Differential roles of fibroblast growth factor-2 during development and maintenance of auditory sensory epithelia

Fibroblast growth factor-2 (FGF2) has been postulated to be a key regulator involved in the proliferation, differentiation, and regeneration of sensory hair cells. Here we have addressed the potential functions of FGF2 during the formation and regeneration of the auditory epithelium in chicken and mice. By using viral gene transfer, based on herpes simplex type 1 virus (HSV-1), we show that ectopically applied FGF2 drastically increases the number of cells expressing early hair cell markers during embryonic development in avians. Intriguingly, FGF2 does not stimulate cell division during this process. These data suggest that FGF2 plays a role during differentiation of sensory hair cells in avians. To address the potential functions of FGF2 during murine inner ear development, we analyzed FGF2 mouse mutants. Mice lacking FGF2 showed normal formation of the inner ear, and no abnormalities were observed at the adult stage. Moreover, FGF2 mouse mutants showed similar hearing thresholds compared with those observed in control mice before and after noise damage. Therefore, endogenous FGF2 appears not to be essential for the development or functional maintenance of the auditory organ in mammals. In light of these results, the differential roles of FGF2 in the vertebrate inner ear are discussed with respect to its previously postulated functions.     

Eight-year experience of pediatric heart transplantation: clinical outcome using non-invasive methods for the evaluation of acute rejection

Combined immunosuppression therapy and acute rejection surveillance after heart transplantation may influence clinical outcome. This prospective, longitudinal study investigated 27 pediatric patients (12 days to 12 yr of age; mean 3.0 yr) who underwent a post-operative regimen that included long-term treatment with cyclosporin A and azathioprine (double immunosuppression) and polyclonal anti-thymocyte serum induction therapy. Non-invasive parameters were used to diagnose acute rejection. The actuarial survival, clinical outcomes, and complications were analyzed. The actuarial survival after double immunosuppression and induction therapy with polyclonal anti-thymocyte serum was 89%, 73%, and 57% at 1, 4, and 8 yr, respectively. The rejection frequency was 2.6 episodes/patient and the infection frequency, 3.7 episodes/patient. One year after transplantation, systemic arterial hypertension was detected in 21% of patients. Hence, double immunosuppression with polyclonal anti-thymocyte serum induction therapy combined with surveillance of acute rejection with non-invasive tests may provide promising clinical outcome in pediatric heart transplant recipients.     

Deprivation and AIDS in a southern European city: different patterns across transmission group

OBJECTIVE: To analyse deprivation and AIDS among three AIDS transmission groups (men who have sex with men--MSM, heterosexuals, and intravenous drug users--IDUs) in Barcelona, Spain, during the period 1990-95. METHODS: This is an ecological study, the unit of analysis being the neighbourhoods. Included were AIDS cases residents in Barcelona. The association among AIDS rate and deprivation was studied using Spearman correlation coefficients and Poisson regression. RESULTS: For MSM, inner city neighbourhood residence meant a greater risk of AIDS; but lower educational level was inversely related with AIDS rates. For heterosexuals, variables related with AIDS rates were younger age, inner city areas and social unrest for women, and extreme poverty for men. Among UDIs variables related with AIDS were unemployment and social unrest for both sexes. CONCLUSION: The association between AIDS rates and deprivation differs across transmission groups in a southern European city.     

Surgical indications for infantile subdural effusion

Thirty-four cases of infantile subdural effusion (ISE) were reviewed in relation to surgical treatment and its prognosis during an average of 4 years of extended follow-up. The surgical indications were determined mainly by the size of the ISE on computed tomography (CT) scan and by metrizamide CT cisternography (MCTC). Consequently, 18 cases were categorized as type A according to MCTC, including 11 cases (61.1%) of ISE CT grade 1. All type A cases were closely observed. This nontreatment regimen yielded excellent results in 15 cases (83.3%). For 10 cases categorized as type B according to MCTC, including 5 cases (50%) of ISE CT grade 3, surgical treatment was indicated and excellent results were obtained in 8 cases (80%). For 6 cases categorized as type C according to MCTC and as ISE CT grade 3, surgery yielded excellent results in 4 cases (66.7%). Antiepleptic drugs have been given to three (27.3%) of the 11 patients who had convulsive attacks. In conclusion, the surgical indications for ISE were based mainly on MCTC in addition to the clinical course, and it is emphasized that, in the early stages, surgery on ISE cases categorized as MCTC types B and C is necessary.     

