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PubMed1997

Testing the hypothalamic-pituitary-adrenal axis in survivors of childhood brain and skull-based tumors.

The objective of this study was to determine whether a low dose of ACTH (0.2 microg/kg) improves the sensitivity of ACTH testing in detecting hypothalamic-pituitary-adrenal (HPA) axis abnormalities in survivors of childhood brain and skull-based tumors. Twenty-two children who had undergone treatment for brain or skull-based tumors were enrolled in a prospective study to extensively evaluate the HPA axis. Five tests of the adrenal axis were evaluated in each patient, including determination of basal serum cortisol, a standard ACTH test (250-microg i.v. bolus), a low dose ACTH test (0.2 microg/kg i.v. bolus), an insulin tolerance test, and a single dose metyrapone test. Cortisol responses to both ACTH tests were nearly identical. Two patients (9%) failed the low dose ACTH test, whereas three (14%) failed the standard ACTH test; five of the children (23%) failed the insulin tolerance test, and five (23%) had abnormal responses to metyrapone. One child who initially passed the metyrapone test failed the test 19 months later after becoming symptomatic. All children with abnormal metyrapone test results had low levels of basal cortisol secretion. In this study, the low dose ACTH test did not improve the sensitivity of ACTH testing for evaluation of the HPA axis. We conclude that a single morning basal cortisol level is a good screen for testing the HPA axis in children. We recommend confirming HPA axis dysfunction with the single dose metyrapone test, although this test also has limitations.

Adrenocorticotropic Hormone↗

PubMed1997

Body composition and physical fitness are major determinants of the growth hormone-insulin-like growth factor axis aberrations in adult Turner's syndrome, with important modulations by treatment with 17 beta-estradiol.

The objectives of this study were to 1) study the GH-insulin-like growth factor (IGF) axis in adult untreated Turner's syndrome compared to that in age-matched controls; 2) examine the effects of sex hormone substitution on this axis, 3) study the effects of route of administration of 17 beta-estradiol on the measured variables, and 4) examine the effects of sex steroids on hepatic function in Turner patients. Twenty-seven patients with Turner's syndrome were evaluated before and during sex hormone replacement, and an age-matched control group (n = 24) was evaluated once. Main outcome variables were GH and other measures of the GH-IGF axis, body composition, maximal oxygen uptake, sex hormone-binding globulin, and hepatic enzymes and proteins. The integrated 24-h GH concentration (IC-GH; micrograms per L/24 h) was reduced in women with Turner's syndrome (T) compared to controls [C; mean +/- SD, 18.3 +/- 12.0 (T) vs. 37.2 +/- 29.7 (C); P = 0.007]. However, multiple regression revealed that fat-free mass (FFM) and maximal oxygen uptake were significant explanatory variables (joint r = 0.77; P < 0.0005), accounting for 60% of the variance in the 24-h IC-GH. This association was also present in controls. After adjustment for these two variables, any difference in GH concentration between Turner patients and controls disappeared. Serum IGF-I and IGF-II were identical in Turner patients and controls despite the difference in 24-h IC-GH. The level of GH-binding protein (GHBP; nanomoles per L) was higher in Turner women [1.87 +/- 0.72 (T) vs. 1.22 +/- 0.33 (C); P = 0.0005]; after adjustment for FFM, the difference in GHBP levels disappeared between Turner patients and controls. During sex hormone treatment a significant increase was seen in the 24-h IC-GH (P = 0.02), FFM (percentage of weight; P < 0.0005) and maximal oxygen uptake (milliliters of O2 per kg/min; P = 0.02). Serum IGF-I was unchanged, whereas serum IGF-II (micrograms per L) decreased significantly [Turner, basal (TB), vs. Turner, treatment (TT), 860 +/- 135 vs. 823 +/- 150; P = 0.04]. Alanine aminotransferase (units per L), gamma-glutamyl transferase (units per L), and alkaline phosphatase (units per L) were significantly elevated during the basal study period, and all decreased during treatment [alanine amino-transferase, 55 +/- 55 (TB) vs. 30 +/- 20 (TT; P = 0.006); gamma-glutamyl transferase, 92 +/- 98 (TB) vs. 43 +/- 65 (TT; P = 0.003); alkaline phosphatase, 211 +/- 113 (TB) vs. 175 +/- 54 (TT); P = 0.06]. The route of administration of 17 beta-estradiol did not affect its actions. In conclusion, we found the GH-IGF axis in Turner's syndrome to be normal, with body composition and physical fitness exerting the same modifying effects on this axis as seen in the normal population. Sex hormone replacement in Turner's syndrome is associated with normalizing effects on the GH-IGF axis, body composition, physical fitness, and hepatic function. The lowering of hepatic enzymes is a surprising and hitherto undiscovered action of sex steroids. Finally, the route of administration of 17 beta-estradiol is of minor importance in Turner's syndrome.

