CD38 expression as a prognostic indicator in chronic lymphocytic leukaemia

Staging systems and laboratory features help predict survival in chronic lymphocytic leukaemia but they do not distinguish patients who will progress from those whose disease will remain indolent. CD38 expression has emerged as an independent prognostic factor, yet there is debate as to what level of CD38 affects prognosis. We plotted the hazard ratios for the treatment-free interval (TFI) between the higher and lower groups defined by CD38 cut-offs from 0 to 100%. The maximum hazard ratio was achieved for a cut-off of 7%. We examined by triple colour analysis the values for CD38 in 289 untreated patients using both >or=30 and >or=7% as thresholds for prognosis. Using a >or=7% threshold (but not >or=30%), we showed a significant correlation with advanced stage and male sex. The interval from diagnosis to first therapy or TFI was longer (median 36 months) in patients with <7% CD38 positive cells than those with >or= 30% (8.7 months) or with intermediate values between 7 and 29% (P<0.00005). The <7% threshold also identified patients in stage A with a long TFI (P=0.0001). Multivariate analysis showed that CD38 has independent prognostic value for TFI in all patients. In 135 patients tested for deletions of p53, 13q14 and 11q23 and for trisomy 12, we showed a correlation between 13q14 deletion and <30%/<7% CD38 positive cells and a tendency for trisomy 12 to be associated with >or=30%/>or=7% CD38 positive cells. We conclude that 7% may be a more useful threshold for disease progression than higher values of CD38.     

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.     

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.     

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     

Degradation and detoxification of cresols in synthetic and industrial wastewater by an indigenous strain of Pseudomonas putida in aerobic reactors

We studied the degradation of mixtures of o-cresol, m-cresol, and p-cresol, by Pseudomonas putida isolated from natural sources, and the application of this degradation to the depuration and detoxification of synthetic and industrial wastewater. Biodegradation assays were performed in batch and continuous-flow fixed-bed aerobic reactors. Biodegradation was evaluated by cresol determination using micellar electrokinetic capillary chromatography, UV spectrophotometry, and chemical oxygen demand (COD). Mineralization of cresols was assessed by gas chromatography performed both at the end of the batch process and in the continuous flow reactor effluent. Microbial growth was measured by the plate count method. Scanning electronic microscopy was employed to observe bacterial cells adsorbed on polyvinyl chloride cylinders in the reactor. Detoxification was evaluated by Vibrio fischeri, Pseudokirchneriella subcapitata, and Daphnia magna toxicity tests. Results obtained show that under batch conditions the strain grew exponentially with 100, 200, and 300 mg/L of each of the isomers in synthetic minimal medium within 48 h; in industrial wastewater with 540 mg/L of cresols similar results were obtained. Removal of cresols and COD was higher than 99.9% and 95.0%, respectively. When assays were performed in continuous flow reactor in synthetic wastewater under operating conditions a removal of total cresols and COD of 99.9% and 96.4%, respectively, was achieved. Results of capillary electrophoresis may suggest a concurrent isomers utilization and simultaneous growth on the substrates. Toxicity was neither detected at the end of the batch process nor in the continuous flow reactor effluent.     

Estrogenic effects of 17 beta-aminoestrogens assessed in uteri of rats and mice

Administration of exogenous estrogens has been associated with an increase of thromboembolic events. The 17β-aminoestrogens produce anticoagulant effects contrasting with the procoagulant effects of the natural occurring estradiol in rodents. This work compares the estrogenic effects induced by 17β-aminoestrogens prolame, butolame, pentolame, and estradiol in vivo models. Dose–response curves were performed using immature CD1 mice and Wistar rats. The animals were injected with estradiol or 17β-aminoestrogens (0.01 to 1000 μg/kg), or vehicle. The uterine wet and dry weights were determined. The 17β-aminoestrogens increased uterine weight in a dose-dependent manner. The uterotrophic effect produced by estradiol induced lower ED₅₀ (6.5 and 4 μg/kg) and higher E_max values (+523–350%) in mice as compared with those from the rat, indicating more susceptibility of the mice model. The 17β-aminoestrogens are partial estrogenic agonists with a relative uterotrophic effect of estradiol (100%) from 9–86%. Only the ED₅₀ values of 17β-aminoestrogens in CD1 mice showed a direct correlation to the length of the amine group substitution in C-17 since their efficacy and potency were in the order: prolame>butolame>pentolame.     

Talking the same language on patient empowerment: Development and content validation of a taxonomy of self‐management interventions for chronic conditions

ContextThe literature on self‐management interventions (SMIs) is growing exponentially, but it is characterized by heterogeneous reporting that limits comparability across studies and interventions. Building an SMI taxonomy is the first step towards creating a common language for stakeholders to drive research in this area and promote patient self‐management and empowerment.ObjectiveTo develop and validate the content of a comprehensive taxonomy of SMIs for long‐term conditions that will help identify key characteristics and facilitate design, reporting and comparisons of SMIs.MethodsWe employed a mixed‐methods approach incorporating a literature review, an iterative consultation process and mapping of key domains, concepts and elements to develop an initial SMI taxonomy that was subsequently reviewed in a two‐round online Delphi survey with a purposive sample of international experts.ResultsThe final SMI taxonomy has 132 components classified into four domains: intervention characteristics, expected patient/caregiver self‐management behaviours, outcomes for measuring SMIs and target population characteristics. The two‐round Delphi exercise involving 27 international experts demonstrated overall high agreement with the proposed items, with a mean score (on a scale of 1‐9) per component of 8.0 (range 6.1‐8.8) in round 1 and 8.1 (range 7.0‐8.9) in round 2.ConclusionsThe SMI taxonomy contributes to building a common framework for the patient self‐management field and can help implement and improve patient empowerment and facilitate comparative effectiveness research of SMIs.Patient or public contribution.Patients’ representatives contributed as experts in the Delphi process and as partners of the consortium.     

Acute sensitivity and acute tolerance to ethanol in preweanling rats with or without prenatal experience with the drug

The present study examined behavioral sensitivity and acute tolerance to ethanol in infants with or without a moderate prenatal ethanol experience. During gestational days 17–20 dams received 0.0 or 2.0 g/kg ethanol. On postnatal day 13 pups were administered 0.0, 0.5 or 2.5 g/kg ethanol prior to assessment of locomotion. One third of the pups were evaluated at 5–10, 30–35 and 60–65 min after ethanol administration; another third was tested only during the last two post-administration periods; and the remaining third was tested only at 60–65 min. At 30–35 min blood ethanol levels were similar to those attained at 60–65 min. The main results of the study were: (a) The 2.5 g/kg ethanol dose induced biphasic motor effects: stimulation 5–10 min after drug administration and sedation after 30–35 or 60–65 min. (b) Infants exhibited acute tolerance to ethanol's sedative effects. (c) Although pups prenatally treated with ethanol exhibited heightened locomotor activity levels, acute sensitivity and tolerance were not affected by prenatal treatment. In summary, infants are sensitive to biphasic motor consequences of ethanol and readily exhibit acute tolerance to ethanol's sedative effects. In addition, moderate prenatal ethanol exposure was sufficient to induce hyper-reactivity in the offspring without affecting habituation.