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Biomedical subjects

A Spagnoli

Publications and source records attributed to A Spagnoli.

At least 19 recordsLinked to original sources
PubMed1998

A ten-year experience of Brescia-Cimino arteriovenous fistula in children: technical evolution and refinements.

PURPOSE: The arteriovenous fistula (AVF) of Brescia-Cimino fulfills nearly all of the criteria for an optimal access for chronic hemodialysis, such as long-term patency rate, low complication rate, and respect of vascular morphologic features. Alternative dialytic methods (i.e., external shunts and vascular grafts) cannot easily be applied to pediatric patients, and in addition, these methods are responsible for higher complication rates. METHODS: From January 1985 to December 1994, 112 Brescia-Cimino AVFs were performed in 90 children (average age, 5.5 years; range, 5 months to 18 years). The average weight of the children was 28 kg (range, 6.5 to 54 kg); 16% of AVFs were performed in children who were less than 5 years old, and 18% in children who were less than 15 kg in body weight. RESULTS: Chronic renal failure was caused by a nephropathy in 53 cases (14 with a nephrotic syndrome), and 37 cases had a uropathy. In all cases a phlebography was performed before the microsurgical treatment. Since 1994 an inflatable tourniquet has been placed on the selected upper arm because of an optimal exsanguination of the operating field. The primary patency rate was obtained in all but six of the children; 35% of AVFs had either immediate or late complications. Thrombosis was the most frequent complication that we observed. In comparison with 79% of late thrombosis, 60% of early thrombosis was cured. Of the 80 AVFs, 63.5% with a 4-year follow-up are still patent. CONCLUSION: We emphasize the following two conclusions: first, microsurgery is essential to create AVFs with good results in children as well as in adult patients; and second, the results improved after the adoption of an upper-arm exsanguination and ischemia (pressure range, 400 mm Hg to 600 mm Hg) that avoided spasm of the vessels with a final 35% reduction in surgical time.

Adolescent↗
PubMed1998

Insulin and IGF binding by IGFBP-3 fragments derived from proteolysis, baculovirus expression and normal human urine.

Recombinant human IGFBP-3 was proteolysed with different concentrations of plasmin for various periods of time. The major IGFBP-3 fragment resulting from this digestion migrated at ca. 15 kDa in nonreducing SDS-PAGE. Following the identification of this fragment as an N-terminal IGFBP-3 fragment, by use of N-terminus-specific monoclonal antibody and amino acid sequence analysis, we constructed and expressed a similar fragment in a baculovirus expression system. The fragments resulting from plasmin digestion, as well as the baculovirus-expressed recombinant human IGFBP-3(1-97), retain weak IGF binding and show specific insulin binding on cross-linking and western ligand blot. RhIGFBP-3(1-97) can inhibit insulin receptor autophosphorylation in insulin receptor-overexpressing NIH 3T3 cells. Insulin and IGF binding to IGFBP-3 fragments could be further demonstrated in normal urine. These data indicate the physiological significance of IGFBP-3 fragments derived from proteolysis in vivo.

Baculoviridae↗
PubMed1997

Drug use by the elderly in Italy.

