bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in bone density and bone markers in rhythmic gymnasts and ballet dancers: implications for puberty and leptin levels
Authors: Munoz MT , de la Piedra C , Barrios V , Garrido G , Argente J
Published: January 2005

OBJECTIVE: Our aim was to compare physical activity and biochemical markers with bone mineral acquisition in rhythmic gymnasts and ballet dancers. METHODS: Weight, height, body mass index, nutritional intake, bone age and menstrual histories were analyzed in nine rhythmic gymnasts, twelve ballet dancers and fourteen controls. Bone mineral density (BMD) was assessed by X-ray absorptiometry at the lumbar spine, hip and radius. Bone alkaline phosphatase (bAP) and amino-terminal propeptide of procollagen I (PNIP) in serum and urinary alpha-isomer of the carboxy-terminal telopeptide of collagen I (alpha-CTX) were measured. RESULTS: Bone age was delayed 2 years and mean age at menarche was 15+/-0.9 years in rhythmic gymnasts and 13.7+/-1 years in ballet dancers, compared with 12.5+/-1 years in controls. Trocanteric and femoral neck BMD was significantly higher in rhythmic gymnasts compared with ballet dancers and controls. Right forearm (non-loaded zone) BMD was significantly decreased in rhythmic gymnasts and ballet dancers compared with controls. All subjects had normal bAP and PNIP levels, but the alpha-CTX/creatinine (Cr) ratio was increased in rhythmic gymnasts (P<0.001) with an inverse correlation between right forearm BMD and the alpha-CTX/Cr ratio (r=-0.74, P<0.001). Serum leptin levels were decreased in rhythmic gymnasts and ballet dancers. Rhythmic gymnasts had a positive correlation between right forearm BMD and leptin levels (r=0.85, P<0.001). CONCLUSIONS: Decreased bone mass in rhythmic gymnasts could be partially explained by an increase in bone resorption. Serum leptin levels could be implicated in the pubertal delay and be a good marker of bone mass in these subjects.
Regulatory role of BMP2 and BMP7 in spermatogonia and Sertoli cell proliferation in the immature mouse
Authors: Puglisi R , Montanari M , Chiarella P , Stefanini M , Boitani C
Published: January 2005

AIM: The aim of this study was to determine the action of bone morphogenetic proteins (BMPs) on testicular cell proliferation during early postnatal life, a definite developmental time at which crucial changes in germ cell and Sertoli cell maturation occur. METHODS: We investigated the effect of BMP2 and BMP7, two factors which belong to the relatively distant decapentaplegic (DPP) and 60 A classes of the large BMP family, upon spermatogonial and Sertoli cell proliferation, and we examined the expression of activin/BMP type II and type I receptors. We used in vitro cultured testis fragments from 7-day-old mice, highly purified populations of somatic and germ cells and total testes from mice of different ages. Cell proliferation was assessed by BrdU labelling and [3H]-thymidine incorporation. Ribonuclease protection assays and Northern blotting were performed to analyse receptor expression. RESULTS AND CONCLUSIONS: We have demonstrated a stimulatory action of BMP2 and BMP7 in spermatogonia and Sertoli cell proliferation respectively. ActRIIB is the type II receptor expressed most in spermatogonia, whereas Sertoli cells specifically expressed BMPRIIB, in addition to ActRIIB. By contrast, the presence of ActRIIA was undetectable in either germ or somatic cells. The type I receptors ActRIA, ActRIB and BMPRIA were all found in both cell types, indicating that the observed effect of BMP2 and BMP7 on testicular cell proliferation may be mediated by a number of combinatorial interactions in the receptor complexes. These findings suggest that BMPs are involved in physiological paracrine signalling during the first wave of spermatogenesis.
Early treatment with GH alone in Turner syndrome: prepubertal catch-up growth and waning effect
Authors: Wasniewska M , De Luca F , Bergamaschi R , Guarneri MP , Mazzanti L , Matarazzo P , Petri A , Crisafulli G , Salzano G , Lombardo F
Published: January 2005

OBJECTIVE: In order to ascertain the advantages of early GH treatment in Turner syndrome (TS), we started a prospective study aimed at evaluating prepubertal height gain in a cohort of 29 girls who were treated with the same pro-kilo GH dose (1.0 IU/kg per week) since they were less than 6 years old and for at least 5 years before entering puberty. PATIENTS AND DESIGN: Following a minimum of 6 months of baseline observations, 29 girls with TS were enrolled for this prospective study provided that they (a) were less than 6 years old, (b) were below -1.0 standard deviation score (SDS) for height, (c) had a projected adult height (PAH) lower than the respective target height (TH) and (d) had a height velocity (HV) lower than -1.0 SDS. All the selected girls underwent a 5-year treatment with biosynthetic GH at a stable dose of 1.0 IU/kg per week and were periodically measured during the treatment period in order to evaluate height, HV and PAH. RESULTS: After a dramatic acceleration during the 1st year, HV was attenuated during the subsequent years, reaching its nadir at the 5th year. Height deficiency under therapy progressively decreased from entry onwards, shifting from -2.4+/-0.7 to -1.0+/-1.2 SDS. In the same period, mean PAH progressively increased, although after 5 years it remained lower than the average TH. CONCLUSIONS: (a) An effective growth-promoting strategy in TS should be based on early GH treatment, as suggested by our results. (b) This strategy could result in a prepubertal normalization of height, thus allowing the appropriate timing for the induction of puberty. (c) An initial GH dose of 1.0 IU/kg per week may be suitable during the first years of therapy, as shown by our data documenting an important waning effect of GH therapy only after the 4th year of treatment. (d) No acceleration of bone maturation was observed under this treatment regimen.
Ectopic Agouti protein overexpression increases stimulated corticosterone production without effect on adenylate cyclase activity in mouse adrenal cells
Authors: Shevchenko AY , Bazhan NM , Makarova EN , Yakovleva TV , Karkaeva NR
Published: January 2005