Adult↗

PubMed2003

LvTbx2/3: a T-box family transcription factor involved in formation of the oral/aboral axis of the sea urchin embryo.

T-box family transcription factors have been identified in many organisms and are frequently associated with patterning events during embryonic development. With an interest in the molecular basis of patterning in the sea urchin embryo, we identified several members of the T-box family in Lytechinus variegatus. Here, we report the cloning and characterization of an ortholog of the Tbx2/3 subfamily, LvTbx2/3. To characterize the spatial distribution of LvTbx2/3 protein throughout sea urchin embryogenesis, a polyclonal antiserum was generated. Nuclear localization of LvTbx2/3 initiated at the mesenchyme blastula stage and protein was present into the pluteus stage. Localization was asymmetric throughout this period and costaining with marker genes indicated that asymmetry was about the oral/aboral (O/A) axis. Asymmetric distribution of LvTbx2/3 was observed in the aboral territories of all three germ layers. In the skeletogenic mesoderm lineage, LvTbx2/3 expression was dynamic because expression appeared initially in all skeletogenic mesenchyme cells (PMCs) but, subsequently, became refined solely to the aboral ones during skeletogenesis. To determine if the aboral expression of LvTbx2/3 is linked between germ layers, and to place LvTbx2/3 in the sequence of events that specifies the O/A axis, the effects of a series of perturbations to O/A polarity on LvTbx2/3 expression in each germ layer were examined. Preventing the nuclear localization of beta-catenin, pharmacological disruption of the O/A axis with NiCl(2), overexpression of BMP2/4 and disruption of the extracellular matrix all blocked LvTbx2/3 expression in all germ layers. This indicates that expression of LvTbx2/3 in the aboral territories of each germ layer is a common aspect of O/A specification, downstream of the molecular events that specify the axis. Furthermore, blocking the nuclear localization of beta-catenin, overexpression of BMP2/4 and disruption of the extracellular matrix also prevented the oral (stomodael) expression of LvBrachyury (LvBrac) protein, indicating that the O/A axis is established by a complex series of events. Last, the function of LvTbx2/3 in the formation of the O/A axis was characterized by examining the phenotypic consequences of ectopic expression of LvTbx2/3 mRNA on embryonic development and the expression of marker genes that identify specific germ layers and tissues. Ectopic expression of LvTbx2/3 produced profound morphogenetic defects in derivatives of each germ layer with no apparent loss in specification events in those tissues. This indicates that LvTbx2/3 functions as a regulator of morphogenetic movements in the aboral compartments of the ectoderm, endoderm and mesoderm.

Amino Acid Sequence↗

PubMed1992

Xenopus maternal RNAs from a dorsal animal blastomere induce a secondary axis in host embryos.