OBJECTIVES: To evaluate drug consumption in the elderly aged 75 years or more living at home. DESIGN: Cross-sectional study. SETTING: Old-old (i.e., > or = 75 y) people living in central Turin, a city in northern Italy. PARTICIPANTS: Thirty-four general practitioners (GPs), with 50 or more old-old people in their patient list, randomly chosen among the GPs working in the Unità Socio-Sanitaria Locale I (Local Health Unit I) of Turin; 261 old-old people (135 men and 126 women) randomly selected from the practice records. METHODS: Data were collected by the GP through a structured questionnaire during an office visit and by a social worker in a home interview within 14 days of the GP visit. GPs were asked to record every diagnosis and drug currently taken by the patient; social workers were trained in the administration of a structured questionnaire exploring sociodemographic variables, drug use (following the medication inventory strategy), disability, cognitive functions, and depressive symptoms. RESULTS: Nearly all subjects (95% of the women and 91% of the men) were taking at least 1 drug. The overall number of drugs recorded was 917 (47.1% for men and 52.9% for women), of which 172 (18.8%) were not reported by the GP but were recorded during the social worker's visit. The mean number of drugs was 3.2 for men and 3.8 for women, with a statistically significant difference (p = 0.02), while the mean number of diagnoses was 2.3 and 2.6, respectively. The study of correlates of drug consumption showed a strong association with number of diagnoses at univariate analysis (p < 0.0001, with a linear correlation coefficient of 0.64). No multivariate model showed a clear superiority over the simple one containing only the number of diagnoses in predicting the total number of drugs taken. Cardiovascular, nervous system, and alimentary tract drugs were the most frequently used. A total of 107 subjects (41%) were taking at least 1 unreported drug. CONCLUSIONS: Our study shows high drug consumption among old-old people, with nearly 20% of drugs taken not reported by the GP. These results emphasize the need for an essential therapeutic approach in old-old people, prescribing only drugs of scientifically proven efficacy. Furthermore, the GP must make more effort when collecting a drug history from old-old patients.

Aged↗
PubMed1997

[Does B-mode ultrasound still have a role in the diagnosis of spermatic cord torsion? Findings in a pediatric series].

INTRODUCTION: Acute scrotum in the pediatric age is mainly related to surgical causes. Spermatic cord torsion and inguinoscrotal hernia must be ruled out first, because of the possible ischemic damage to gonadal tissue and therefore surgery is sometimes performed directly, thus representing also a diagnostic tool. Spermatic cord torsion is found in two age ranges, namely: the neonatal period, where it usually represents the evolution of an intrauterine process, and the peripubertal period, which is more frequent. An unquestionable and prompt diagnosis is particularly needed because of the extreme sensitivity of gonadal tissue to ischemia. In this particular field, color and power Doppler US, depicting gonadal flow, have greatly increased diagnostic imaging capabilities, which were previously limited to B-mode US. MATERIAL AND METHODS: We examined 19 peripubertal patients with the diagnosis of spermatic cord torsion made on the basis of B-mode US and then confirmed with color Doppler. RESULTS: We found two signs which can be considered highly suggestive of spermatic cord torsion: the spiral twist of spermatic vessels and the peculiar extent of reactive hydrocele, caused by the bell clapper anomaly of the vaginal sac. CONCLUSIONS: The above US patterns are very helpful to diagnose spermatic cord torsion.

Adolescent↗
PubMed1996

The mechanisms by which growth hormone brings about growth. The relative contributions of growth hormone and insulin-like growth factors.

Growth hormone is the major regulator of postnatal growth. Although intrauterine growth seems to be largely growth hormone independent, gene knockout studies have established the pivotal role of the IGF system in both prenatal and postnatal growth. The original "somatomedin hypothesis" postulated that all of the growth-promoting actions of growth hormone were mediated by IGFs. Several in vitro and in vivo studies have suggested, however, that growth hormone may have specific growth-related actions in addition to stimulating IGF production, including promoting differentiation of prechondrocytes at the growth plate and stimulation of synthesis of proteins involved in IGF transport and clearance. An integrated model of interrelated role(s) of growth hormone and IGF in skeletal growth is proposed.

Animals↗
PubMed1996

Preliminary validation of a prediction model for the short-term growth response to growth hormone therapy in children with idiopathic short stature.

A discriminant scoring system, using multivariate analysis, has been developed for pretreatment prediction of responsiveness to a 6-month trial of growth hormone (GH) treatment in short children with subnormal growth velocity, but without GH deficiency. Inclusion criteria included a birth weight above 2.5 kg, height below the 3rd centile for chronological age, height velocity below the 25th centile for bone age, no signs of puberty, a maximal GH response to pharmacological stimulation of above 10 micrograms/l and treatment with GH at a dose of 12-16 IU/m2/week. Children with an increase in height velocity greater than 2.5 cm/year after therapy were considered to be responders. Pretreatment clinical data from 67 patients were employed in a discriminant analysis in order to establish the model. The scoring system developed was as follows: score = -0.4 + 0.92X1 - 0.87X2, where X1 is the height velocity SD score (SDS) for chronological age, and X2 is the bone age SDS for chronological age. This model had a specificity of 96.3% and a sensitivity of 92.5% in predicting the responsiveness to GH. The model has subsequently been applied to a group of 14 patients in order to establish its validity; in this group its sensitivity was 83.3% and its specificity 100%. These preliminary data suggest that the model can be used as a guideline for selecting short, slowly growing, non-GH-deficient children who will respond to short-term GH therapy.

