Growth hormone deficiency during young adulthood and the benefits of growth hormone replacement

Until quite recently, the management of children with growth hormone deficiency (GHD) had focussed on the use of recombinant human GH (rhGH) therapy to normalise final adult height. However, research over the past two decades that has demonstrated deficits in bone health and cardiac function, as well as impaired quality of life in adults with childhood-onset GHD (CO-GHD), has questioned this practice. Some of these studies suggested that there may be short-term benefits of rhGH in certain group of adolescents with GHD during transition, although the impact of GHD and replacement during the transition period has not been adequately investigated and its long-term benefits remain unclear. GH therapy remains expensive and well-designed long-term studies are needed to determine the cost effectiveness and clinical benefit of ongoing rhGH during transition and further into adulthood. In the absence of compelling data to justify widespread continuation of rhGH into adult life, there are several questions related to its use that remain unanswered. This paper reviews the effects of growth hormone deficiency on bone health, cardiovascular function, metabolic profile and quality of life during transition and young adulthood

The relationship between adiposity, bone density and microarchitecture is maintained in young women irrespective of diabetes status

Background: The relationship between bone health and adiposity and how it may be affected in people with chronic metabolic conditions is complex. Methods: 17 women with Type 1 diabetes mellitus (T1DM) and 9 age-matched healthy women with a median age of 22.6 yrs (range, 17.4, 23.8) were studied by 3T-MRI and MR spectroscopy to assess abdominal adiposity, tibial bone microarchitecture and vertebral bone marrow adiposity. Additional measures included DXA-based assessments of total body (TB), femoral neck (FN) and lumbar spine (LS) bone mineral density (BMD) and fat mass (FM). Results: Although women with T1DM had similar BMI and bone marrow adiposity to the controls, they had higher visceral and subcutaneous adiposity on MRI (p<0.05) and total body FM by DXA (p=0.03). Overall, in the whole cohort, a clear inverse association was evident between bone marrow adiposity and BMD at all sites (p<0.05). These associations remained significant after adjusting for age, BMI, FM, and abdominal adiposity. In addition, visceral adiposity, but not subcutaneous adiposity, showed a positive association with bone marrow adiposity (r,0.4, p=0.03), and a negative association with total body BMD (r,0.5, p=0.02). Apparent trabecular separation as assessed by MRI showed an inverse association to total body BMD by DXA (r,–0.4, p=0.04). Conclusion: Irrespective of the presence of an underlying metabolic condition, young women display a negative relationship between MRI-measured bone marrow adiposity and DXA-based assessment of bone mineral density. Furthermore, an association between bone marrow adiposity and visceral adiposity supports the notion of a common origin of these two fat depots

Ab Initio Evidence for the Formation of Impurity d(3z^2-r^2) Holes in Doped La_{2-x}Sr_xCuO_4

Using the spin unrestricted Becke-3-Lee-Yang-Parr density functional, we computed the electronic structure of explicitly doped La_{2-x}Sr_xCuO_4 (x = 0.125, 0.25, and 0.5). At each doping level, an impurity hole band is formed within the undoped insulating gap. This band is well-localized to CuO_6 octahedra adjacent to the Sr impurities. The nature of the impurity hole is A_{1g} in symmetry, formed primarily from the z^2 orbital on the Cu and p_z orbitals on the apical O's. There is a strong triplet coupling of this hole with the intrinsic B_{1g} Cu x^2-y^2/O1 p_{sigma} hole on the same site. Optimization of the c coordinate of the apical O's in the doped CuO_6 octahedron lead to an asymmetric anti-Jahn-Teller distortion of the O2 atoms toward the central Cu. In particular, the O2 atom between the Cu and Sr is displaced 0.26 A while the O2 atom between the Cu and La is displaced 0.10 A. Contrary to expectations, investigation of a 0.1 A enhanced Jahn-Teller distortion of this octahedron does not force formation of an x^2-y^2 hole, but instead leads to migration of the z^2 hole to the four other CuO_6 octahedra surrounding the Sr impurity. This latter observation offers a simple explanation for the bifurcation of the Sr-O2 distance revealed in x-ray absorption fine structure data.Comment: Submitted to Phys. Rev. B. See http://www.firstprinciples.com for more informatio

Non-Singularity of the Exact Two-Dimensional String Black Hole

We study the global structure of the exact two-dimensional space-time which emerges from string theory. Previous work has shown that in the semi-classical limit, this is a black hole similar to the Schwarzschild solution. However, we find that in the exact case, a new Euclidean region appears "between" the singularity and black hole interior. However the boundary between the Lorentzian and Euclidean regions is a coordinate singularity, which turns out to be a surface of time reflection symmetry in an extended space-time. Thus strings having fallen through the black hole horizon would eventually emerge through another one into a new asymptotically flat region. The maximally extended space-time consists of an infinite number of universes connected by wormholes. There are no singularities present in this geometry. We also calculate the mass and temperature associated with the space-time.Comment: 9 pages, latex, DAMTP R93/