OBJECTIVE: The antagonism of Agouti protein (AP) and Agouti-related protein on melanocortin receptors suggests an inhibitory role in the regulation of steroidogenesis. However, we have previously demonstrated that ectopic AP overexpression increased restraint-induced corticosterone release and adrenal reactivity to ACTH in mice. A high steroidogenic response to ACTH may be a consequence of a stimulatory AP action on the adenylate cyclase (AC) and/or intracellular steroidogenic enzymes. The aim of the present study was to estimate the effect of ectopic AP overexpression on the activity of AC and steroidogenic intracellular enzymes. METHODS: ACTH and forskolin were used for AC stimulation, and dibutyryl cAMP and progesterone were used for stimulation of intracellular steroidogenic enzymes in isolated adrenal cells in male C57Bl/6J mice of two Agouti genotypes: A(y)/a (ectopic AP overexpression) and a/a (absence of AP in all tissues). RESULTS: ACTH and forskolin increased cAMP accumulation to the same extent in both A(y)/a and a/a mouse adrenal cells (P<0.001; ANOVA), but resulted in higher corticosterone production in A(y)/a mice (P<0.001 for ACTH and P<0.01 for forskolin; ANOVA). Dibutyryl cAMP- and progesterone-induced corticosterone production was higher in A(y)/a mice than in a/a mice (P<0.001 for dibutyryl cAMP and P<0.01 for progesterone; ANOVA). CONCLUSIONS: Ectopic AP overexpression increased stimulated corticosterone production and intracellular steroidogenic enzyme reactivity to cAMP without an effect on AC activity.
Gonadotropin-releasing hormone (GnRH) agonist triptorelin inhibits estradiol-induced serum response element (SRE) activation and c-fos expression in human endometrial, ovarian and breast cancer cells
Authors: Grundker C , Gunthert AR , Hellriegel M , Emons G
Published: January 2005

BACKGROUND AND METHODS: The majority of human endometrial (>80%), ovarian (>80%) and breast (>50%) cancers express GnRH receptors. Their spontaneous and epidermal growth-factor-induced proliferation is dose- and time-dependently reduced by treatment with GnRH and its agonists. In this study, we demonstrate that the GnRH agonist triptorelin inhibits estradiol (E2)-induced cancer cell proliferation. RESULTS: The proliferation of quiescent estrogen receptor alpha (ER alpha)-/ER beta-positive, but not of ER alpha-negative/ER beta-positive endometrial, ovarian and breast cancer cell lines, was significantly stimulated (P<0.001) (ANOVA) after treatment with E2 (10(-8) M). This effect was time- and dose-dependently antagonized by simultaneous treatment with triptorelin. The inhibitory effect was maximal at 10(-5) M concentration of triptorelin (P<0.001). In addition, we could show that, in ER alpha-/ER beta-positive cell lines, E2 induces activation of serum response element (SRE) and expression of the immediate early-response gene c-fos. These effects were blocked by triptorelin (P<0.001). E2-induced activation of estrogen-response element (ERE) was not affected by triptorelin. CONCLUSIONS: The transcriptional activation of SRE by E2 is due to ER alpha activation of the mitogen-activated protein kinase (MAPK) pathway. This pathway is impeded by GnRH, resulting in a reduction of E2-induced SRE activation and, in consequence, a reduction of E2-induced c-fos expression. This causes downregulation of E2-induced cancer cell proliferation.
Effects of increased thyroxine dosage pre-conception on thyroid function during early pregnancy
Authors: Rotondi M , Mazziotti G , Sorvillo F , Piscopo M , Cioffi M , Amato G , Carella C
Published: January 2005

OBJECTIVE: To compare the effects of pregnancy on the serum free thyroxine (FT4) levels in two cohorts of primary hypothyroid women treated with different levothyroxine (L-T4) doses before gestation. DESIGN AND METHOD: Twenty-five women with compensated hypothyroidism of different aetiology (thyroidectomized and Hashimoto's thyroiditis) were enrolled in this prospective study. The women were receiving substitutive doses of L-T4 and were anticipating pregnancy. They were assigned to two groups: 14 patients (group I) were switched to partially suppressive treatment while 11 patients (group II) continued the same therapeutic regimen. RESULTS: Pre-conceptional thyroid function evaluation demonstrated significantly higher FT4 and lower TSH in group I (P<0.001, for both hormones) and comparable free 3,5,3'-triiodothyronine (FT3) levels. The first post-conception thyroid function evaluation occurred at a median time of 6 (5-8) and 7 (5-9) weeks of gestation, for groups I and II respectively (P<0.05); all women in group I showed adequate serum FT4 levels while three patients in group II showed low-normal FT4 levels and one case was below normal levels. Statistical analysis demonstrated significantly higher frequencies (0% vs 36.4%; P<0.05) of low-normal FT4 levels in patients receiving substitutive doses of L-T4. None of the Hashimoto's-affected patients showed low or low-normal serum FT4 levels regardless of their therapeutic regimen. CONCLUSION: Our results suggest that in hypothyroid women anticipating pregnancy (with serum TSH in the lower quartile of normal range), the pre-conception adjustment of L-T4 doses may result in adequate maternal thyroid function up to the first post-conception evaluation. The procedure seems safe and inexpensive; it may be a worthwhile treatment, at least in thyroidectomized women, in view of the well-known potential effects of even marginal maternal thyroid hypofunction on the subsequent IQ of the progeny.
A longitudinal study of dehydroepiandrosterone sulphate (DHEAS) change in older men and women: the Rancho Bernardo Study
Authors: Tannenbaum C , Barrett-Connor E , Laughlin GA , Platt RW
Published: January 2005