The initial steps of dorsal axis formation are controlled by localized maternal determinants in Drosophila, and a similar process has been proposed in Xenopus. The present study demonstrates that there are axis-inducing RNA molecules located in a specific dorsal midline, animal blastomere (D1.1) of the 16-cell-stage embryo. This blastomere, although in the animal hemisphere at cleavage stages, populates most of the dorsal lip of the blastopore, the region of Spemann's organizer, during gastrulation, and is the major progenitor for dorsal mesodermal tissues. Cytosol from this blastomere causes ventral cells to take a more dorsal fate. RNA from this blastomere induces a secondary axis when injected into ventral blastomeres and restores the dorsal axis in UV-irradiated embryos. In Xenopus, activin beta B, goosecoid and Xwnt-8 RNAs can ectopically induce a dorsal axis; however, none is a maternal transcript. Therefore, the D1.1 blastomere probably contains dorsal determinant(s) that are either maternal members of these gene families, or other presently unknown molecule(s). Regardless of the identity of the determinant(s), this study presents the first indication that Xenopus maternal RNAs in the dorsal animal hemisphere are able to organize the dorsal axis.

Animals↗

PubMed1993

Mechanisms of dorsal-ventral axis determination in Drosophila embryos revealed by cytoplasmic transplantations.

The establishment of the dorsal-ventral pattern in Drosophila embryos depends on a signal transduction process: a putative extracellular ligand released into the perivitelline space surrounding the embryo binds to the Toll receptor. Toll activation triggers the formation of the nuclear gradient of dorsal protein, the morphogen of the dorsal-ventral axis. Here, I analyse the dorsal protein distribution and the expression of zygotic dorsal-ventral genes in Toll- embryos that have been injected with wild-type cytoplasm under a variety of different injection conditions. Injections into two positions within a single embryo lead to the formation of two dorsal-ventral patterns in one embryo, allowing the analysis of interactions between pattern-forming processes. The results of single and double injections suggest that the spatial information for the embryonic dorsal-ventral axis is largely derived from spatial cues present in the extraembryonic compartment, which restrict the release of the putative Toll ligand. They argue against a Toll-dependent pattern-formation process employing local self-enhancement and lateral inhibition to enhance a weak initial asymmetry. The putative Toll ligand appears to originate from a ventrally restricted zone which extends along the entire anterior-posterior axis. Ligand diffusion or its graded release are required to determine the slope of the nuclear dorsal protein gradient. Both the Toll receptor and the putative ligand of Toll are in excess in wild-type embryos. Since spatial information for the embryonic dorsal-ventral axis is already present in the vitelline membrane or the perivitelline space, it is most likely generated during oogenesis. Oogenic pattern formation is also responsible for the perpendicular orientation the dorsal-ventral axis maintains with respect to the anterior-posterior axis.

Animals↗

PubMed1997

Multiple signaling events specify ectoderm and pattern the oral-aboral axis in the sea urchin embryo.

In the sea urchin embryo, the animal-vegetal axis is established during oogenesis and the oral-aboral axis is specified sometime after fertilization. The mechanisms by which either of these axes are specified and patterned during embryogenesis are poorly understood. Here, we investigated the role of cellular interactions in the specification of the ectoderm territories and polarization of the ectoderm along the oral-aboral axis. Isolated animal halves (mesomeres), which are fated to give rise to oral and aboral ectoderm, developed into polarized embryoids that expressed an oral ectoderm-specific marker uniformly. These embryoids also produced neuron-like cells and serotonergic neurons, suggesting that mesomeres are autonomously specified as oral ectoderm. Mesomere-derived embryoids did not express any aboral ectoderm-specific markers, although we previously showed that aboral ectoderm-specific genes can be induced by 25 mM lithium chloride, which also induced endoderm formation (Wikramanayake, A. H., Brandhorst, B. P. and Klein, W. H.(1995). Development 121, 1497-1505). To ascertain if endoderm formation is a prerequisite for induction of aboral ectoderm by lithium and for normal ectoderm patterning in animal halves, we modulated the lithium treatment to ensure that no endoderm formed. Remarkably, treating animal halves with 10 mM LiCl at approximately 7 hours postfertilization resulted in embryoids that displayed oral-aboral axis patterning in the absence of endoderm. Application of 25 mM LiCl to animal halves at approximately 16 hours postfertilization, which also did not induce endoderm, resulted in polarized expression of the aboral ectoderm-specific LpS1 protein, but global expression of the Ecto V antigen and no induction of the stomodeum or ciliary band. These results suggest that at least two signals, a positive inductive signal to specify the aboral ectoderm and a negative suppressive signal to inactivate oral ectoderm-specific genes in the prospective aboral ectoderm territory, are needed for correct spatial expression of oral and aboral ectoderm-specific genes. Transmission of both these signals may be prerequisite for induction of secondary ectodermal structures such as the ciliary band and stomodeum. Thus, differentiation of ectoderm and polarization of the oral-aboral axis in Lytechinus pictus depends on cellular interactions with vegetal blastomeres as well as interactions along the oral-aboral axis.