Body Height↗
PubMed1996

Urinary pyridinium collagen cross-links predict growth performance in children with idiopathic short stature and with growth hormone (GH) deficiency treated with GH. Skeletal metabolism during GH treatment.

GH is able to promote longitudinal growth in children with GH-deficiency (GHD) and in some children with idiopathic short stature (ISS). The objectives of this study were to evaluate the predictive value of bone and collagen markers on the growth response to GH therapy in children with ISS and with GHD, and to characterize the effects of GH treatment on bone and collagen turnover in children with ISS and with GHD. Twenty prepubertal short, slowly growing, children treated with GH, 15 IU/m2 per week, were studied; of them 13 (10 males) had ISS and 7 (5 males) had GHD. An overnight 12-h urinary collection and a fasting morning blood sample were obtained at baseline, 1, 3, 6, and 12 months of treatment. Urinary levels of collagen cross-links, pyridinoline (Pyd) and deoxypyridinoline (Dpd), and circulating levels of osteocalcin, intact PTH, calcitonin, procollagen type III aminoterminal propeptide (PIIINP), insulin-like growth factor-I, and alkaline phosphatase were determined. Urinary collection was also obtained from 127 healthy children (51 males) aged 6-13 yr. In children with ISS, the changes in Dpd over 1 month of GH therapy were related to the changes in height velocity (HV) over 1 yr of therapy (r = 0.67; P < 0.05); the changes in Pyd after 1 month of GH treatment were related to the changes in HV at 6 months of GH treatment (r = 0.57; P < 0.05). All the other markers evaluated were not related to the HV changes in children with ISS. In children with GHD, the changes in Pyd and in Dpd after 1 month of GH treatment were positively related to the changes in HV after 12 months of therapy (r = 0.82; P < 0.05, and r = 0.82; P < 0.05, respectively). The changes in Pyd after 1 month were also related to the HV changes after 6 months of GH (r = 0.77; P < 0.05). Positive relationships between the HV after 6 months of GH and the increases of PIIINP (r = 0.80; P < 0.05) and osteocalcin (r = 0.77; P < 0.05) after 3 months of GH therapy were observed. All patients showed urinary Dpd and Pyd excretions in the normal range. In patients with ISS, Pyd (P < 0.05), Dpd (P < 0.05), osteocalcin (P < 0.01), PIIINP (P < 0.01), and alkaline phosphatase (P < 0.01) increased longitudinally during the GH treatment and the increments reached a maximum after 3-6 months of therapy. Patients with GHD showed an increase of the same markers but the increases occurred earlier, after 1 month of GH therapy. The collagen cross-links, Pyd and Dpd, could be helpful early markers in predicting the responsiveness to GH therapy in children with ISS and with GHD. GH treatment stimulates bone and collagen metabolism.

Adolescent↗
PubMed1996

Do insulin-like growth factor binding proteins (IGFBPs) modulate the IGF-I growth promoting and differentiating effects in human neuroblastoma cells?