OBJECTIVE: To examine the age-related and sex-specific rates and determinants of change in endogenous dehydroepiandrosterone sulphate (DHEAS) levels in older community-dwelling adults, taking into account regression to the mean. DESIGN: Prospective cohort study from Rancho Bernardo, California, USA. METHODS: Plasma for DHEAS was collected at baseline and 10-14 years later from 242 men and 207 postmenopausal women (age range, 60-77 years), who were not taking hormone therapy or corticosteroids. Age-related and sex-specific changes in DHEAS were calculated according to four different definitions of change: absolute change, annual percentage change, change exceeding 10% of baseline and change exceeding that expected from statistical regression to the mean. Determinants of DHEAS change were assessed using regression analyses. RESULTS: Baseline DHEAS levels were higher for men than women (age-adjusted means, 1.37+/-0.73 mug/ml (3.72+/-1.98 mumol/l) vs 0.73+/-0.48 mug/ml (1.98+/-1.30 mumol/l) respectively, P<0.0001), with more pronounced declines observed in men (-4.0%/year) compared with women (-2.1%/year; P<0.001). Some 28% of women and 5% of men had DHEAS levels that increased or stayed the same according to a 10% definition of change. When regression to the mean artifact was accounted for, only 15% of women and 5% of men showed true increases in DHEAS. In both sexes, baseline DHEAS levels accounted for three-quarters of the variability in absolute DHEAS change over time, with higher baseline levels resulting in greater loss. Sex, baseline weight, age and smoking status were significantly associated with DHEAS change in univariate models; only sex remained independently associated with DHEAS change in multivariate analyses, with men showing greater annual declines than women (estimated coefficient=0.006, P=0.008). CONCLUSION: In this sample, over 30% of the observed changes in DHEAS could be attributed to regression to the mean. Potential underlying mechanisms of change in DHEAS levels, and sex differences, are discussed.
Symptomatic epidural lipomatosis in ectopic Cushing's syndrome
Authors: Bodelier AG , Groeneveld W , van der Linden AN , Haak HR
Published: January 2005

We report a case of spinal epidural lipomatosis (SEL) caused by ectopic Cushing's syndrome and give a review of the literature. The most common cause of SEL is prolonged therapy with glucocorticoids, only a very few cases are related to endogenous Cushing's syndrome. The pathophysiological mechanism is not clear but there is a possible role for the autonomic nervous system in the stimulation of growth of epidural fat. Severe neurological symptoms which indicate myelopathy and radiculopathy can occur, but there is often a delay in diagnosis because the non-specific initial symptoms are not recognized. The epidural fat is mostly located in the thoracic and lumbar region. Magnetic resonance imaging can establish the diagnosis rapidly. In patients with severe neurological symptoms, surgical decompression of the myelum and removal of the epidural fat is the treatment of choice. Most patients have partial or complete recovery of neurological deficits after surgical treatment or after discontinuing glucocorticoid therapy; mild cases can also be treated conservatively. Routine imaging for the detection of epidural-located lipomatosis in patients at risk is probably useful.
Multiple endocrine neoplasia 2A syndrome presenting as peripartum cardiomyopathy due to catecholamine excess
Authors: Kim J , Reutrakul S , Davis DB , Kaplan EL , Refetoff S
Published: January 2005

We report the case of a 24-year-old female with a history of medullary thyroid carcinoma who presented at 38 weeks gestation with acute chest pain and shortness of breath. She was found to be in pulmonary edema and respiratory failure. An emergency cesarean section was performed. Subsequently, an echocardiogram revealed an ejection fraction of 10%. After medical therapy with digoxin, milrinone, captopril and diuretics, her condition improved rapidly and a repeat echocardiogram showed that the left ventricular function had normalized. Diagnosis of pheochromocytoma was made by urine and plasma catecholamine measurements. Magnetic resonance imaging revealed a 3.7 cm left adrenal mass. Increased uptake activity was seen in the same region by an (131)I-metaiodobenzylguanidine (MIBG) scan. The patient underwent successful surgical resection of the pheochromocytoma. Subsequent DNA analysis revealed that the patient had a mutation of the RET proto-oncogene. The same mutation was also found in several of her family members. In summary, we report a case of multiple endocrine neoplasia 2A presenting as peripartum cardiomyopathy and cardiovascular collapse. Pheochromocytoma should be considered as a potential cause of peripartum cardiomyopathy.
Novel ghrelin analogs with improved affinity for the GH secretagogue receptor stimulate GH and prolactin release from human pituitary cells
Authors: Rubinfeld H , Hadani M , Taylor JE , Dong JZ , Comstock J , Shen Y , Deoliveira D , Datta R , Culler MD , Shimon I
Published: January 2005