Animals↗

PubMed2004

Swimming of larval zebrafish: fin-axis coordination and implications for function and neural control.

Adult actinopterygian fishes typically perform steady forward swimming using either their pectoral fins or their body axis as the primary propulsor. In most species, when axial undulation is employed for swimming, the pectoral fins are tucked (i.e. adducted) against the body; conversely, when pectoral fins are beating, the body axis is held straight. In contrast to adults, larval fishes can combine their pectoral fin and body-axis movements during locomotion; however, little is known about how these locomotor modes are coordinated. With this study we provide a detailed analysis of the coordinated fin and axial movements during slow and fast swimming by examining forward locomotion in larval zebrafish (Danio rerio L.). In addition, we describe the musculature that powers pectoral fin movement in larval zebrafish and discuss its functional implications. As larvae, zebrafish alternate their pectoral fins during slow swimming (0.011+/-0.001 mm ms(-1)) in conjunction with axial undulations of the same frequency (18-28 Hz). During fast swimming (0.109+/-0.030 mm ms(-1); 36-67 Hz), the fins are tucked against the body and propulsion occurs by axial undulation alone. We show that during swimming, larval fishes can use a similar limb-axis coordination pattern to that of walking and running salamanders. We suggest that the fin-axis coordination observed in larval zebrafish may be attributed to a primitive neural circuit and that early terrestrial vertebrates may have gained the ability to coordinate limbs and lateral bending by retaining a larval central pattern generator for limb-axis coordination in the adult life history stage.

Animals↗

PubMed2000

Axially symmetric on-axis flat-top beam.

A synthesis method for arbitrary on-axis intensity distributions from axially symmetric fields is developed in the paraxial approximation. As an important consequence, a new pseudo-nondiffracting beam, the axially symmetric on-axis flat-top beam (AFTB), is given by an integral transform form. This AFTB is completely determined by three simple parameters: the central spatial frequency S(c), the on-axis flat-top length L, and the on-axis central position z(c). When LS(c) >> 1, this AFTB can give a nearly flat-top intensity distribution on the propagation axis. In particular, this AFTB approaches the nondiffracting zero-order Bessel J0 beam when L--> infinity. It is revealed that the superposition of multiple AFTB fields can give multiple on-axis flat-top intensity regions when some appropriate conditions are satisfied.

Models, Theoretical↗

PubMed1998

Insulin-like growth factor axis parameters in sick hospitalized neonates.

The circulating insulin-like growth factor (IGF) axis consists of the IGF peptides, the IGF binding proteins (IGFBPs), and the IGFBP proteases. Little is known about the IGF axis in newborns, its possible perturbations in sick neonates, and the effect of nutrition on the IGF axis of such patients. The aims of this study were to define IGF axis parameters in the sera of hospitalized newborns and to correlate these parameters with the nutritional status of the infants. Serum samples obtained from twenty four hospitalized infants in the intensive care nursery were analyzed for IGF axis parameters. Insulin-like growth factor-I and IGFBP-3 by RIA were mostly within the normal range for age and were only minimally affected by gestational age. In comparison, 8 newborn infants with congenital growth hormone deficiency had IGFBP-3 levels which were below the normal range. Two infants on ECMO had elevated levels of IGFBP-3 by RIA. Western ligand blotting (WLB) demonstrated that IGFBP-2 was the major binding protein in infant serum and the 44 kDa IGFBP-3 in critically ill neonatal serum was approximately 10% of adult serum levels. IGFBP-3 by RIA in neonatal serum averaged approximately 25% of adult serum levels. Compatible with this discrepancy, a number of sick neonates had detectable levels of IGFBP-3 proteolytic activity and higher levels of IGFBP-3 fragments compared to normal adult serum in both the protease assays and Western immunoblotting. There was no correlation between any IGF axis parameter and nutritional status. In summary, sick hospitalized neonates display mostly normal IGF and IGFBP-3 levels, which are not correlated to nutritional intake. Thus serum IGFBP-3 levels maintain their diagnostic utility for growth hormone deficiency in critically ill neonates.