The insulin-like growth factors (IGFs) are known to stimulate both the proliferation and differentiation of neuroblastoma cells, but the role of the IGF binding proteins (IGFBPs) has not yet been established. In this study, human neuroblastoma SH-SY5Y cells have been treated with IGF-I and its potent analogue des(1-3)IGF-I alone or following preincubation with a differentiating agent such as 12-o-tetradecanoylphorbol-13-acetate (TPA). Cell proliferation and differentiation were evaluated. Conditioned medium was tested for the presence of IGFBPs by ligand blotting. The SH-SY5Y cell proliferation was maximally stimulated by des(1-3)IGF-I. The TPA-induced differentiation of SH-SY5Y, evaluated by assessment of cell morphology and GAP-43 expression as a biochemical marker of differentiation was potentiated by nanomolar concentrations of des(1-3)IGF-I and, to a smaller extent, IGF-I Conditioned medium showed the presence of a major IGFBP band with an approximate molecular weight of 32.5 kD and a very faint band of approximately 24kD. The IGFBP immunoblotting results suggest that the predominant band might represent IGFBP-2. Our data represent a first demonstration of the presence of IGFBPs in conditioned medium of human neuroblastoma SH-SY5Y cells. The finding that the potent IGF-I analogue des(1-3)IGF-I with reduced affinity for IGFBPs induce major effects on cell growth and differentiation suggests that the IGFBPs may play an active role in the neuronal response to the proliferative and differentiative effects of IGF-I.

Animals↗
PubMed1996

[Surgical therapy of chronic constipation in pediatric age].

The authors report their experience in the treatment of the chronic constipation in paediatric age. During the last 3 years (1991-1994), 230 children presenting chronic constipation have been studied at the Strumental Gastroenterologic Department of Children Hospital Bambino Gesù; 19 of them (8%), 10 male and 9 female, were studied with anorectal manometry, defecography and Intestinal Transit test. All the patients had a overtone (high squeeze) of the anal sphincter and the medical treatment was unsuccessful. They underwent sphincteromyectomy by posterior approach. In 17 patients it has been obtained a notable improvement of the symptomatology with regularization of the evacuations. The simplicity of the surgical technique, the absence of complications and the obtained results confirm the validity of sphinteromyectomy in the therapy of the chronic constipation in paediatric age. Interoperating anorectal manometry proved to be essential both in modulating sphincteromyectomy and in its eventual complications.

Adolescent↗
PubMed1995

Prediction of the outcome of growth hormone therapy in children with idiopathic short stature. A multivariate discriminant analysis.

OBJECTIVE: To identify, with the use of pretreatment clinical data, the children with idiopathic short stature responsive to treatment with growth hormone (GH). DESIGN: Open, prospective study in a university hospital. SUBJECTS: Patients admitted to the study met the following criteria: birth weight at least 2.5 kg, no sign of dysmorphic disease, stature less than the 3rd percentile for chronologic age (CA), linear growth velocity (GV) less than the 25th percentile for bone age (BA), no sign of puberty, maximal GH response to pharmacologic stimulation greater than 10 micrograms/L, no evidence of organic disease, treatment with daily subcutaneous administration of GH at a dose of 12 to 16 IU/m2 per week. MAIN OUTCOME MEASURES: Eight pretreatment growth variables and the increase of GV after 6 months of therapy were measured. Children with a change in GV that was greater than 2.5 cm/yr after 6 months of GH therapy were considered responders to GH. RESULTS: We studied 67 patients (44 boys). Forty patients (60%) were responders. With univariate analysis the variables found to have predictive value were GV (z score for gender and CA), bone age (z score for gender and CA), and percentage of ideal body weight. These variables were employed in a multivariate discriminant analysis. Growth velocity and BA showed the best independent discriminant analysis. Growth velocity and BA showed the best independent discriminant significance in predicting responsiveness to the initial 6 months of GH therapy. The obtained equation was as follows: Score = -0.40 + 0.92X1 - 0.87X2, where X1 is the GV z value for CA and X2 is the BA z value for CA). Using this scoring system, we obtained a specificity of 96.3% and a sensitivity of 92.5% in predicting responsiveness to GH (chi-square with Yates correction, 48.2; p < 0.001). CONCLUSIONS: Discriminant analysis may permit the pretreatment prediction of responsiveness to the initial 6 months of GH therapy in short children without GH deficiency.

Analysis of Variance↗
PubMed1995

Is IGF binding protein-3 assessment helpful for the diagnosis of GH deficiency?

