Somatostatin infusion withdrawal in the diagnosis of childhood growth hormone deficiency

OBJECTIVE: An evaluation of growth hormone (GH) testing for GH deficiency (GHD) in childhood is confounded by the lack of a world-wide consensus on the definition of GHD. Although a single GH test remains the most powerful biochemical tool in the evaluation of a child with growth failure, the test remains far from ideal. Withdrawal of somatostatin (SS) infusion is followed by a rebound rise of GH thought to be mediated by endogenous GH-releasing hormone (GHRH) function. This study was designed to compare the GH response to 90 min SS infusion in children with normal GH secretion versus children with GH deficiency. METHODS: Ten children with GHD and 10 healthy controls (NC) have been evaluated for GH response to somatostatin infusion withdrawal (SSIW) and compared with response of two provocative tests, glucagon plus propranolol test and L-Dopa test. All children received constant infusion of somatostatin for 90 min (3 microg/kg per h, Stilamin, Serono, Aubonne, Switzerland). In order to determine GH, blood samples were obtained 90 min before the SS infusion and 0, 15, 30, 45, 60, 75, and 90 min after the cessation of infusion. RESULTS: Growth hormone peak levels with SSIW were significantly lower in GH deficient children than in healthy children (2.5 +/- 1.2 ng/dL, vs 21.9 +/- 5.3 ng/dL, respectively, P < 0.01). No adverse effects were observed during or after somatostatin infusion. CONCLUSION: In the present study, SSIW elicited a significant GH rise in healthy children but not in children with GH deficiency. Although further controlled studies using more data are necessary to expand these findings, the results suggested that children with GH deficiency can be reliably discriminated from healthy children by SSIW.     

Low scores on the Benton Facial Recognition Test associated with vertebrobasilar insufficiency

Background

Decreased posterior cerebral circulation has been observed in patients with vertebrobasilar insufficiency (VBI). Reduced cerebral perfusion may have an impact on mental performance as measured by the Benton Facial Recognition Test (BFRT). We evaluated the usefulness of BFRT in identifying cognitive decline in patients with VBI by correlating test performance with total blood flow in the vertebrobasilar system and other variables such as educational level and gender.

Materials and methods

Thirty-three participants without dementia (mini-mental state examination; MMSE >27) and cranial magnetic resonance imaging abnormality, but with atherosclerotic risk factors were involved in the study. Nineteen subjects had a total vertebrobasilar flow volume less than 200 ml/min (Group I), and 14 subjects had a flow volume more than 200 ml/min (Group II).

Results

The groups were similar in regard to gender, age, and educational level. BFRT results were 19.53 ± 3.12 and 22.36 ± 2.73 for Groups I and II, respectively (p = 0.01). The educational level was the main factor affecting the BFRT score in Group I (p = 0.04).

Discussion

BFRT is clearly impaired in VBI as measured by Doppler ultrasound examination. We concluded that the test appears to adequately distinguish cognitive levels between VBI and other patients. Additionally, our results suggest that education is associated with BFRT results, and for normative purposes, gender consideration is unnecessary. Further studies are needed to investigate the association between VBI and memory dysfunction in early dementia.     

Linear β-amino alcohol catalyst anchored on functionalized magnetite nanoparticles for enantioselective addition of dialkylzinc to aromatic aldehydes

A linear β-amino alcohol ligand, previously found to be a very efficient catalyst for enantioselective addition of dialkylzinc to aromatic aldehydes, has been anchored on differently functionalized superparamagnetic core–shell magnetite–silica nanoparticles (1a and 1b). Its catalytic activity in the addition of dialkylzinc to aldehydes has been evaluated, leading to promising results, especially in the case of 1b for which the recovery by simple magnetic decantation and reuse was successfully verified.

The catalytic activity of a linear β-amino alcohol ligand anchored on functionalized magnetite/silica core–shell nanoparticles has been evaluated in the addition of dialkylzinc to aldehydes leading to promising results.     

