Somatisation in primary care: experiences of primary care physicians involved in a training program and in a randomised controlled trial

Background: A new intervention aimed at managing patients with medically unexplained symptoms (MUS) based on a specific set of communication techniques was developed, and tested in a cluster randomised clinical trial. Due to the modest results obtained and in order to improve our intervention we need to know the GPs' attitudes towards patients with MUS, their experience, expectations and the utility of the communication techniques we proposed and the feasibility of implementing them. Physicians who took part in 2 different training programs and in a randomised controlled trial (RCT) for patients with MUS were questioned to ascertain the reasons for the doctors' participation in the trial and the attitudes, experiences and expectations of GPs about the intervention. Methods: A qualitative study based on four focus groups with GPs who took part in a RCT. A content analysis was carried out. Results: Following the RCT patients are perceived as true suffering persons, and the relationship with them has improved in GPs of both groups. GPs mostly valued the fact that it is highly structured, that it made possible a more comfortable relationship and that it could be applied to a broad spectrum of patients with psychosocial problems. Nevertheless, all participants consider that change in patients is necessary; GPs in the intervention group remarked that that is extremely difficult to achieve. Conclusion: GPs positively evaluate the communication techniques and the interventions that help in understanding patient suffering, and express the enormous difficulties in handling change in patients. These findings provide information on the direction in which efforts for improving intervention should be directed.

Efficacy and safety of autologous platelet rich plasma for the treatment of vascular ulcers in primary care: Phase III study

Background: Vascular ulcers are commonly seen in daily practice at all levels of care and have great impact at personal, professional and social levels with a high cost in terms of human and material resources. Given that the application of autologous platelet rich plasma has been shown to decrease healing times in various different studies in the hospital setting, we considered that it would be interesting to assess the efficacy and feasibility of this treatment in primary care. The objectives of this study are to assess the potential efficacy and safety of autologous platelet rich plasma for the treatment of venous ulcers compared to the conventional treatment (moist wound care) in primary care patients with chronic venous insufficiency (C, clinical class, E, aetiology, A, anatomy and P, pathophysiology classification C6). Design: We will conduct a phase III, open-label, parallel-group, multicentre, randomized study. The subjects will be 150 patients aged between 40 and 100 years of age with an at least 2-month history of a vascular venous ulcer assigned to ten primary care centres. For the treatment with autologous platelet rich plasma, all the following tasks will be performed in the primary care setting: blood collection, centrifugation, separation of platelet rich plasma, activation of coagulation adding calcium chloride and application of the PRP topically after gelification. The control group will receive standard moist wound care. The outcome variables to be measured at baseline, and at weeks 5 and 9 later include: reduction in the ulcer area, Chronic Venous Insufficiency Quality of Life Questionnaire score, and percentage of patients who require wound care only once a week. Discussion: The results of this study will be useful to improve the protocol for using platelet rich plasma in chronic vascular ulcers and to favour wider use of this treatment in primary care.

Meteorological signals in primary productivity at two mountain lakes

Fluctuations in primary productivity at two subalpine lakes reveal both meteorological and biological influences. At Castle Lake, California, large-scale climate events such as the El Niño/Southern Oscillation affect total annual production and, combined with human fishing activity, modify the seasonal pattern of productivity. At Lake Tahoe, California-Nevada, local spring weather conditions modulate annual production and its seasonality by determining the depth of mixing and resulting internal nutrient load. Climatic conditions also contribute to deviations from the long-term trend in productivity by increasing the incidence of forest fires and through anomalous external nutrient loads during precipitation extremes. A 3-year cycle in productivity of as yet unknown origin has also been detected at Lake Tahoe.

Seasonal fluctuation in primary production in relation to the physicochemical parameters of two weed-infested ponds of Kalyani, West Bengal

Kalyani lake (P sub(1)), a weed infested recreational water body and a weed chocked derelict water body (P sub(2)) in the heart of Kalyani city of West Bengal were studied for a period of one year for their primary productivity and other physicochemical parameters. Very low primary productivity (GPP=360-1237mg C m super(-2) d super(-1); NPP=157-787 mg C m super(-2) d super(-1)) was recorded in P sub(2) in spite of having a high concentration of nutrients (PO sub(4)–P=0.052-0.260mg l super(- 1); NO sub(3)-N=0.110-0.412mg l super(-1)). On the other hand, moderate primary productivity (GPP=1687-3195mg C m super(-2) d super(-1); NPP=900-2700mg C m super(-2) d super(-1)) was found in P sub(1) with comparatively low range of nutrients (P0 sub(4)-P =0.010-0.058mg l super(-1); NO sub(3)-N=0.032-0.118mg l super(-1)). After studying the other physicochemical parameters (temperature, transparency, dissolved oxygen, free carbon dioxide, pH, alkalinity and macrophytic biomass), it was found that the overall hydro-biological conditions of the weed-chocked derelict water body (P sub(2)) is not congenial for biological production as compared to Kalyani Lake (P sub(1)). Kalyani Lake may be used for fish culture with proper management practices.

