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Biomedical subjects

R Rapaport

Publications and source records attributed to R Rapaport.

At least 19 recordsLinked to original sources
PubMed2007

Management of the child born small for gestational age through to adulthood: a consensus statement of the International Societies of Pediatric Endocrinology and the Growth Hormone Research Society.

OBJECTIVE: Low birth weight remains a major cause of morbidity and mortality in early infancy and childhood. It is associated with an increased risk of health problems later in life, particularly coronary heart disease and stroke. A meeting was convened to identify the key health issues facing a child born small for gestational age (SGA) and to propose management strategies. PARTICIPANTS: There were 42 participants chosen for their expertise in obstetrics, peri- and neonatal medicine, pediatrics, pediatric and adult endocrinology, epidemiology, and pharmacology. EVIDENCE: Written materials were exchanged, reviewed, revised, and then made available to all. This formed the basis for discussions at the meeting. Where published data were not available or adequate, discussion was based on expert clinical opinions. CONSENSUS PROCESS: Each set of questions was considered by all and then discussed in plenary sessions with consensus and unresolved issues identified. The consensus statement was prepared in plenary sessions and then edited by the group chairs and shared with all participants. CONCLUSIONS: The diagnosis of SGA should be based on accurate anthropometry at birth including weight, length, and head circumference. We recommend early surveillance in a growth clinic for those without catch-up. Early neurodevelopment evaluation and interventions are warranted in at-risk children. Endocrine and metabolic disturbances in the SGA child are recognized but infrequent. For the 10% who lack catch-up, GH treatment can increase linear growth. Early intervention with GH for those with severe growth retardation (height sd score, <-2.5; age, 2-4 yr) should be considered at a dose of 35-70 microg/kg x d. Long-term surveillance of treated patients is essential. The associations at a population level between low birth weight, including SGA, and coronary heart disease and stroke in later life are recognized, but there is inadequate evidence to recommend routine health surveillance of all adults born SGA outside of normal clinical practice.

Adult↗
PubMed2006

Safety of growth hormone treatment in children born small for gestational age: the US trial and KIGS analysis.

BACKGROUND: Recently, growth hormone (GH) therapy for children with short stature born small for gestational age (SGA) has been approved in the USA and Europe. There have been few reports examining adverse events during GH treatment of these children. AIMS: (i) To examine glucose tolerance and insulin sensitivity during GH treatment of children born SGA in a US trial. (ii) To determine and compare adverse events reported in children born SGA with those reported in children with idiopathic short stature (ISS) enrolled in KIGS - Pfizer International Growth Database. METHODS: In the US SGA trial, an oral glucose tolerance test was performed and fasting plasma glucose, insulin and glycosylated haemoglobin (HbA(1C)) concentrations were measured at baseline and after 12 months of GH therapy. Insulin sensitivity was calculated using the homeostasis model assessment (HOMA) and the quantitative insulin sensitivity check index (QUICKI). In the KIGS analysis, a retrospective audit of spontaneously logged cumulative adverse events in children born SGA and those with ISS was undertaken. Adverse events are reported per 1,000 patients. Values are expressed as mean with 10th-90th percentiles. RESULTS: In the US trial, 84 patients had complete data sets for analysis. Median birth weight was 1.78 kg (SDS, -2.5) and birth length 43 cm (SDS, -2.2) at a median gestational age of 36.5 weeks; 79% were Caucasian. At entry, median age of the patients analysed was 6.6 years, and 65% were male. Median height was 104.3 cm (SDS, -2.97), median weight 15.95 kg (SDS, -2.21) and body mass index 14.66 kg/m(2) (SDS, -0.67). No patients developed impaired glucose tolerance or overt diabetes mellitus. The 0-min glucose concentration was 81 mg/dl at baseline and 86 mg/dl at 1 year, while the 120-min glucose concentration was 90 mg/dl at baseline and 96 mg/dl at 1 year. The 0-min insulin concentrations were 2.9 mU/l at baseline and 5.3 mU/l at 1 year, while the 120-min insulin levels were 7.7 mU/l at baseline and 11 mU/l at 1 year. The proportions of HbA(1C) were 5.2 and 5.4% at baseline and 1 year, respectively. HOMA and QUICKI values were 0.59 and 0.42, respectively, at baseline, and 1.13 and 0.38 at 1 year. In KIGS, there were 1909 children born SGA aged 9.1 (3.9-13.3) years with a birth weight SDS of -2.6 (-4.0 to -1.5), birth length SDS of -2.7 (-4.3 to -1.3) and height SDS of -2.71 (-3.9 to -1.8) prior to treatment. GH doses ranged from 0.032 to 0.037 in the USA and from 0.022 to 0.023 mg/kg/day in the remaining countries in KIGS. Neither total (187 vs. 183) nor serious (14 vs. 10) adverse events occurred more commonly in the SGA group than in the ISS group. Although respiratory adverse events occurred more commonly in children born SGA (34.3 vs. 16.8; p < 0.05), endocrine (12.0 vs. 2.7; p < 0.05) and hepatobiliary (6.2 vs. 1.1; p < 0.05) adverse events occurred more commonly in children with ISS. CONCLUSIONS: As expected, a reduction in insulin sensitivity occurred during GH treatment of children born SGA; however, glucose tolerance remained normal. No adverse events were reported more commonly in children born SGA than in those with ISS. Minor differences in adverse events reporting within organ systems between children born SGA and those with ISS are probably due to variable under-reporting of adverse events. GH appears to be a safe drug to use at current doses as a growth-promoting agent in short children born SGA.