Gene control of tyrosine kinase TIE2 and vascular manifestations of infections

Ligands of the endothelial-enriched tunica interna endothelial cell kinase 2 (Tie2) are markedly imbalanced in severe infections associated with vascular leakage, yet regulation of the receptor itself has been understudied in this context. Here, we show that TIE2 gene expression may constitute a novel vascular barrier control mechanism in diverse infections. Tie2 expression declined rapidly in wide-ranging models of leak-associated infections, including anthrax, influenza, malaria, and sepsis. Forced Tie2 suppression sufficed to attenuate barrier function and sensitize endothelium to permeability mediators. Rapid reduction of pulmonary Tie2 in otherwise healthy animals attenuated downstream kinase signaling to the barrier effector vascular endothelial (VE)-cadherin and induced vascular leakage. Compared with wild-type littermates, mice possessing one allele of Tie2 suffered more severe vascular leakage and higher mortality in two different sepsis models. Common genetic variants that influence TIE2 expression were then sought in the HapMap3 cohort. Remarkably, each of the three strongest predicted cis-acting SNPs in HapMap3 was also associated with the risk of acute respiratory distress syndrome (ARDS) in an intensive care unit cohort of 1,614 subjects. The haplotype associated with the highest TIE2 expression conferred a 28% reduction in the risk of ARDS independent of other major clinical variables, including disease severity. In contrast, the most common haplotype was associated with both the lowest TIE2 expression and 31% higher ARDS risk. Together, the results implicate common genetic variation at the TIE2 locus as a determinant of vascular leak-related clinical outcomes from common infections, suggesting new tools to identify individuals at unusual risk for deleterious complications of infection.Among vascular-enriched receptor tyrosine kinases, Tie2 is unusual in at least two functional aspects. First, Tie2 phosphorylation is tightly controlled by the interplay of several proteins: a paralogous receptor, Tie1; a tyrosine phosphatase, vascular endothelial-protein tyrosine phosphatase (VE-PTP); and two secreted ligands, angiopoietin (Angpt)-1 and Angpt-2, the latter of which can act as an agonist, partial agonist, or antagonist depending upon context (1–6). Second, unlike classic growth factor receptors, Tie2 is heavily expressed and phosphorylated throughout the quiescent adult vasculature (7), suggesting that Tie2 signaling has one or more roles in vascular maintenance.Based largely on Angpt-1 overexpression studies, Tie2 has been implicated in vascular barrier defense (8, 9). However, adult-specific deletion of Angpt-1 does not appear to trigger vascular leakage (10). Moreover, Angpt-1 has repeatedly been ascribed functions that are independent of Tie2 (11–13). Finally, observational studies in humans suffering clinical manifestations of vascular leakage have consistently shown a marked imbalance in Tie2 ligands tilting in favor of Angpt-2 (reviewed in 14). Although decreased Tie2 activity has been inferred from these reports, the role of TIE2 gene expression has not been directly queried experimentally or in clinical settings.This question is important not only for understanding control mechanisms of the circulatory system but also to guide the development of strategies to predict, stratify, and treat patients affected by acute vascular leakage. If tonic Tie2 signaling is indeed necessary for vascular barrier maintenance, then reducing the pool of receptors could constitute a ligand-independent means to attenuate barrier-protective signaling in the endothelium. We therefore hypothesized that the level of Tie2 expression modulates the sensitivity of blood vessels, and thereby the entire organism, to noxious stimuli. Cellular, rodent, and human genetics studies were undertaken to test this concept.     

The Effect of Strut Allograft and Its Position on Vancouver Type B1 Periprosthetic Femoral Fractures: A Biomechanical Study

The aim of this study is to assess the biomechanical advantage of adding strut allograft and the effect of its position on the construct in Vancouver type B1 fractures. Fifteen forth-generation synthetic femurs were used and created a fracture model at the tip of prosthesis, and subsequently fixated with a lateral plate only, lateral plate and medial strut, lateral plate and anterior strut. Rotational and axial tests were performed. In all loading tests, the plate with medial strut group was stiffer than the other constructs and had higher failure load values and had less displacement in the fracture site. A combination of a plate with a medial strut allograft provides more mechanical stability on periprosthetic femoral fractures near the tip of a total hip arthroplasty.     