OBJECTIVE: The measurement of serum immunoreactive IGFBP-3 levels has been proposed as a screening test to identify children with growth hormone deficiency (GHD). We tested the sensitivity and specificity of the IGFBP-3 assessment in comparison with the measurement of IGF-I. DESIGN: We assessed the IGFBP-3 and IGF-I circulating levels in normal subjects and patients with GHD or idiopathic short stature (ISS). PATIENTS: Eighty-two normal subjects, 16 GHD, and 10 children with ISS were studied. Controls were divided into three age groups: group A, 1-4 years (n = 16); group B, 5-9 years (n = 35), and group C, 10-14 years (n = 31). MEASUREMENTS: All subjects underwent standard anthropometry. In short patients, GH secretory status was assessed by clonidine and arginine stimulation tests. IGFBP-3 and IGF-I circulating levels were measured by radioimmunoassay. RESULTS: IGFBP-3 and IGF-I levels were closely related (r = 0.51, P < 0.0001) and IGFBP-3 was less age dependent than IGF-I (r = 0.57, P < 0.02 vs r = 0.64, P = 0.0001). Sensitivity (true positive ratio) and specificity (true negative ratio) of IGFBP-3 measurement were 50 and 92% respectively, whereas sensitivity and specificity of IGF-I assessment were 75 and 90% respectively. Below the age of 5 years, sensitivity was 20% for IGFBP-3 and 40% for IGF-I; specificity was 94% for IGFBP-3 and 88% for IGF-I. CONCLUSIONS: IGFBP-3 measurement had poor sensitivity in detecting growth hormone deficient patients, offering no diagnostic advantage over IGF-I, even in the first years of life, although, due to the high specificity, the finding of subnormal levels of IGFBP-3 was strongly suggestive of growth hormone deficiency. The presence of low IGFBP-3 and IGF-I levels in a short child with normal GH response to provocative tests should prompt further investigations, such as the determination of spontaneous GH secretion or assessment of the GH binding proteins together with an IGF-I and/or IGFBP-3 generation test, in order to identify neurosecretory dysfunction or GH receptor deficiency. Finally, we believe that there is no definitive test for diagnosing or excluding growth hormone deficiency and detailed analysis of the results of endocrine tests, clinical findings and other laboratory and radiological information is necessary to maximize diagnostic accuracy.

Adolescent↗
PubMed1995

Effect of insulin on hydrogen peroxide production by human polymorphonuclear leukocytes. Studies with monoclonal anti-insulin receptor antibodies, and an agonist and an inhibitor of protein kinase C.

This study evaluated the effect of insulin on the respiratory burst of human polymorphonuclear leukocytes (PMNLs) and the signalling pathways involved in this process, especially the involvement of protein kinase C (PKC). Isolated human PMNLs from healthy volunteers were incubated with different concentrations of insulin (10-10-10-7 mol/l) and for different durations of incubation (5-90 min). The intracellular production of hydrogen peroxide (H2O2) was detected employing a previously validated flow cytometric assay using 2',7'-dichlorofluorescein-diacetate (DCFH-DA) as a marker for H202 production. Specificity of insulin action was verified using an insulin antagonist (the monoclonal antibody MA-10). To identify the signalling pathway involved, we used; (a) monoclonal antibody MA-5, directed against the alpha-subunit of the insulin receptor, that partially mimics insulin without activating tyrosine kinase; (b) H7, an inhibitor of PKC involved in O2- production in PMNLs, and (c) phorbol myristate acetate (PMA) that binds and stimulates PKC. Insulin caused a dose- and time-dependent stimulation of H202 release by human PMNLs. The effect of insulin was blocked MA-10. The actions of insulin and PMA on H2O2 release were additive, whereas the actions of MA-5 and PMA were not. H7 partially inhibited the H2O2 production stimulated by insulin and completely inhibited MA-5 action. We conclude that insulin stimulates, in a dose- and time-related manner, the respiratory burst of human PMNLs. PKC activation can only partially account for the intracellular mechanisms involved in this process.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1995

Characterization of a low molecular mass form of insulin-like growth factor binding protein-3 (17.7 kilodaltons) in urine and serum from healthy children and growth hormone (GH)-deficient patients: relationship with GH therapy.