Mass Spectra of Supersymmetric Yang-Mills Theories in 1+1 Dimensions

Physical mass spectra of supersymmetric Yang-Mills theories in 1+1 dimensions are evaluated in the light-cone gauge with a compact spatial dimension. The supercharges are constructed and the infrared regularization is unambiguously prescribed for supercharges, instead of the light-cone Hamiltonian. This provides a manifestly supersymmetric infrared regularization for the discretized light-cone approach. By an exact diagonalization of the supercharge matrix between up to several hundred color singlet bound states, we find a rapidly increasing density of states as mass increases.Comment: LaTeX file, 32 page, 7 eps figure

Donor states in modulation-doped Si/SiGe heterostructures

We present a unified approach for calculating the properties of shallow donors inside or outside heterostructure quantum wells. The method allows us to obtain not only the binding energies of all localized states of any symmetry, but also the energy width of the resonant states which may appear when a localized state becomes degenerate with the continuous quantum well subbands. The approach is non-variational, and we are therefore also able to evaluate the wave functions. This is used to calculate the optical absorption spectrum, which is strongly non-isotropic due to the selection rules. The results obtained from calculations for Si/Si$_{1-x}$Ge$_x$ quantum wells allow us to present the general behavior of the impurity states, as the donor position is varied from the center of the well to deep inside the barrier. The influence on the donor ground state from both the central-cell effect and the strain arising from the lattice mismatch is carefully considered.Comment: 17 pages, 10 figure

Two-dimensional Quantum-Corrected Eternal Black Hole

The one-loop quantum corrections to geometry and thermodynamics of black hole are studied for the two-dimensional RST model. We chose boundary conditions corresponding to the eternal black hole being in the thermal equilibrium with the Hawking radiation. The equations of motion are exactly integrated. The one of the solutions obtained is the constant curvature space-time with dilaton being a constant function. Such a solution is absent in the classical theory. On the other hand, we derive the quantum-corrected metric (\ref{solution}) written in the Schwarzschild like form which is a deformation of the classical black hole solution \cite{5d}. The space-time singularity occurs to be milder than in classics and the solution admits two asymptotically flat black hole space-times lying at "different sides" of the singularity. The thermodynamics of the classical black hole and its quantum counterpart is formulated. The thermodynamical quantities (energy, temperature, entropy) are calculated and occur to be the same for both the classical and quantum-corrected black holes. So, no quantum corrections to thermodynamics are observed. The possible relevance of the results obtained to the four-dimensional case is discussed.Comment: Latex, 28 pges; minor corrections in text and abstract made and new references adde

Right ventricular myocardial deoxygenation in patients with pulmonary artery hypertension

Background: In pulmonary arterial hypertension (PAH), progressive right ventricular (RV) dysfunction is believed to be largely secondary to RV ischaemia. A recent pilot study has demonstrated the feasibility of Oxygen-sensitive (OS) cardiovascular magnetic resonance (CMR) to detect in-vivo RV myocardial oxygenation. The aims of the present study therefore, were to assess the prevalence of RV myocardial ischaemia and relationship with RV myocardial interstitial changes in PAH patients with non-obstructive coronaries, and corelate with functional and haemodynamic parameters. Methods: We prospectively recruited 42 patients with right heart catheter (RHC) proven PAH and 11 healthy age matched controls. The CMR examination involved standard functional imaging, OS-CMR imaging and native T1 mapping. An ΔOS-CMR signal intensity (SI) index (stress/rest signal intensity) was acquired at RV anterior, RV free-wall and RV inferior segments. T1 maps were acquired using Shortened Modified Look-Locker Inversion recovery (ShMOLLI) at the inferior RV segment. Results: The inferior RV ΔOS-CMR SI index was significantly lower in PAH patients compared with healthy controls (9.5 (– 7.4–42.8) vs 12.5 (9–24.6)%, p = 0.02). The inferior RV ΔOS-CMR SI had a significant correlation to RV inferior wall thickness (r = – 0.7, p < 0.001) and RHC mean pulmonary artery pressure (mPAP) (r = – 0.4, p = 0.02). Compared to healthy controls, patients with PAH had higher native T1 in the inferior RV wall: 1303 (1107–1612) vs 1232 (1159–1288) ms, p = 0.049. In addition, there was a significant difference in the inferior RV T1 values between the idiopathic PAH and systemic sclerosis associated PAH patients: 1242 (1107–1612) vs 1386 (1219–1552)ms, p = 0.007. Conclusion: Blunted OS-CMR SI suggests the presence of in-vivo microvascular RV dysfunction in PAH patients. The native T1 in the inferior RV segments is significantly increased in the PAH patients, particularly among the systemic sclerosis associated PAH group.Karthigesh Sree Raman, Ranjit Shah, Michael Stokes, Angela Walls, Richard J. Woodman, Rebecca Perry, Jennifer G. Walker, Susanna Proudman, Carmine G. De Pasquale, David S. Celermajer, and Joseph B. Selvanayaga