Critical Illness↗

PubMed2002

Development of the hypothalamic-pituitary-adrenal axis in the fetus and preterm infant.

The development of the hypothalamic-pituitary-adrenal (HPA) axis in the human fetus is a complex process. The feto-placental unit may be responsible for important maturational processes in vital organ systems in the fetus. A late gestational cortisol surge may be important in fetal maturation, particularly maturation of the lungs. Several striking differences exist between the function of the HPA axis in the fetus and in adults, such as a relative deficiency of 3beta-hydroxysteroid dehydrogenase in the fetal adrenal cortex. With the transition from intrauterine to extra-uterine life several changes occur in the function of the HPA axis. In infants born before term, the function of the HPA axis may still be immature at both the central and adrenal level. This immaturity of the HPA axis may be important in the development of neonatal morbidity. The present review describes the development of the HPA axis in the fetus and in preterm infants and discusses the possible role of HPA immaturity in the development of neonatal morbidity.

Adrenal Glands↗

PubMed1997

Adolescent personality disorder symptoms mediate the relationship between perceived parental behavior and Axis I symptomatology.

A study was conducted to investigate whether adolescent personality disorder symptoms mediate the relationship between perceived parental behavior and Axis I psychiatric symptomatology. The Parental Behavior Form, Personality Diagnostic Questionnaire-Revised, and Revised Hopkins Symptom Checklist (SCL-90-R) were administered to 187 first-year undergraduate students during their first week of college enrollment. One hundred fifty seven participants were readministered the SCL-90-R two months later. Results of correlational and hierarchical multiple regression analyses indicated that: (1) Adolescents' perceptions of parental acceptance/nurturance and harsh, controlling parental behavior were associated with baseline personality disorder symptom levels. (2) Perceived harsh parental control predicted both baseline and follow-up Axis I symptomatology. (3) In turn, baseline personality disorder symptoms were associated with Axis I symptom levels, both at baseline and at follow-up assessment after baseline Axis symptoms were accounted for. (4) Perceived parental behavior did not predict baseline or subsequent Axis I symptomatology after personality disorder symptom levels were accounted for. The present findings thus indicate that personality disorder symptoms completely mediated the relationship between adolescent perceptions of harsh, controlling parental behavior and Axis I psychiatric symptomatology.

Adolescent↗

PubMed2006

Hypothalamic-pituitary-adrenal axis activity in adults who were prenatally exposed to the Dutch famine.

OBJECTIVE: The hypothalamic-pituitary-adrenal (HPA) axis has been proposed to be susceptible to fetal programming, the process by which an adverse fetal environment elicits permanent physiological and metabolic alterations predisposing to disease in later life. It is hypothesized that fetal exposure to poor circumstances alters the set point of the HPA axis, leading to increased HPA axis activity and subsequent increased cortisol concentrations. In this study, we tested the hypothesis that prenatal exposure to famine during different periods of gestation is associated with increased activity of the HPA axis. DESIGN AND METHODS: We assessed plasma cortisol concentrations after a dexamethasone suppression and an ACTH1-24 -stimulation test in a group of 98 men and women randomly sampled from the Dutch famine birth cohort. Cohort members were born as term singletons around the 1944-1945 Dutch famine. RESULTS: Cortisol profiles after dexamethasone suppression and ACTH1-24 stimulation were similar for participants exposed to famine during late, mid- or early gestation (P = 0.78). Cortisol concentrations after dexamethasone suppression test did not differ between those exposed and those unexposed to famine in utero (mean difference -2% (95% confidence interval (CI) -27 to 23)). Neither peak cortisol concentration (20 nmol/l (95% CI -27 to 66)), cortisol increment (-5 nmol/l (95% CI -56 to 47)) or cortisol area under the curve post-ACTH1-24 injection (4% (95% CI -4 to 12)) differed between exposed and unexposed participants. CONCLUSIONS: Prenatal famine exposure does not seem to affect HPA axis activity at adult age, at least not at the adrenal level. This does not exclude altered HPA axis activity at the levels of the hippocampus and hypothalamus.