The insulin-like growth factor binding proteins (IGFBPs) are the carriers for insulin-like growth factor (IGF0-I and IGF-II. IGFBP-3 is GH-dependent and circulates associated with IGFs and an acid-labile subunit to form a 150-kilodalton (kDa) complex. In human serum, two immunoreactive molecular weight forms of IGFBP-3 have been identified. In human urine, radioimmunoassayable levels of IGFBP-3 have been detected. The objectives of this study were to characterize the molecular weight forms of IGFBP-3 in urine and serum of healthy children and adults and in children with GH deficiency (GHD), to quantify the urinary molecular weight forms of IGFBP-3, and to evaluate the relationship of these forms with GH therapy. Urine and serum were obtained from 12 prepubertal children with GHD, before and after 6 months of GH therapy, from 30 prepubertal healthy children, and from 8 healthy adults. Western immunoblotting (WIB) with IGFBP-3 antiserum (alpha IG-FBP-3g1) showed that in urine the most representative IGFBP-3 was a 17.7-kDa form. The 17.7-kDa IGFBP-3 was high in urine of healthy children compared with healthy adults and was low in children with GHD but increased after GH therapy. Urinary IGFBP-3 immunoreactive profile was determined by neutral-size exclusion chromatography, followed by IGFBP-3 RIA analysis of the fractions. Urine showed a major peak of IGFBP-3 immunoreactivity around 17 kDa. The 17-kDa urinary IGFBP-3 chromatographic peak averaged 8461 +/- 367 ng/12 h.m2 of body surface in healthy children, 3415 +/- 739 in adults (P < 0.001), 2294 +/- 354 in children with GHD before GH therapy (P < 0.001), and 7940 +/- 1874 in children with GHD after GH therapy. Urinary IGFBP-3 was also measured by RIA in unfractionated urine; healthy children showed levels significantly higher (14575 +/- 460 ng/12 h.m2) than adults (7823 +/- 1083, P < 0.001) and higher than children with GHD before GH therapy (4710 +/- 703, P < 0.001). Again, however, immunoreactive IGFBP-3 increased after GH treatment (12294 +/- 3394). In the serum of the healthy children we characterized by specific IGFBP-3 WIB analysis, a 17.7-kDa immunoreactive form of IGFBP-3 that was absent in the serum of healthy adults and low in patients with GHD, increased during GH therapy. Serum samples were subjected to neutral-size exclusion chromatography and the fractions were analyzed by WIB.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1994

Multiple-dose pharmacokinetics and safety of a potential memory-enhancing compound, CL 275,838, in healthy male volunteers.

The pharmacokinetics and safety of CL 275,838, a new potential memory-enhancing compound, were examined after 14 daily doses (50 and 100 mg) in 16 healthy male volunteers, age 20 to 59 years, in a randomized, double-blind, placebo-controlled, parallel group study. Trough blood samples (predose) were collected on days 2, 4, 7, 10, and 14, and further samples were drawn after the final dose (day 14) to define the multiple-dose kinetics of the parent compound and its metabolites II and IV. Intercurrent clinical events, vital functions, EEG, ECG, and cognitive tests (attention, verbal memory, and spatial memory) were considered as outcome measures of safety. Performance in cognitive tests was also studied to collect preliminary information on possible therapeutic action. Predose plasma concentrations of the parent compound and its two metabolites increased approximately in proportion to the dose, and accumulation was complete within 7 days, regardless of the dose. At steady state, mean Cmax and AUC of the parent compound and its two metabolites were dose related. Mean wash-out t1/2 was 18 to 20 hours for the parent compound, 22-23 hours for metabolite II, and 28-33 hours for metabolite IV; these elimination t1/2 are comparable for the two doses, and are similar to those observed in single-dose studies. For the 50-mg-dose group, predicted and observed average plasma concentrations (Css) of CL 275,838 and its two metabolites did not differ significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Expression and down-regulation by retinoic acid of IGF binding protein-2 and -4 in medium from human neuroblastoma cells.