OBJECTIVE: Ghrelin, a recently identified 28-amino acid peptide is a potent GH secretagogue (GHS) produced predominantly by the stomach. Ghrelin stimulates GH secretion through binding to the GHS receptor in the hypothalamus and pituitary. In addition to the GH-releasing action, ghrelin has been found to be a powerful orexigenic factor. To assess the direct in vitro effects of ghrelin on human pituitary hormone secretion we have produced a panel of novel ghrelin analogs (molecular weight, 3323-3384; human native ghrelin, 3371) with enhanced affinity for the human GHS receptor (IC(50) 0.38-1.09 nM; human ghrelin, 1.2-2.2 nM). METHODS: The peptidic analogs were tested for their effect on GH secretion using dispersed human fetal pituitaries (21 to 23 weeks of gestation) and cultured GH- and prolactin (PRL)-secreting adenomas. The expression of the GHS receptor in normal (fetal and adult) human pituitary tissues, GH- and PRL-cell adenomas was established using RT-PCR. RESULTS: The effects of ghrelin, its analogs and GH-releasing hormone (GHRH) alone or in combination on GH and PRL secretion were compared at various concentrations. The ghrelin analogs stimulated GH release by 35-60% from human fetal pituitary cells (1-10 nM; P<0.05) and by 50-75% from cultured pituitary adenomas (10 nM; P<0.05). This releasing effect was dose-dependent, achieving maximal stimulation with analog concentrations at 100 nM. Human ghrelin was less potent as compared with its analogs in stimulating human GH, in keeping with the improved binding affinity of the analogs for the GHS-1a receptor. The ghrelin analogs and GHRH had comparable effects on GH secretion from both normal and adenomatous cells, and in combination produced an additive stimulatory effect on GH (150%; P<0.0001). In contrast, ghrelin and its analogs induced a comparable increase in PRL release ranging between 25 and 40% (P<0.05) from fetal cells and 30 and 70% (P<0.001) from cultured PRL-cell and mixed GH-PRL adenomas. CONCLUSIONS: Our results have demonstrated for the first time that ghrelin analogs with enhanced affinity for the GHS receptor are potent stimulators of GH secretion from human pituitary cells, and thus may possess potential clinical therapeutic benefits.
Recovery of renal tubule phosphate reabsorption despite reduced levels of sodium-phosphate transporter
Authors: Friedlaender MM , Wald H , Dranitzky-Elhalel M , Levi M , Popovtzer MM
Published: January 2005

BACKGROUND: The acute effect of parathyroid hormone (PTH) on phosphate transport has been reported to be mediated by rapid downregulation of sodium-phosphate transporter (NaPi-IIa) protein, but the association was observed with pharmacological doses of PTH. OBJECTIVE: To explore the effects of physiological doses of PTH on NaPi-IIa protein and its relationship to phosphate transport. METHODS: Acute clearance studies were performed in parathyroidectomized rats given a bolus i.v. physiological dose (1 mug) of bovine PTH(1-34) and NaPi-IIa protein concentrations were examined at different time intervals. RESULTS: Fractional excretion of phosphate increased from 0.031+/-0.006 (mean+/-s.e.) to 0.238+/-0.059 (P<0.01 compared with baseline and compared with controls) at 40 min and returned to control values by 120 min. Urinary cAMP concentrations were increased at 20 min only. Superficial cortex brush-border membrane (BBM) NaPi-IIa protein was decreased from baseline at both 40 and 120 min (P<0.01) and did not recover at 240 min (P<0.01 compared with baseline and compared with controls). CONCLUSION: These results confirm that PTH, even in physiological dosage, causes a rapid decrease in BBM NaPi-IIa, but subsequent recovery of phosphate reabsorption is poorly correlated with BBM concentrations of NaPi-IIa protein. This suggests that transport mechanisms other than NaPi-IIa are important in renal phosphate reabsorption.
Bone development during GH and GnRH analog treatment
Authors: Antoniazzi F , Zamboni G , Bertoldo F , Lauriola S , Tato L
Published: January 2005

Estrogens, GH and IGFs are essential in the development and growth of the skeleton and for the maintenance of bone mass and density. Treatment of precocious puberty with GnRH analogs (GnRHa), by reducing sex steroid levels, leads to a situation of hypoestrogenism that may theoretically have a detrimental effect on bone mass during pubertal development. A reduction in bone mineral density (BMD) during GnRHa treatment has been demonstrated, but GnRHa treatment in patients with central precocious puberty (CPP) does not seem to impair the achievement of normal peak bone mass (PBM) at final height. However, calcium supplementation is effective in improving bone densitometric levels and may promote better PBM achievement. In children and adolescents with GH deficiency (GHD), BMD assessed by dual-energy X-ray absorptiometry (DEXA) and bone turnover are significantly reduced, but they are stimulated by GH treatment. GH treatment leads to improved bone density, function of the dose and duration of treatment, and patients may require prolonged GH treatment beyond the time of growth to improve PBM. After the discontinuation of GH therapy, the more active population had higher bone mineral content (BMC) levels than patients with low physical activity. In our experience, the therapeutic association of GH and calcium also represents a valuable tool in pursuing a proper BMC in GHD patients. We concluded that nonhormonal factors, such as physical activity and nutritional factors, are important in determining bone metabolism and bone mass.
Transitional care of GH deficiency: when to stop GH therapy
Authors: Savage MO , Drake WM , Carroll PV , Monson JP
Published: January 2005