Flow-through, functioning, free musculocutaneous flap transfer for restoration of a mangled extremity

Reconstructing a mangled extremity requires careful, complete examination of the functional and structural status of the injured part. Although the vascular status of the injured extremity is a priority, simultaneous reconstruction of skeletal, vascular, and neuromuscular structures should be considered in a combined approach. The purpose of this study was to describe a one-stage reconstruction of both soft-tissue coverage and revascularization for a lower extremity, along with functional restoration of an anterior lower leg. For this purpose, the functioning transfer of a free latissimus dorsi musculocutaneous flap as a flow-through type was performed. The results demonstrate that the technique is extremely useful in limb-salvage procedures from both functional and structural viewpoints.     

A rare and serious complication of the radial forearm flap donor site: osteomyelitis of the radius

Although the radial forearm flap has become a workhorse for the reconstructive surgeon, it has some known disadvantages, especially relating to donor area complications. The authors present a serious but rare complication of the radial forearm donor site. Osteomyelitis of the radius at the flap donor site was observed in a 48-year-old man 5 weeks after flap surgery. Although the flap was raised fasciocutaneously without a bony portion, infection of the radius was determined. The infection was successfully treated with surgical debridement and simultaneous administration of a proper antibiotic regimen. One should keep in mind that osteomyelitis of the radius may be encountered as one of the serious donor site complications of the radial forearm flap that may have detrimental effects on hand functions.     

Current therapeutic approaches in childhood chronic hepatitis B infection: a multicenter study

BACKGROUND AND AIM: The aim of the present study was to compare the therapeutic efficacy of three different regimens in childhood chronic hepatitis B (CHB) infection. METHODS: A total of 182 children with CHB infection were prospectively allocated to three random groups. Sixty-two patients in the first group received high-dose interferon (IFN)-alpha 2b (10 MU/m2) thrice/weekly alone for 6 months. In the second (n = 60) and third groups (n = 60), IFN-alpha was used for 6 months (5 MU/m2) thrice/weekly in combination with lamivudine (LAM) (4 mg/kg, maximum 100 mg/day) for 12 months. Lamivudine was started simultaneously with IFN in the second group, while it was started 2 months prior to IFN injections in the third group. RESULTS: The initial mean alanine aminotransferase (ALT) values for the first, second and third groups were 109 +/- 93 IU/L, 101 +/- 64 IU/L and 92 +/- 42 IU/L, respectively (P > 0.05). At the end of the therapy, ALT values decreased to 82 +/- 111 IU/L, 38 +/- 41 IU/L and 29 +/- 16 IU/L in groups 1, 2 and 3, respectively. The mean ALT value of the first group was significantly different to the second and third groups (P = 0.046 and P = 0.002, respectively) at the end of the therapy and these differences were found to be sustained after 18 months. However, results in the second and third groups were similar (P > 0.05). There were no significant differences in HBeAg clearance and anti-HBe seroconversion at the initial stage, 12 months and 18 months between the three groups (P > 0.05). Hepatitis B virus (HBV) DNA clearance in the first group was different from the second and third groups, while the second and third groups had similar HBV DNA clearance ratios at 12 and 18 months. No significant difference was found in the complete response (normalization of ALT, clearance of HBV DNA and seroconversion of anti HBe) ratios of all groups (at 12 months: 28.8, 45.5, 35.8% and at 18 months 33.3, 49 and 34% in groups 1, 2 and 3, respectively, P > 0.05). CONCLUSIONS: Although the ALT normalization and HBV DNA clearance ratios of IFN plus LAM combination groups were better than the high-dose IFN-alpha monotherapy group, no significant difference was found in the complete response ratios of all three groups.