Alpha-fetoprotein in the early neonatal period--a large study and review of the literature

BACKGROUND: Alpha-fetoprotein (AFP) is a glycoprotein molecule, which has similarity to albumin and is produced by the fetal liver. Its biological role is unclear and factors that may influence its concentrations in neonates are only partially identified. However, it has an important role as a diagnostic marker, especially in certain tumors and liver diseases of childhood. Its normal reference values in newborns have not been well defined. METHODS: Serum AFP concentrations were measured and characterized in 260 term and near-term newborns [gestational age (GA)> or =34 weeks, birthweight (BW)> or =1700 g] at birth [umbilical cord (UC) blood] and upon discharge from the nursery at 60+/-24 h of life (venous sample). RESULTS: Due to the nonnormal distribution of AFP levels, it is useful to relate to reference interval for AFP concentrations at birth that was 15.7-146.5 microg/ml, based on 95% confidence interval (CI). The median value of 48.3 microg/ml is also a useful reference. However, mean AFP concentrations at birth that were 61.6+/-44.8 microg/ml are less informative due to the large standard deviation (S.D.). Upon discharge, AFP concentrations dropped to 9.7-111.9 microg/ml (95% CI) with a median of 34.2 microg/ml. A significant negative correlation was found between AFP serum levels and gestational age and to a lesser extent with birthweight. No significant differences were found between males and females. CONCLUSIONS: Normal reference intervals for AFP in term and near-term newborns have been defined, but need to be addressed with caution due to the wide range of normal values. AFP levels at birth decrease as gestation advances and the newborn weighs more.     

Clinical Outcome of Prostate Cancer Patients with Germline DNA Repair Mutations: Retrospective Analysis from an International Study

Background

Germline DNA damage repair gene mutation (gDDRm) is found in >10% of metastatic prostate cancer (mPC). Their prognostic and predictive impact relating to standard therapies is unclear.

Butyric acid prodrugs are histone deacetylase inhibitors that show antineoplastic activity and radiosensitizing capacity in the treatment of malignant gliomas

Histone modification has emerged as a promising approach to cancer therapy. We explored the efficacy of a novel class of histone deacetylase inhibitors in the treatment of malignant gliomas. Treatment of glioma cell lines with two butyric acid derivatives, pivaloylomethyl butyrate (AN-9) and butyroyloxymethyl butyrate (AN-1), induced hyperacetylation, increased p21(Cip1) expression, inhibited proliferation, and enhanced apoptosis. Histone deacetylase inhibitor-induced apoptosis was mediated primarily by caspase-8. Treatment of cells with AN-1 or AN-9 for 24 hours before exposure to gamma-irradiation potentiated further caspase-8 activity and resultant apoptosis. Clonogenic survival curves revealed marked reductions in cell renewal capacity of U251 MG cells exposed to combinations of AN-1 and radiation. Preliminary in vivo experiments using human glioma cell lines grown as xenografts in mouse flanks suggest in vivo efficacy of AN-9. The data suggest that novel butyric acid prodrugs provide a promising treatment strategy for malignant gliomas as single agents and in combination with radiation therapy.     

Work-related thumb pain in physiotherapists is associated with thumb alignment during performance of PA pressures

Pain is common in the thumbs of physiotherapists. The purpose of this observational study was to investigate whether there is an association between the alignment of the thumb during performance of postero-anterior (PA) pressures and the presence of thumb pain. One hundred and twenty-nine physiotherapists who attended the Musculoskeletal Physiotherapy Association Conference (2003) participated. After providing a history of any work-related thumb pain, participants applied a PA pressure mimicking the technique they would use on a cervical spine, while the position of their metacarpophalangeal (MP) and interphalangeal (IP) joints was photographed. There was an association (p<0.05) between work-related thumb pain and alignment of the thumb during performance of PA pressures: participants who were able to maintain their MP and IP joints in extension were less likely to report pain. These findings serve as a guide to the safe performance of mobilization techniques, both for beginning practitioners and for experienced therapists complaining of thumb pain.     

Mental health policy and mental health service user perspectives on involvement: a discourse analysis

AIM: This paper is a report of an exploration of the concept of service user involvement in mental health nursing using a discourse analysis approach. BACKGROUND: Service user involvement has come to be expected in mental health nursing policy and practice. This concept, however, is often applied somewhat ambiguously and some writers call for a clearer understanding of what service users actually want. METHOD: A Foucauldian discourse analysis was conducted in 2005, examining literature and health policies published by the United Kingdom government and service users. The discursive perspectives of both were explored and conceptual themes were generated from the data. FINDINGS: Concepts occurring within government discourse include language relating to service users, the notion of service user involvement and power. Concepts from the service user discourse include power, change and control, theory, policy and practice, and experiential expertise. Differences in perspectives were found within these themes which distinguished government from service user discourses. Greater flexibility in ideas and perspectives was demonstrated by service users, with a seemingly greater range of theoretical underpinnings. CONCLUSION: Greater awareness is needed of the significance of language, of how subtle inferences may be drawn from the rhetorical language of policies, of how these might affect the involvement of service users, and of the implications for the role of mental health nurses. Nurses need to be aware of these tensions and conflicts in managing their practice and in creating a mental health nursing philosophy of 'involvement'. If true 'involvement' is to ensue, nurses may also need to consider the transfer of power to service users.     