Adult↗

PubMed1986

Exercise-induced QRS axis shift and its clinical significance.

Exercise tests occasionally induce a QRS axis shift. Reviewing single Master's two-step test electrocardiograms of 1810 patients, we examined the incidence of the QRS axis shift and the relations of the QRS axis shifts to ischemic heart disease. The QRS axis shift was 30 degrees or more to the right in 38 (2.1%), 15 to 29 degrees to the right in 304 (16.8%), less than 15 degrees to the right or to the left in 1375 (75.9%), 15 to 29 degrees to the left in 81 (4.5%), and 30 degrees or more to the left in 12 patients (0.7%). The frequency of positive Master's tests and clinical ischemic heart disease were both significantly greater in the patients with QRS axis shifts of 30 degrees or more to the right (15.8% and 26.3%, respectively) and the patients with those of 30 degrees or more to the left (33.3% and 50.0%, respectively) than in the patients with shifts less than 15 degrees (6.5% and 8.5%, respectively). These results indicate that the exercise-induced QRS axis shift is a useful clue for the diagnosis of ischemic heart disease.

Adolescent↗

PubMed1997

Food and the circadian activity of the hypothalamic-pituitary-adrenal axis.

Temporal organization is an important feature of biological systems and its main function is to facilitate adaptation of the organism to the environment. The daily variation of biological variables arises from an internal time-keeping system. The major action of the environment is to synchronize the internal clock to a period of exactly 24 h. The light-dark cycle, food ingestion, barometric pressure, acoustic stimuli, scents and social cues have been mentioned as synchronizers or "zeitgebers". The circadian rhythmicity of plasma corticosteroids has been well characterized in man and in rats and evidence has been accumulated showing daily rhythmicity at every level of the hypothalamic-pituitary-adrenal (HPA) axis. Studies of restricted feeding in rats are of considerable importance because they reveal feeding as a major synchronizer of rhythms in HPA axis activity. The daily variation of the HPA axis stress response appears to be closely related to food intake as well as to basal activity. In humans, the association of feeding and HPA axis activity has been studied under physiological and pathological conditions such as anorexia nervosa, bulimia, malnutrition, obesity, diabetes mellitus and Cushing's syndrome. Complex neuroanatomical pathways and neurochemical circuitry are involved in feeding-associated HPA axis modulation. In the present review we focus on the interaction among HPA axis rhythmicity, food ingestion, and different nutritional and endocrine states.

Animals↗

PubMed2006

Differential responses of the growth hormone axis in two rat models of streptozotocin-induced insulinopenic diabetes.