Insulin-like growth factors (IGFs) regulate the autocrine/paracrine growth of neuroblastomas. The IGFs bind to specific binding proteins (IGFBPs) which modulate their biological activity. We investigated, by Western ligand blotting (WLB), the presence of IGFBPs and their possible modulation by retinoic acid (RA), IGF-I, IGF-II and truncated Des(1-3)IGF-I in conditioned medium (CM) of the human neuroblastoma SK-N-BE(2) cell line. We demonstrated the presence of two IGFBPs, with MW 37 kDa and 25 kDa. Following immunoprecipitation, they turned out to be IGFBP-2 and -4, respectively. The RA-induced differentiation in SK-N-BE(2) cells was accompanied by a marked reduction of the intensity of both IGFBP bands after 48 h (32% and 24% of control, respectively) and 72 h (2% and 0% of control, respectively) incubation. The addition of exogenous IGFs, which did not induce cell differentiation, did not change the IGFBP pattern significantly, except for the truncated form of IGF-I, which induced a marked decrease in both the 37 kDa and 25 kDa bands after 72 h incubation (45% and 18% of control, respectively). These findings suggest that IGFBPs have a role in RA-induced differentiation in human neuroblastoma cells.

Blotting, Western↗
PubMed1994

Reduced growth hormone secretion in Turner syndrome: is body weight a key factor?

The age-related decline in spontaneous growth hormone (GH) secretion has been suggested to cause growth failure in girls with Turner syndrome (TS). We studied 23 girls (mean age +/- SD: 11.1 +/- 2.7 years) diagnosed to have TS by karyotype analysis. The control group consisted of 18 prepubertal age-matched subjects (10.7 +/- 2.5 years) with growth retardation due to familial short stature and/or constitutional growth delay. In addition, 18 children (10.9 +/- 3.3 years) diagnosed to have GH deficiency by two different provocative tests were chosen as a further comparison group. Spontaneous 12-hour nocturnal GH secretion was assessed by RIA at 30-min intervals. Plasma insulin-like growth factor 1 (IGF-1) levels were determined by RIA after acid-ethanol extraction. Girls with TS had a percentage of ideal body weight significantly higher than controls (p < 0.0001) and showed spontaneous GH secretion significantly lower than controls (mean +/- SD: 3.2 +/- 1.6 in TS vs. 5.5 +/- 1.3 microgram/l in controls; p < 0.0001) but higher than GH-deficient patients (1.3 +/- 0.8 microgram/l; p < 0.0001). No significant difference was found in IGF-1 levels between TS patients and controls, whereas GH-deficient children showed IGF-1 levels significantly lower than those of TS patients (p < 0.0005). As expected, GH concentrations correlated with bone age in controls (r = 0.51, p < 0.05), whereas no relationship was seen in TS. interestingly, in TS, GH levels were negatively related to the percentage of ideal body weight (r = -0.43, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Single-dose safety and pharmacokinetics of a potential cognition-enhancing compound, CL 275,838, in healthy volunteers.

The pharmacokinetics and safety of CL 275,838, a potential cognition-enhancing compound, were studied after single escalating oral doses first in young healthy male volunteers and then in old (60-74 years) and very old (over 75 years) volunteers of both sexes. In all age groups absorption of CL 275,838 was rapid as assessed by the mean time to reach maximum plasma concentrations (Cmax) which averaged 1-2 hr, regardless of the dose administered. In young male volunteers both Cmax and area under the curve (AUC) increased proportionally with dose from 10 to 100 mg. Mean elimination half-lives (t1/2) of the parent compound (18-21 hr) and of its circulating metabolites II (20-22 hr) and IV (27-30 hr) were well comparable for the doses tested (50 and 100 mg). Age did not appreciably affect plasma Cmax of CL 275,838 or its two metabolites. Mean AUC and elimination half-life did not appreciably differ between old and very old subjects given 50 mg CL 275,838, with the limitations dictated by the small number of elderly subjects examined. Compared with younger volunteers receiving comparable doses, however, the elderly had higher mean plasma AUC of the unchanged compound and its two metabolites, although the parameter varied widely between subjects. The mean elimination t1/2 (+/- SD) was longer in the elderly (38.8 +/- 19.6, 50.5 +/- 24.5 and 41.7 +/- 12.1 hr, respectively, for the parent compound and its metabolites II and IV) than in the young subjects. The cause(s) of these variations and the possible clinical implications remain to be established.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