Adolescent↗
PubMed2004

Charge separation of dense two-dimensional electron-hole gases: mechanism for exciton ring pattern formation.

We report on new experiments and theory that unambiguously resolve the recent puzzling observation of large diameter exciton emission halos around a laser excitation spot in two dimensional systems. We find a novel separation of plasmas of opposite charge with emission from the sharp circular boundary between these two regions. This charge separation allows for cooling of initially hot optically generated carriers as they dwell in the charge reservoirs for very long times.

Journal Article↗
PubMed2000

Negatively charged quantum well polaritons in a GaAs/AlAs microcavity: An analog of atoms in a cavity

The negatively charged exciton (X-) is observed to strongly couple with the microcavity- (MC-)confined photons in a GaAs quantum well containing a two-dimensional electron gas with 0<n(e)</=3x10(10) cm(-2). This strong coupling results in a formation of charged polaritons. The coupling strength is found to depend on sqrt[n(e)], in analogy to two-level atoms in a cavity. The analysis of the reflection and photoluminescence spectra shows that X- is strongly admixed with the neutral exciton via their coupling with the MC photons. The linewidth dependence on n(e) indicates that electron-polariton scattering is effective.

Journal Article↗
PubMed1998

Modulating effect of human growth hormone on tumour necrosis factor-alpha and interleukin-1beta.

We measured serum tumour necrosis factor-alpha (TNF-alpha) as well as interleukin-1betta (IL-1beta) and GH concentrations in 15 children with isolated growth hormone deficiency (GHD), age range 5.1-13.9 years, before and 4 and 24h after the first GH injection (0.1 IU/kg s.c.). No differences were found in basal concentrations of serum TNF-alpha and IL-1beta between GHD children (10.01 +/- 1.55 pg/ml and 2.14 +/- .16 ng/ml respectively) and sex- and age-matched controls (11.57 +/- 2.16 pg/ml and 3.78 +/- 1.46 ng/ml respectively). In GHD children, serum TNF-alpha and IL-1beta values had significantly increased (P < 0.002) 4h (26.75 +/- 5.57 pg/ml and 2.99 +/- 0.21 ng/ml respectively) and decreased again 24 h after GH administration. Likewise, serum GH levels had significantly increased 4 h (from 1.29 +/- 0.69 to 48.71 +/- 13.35 ng/ml, P < 0.001) and decreased to basal values 24h after GH administration. A significant correlation was found between basal serum concentrations of GH and those of both TNF-alpha (P < 0.01) and IL-1beta (P < 0.05). However, no correlation was found between serum GH concentration and either TNF-alpha or IL-1beta levels 4 and 24h after GH administration. Our data suggest that GH plays a role in modulating TNF-alpha and IL-1beta release in humans.

