Growth hormone treatment in Turner''s syndrome: short and long-term effects on metabolic parameters

OBJECTIVE: The effect of GH administration on various metabolic parameters and on growth and bone age development was studied in patients with Turner's syndrome. DESIGN: Patients were treated with daily s.c. GH (20 IU/m2/week) and ethinyloestradiol p.o. (100 ng/kg/day) during the first year and with additional oxandrolone (0.125 mg/kg/day) during the second year. The responses of free fatty acids (FFA), urinary excretion of hydroxyproline (HP) and IGF-I were evaluated after short-term GH application. Glucose tolerance was investigated before any therapy, during treatment with GH and oestradiol and after adding oxandrolone, respectively. The course of growth, bone age and IGF-I levels was followed throughout the study. PATIENTS: Eleven patients with Turner's syndrome aged 12.6 +/- 1.9 years (mean +/- SD) were included. RESULTS: Free fatty acids increased significantly 4 hours after one s.c. injection of GH (0.7 +/- 0.2-1.1 +/- 0.3 mmol/l; mean +/- SD). Mean urinary hydroxyproline excretion remained unchanged after 6 weeks of GH therapy (337 +/- 206-299 +/- 145 mumol/m2/24 h), but there was a significant negative correlation between individual hydroxyproline values and the peak serum GH followed stimulation. IGF-I was in the prepubertal range and increased significantly after 3 days of GH injection (30.0 +/- 10.0-42.5 +/- 10.0 nmol/l). Growth velocity (in Turner's syndrome related SD) increased from 0.0 +/- 0.3 SD before treatment to 0.9 +/- 0.8 SD after the first year and to 3.4 +/- 1.3 SD during the second year of treatment. There was no undue acceleration of bone age. During long-term treatment, IGF-I increased significantly only when oxandrolone was added. Two patients had impaired glucose tolerance prior to GH therapy and three additional children developed impaired or abnormal glucose tolerance after GH therapy. Insulin concentrations increased significantly only after introduction of oxandrolone. CONCLUSIONS: Patients with Turner's syndrome who had lower basal IGF-I levels had significantly higher responses of IGF-I, free fatty acids and hydroxyproline (P less than 0.01 for all parameters) after short-term GH application. The data indicate adequate endocrine and metabolic responses in patients with Turner's syndrome which are the basis for growth promoting action. A considerable number of patients had impaired glucose tolerance during GH treatment.     

Association between anorexia nervosa and the hsKCa3 gene: a family-based and case control study.

Familial and twin studies have suggested that anorexia nervosa (AN) is a multifactorial disorder with a substantial genetic contribution. The hSKCa3 potassium channel gene, which contains polymorphic CAG repeats in the coding region and is involved in the regulation of neuronal activity, may be a candidate gene for AN because alleles with longer repeats have been found to be associated with mental disorders. Forty Israeli AN family trios were genotyped for the hSKCa3 CAG repeat polymorphism using the haplotype relative risk (HRR) method. The distribution of alleles transmitted to the patients was found to be significantly different from that of the non-transmitted parental alleles, with the longer alleles being over-represented in the patients (Wilcoxon rank test, P = 0.008). The transmission disequilibrium test (TDT) revealed that longer (>19) repeat alleles were preferentially transmitted to AN patients (McNemar's chi(2) = 10.31, P = 0.0013). These results were corroborated by comparing the distribution of alleles between patients and healthy controls (Mann-Whitney test, P = 0.005). Our study suggests that the longer repeat alleles of the hSKCa3 gene may contribute to the genetic susceptibility to AN.     

The negative effect of prolonged somatotrophic/insulin signaling on an adult bone marrow-residing population of pluripotent very small embryonic-like stem cells (VSELs)

It is well known that attenuated insulin/insulin-like growth factor signaling (IIS) has a positive effect on longevity in several animal species, including mice. Here, we demonstrate that a population of murine pluripotent very small embryonic-like stem cells (VSELs) that reside in bone marrow (BM) is protected from premature depletion during aging by intrinsic parental gene imprinting mechanisms and the level of circulating insulin-like growth factor-I (IGF-I). Accordingly, an increase in the circulating level of IGF-I, as seen in short-lived bovine growth hormone (bGH)-expressing transgenic mice, which age prematurely, as well as in wild-type animals injected for 2 months with bGH, leads to accelerated depletion of VSELs from bone marrow (BM). In contrast, long-living GHR-null or Ames dwarf mice, which have very low levels of circulating IGF-I, exhibit a significantly higher number of VSELs in BM than their littermates at the same age. However, the number of VSELs in these animals decreases after GH or IGF-I treatment. These changes in the level of plasma-circulating IGF-I corroborate with changes in the genomic imprinting status of crucial genes involved in IIS, such as Igf-2-H19, RasGRF1, and Ig2R. Thus, we propose that a chronic increase in IIS contributes to aging by premature depletion of pluripotent VSELs in adult tissues.     