While the benefits of growth hormone (GH) therapy in adult hypopituitary patients with GH deficiency (GHD) are established, the role of continued GH therapy after final height in adolescent GH-deficient patients remains unclear. Preliminary data suggest that cessation of GH on completion of linear growth may be associated with impairment of somatic development and adverse changes in body composition. For the present time, the decision whether to continue GH treatment in adolescent patients with GHD is best made on an individual basis. For such patients, continuity of care is crucial. Children and adults with GHD are usually managed by physicians in separate departments, who may focus on different aspects of treatment and care. Close collaboration between paediatric and adult physicians is essential to ensure smooth transition and to minimize the drop-out rate from follow-up. Given the previous period of treatment during childhood, paediatric physicians should be best placed to discuss the potential benefits of continuing GH therapy and instigate retesting of GH secretion. Many children with isolated idiopathic GHD will produce normal GH responses if retested at adult height. Patients with multiple pituitary hormone deficits are more likely to have ongoing GHD, as are patients who have received CNS irradiation. Quality of life does not appear to be decreased in adolescents with GHD who stop treatment, so achievement of satisfactory bone mass is a major determinant of the decision whether to continue therapy.
GH improves growth and clinical status in children with cystic fibrosis -- a review of published studies
Authors: Hardin DS
Published: January 2005

Children with cystic fibrosis (CF) have problems with poor linear growth and inadequate weight gain. Nutritional augmentation has been the mainstay of therapy for improving both weight and height in CF; however, inadequate growth continues to be a problem. Furthermore, protein catabolism has been documented even in non-acutely ill adults and children with CF, and could adversely affect longitudinal growth. Human recombinant GH has positive effects on nitrogen balance, and multiple studies have demonstrated improved height and weight in children treated with GH. The purpose of this article is to summarize studies evaluating GH use in children with CF.All published studies of GH use in children with CF have demonstrated significant improvement in height velocity and height Z score. All studies but one, in which subjects were treated only three times per week with GH, have demonstrated improvement in weight as reported by weight velocity and/or weight Z score, and one trial has demonstrated a substantial improvement when GH was used to augment nutritional therapy. Several reports suggest that GH treatment results in improved forced vital capacity, and multiple studies have found improved clinical status as measured by decreased hospitalizations and courses of intravenous antibiotics. Furthermore studies to date also suggest that GH results in improvement in exercise tolerance and bone accumulation. To date significant side effects, including glucose intolerance, have not been reported. Thus mounting evidence suggests that human recombinant GH provides safe and effective therapy in children with CF.
The bone mass concept: problems in short stature
Authors: Schoenau E , Land C , Stabrey A , Remer T , Kroke A
Published: January 2005

Bone densitometry is currently one of the mainstays in the evaluation of systemic bone diseases in adults and is also increasingly used to assess primary or secondary bone disorders in children and adolescents. The purpose of carrying out densitometric studies in such circumstances is to measure the densitometric indicators of bone stability. Following procedures which were established for diagnosing adult osteoporosis, a decrease in densitometric surrogates of bone stability is usually interpreted as indicating increased fracture risk. The most basic densitometric parameter is bone mineral content (BMC), which can be measured with most densitometric techniques. BMC is either defined as the mass of mineral contained in an entire bone or as the mass of mineral per unit bone length. While mineral mass can be expected to be a good surrogate for bone stability, BMC is obviously a size-dependent parameter, since small bones weigh less than big bones. This is a drawback in paediatric use, since many children and adolescents who are examined by densitometry suffer from chronic disorders and are small-for-age. Short children will have a lower BMC than their healthy age-matched peers, even if their (smaller) bones are otherwise completely normal.
On the origin, use and destination of human embryos
Authors: van Leeuwen E
Published: January 2005

The moral acceptability or non-acceptability of the use of human embryos in research raises questions on several philosophical levels. The mixing-up of these levels results in strongly defended and endless debates. In this contribution, arguments on three levels will be discussed, the ontological, the practical and instrumental and the level of human relationships. It is concluded that, on the latter level, the moral problems of the other two are significant, but not conclusive. The decision to allow or to ban research with human embryos is charged with full human responsibility.
An ontological view of the human embryo. A paradigm
Authors: Alonso C
Published: January 2005

In the present paper I analyze the existing paradigms explaining the ontological status of the organisms originating during a given developmental process and the potentiality these paradigms offer. These paradigms give us a hint of the ontological and ethical status of these organisms. It is described that during the history of human thought two theories have been developed to explain the origin of living organisms. One theory placed the world's origin and the origin of living organisms in a transcendent reality while the second stated that the growing complexity of these organisms was rooted in an internal 'dynamis' (the internal potential of a thing, generally a living thing, to acquire new properties) that is present in each one of them. These paradigms are analysed concluding that at the time they were formulated there was no formal understanding of the process of development because the emergence of novelties through evolution was not included in them. At that time growth and development were two aspects of the same thing. A critical turning point in biological and philosophical thinking was provided by the founders of the DNA paradigm as the program directing development. Due to new insights, a paradigm is presented here which includes the epigenesic information as an essential element of the program of development together with the DNA. The consequence of this paradigm is that the program of development is time- and space-dependent and that the biological elements which originate during the process are not preformed but adopt specific values. This way of thinking introduces new approaches to the analysis of the value of the human embryo with repercussions in the ethical discussions on research programs using embryonic stem cells.
Neonatal screening for congenital adrenal hyperplasia
Authors: van der Kamp HJ , Wit JM
Published: January 2005

