevention of restenosis. The drug release rate from mithramycin-loaded EVA matrices (0.1%) was evaluated, and their antirestenotic effect was studied in the rat carotid model and rabbit model of vascular grafts. The modulation of c-myc expression by mithramycin treatment was examined by immunohistochemistry in the rat carotid model. The proliferative response of injured rat arteries was studied by bromdeoxyuridine (BrdU) immunostaining. The impact of mithramycin treatment on vasomotor responses of the venous segments grafted into arterial circulation was studied ex vivo using vasoreactive compounds. Mithramycin was released exponentially from EVA matrices in PBS. Matrices co-formulated with PEG-4600 revealed enhanced release kinetics. The perivascular implantation of drug-loaded EVA-PEG matrices led to 50% reduction of neointimal formation, and reduced the c-myc expression and BrdU labeling in comparison to control implants. Decreased sensitivity of mithramycin-treated grafts to serotonin-induced vasoconstriction was observed. Local perivascular mithramycin treatment limits the functional alteration caused by the grafting of venous segments in high-pressure arterial environment, and potently inhibits stenosis secondary to grafting and angioplasty injury. The antirestenotic effect is associated with reduced c-myc expression and with subsequent decrease in SMC proliferation.

Animals↗