Adolescent↗
PubMed1996

Prediction of neonatal hyperthyroidism in infants born to mothers with Graves disease.

OBJECTIVE: To determine whether determinations of thyrotropin-receptor antibody (TRAb) levels in newborn infants of women with Graves disease would predict which infants will have hyperthyroidism. METHODS: The TRAb levels, assayed in the sera of 14 infants born to 14 women with Graves disease, were measured sequentially in the infants with hyperthyroidism during the course of antithyroid medication therapy. RESULTS: Seven infants had TRAb values less than 0.15 and remained euthyroid. In seven infants whose initial TRAb values were more than 0.25 (range, 0.48 to 0.88), clinical and biochemical signs of hyperthyroidism developed. The infants were treated with antithyroid medication until day 57 to day 123 of life. Therapy was discontinued when the infants were free of symptoms and when serum thyroxine and triiodothyronine and free thyroxine levels remained normal during therapy with decreasing doses of antithyroid medication. When the medication was discontinued, TRAb values were less than 0.20. CONCLUSIONS: Infants born to mothers with Graves disease with initial TRAb values less than 0.15 remained euthyroid. The TRAb values greater than 0.25 were associated with the development of neonatal hyperthyroidism. During treatment of neonatal hyperthyroidism, TRAb values less than 0.20 may be helpful in deciding when to withdraw antithyroid medication.

Antithyroid Agents↗
PubMed1995

Relationship of growth hormone deficiency and leukemia.

The use of growth hormone (GH) has been implicated as a possible risk factor for leukemia. We present data from six patients that support a working hypothesis that an increased risk of leukemia may exist in patients with GH deficiency not related to exogenous use of GH.

Adolescent↗
PubMed1995

Scanning slit confocal microscopic observation of cell morphology and movement within the normal human anterior cornea.

PURPOSE: Noninvasive in vivo observations of the anterior human cornea were performed to study cell structure and dynamics. Cellular elements were identified by their location, morphology, and pattern of movement. The hypothesis that cells in the epithelial layer of the normal cornea migrate centripetally was tested. METHODS: Using a scanning slit confocal microscope with a new 0.75-numeric aperture contact objective, individual cells of normal human corneas were observed over time, quantifying the velocity and direction of cellular movement within the basal epithelial layer. RESULTS: Basal epithelial cells, wing cells, the basal epithelial nerve plexus, and the subepithelial nerve plexus were identified readily. Centripetal motion was observed for three corneal cell types: basal epithelial cells, basal epithelial nerves, and unidentified cellular elements (possibly Langerhans cells). The unidentified cellular elements moved along the length of the basal epithelial nerves. The basal epithelial nerve plexus maintained a roughly stable topology as it slid centripetally. New nerve material appeared at the site of entry of the nerve into the epithelium. No growth cones were present at the distal termini of the growing epithelial nerves. CONCLUSION: In the midperiphery of the normal human cornea, basal epithelial cells and nerves slide centripetally, probably in concert. Unidentified cellular elements used the basal epithelial nerve plexus as a pathway for intraepithelial movement. Observations in this study suggest that neurite growth occurred by the addition of new membrane material along the length of the axon rather than at a distal growth cone.

Adult↗
PubMed1995

No apparent mineralocorticoid receptor defect in a series of sporadic cases of pseudohypoaldosteronism.