Celecoxib enhances the detoxification of diethylnitrosamine in rat liver cancer

AIM： To study the effect of celecoxib （CXB） on diethylnitrosamine activation through the regulation of cytochrome P450 in a hepatocarcinogenesis model.METHODS： Six-week-old male Sprague-Dawley rats were randomly divided into five groups, a non-treated group （NT）, a diethylnitrosamine-treated group （DEN）, a DEN＋CXB-treated group （DEN＋CXB）,and CXB 8 d-treated and CXB 32 d-treated groups. The effects of celecoxib on the enzymatic activities of CYP1A1, 2A, 2B1/2, and 2E1 were assessed in hepatic microsomes 24 h after DEN administration.Changes in CYPIA1 and CYP2B1/2 protein expression were also evaluated. The rate of DEN metabolism was measured by the production of the deethylation metabolite acetaldehyde, and the denitrosation metabolite nitrite.RESULTS： DEN＋CXB administration produced a significant increase in the enzymatic activities ofCYP2B1/2 and 1A1, whereas it did not change the activities of CYP2A and 2E1, compared to that of the DEN group. CXB treatment for eight days did not produce a significant effect on enzymatic activity when compared to the NT group; however, when it was administered for prolonged times （CXB 32 d group）,the enzymatic activities were increased in a similar pattern to those in the DEN＋CXB group. The observed increase in the enzymatic activities in the DEN＋CXB group was accompanied by an increase in the CYP2B1/2 protein levels; no changes were observed in the levels of CYPIA1. In vitro, CXB increased the denitrosation of DEN, a pathway of metabolic detoxification. The addition of SKF-525A, a preferential inhibitor of CYP2B, abrogated the denitrosation of DEN.CONCLUSION： These results suggest that the mechanism of action of CXB involves enhancement of the detoxification of DEN by an increasing denitrosation via CYP2B1/2.     

The effects of electronic documentation in the ambulatory surgery setting

ELECTRONIC DOCUMENTATION can improve organizational processes in health care settings and may be of particular benefit to ambulatory surgery centers.A DECISION SUPPORT SYSTEM (DSS) can be integrated with an electronic documentation system. A DSS can identify potential errors and deviations from best practices and provide electronic alerts for health care clinicians to support patient screening and care.BARRIERS TO IMPLEMENTATION of a DSS include practitioner noncompliance with alerts and limitations in system design.NURSES CAN BE INSTRUMENTAL in overcoming the barriers that prevent some clinicians from adopting these useful information systems. AORN J 86 (December 2007) 970-979. © AORN, Inc, 2007.     

The emerging role of epigenetics in cellular and organismal aging

Genome modifications resulting from epigenetic changes appear to play a critical role in the development and/or progression of cancer. Scatter experimental evidence suggests that epigenetic changes could also be critical determinants of cellular senescence and organismal aging. Here we review the current evidence and discuss how imbalances in chromatin remodelers might trigger irreversible growth arrest in proliferating cells and tissues. Experimental data using drugs that target specific chromatin remodeling enzymes suggest that such approach could lead to the development of novel therapeutic modalities for the prevention or amelioration of some age-related dysfunctions.     

Tyrosine hydroxylase deficiency in three Greek patients with a common ancestral mutation

We present the clinical, biochemical, and molecular findings of three Greek patients with tyrosine hydroxylase (TH) deficiency. All patients presented with a severe clinical phenotype characterized by prominent motor delay, infantile parkinsonism, oculogyric crises, and signs of autonomic dysfunction. Cerebrospinal fluid analysis disclosed reduced dopamine metabolites and normal pterins. Response to levodopa was favorable though not dramatic. All patients were homozygous for a previously reported mutation (p.L236P). SNP haplotype analysis was consistent with a common ancestral mutation, thus indicating a founder effect in Greek patients with TH deficiency. © 2010 Movement Disorder Society