The impact of streptozotocin (STZ)-induced, insulinopenic diabetes on the GH axis of rats and mice differs from study to study, where this variation may be related to the induction scheme, severity of the diabetes and/or the genetic background of the animal model used. In order to begin differentiate between these possibilities, we compared the effects of two different STZ induction schemes on the GH axis of male Sprague-Dawley rats: (1) a single high-dose injection of STZ (HI STZ, 80 mg/kg, i.p.), which results in rapid chemical destruction of the pancreatic beta-cells, and (2) multiple low-dose injections of STZ (LO STZ, 20 mg/kg for 5 consecutive days, i.p.), which results in a gradual, autoimmune destruction of beta-cells. STZ-treated animals were killed after 3 weeks of hyperglycemia (>400 mg/dl), and in both paradigms circulating insulin levels were reduced to <40% of vehicle-treated controls. HI STZ-treated rats lost weight, while body weights of LO STZ-treated animals gradually increased over time, similar to vehicle-treated controls. As previously reported, HI STZ resulted in a decrease in circulating GH and IGF-I levels which was associated with a rise in hypothalamic neuropeptide Y (NPY) mRNA (355% of vehicle-treated controls) and a fall in GH-releasing hormone (GHRH) mRNA (45% of vehicle-treated controls) levels. Changes in hypothalamic neuropeptide expression were reflected by an increase in immunoreactive NPY within the arcuate and paraventricular nuclei and a decrease in GHRH immunoreactivity in the arcuate nucleus, as assessed by immunohistochemistry. Consistent with the decline in circulating GH and hypothalamic GHRH, pituitary GH mRNA levels of HI STZ-treated rats were 58% of controls. However, pituitary receptor mRNA levels for GHRH and ghrelin increased and those for somatostatin (sst2, sst3 and sst5) decreased following HI STZ treatment. The impact of LO STZ treatment on the GH axis differed from that observed following HI STZ treatment, despite comparable changes in circulating glucose and insulin. Specifically, LO STZ treatment did suppress circulating IGF-I levels to the same extent as HI STZ treatment; however, the impact on hypothalamic NPY mRNA levels was less dramatic (158% of vehicle-treated controls) where NPY immunoreactivity was increased only within the paraventricular nucleus. Also, there were no changes in circulating GH, hypothalamic GHRH or pituitary receptor expression following LO STZ treatment, with the exception that pituitary sst3 mRNA levels were suppressed compared with vehicle-treated controls. Taken together these results clearly demonstrate that insulinopenia, hyperglycemia and reduced circulating IGF-I levels are not the primary mediators of hypothalamic and pituitary changes in the GH axis of rats following HI STZ treatment. Changes in the GH axis of HI STZ-treated rats were accompanied by weight loss, and these changes are strikingly similar to those observed in the fasted rat, which suggests that factors associated with the catabolic state are critical in modifying the GH axis following STZ-induced diabetes.

Animals↗

PubMed2002

Prevalence of neural axis abnormalities in patients with infantile idiopathic scoliosis.

BACKGROUND: Although reports in the literature have demonstrated an approximately 20% prevalence of neural axis abnormalities in patients with juvenile idiopathic scoliosis who have a curve of >20 degrees, the prevalence of neural axis abnormalities in patients with infantile idiopathic scoliosis is not well documented. In two previous studies involving a total of only ten patients with infantile idiopathic scoliosis, five patients were noted to have a neural axis abnormality on magnetic resonance images. METHODS: The records of forty-six consecutive patients who were seen between 1992 and 2000 at three spinal deformity clinics were retrospectively reviewed. The inclusion criteria included presumed idiopathic scoliosis at the time of presentation, an age of three years or less, a curve magnitude of > or = 20 degrees, normal neurological findings, no associated syndromes, and no congenital abnormalities. All patients were evaluated with a total spine magnetic resonance imaging protocol for examination of neural axis abnormalities from the skull to the coccyx. RESULTS: Ten (21.7%) of the forty-six patients were found to have a neural axis abnormality on magnetic resonance imaging. This group included five patients with an Arnold-Chiari malformation and an associated cervicothoracic syrinx, three with syringomyelia, one with a low-lying conus, and one with a brainstem tumor. Eight of these ten patients needed neurosurgical intervention for treatment of the abnormality. CONCLUSIONS: The 21.7% prevalence of neural axis abnormalities in this group of patients with infantile idiopathic scoliosis was found to be almost identical to that reported in the literature on patients with juvenile idiopathic scoliosis. Because of the high prevalence of abnormalities and the fact that eight of the ten patients with abnormal findings on magnetic resonance images required neurosurgical intervention, a total spine magnetic resonance imaging evaluation at the time of presentation is recommended for all patients with infantile idiopathic scoliosis who have a curve measuring > or = 20 degrees.

Child, Preschool↗

PubMed2005

Effect of amlodipine and lacidipine on left ventricular diastolic and long axis functions in arterial hypertension and stable angina pectoris.