Pseudohypoaldosteronism (PHA) is characterized by congenital resistance of the kidney and/or other mineralocorticoid target tissues to aldosterone, resulting in excessive salt wasting. Although the mineralocorticoid receptor (MR) was suggested as a potential locus of the defect in this disease, no such abnormality was found in 3 recently reported cases, one of whom belongs to this series of 5 patients. Molecular studies of the MR complementary DNA and gene in this series of sporadic cases of pseudohypoaldosteronism are reported. Four of these patients had multiple mineralocorticoid target tissue resistance, whereas 1 had transient isolated resistance in the kidney. A nonconservative homozygous mutation (C944-->T944, Ala241-->Val241) was identified in the complementary DNA of 4 of the patients but was also found in 62 of 100 normal alleles. One of these 4 patients had an additional conservative heterozygous mutation (A760-->G760, Ileu180-->Val180), which was also present in 11 of 100 normal alleles. None of the patients had any abnormalities in the first untranslated exon and 0.9 kilobases of the 5'-regulatory region of the MR gene, which were fully sequenced and compared with the normal sequence. It is concluded that the mutations identified in 4 of these 5 patients with PHA are polymorphisms, which on their own have no apparent pathophysiological significance. It is hypothesized that the defect causing PHA might be in a post-MR step of aldosterone action or in an unsuspected nonclassic receptor for this hormone.

Adolescent↗
PubMed1995

A novel mutation of the adrenocorticotropin receptor (ACTH-R) gene in a family with the syndrome of isolated glucocorticoid deficiency, but no ACTH-R abnormalities in two families with the triple A syndrome.

Isolated glucocorticoid deficiency (IGD) is an autosomal recessive disorder characterized by primary adrenocortical insufficiency, usually without mineralocorticoid deficiency. Occasionally, the disorder is associated with alacrima and achalasia of the esophagus (triple A syndrome), suggesting potential heterogeneity in its etiology. Mutations in the ACTH receptor gene have been reported in several families with IGD. We have amplified and directly sequenced the entire intronless ACTH receptor gene in 1 other family with IGD and 2 families with triple A syndrome. The proband with IGD was a homozygote for an A-->G substitution, changing tyrosine 254 to cysteine in the third extracellular loop of the receptor protein, probably interfering with ligand binding. Both of her parents were heterozygotes for this mutation, which was not detected in 100 normal alleles. No mutations were identified in the entire coding area of the ACTH receptor in the 2 families with triple A syndrome, supporting the idea of a developmental or postreceptor defect in this syndrome.

Adenine↗
PubMed1995

Detection of human growth hormone receptors on IM-9 cells and peripheral blood mononuclear cell subsets by flow cytometry: correlation with growth hormone-binding protein levels.

We have developed a method using flow cytometry to identify fluorescein-conjugated GH receptors (GHR) on IM-9 lymphocytes and circulating peripheral blood mononuclear cell subsets. Binding to IM-9 cells and peripheral blood mononuclear cells was concentration dependent and could be competitively blocked by the addition of unlabeled human GH, but not by the addition of rat or bovine GH or human insulin or PRL. Using two-color flow cytometric analysis, fluorescein-conjugated human GHR were readily detected on more than 90% of B lymphocytes and monocytes, but only variably on T lymphocytes. B Lymphocytes and monocytes had approximately 6000 GHR/cell. Using two-color flow cytometry, we identified GHR on circulating B lymphocytes in subjects with GH deficiency (n = 9), precocious puberty (n = 6), and Turner syndrome (n = 5) and in seven subjects with miscellaneous disorders, including familial short stature, bone dysplasia, Crohn disease, congenital adrenal hyperplasia, and acromegaly. The percentage of B lymphocytes expressing GHR in subjects with GH deficiency (mean +/- SD, 95 +/- 9%), precocious puberty (91 +/- 15%), and Turner syndrome (84 +/- 15%) was not different from that in normal volunteers (90 +/- 12%; n = 14). In 10 subjects, serum GH-binding protein levels were assayed simultaneously with B lymphocyte GHR. GH-binding protein was normal in all (mean, 1255 pmol/L; range, 773-1809). There was a good correlation between GHR expression on B lymphocytes and GH-binding protein levels (r = 0.75; P = 0.01). We postulate that GHR found on circulating B lymphocytes may contribute to the pool of receptors identified in serum as GH-binding proteins. Two-color flow cytometry appears to be an effective method for the detection of GHR on circulating peripheral blood mononuclear cell subsets. The evaluation of GHR on circulating B lymphocytes may prove to be a useful means of evaluating GH-GHR interactions in subjects with growth disorders.

Adult↗