Congenital adrenal hyperplasia (CAH) is well suited for newborn screening, as it is a common and potentially fatal disease which can be easily diagnosed by a simple hormonal measurement in blood. Moreover, early recognition and treatment can prevent severe salt wasting, dehydration and death and shorten the time of male sex assignment in virilised females.In screening programmes, 17alpha-hydroxyprogesterone (17OHP) is measured in filter paper blood spots obtained by a heel puncture preferably between 2 and 4 days after birth. Three assay techniques are utilised for initial screening: radio-immunoassay (USA), enzyme-linked immunosorbent assay (Japan) and time-resolved fluoro-immunoassay (Europe). Preterm newborns have higher 17OHP concentrations in serum than babies born at term. Therefore, cut-off levels are based on gestational age (in Japan and Europe) or on birth weight (in the USA). There is a considerable variation in cut-off levels from one programme to another. This is most likely due to the different antibodies and reagents used, varying thickness and density of filter paper used for sample collection and, most significantly, the characteristics of the reference population (in terms of birth weight and gestational age).More than 30 million newborns have been screened. The prevalence of CAH in the USA and Europe is approximately 1:15 000-16 000, and slightly lower in Japan (1:19 000). In general, severe salt wasting can be prevented, but there is a remarkable variation in the number of false-positives and false-negatives among the various programmes. Ongoing refinement of cut-off levels is needed to improve specificity and sensitivity.
Birth weight, infant growth and insulin resistance
Authors: Ong KK , Dunger DB
Published: January 2005

Size at birth and early postnatal growth rates are important determinants of human perinatal survival; they also predict the tempo of growth, adult height and long-term risks for obesity, type 2 diabetes and cardiovascular disease.Results from the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC) show that fetal growth is influenced by both fetal genes and maternal-uterine-placental factors. Important maternal-placental factors include parity, smoking and weight gain, but also maternal genetic factors in the mother or fetal placenta, including the mitochondrial DNA 16189 variant and H19. These maternal genetic factors particularly influence smaller, growth-restrained infants, as in first pregnancies. Fetal genes include the insulin gene (INS) VNTR (variable number of tandem repeat), which we recently confirmed to be associated with birth size and cord blood IGF-II levels; these fetal gene effects are more evident in the absence of maternal-uterine growth restraint.During postnatal life, the INS VNTR III/III genotype remains associated with body size, including body mass index and waist circumference, and also lower insulin sensitivity among girls. However, as at birth, significant gene-environment interactions are seen. Rapid 'catch-up' early postnatal weight gain follows maternal-uterine restraint, and strongly predicts later childhood obesity and insulin resistance; among these children, those with INS VNTR class I alleles are more obese.Genetic factors that influence early growth may have conferred some early survival advantage in human history during times of undernutrition. With abundant nutrition and rising obesity rates, these genetic factors and their interactions with maternal and childhood environmental factors that influence childhood growth may now contribute to the early development of adult disease risk. Their recognition may help the development of targeted early interventions to prevent the progression towards adult disease.
Very short term dehydroepiandrosterone treatment in female adrenal failure: impact on carbohydrate, lipid and protein metabolism
Authors: Christiansen Jens Juel , Gravholt Claus Højbjerg , Fisker Sanne , Møller Niels , Andersen Marianne , Svenstrup Birgit , Bennett Paul , Ivarsen Per , Christiansen Jens Sandahl , Jørgensen Jens Otto Lunde
Published: January 2005

Objective: In female adrenal insufficiency, dehydroepiandrosterone (DHEA) secretion is impaired and circulating androgen levels are severely reduced. We wanted to analyse the acute effects of physiological DHEA substitution on substrate metabolism.

Design: We studied nine females with adrenal insufficiency after 9 days of oral DHEA replacement (50 mg/day) in a double-blind, placebo-controlled crossover study.

Methods: Whole body and regional substrate metabolism was assayed in the basal state and during a euglycemic hyperinsulinemic glucose clamp by means of isotope dilution techniques (glucose, phenyl-alanine, tyrosine), indirect calorimetry and in situ lipolysis (microdialysis technique).

Results: DHEA treatment normalized the levels of all androgens. Basal and insulin-stimulated total energy expenditure and rates of protein, lipid and glucose oxidation were unaffected by DHEA. Whole body turnover of glucose and protein were also unaffected by DHEA. Forearm breakdown of protein was reduced by insulin to the same extent after placebo and DHEA. Insulin sensitivity as expressed by the glucose infusion rate during the euglycemic clamp was similar after placebo and DHEA. Finally, the interstitial release of glycerol in adipose tissue was not significantly influenced by DHEA.

Conclusions: Short-term oral DHEA replacement in women with adrenal insufficiency was not associated with measurable changes in total or regional substrate metabolism.
One year of GH replacement therapy with a fixed low-dose regimen improves body composition, bone mineral density and lipid profile of GH-deficient adults
Authors: Boguszewski Cesar L , Meister Ludimyla H F , Zaninelli Daniele C T , Radominski Rosana B
Published: January 2005

Objective: We have studied the effects on body composition and metabolism of a fixed low dose of growth hormone (GH), 0.6 IU (0.2 mg)/day, administered for 12 months to GH-deficient (GHD) adults.

Design and methods: Prospective open-label study, using 18 GHD patients (11 women, 7 men; aged 21–58 years). All investigations were performed at baseline and after 12 months. Body composition was determined by dual energy X-ray absorptiometry.