Application of color-coded digital subtraction angiography in treatment of indirect carotid-cavernous fistulas: Initial experience

BackgroundParametric-colored digital subtraction angiography using Tmax is almost a routine angiographic imaging procedure, currently. The current feasibility study is aimed to using the imaging to monitor treatment effects while embolizing indirect carotid-cavernous fistulas (CCF).MethodsTen patients with CCFs receiving embolization and 40 patients with normal circulation time were recruited. Their color-coded DSAs were used to define the Tmax of selected intravascular ROIs. A total of 19 ROIs in the internal carotid artery (ICA) (cervical segment of ICA in AP view (I0), cavernous segment of ICA in AP view (I1), supraclinoid segment of ICA in AP view (I2) and cervical segment of ICA in lateral view (I0′), cavernous portion of ICA in lateral view (IA), supraclinoid portion of ICA in lateral view (IB)), ACA (first segment of anterior cerebral artery, second segment of anterior cerebral artery (A1, A2)), middle cerebral vein (MCA) first segment of MCA ((M1), second segment of MCA (M2)), frontal vein (FV), parietal vein (PV), superior sagittal sinus (SSS), sigmoid sinus (SS), internal jugular vein (JV), fistula, superior ophthalmic vein (SOV), inferior petrosal vein (IPS), and MCV were selected. Relative Tmax was defined as the Tmax at selected ROIs minus Tmax at I0 or I0′. An intergroup comparison between the normal and treatment groups and pre- and post-treatment comparison of the peri-therapeutic rTmax for the treatment group were performed.ResultsrTmax's for the normal group were as follows: Anterior-posterior view: I1: 0.16, I2: 0.32, A1: 0.31, M1: 0.35, SSS: 6.16, SS: 6.56, and MCV: 3.86 seconds. Lateral view: IA: 0.05, IB: 0.20, A2: 0.53, M2: 0.95, FV: 4.84, PV: 5.12, IPS: 4.62, JV: 6.81, and MCV: 3.86 seconds. Before embolization, rTmax of the IPS, SS, and JV for the treatment group were shortened (p < 0.05). No rTmaxs for any arterial ROIs in the fistula group were significantly different. After embolization, the rTmaxs for all venous ROIs returned to normal except for two which were partially obliterated.ConclusionThis postprocessing method does not require extra radiation exposure and contrast media. It facilitates real-time hemodyamic monitoring and may help determining the endpoint of embolization, which increases patient safety.     

Anterior chamber depth in relation to refractive status measured with the Orbscan II Topography System

PURPOSE: To evaluate the anterior chamber depth (ACD) according to refractive status, assess the reliability of repeated ACD measurements using the Orbscan II Topography System (Bausch and Lomb), compare Orbscan II and IOLMaster (Carl Zeiss Meditec AG) ACD measurements, and investigate the correlation between refraction, axial length (AL), and ACD. SETTING: Department of Ophthalmology, Ruprecht-Karls-University of Heidelberg, Heidelberg, Germany. METHODS: In this clinical study, 60 patients with a mean age of 43.8 years +/- 18.74 (SD) were assigned to 1 of 3 groups of 20 patients each according to refraction: emmetropia group; hyperopia group (mean +4.84 +/- 1.60 diopters [D]); myopia group (mean -9.64 +/- 3.79 D). Using the Orbscan II system, 3 consecutive ACD measurements (apex and 3.0 mm zone) were performed. The IOLMaster was used to measure ACD and AL. RESULTS: The mean ACD (from epithelium) with the Orbscan II and IOLMaster, respectively, was 3.61 +/- 0.24 mm and 3.61 +/- 0.24 mm in the emmetropia group, 3.03 +/- 0.21 mm and 3.06 +/- 0.24 mm in the hyperopia group, and 3.72 +/- 0.26 mm and 3.73 +/- 0.23 mm in the myopia group. The standard deviation of the repeated Orbscan II measurements increased from 13 to 15 microm from the apex to the 3.0 mm zone. The difference between the apex and 3.0 mm zone of the cornea in all groups ranged from 0.1 to 0.12 mm. The mean AL was 23.52 +/- 0.82 mm in the emmetropia group, 22.14 +/- 0.64 mm in the hyperopia group, and 27.44 +/- 1.67 mm in the myopia group. There was a significant correlation between the spherical equivalent and AL (r = 0.94). CONCLUSIONS: Significantly lower ACD values were found in the hyperopia group than in the other 2 groups. There was no difference in ACD between the emmetropia and myopia groups even though the AL in the myopia group was 4.0 mm longer. No statistical difference in ACD measurements was found between the Orbscan II and IOLMaster.     

Extracellular matrix components in breast carcinomas

A malignant process interferes with the normal 'programme' of extracellular matrix biosynthesis and can modify extensively the structure and composition of the matrix. This effect appears to be attributable to several processes such as direct production of some selected matrix macromolecules by malignant cells or indirectly by the production of factors by malignant cells interfering with the regulation of normal matrix production. Other possibilities may also exist, such as the direct action of an environmental carcinogen on otherwise normal mesenchymal cells. The result is a more or less profound modification of tissue structure and composition with possible feedback effects on the malignant process. Some examples will be discussed such as elastin production by some tumours as well as the biosynthesis of some other selected matrix macromolecules as tenascin and osteopontin by breast tumours. Although the detailed mechanisms of these specific matrix productions is not yet completely elucidated, the rapidly increasing knowledge on the regulation of specific matrix production process and deranged matrix production might represent a new area of crosstalk between cancer research and matrix biology.     

Responses of diencephalic neurons to sensory stimulation in the goldfish, Carassius auratus

We studied the responses to sensory stimulation in two diencephalic areas, the central posterior nucleus of the dorsal thalamus (CP) and the anterior tuberal nucleus of the hypothalamus (TA). In both the CP and the TA, units sensitive to acoustic (500-Hz sound), hydrodynamic (25-Hz dipole stimulus), and visual (640-nm light flash) stimuli were found. In the CP, most units were unimodal and responded exclusively to visual stimulation. In contrast, in the TA, most units responded to more than one modality. The data suggest that the CP is primarily involved in the unimodal processing of sensory information, whereas the TA may be involved in multisensory integration.