OBJECTIVE: Impaired left ventricular (LV) diastolic and long axis functions are common in arterial hypertension and stable angina pectoris patients despite normal LV ejection fraction. Data concerning the effect of calcium channel blockers (CCB) on the LV long axis function in this context are lacking. METHODS AND RESULTS: Fifty-nine hypertensive patients with associated coronary artery disease (stable angina pectoris) and isolated diastolic dysfunction were randomized to receive amlodipine (30 patients) or lacidipine (29 patients) for 4 weeks. Clinical investigation, exercise testing, echocardiography were performed before and after the active treatment period. LV diastolic function was analysed from transmitral flow using Doppler echocardiography. Mitral annulus motion was investigated for LV long axis function analysis using 2-D guided M-mode echocardiography (amplitudes of motion) and pulsed wave tissue Doppler (velocities). Amlodipine and lacidipine affected LV diastolic and long axis functions differently: during treatment with amlodipine isovolumic relaxation time (IVRT) and deceleration time of LV early filling (DT) decreased (IVRT--from 93 +/- 19 ms to 79 +/- 15 ms, DT--from 206 +/- 36 ms to 188 +/- 27 ms; p < 0.05), early diastolic velocity of mitral annulus motion (E') increased (from 10.0 +/- 1.9 cm/s to 10.8 +/- 1.8 cm/s after treatment; p < 0.05). Lacidipine did not significantly change these parameters (IVRT-- 88 +/- 15 ms before, 87 +/- 13 ms after treatment, DT--214 +/- 34 ms and 218 +/- 42 ms, E'-- 10.4 +/- 1.5 cm/s and 10.6 +/- 1.5 cm/s, respectively). More favourable effects of CCB on LV long axis function was found in patients with post-systolic shortening. CONCLUSIONS: Amlodipine can improve diastolic and long axis functions of the left ventricle in patients with arterial hypertension and stable angina pectoris.

Aged↗

PubMed1995

Demography of DSM-III borderline personality disorder (PD): a comparison with Axis II PDs, affective illness and schizophrenia convergent and discriminant validation.

Demographic characteristics of borderline personality disorder (PD) defined according to DSM-III criteria were compared with those found for schizophrenia, affective illness, and other Axis II PDs. Borderline PD, unlike affective illness and most other Axis II PDs, usually occurs before the age of 30. By contrast to antisocial PD and schizophrenia, borderline PD usually occurs after the age of 25. For borderline PD (N = 280) average age was significantly more homogeneous compared with affective illness (N = 157) and Axis II PDs (N = 71) across 9 studies. By contrast, variability for 63 predominantly male schizophrenics in 3 studies was significantly less, reflecting the younger age at admission compared with borderline PD (N = 84). According to predictions based upon an age-of-risk hypothesis (Dahl, 1985) for 106 borderline PD patients, a significantly lower percentage were > or = 40 years of age than diagnostic controls (N = 181) predominantly with DSM-III affective illness. Borderline PD is predominantly diagnosed in females either single or who have been divorced compared with Axis II PDs and affective illness, to a lesser extent. Unlike antisocial PD, as well as schizophrenia, the preponderance of male and single/divorced patients usually occur significantly less than for borderline PD. Borderline PD usually occur significantly less than Axis II PDs, affective illness and schizophrenia and ethnic minorities, particularly Afro-Americans. These differences in ethnic/racial distribution are explained in terms of two hypotheses. From the perspective of demographic variables, borderline PD closely converges with neither (a) schizophrenia, (b) antisocial PC, (c) other Axis II PDs, nor (d) affective illness. Evidence for discriminant and convergent validation of these data is provided by (a) cluster analyses and intersample pairwise contrasts, as well as comparisons with (b) clinical samples selected on the basis of DSM-III-R and criteria of the (c) Diagnostic Interview for Borderline Patients, (d) a longitudinal case registry study conducted in Denmark, and (e) prospective surveys conducted among (i) North Carolina community residents and (ii) first degree (nonpatients) relatives of psychiatric patients in Iowa.

Adult↗