Results: Total body fat decreased (−1.74±2.87%) and lean body mass (LBM) increased (1.27±2.08 kg) after therapy (P < 0.05). Changes in truncal fat did not reach statistical significance, but a decrease varying from 0.72 to 2.78 kg (1 to 8.7%) was observed in 13 (72%) patients. Bone mineral density (BMD) increased at lumbar spine, total femur and femoral neck (P < 0.05). Levels of total and low-density lipoprotein (LDL)-cholesterol were lower after therapy (P < 0.05), and their changes were directly associated with values at baseline. Insulin levels increased and the insulin resistance index worsened at 12 months (P < 0.05). Median IGF-I s.d. score was −4.30 (range, −11.03 to −0.11) at baseline and −1.73 (range, −9.80 to 2.26) at 12 months. Normal age-adjusted IGF-I levels were obtained with therapy in 5 of 11 patients who had low IGF-I levels at baseline. Changes in IGF-I levels were not correlated with any biological end point, except changes in LBM (r = 0.53, P = 0.02). Side effects were mild and disappeared spontaneously.

Conclusions: One-year of a fixed low-dose GH regimen in GHD adults resulted in a significant reduction in body fat, total cholesterol and LDL-cholesterol, and a significant increase in LBM and BMD at lumbar spine and femur, regardless of normalization of IGF-I levels. This regimen led to an elevation of insulin levels and a worsening of the insulin resistance index.
Plasma adiponectin is decreased in nonalcoholic fatty liver disease
Authors: Pagano Claudio , Soardo Giorgio , Esposito Walter , Fallo Francesco , Basan Lorenza , Donnini Debora , Federspil Giovanni , Sechi Leonardo A , Vettor Roberto
Published: January 2005

Objectives: Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver-related morbidity and is frequently associated with obesity and metabolic syndrome. The recently discovered hormone adiponectin is produced by adipose tissue, and low plasma adiponectin is considered a key factor in the development of the insulin resistance underlying metabolic syndrome. Animal studies suggest that adiponectin may protect against non-alcoholic steatohepatitis, but direct evidence in humans is lacking. We therefore conducted this study to assess the relationship between plasma adiponectin and nonalcoholic fatty liver disease to explore its role in the pathogenesis of this disease.

Design and methods: We measured plasma adiponectin and anthropometric, biochemical, hormonal and metabolic correlates in a group of 17 NAFLD patients with diagnosis confirmed by biopsy, and 20 controls with comparable age, body-mass index and sex. Furthermore we compared plasma adiponectin in patients with simple steatosis and steatohepatitis.

Results: Plasma adiponectin was significantly lower in NAFLD patients than controls (5.93±0.45 vs 15.67±1.60 ng/ml). Moreover, NAFLD patients were significantly more insulin resistant while having similar serum leptin. Adiponectin was similar in simple steatosis and in steatohepatitis (6.16±0.78 vs 5.69±0.49 ng/ml). An inverse correlation was observed between adiponectin and homeostatic model assessment (HOMA) of insulin resistance (P = 0.008), while adiponectin did not correlate with serum transaminases and lipid values.

Conclusions: These data support a role for low circulating adiponectin in the pathogenesis of NAFLD and confirm the strict association between reduced adiponectin production by adipose tissue, NAFLD and insulin resistance.
Defective glucose and lipid metabolism in human immunodeficiency virus-infected patients with lipodystrophy involve liver, muscle tissue and pancreatic β-cells
Authors: Haugaard Steen B , Andersen Ove , Dela Flemming , Holst Jens Juul , Storgaard Heidi , Fenger Mogens , Iversen Johan , Madsbad Sten
Published: January 2005

Objectives: Lipodystrophy and insulin resistance are prevalent among human immunodeficiency virus (HIV)-infected patients on combined antiretroviral therapy (HAART). Aiming to provide a detailed description of the metabolic adverse effects of HIV-lipodystrophy, we investigated several aspects of glucose metabolism, lipid metabolism and β-cell function in lipodystrophic HIV-infected patients.

Methods: [3-3H]glucose was applied during euglycaemic hyperinsulinaemic clamps in association with indirect calorimetry in 43 normoglycaemic HIV-infected patients (18 lipodystrophic patients on HAART (LIPO), 18 patients without lipodystrophy on HAART (NONLIPO) and seven patients who were naïve to antiretroviral therapy (NAÏVE) respectively). β-cell function was evaluated by an intravenous glucose tolerance test.

Results: Compared with NONLIPO and NAÏVE separately, LIPO displayed markedly reduced ratio of limb to trunk fat (RLF; >34%, P < 0.001), hepatic insulin sensitivity (>40%, P < 0.03), incremental glucose disposal (>50%, P < 0.001) and incremental exogenous glucose storage (>50%, P < 0.05). Furthermore, LIPO displayed reduced incremental glucose oxidation (P < 0.01), increased clamp free fatty acids (P < 0.05) and attenuated insulin-mediated suppression of lipid oxidation (P < 0.05) compared with NONLIPO. In combined study groups, RLF correlated with hepatic insulin sensitivity (r = 0.69), incremental glucose disposal (r = 0.71) and incremental exogenous glucose storage (r = 0.40), all P < 0.01. Disposition index (i.e. first-phase insulin response to intravenous glucose multiplied by incremental glucose disposal) was reduced by 46% (P = 0.05) in LIPO compared with the combined groups of NONLIPO and NAÏVE, indicating an impaired adaptation of β-cell function to insulin resistance in LIPO.