Pituitary Gland: SITE OF SHORT-LOOP FEEDBACK FOR LUTEINIZING HORMONE IN THE RABBIT

The development of a species specific radioimmunoassay for rabbit luteinizing hormone (LH) has permitted the direct demonstration of LH feedback control of LH secretion (short-loop feedback control). In previous studies we showed that small bolus injections of human LH (hLH) intravenously administered to castrate female rabbits suppressed rabbit LH for 20-30 min. Human LH had no effect on rabbit follicle-stimulating hormone secretion. This control system was responsive to amounts of hLH estimated to be present in blood of eugonadal men and women. These studies were designed to determine whether this feedback control was exerted at a pituitary or hypothalamic level. Two groups of studies were carried out: (a) in vivo studies: Rabbit LH was quantified in the blood of castrated female New Zealand White rabbits receiving either constant hLH perfusion (2.75 IU/min) or saline perfusion, plus a bolus injection of 0.5, 6, or 20 mug of gonadotropin-releasing hormone (GnRH). Human LH decreased the response to 6 and 20 mug of GnRH by 31 and 36%, respectively, and abolished the response to 0.5 mug, GnRH. (b) in vitro studies: Rabbit pituitary slices were incubated in the presence of medium alone, medium plus hLH (25 mIU/ml), medium plus GnRH (20 mug/ml), and medium plus both GnRH and hLH. hLH decreased basal rabbit LH release into the medium and abolished GnRH-stimulated rabbit LH release. hLH had no effect on rabbit follicle-stimulating hormone release. From these results we conclude that a direct and specific feedback control of LH on LH exists at a pituitary level.     

Integrase strand transfer inhibitor-based regimen is related with a limited HIV-1 V3 loop evolution in clinical practice

Virus Genes - Integrase-strand-transfer inhibitors (INSTIs) are known to rapidly reduce HIV-1 plasma viral load, replication cycles, and new viral integrations, thus potentially limiting viral...     

Selection of relevant genes in cancer diagnosis based on their prediction accuracy

MOTIVATIONS: One of the main problems in cancer diagnosis by using DNA microarray data is selecting genes relevant for the pathology by analyzing their expression profiles in tissues in two different phenotypical conditions. The question we pose is the following: how do we measure the relevance of a single gene in a given pathology? METHODS: A gene is relevant for a particular disease if we are able to correctly predict the occurrence of the pathology in new patients on the basis of its expression level only. In other words, a gene is informative for the disease if its expression levels are useful for training a classifier able to generalize, that is, able to correctly predict the status of new patients. In this paper we present a selection bias free, statistically well founded method for finding relevant genes on the basis of their classification ability. RESULTS: We applied the method on a colon cancer data set and produced a list of relevant genes, ranked on the basis of their prediction accuracy. We found, out of more than 6500 available genes, 54 overexpressed in normal tissues and 77 overexpressed in tumor tissues having prediction accuracy greater than 70% with p-value 相似文献   

Tethered epidermal growth factor provides a survival advantage to mesenchymal stem cells

MSC can act as a pluripotent source of reparative cells during injury and therefore have great potential in regenerative medicine and tissue engineering. However, the response of MSC to many growth factors and cytokines is unknown. Many envisioned applications of MSC, such as treating large defects in bone, involve in vivo implantation of MSC attached to a scaffold, a process that creates an acute inflammatory environment that may be hostile to MSC survival. Here, we investigated cellular responses of MSC on a biomaterial surface covalently modified with epidermal growth factor (EGF). We found that surface-tethered EGF promotes both cell spreading and survival more strongly than saturating concentrations of soluble EGF. By sustaining mitogen-activated protein kinase kinase-extracellular-regulated kinase signaling, tethered EGF increases the contact of MSC with an otherwise moderately adhesive synthetic polymer and confers resistance to cell death induced by the proinflammatory cytokine, Fas ligand. We concluded that tethered EGF may offer a protective advantage to MSC in vivo during acute inflammatory reactions to tissue engineering scaffolds. The tethered EGF-modified polymers described here could be used together with structural materials to construct MSC scaffolds for the treatment of hard-tissue lesions, such as large bony defects. Disclosure of potential conflicts of interest is found at the end of this article.