Conclusion: Our data suggest that normoglycaemic lipodystrophic HIV-infected patients display impaired glucose and lipid metabolism in multiple pathways involving liver, muscle tissue and β-cell function.
The Taiwan National Health Insurance Program and Full Infant Immunization Coverage
Authors: Chen Chin-Shyan , Liu Tsai-Ching
Published: January 2005

Objectives. We compared hospital-born infants and well-baby care use associated with complete immunizations in Taiwan before and after institution of National Health Insurance (NHI).

Methods. We used logistic regression to analyze data from 1989 and 1996 National Maternal and Infant Health Surveys of 1398 and 3185 1-year-old infants, respectively.

Results. Infants born in hospitals were found to receive fewer immunizations than those born elsewhere before NHI but significantly more after NHI. Use of well-baby care correlates strongly and positively with the probability that a child will receive a full course of immunization after NHI.

Conclusions. The NHI policy of including hospitals as immunization providers facilitates access to immunization services for children born in those facilities. Through NHI provision of free well-baby care, health planners have stimulated the demand for immunization.
Attributable Risk of Injury Associated With Alcohol Use: Cross-National Data From the Emergency Room Collaborative Alcohol Analysis Project
Authors: Cherpitel Cheryl J. , Ye Yu , Bond Jason
Published: January 2005

Objectives. We sought to determine gender- and age-specific attributable risks of all-cause and violence-related injuries associated with alcohol use.

Methods. We used meta-analytic techniques to estimate attributable risks observed in emergency room studies conducted in 7 countries (n=17708).

Results. In the case of both alcohol consumption before the injury event and individual drinking patterns, pooled attributable risk effect sizes for all-cause injuries were significant but minimal (2% to 6%). Effect sizes for violence-related injuries were 43% for drinking before an injury event and 27% for individual drinking pattern. Risks were greater for men, but no age-specific differences were found.

Conclusions. This meta-analysis showed that attributable risk of injury is greater for drinking before the injury event than for drinking pattern; in addition, risks were more pronounced for violence-related injuries. Differences in risk were explained by variables related to sociocultural contexts.
Perception of Unmet Basic Needs as a Predictor of Mortality Among Community-Dwelling Older Adults
Authors: Blazer Dan G. , Sachs-Ericsson Natalie , Hybels Celia F.
Published: January 2005

Objectives. We sought to determine whether, among older adults (>65 years), a perception that their basic needs are not being met increased mortality risk and whether this risk varied by race/ethnicity.

Methods. We used Cox proportional hazards modeling to estimate the effect of perceived inadequacy in having one’s basic needs (adequacy of income, quality of housing, and neighborhood safety) met on 10-year mortality rates.

Results. After control for age, gender, race/ethnicity, marital status, education, income, and cognitive and functional status at baseline, perceived inadequacy in having one’s basic needs met was shown to be a significant predictor of mortality (P<.0001), but no significant differences by race/ethnicity were observed.

Conclusions. Perceived inadequacy in having one’s basic needs met predicted mortality during a 10-year follow-up among community-dwelling elderly persons.
Perceived Racial/Ethnic Harassment and Tobacco Use Among African American Young Adults
Authors: Bennett Gary G. , Wolin Kathleen Yaus , Robinson Elwood L. , Fowler Sherrye , Edwards Christopher L.
Published: January 2005

We examined the association between perceived racial/ethnic harassment and tobacco use in 2129 African American college students in North Carolina. Age-adjusted and multivariate analyses evaluated the effect of harassment on daily and less-than-daily tobacco use. Harassed participants were twice as likely to use tobacco daily (odds ratio = 2.01; 95% confidence interval=1.94, 2.08) compared with those with no reported harassment experiences. Experiences of racial/ethnic harassment may contribute to tobacco use behaviors among some African American young adults.
State Tobacco Control Spending and Youth Smoking
Authors: Tauras John A. , Chaloupka Frank J. , Farrelly Matthew C. , Giovino Gary A. , Wakefield Melanie , Johnston Lloyd D. , O’Malley Patrick M. , Kloska Deborah D. , Pechacek Terry F.
Published: January 2005

Objective. We examined the relationship between state-level tobacco control expenditures and youth smoking prevalence and cigarette consumption.

Methods. We estimated a 2-part model of cigarette demand using data from the 1991 through 2000 nationally representative surveys of 8th-, 10th-, and 12th-grade students as part of the Monitoring the Future project.

Results. We found that real per capita expenditures on tobacco control had a negative and significant impact on youth smoking prevalence and on the average number of cigarettes smoked by smokers.

Conclusions. Had states represented by the Monitoring the Future sample and the District of Columbia spent the minimum amount of money recommended by the Centers for Disease Control and Prevention, the prevalence of smoking among youths would have been between 3.3% and 13.5% lower than the rate we observed over this period.
The Influence of the Ionic Medium on the Behaviour of Sodium Glycocholate and Cholate Aqueous Solutions
Authors: Bottari Emilio , Buonfigli Alessio , Festa Maria Rosa
Published: January 2005

In the framework of research on the sodium bile salts, solutions of sodium cholate and glycocholate had been studied only at three ionic medium concentrations. In this paper, experiments in two other concentrations of ionic medium are carried out both to verify the behaviour dependence on the ionic medium and to apply the results of this paper to a future investigation on solutions containing contemporary sodium cholate and glycocholate. To this aim, solubility, protonation constants, lead (II) salts solubility products at 25 °C and in 0.300 and 0.750 mol dm‐3 N(CH3)4Cl were determined. The formed species in solutions containing lead (II) together with the selected bile salts and the behaviour of the sodium salts in micellar and premicellar solutions were investigated, too. The obtained results were compared with those obtained at the other ionic medium concentrations.