Evaluation of estrogenic activities and mechanism of action of perfluorinated chemicals determined by vitellogenin induction in primary cultured tilapia hepatocytes

Perfluorochemicals (PFCs) are emerging persistent organic pollutants (POPs) and are widely present in the environment, wildlife and humans. Recently, reports have suggested that PFCs may have endocrine-disrupting activities. In the present study, we have developed a non-competitive enzyme-linked immunosorbent assay (ELISA) method to investigate estrogenic activities of selected PFCs using vitellogenin (VTG) induction in primary cultured hepatocytes of freshwater male tilapia (Oreochromis niloticus). Cultured hepatocytes were exposed to various concentrations of perfluorooctanyl sulfonate (PFOS), pentadecafluorooctanoic acid (PFOA), 1H, 1H, 2H, 2H-nonafluoro-1-hexanol (4:2 FTOH), 1H, 1H, 2H, 2H-perfluorooctanol (6:2 FTOH) and 1H, 1H, 2H, 2H-perfluoro-1-decanol (8:2 FTOH) for 48h, while 17 beta-estradiol (E2) and 4-nonylphenol (4-NP) were used as positive controls. A dose-dependent induction of VTG was observed in E2-, 4-NP-, PFOS-, PFOA- and 6:2 FrOH-treated cells, whereas VTG levels remained unchanged in the 4:2 FTOH and 8:2 FTOH exposure groups at the concentrations tested. The estimated 48-h EC50 values for E2,4-NP, PFOS, PFOA and 6:2 FTOH were 4.7 x 10(-7), 7.1 x 10(-6), 1.5 x 10(-5), 2.9 x 10(-5) and 2.8 x 10(-5) M, respectively. In the time-course study, significant VTG induction took place at 24 h (E2), 6 It (4-NP), 48 It (PFOS), 48 It (PFOA), 72 It (4:2 FTOH), 12 h (6:2 FTOH), 72 h (8:2 FTOH), and increased further after 96 It of exposure. Co-exposure to binary mixtures of individual PFCs and E2 for 48 It significantly inhibited E2-induced hepatocellular VTG production in a dose-dependent manner except for 4:2 FTOH. The estimated 48-h IC50 (concentration of a compound that elicits 50% inhibition of maximally E2-induced VTG) values for PFOS, PFOA, 6:2 FTOH and 8:2 FTOH were 3.1 x 10(-7), 5.1 X 10(-7), 1.1 X 10(-6) and 7.5 x 10(-7) M, respectively. In order to further investigate the estrogenic mechanism of PFCs, the hepatocytes were co-exposed to binary mixtures of individual chemicals (E2,4-NP, PFOS, PFOA and 6:2 FTOH) and the known estrogen receptor inhibitor tamoxifen for 48 h; tamoxifen significantly inhibited the ability of these chemicals to stimulate vitellogenesis. The overall results demonstrated that PFOS, PFOA and FTOHs have estrogenic activities and that exposure to a combination of E2 and PFCs produced anti-estrogenic effects. The results of the estrogen receptor inhibition assay further suggested that the estrogenic effect of PFCs may be mediated by the estrogen receptor pathway in primary cultured tilapia hepatocytes. (c) 2007 Elsevier B.V. All rights reserved.

Induction of oxidative stress and apoptosis by PFOS and PFOA in primary cultured hepatocytes of freshwater tilapia (Oreochromis niloticus)

Perfluorinated organic compounds (PFOCs) are emerging persistent organic pollutants (POPs) widely present in the environment, wildlife and human. We studied the cellular toxicology of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) on oxidative stress and induction of apoptosis in primary cultured hepatocytes of freshwater tilapia (Oreochromis niloticus). Cultured hepatocytes were exposed to PFOS or PFOA (0, 1, 5, 15 and 30 mg L-1) for 24 h, and a dose-dependent decrease in cell viability was determined using trypan blue exclusion method. Significant induction of reactive oxygen species (ROS) accompanied by increases in activities of superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GR) were found, while activities of glutathione peroxidase (GPx) and glutathione-S-transferase (GST) were decreased. Glutathione (GSH) content was reduced following treatment of PFOA and PFOS. A dose-dependent increase in the lipid peroxidation (LPO) level (measured as maleic dialdehyde, MDA) was observed only in the PFOA exposure groups, whereas LPO remained unchanged in the PFOS exposure groups. Furthermore, a significant activation of caspase-3, -8, -9 activities was evident in both PFOS and PFOA exposure groups. Typical DNA fragmentation (DNA laddering) was further characterized by agarose gel electrophoresis. The overall results demonstrated that PFOS and PFOA are able to produce oxidative stress and induce apoptosis with involvement of caspases in primary cultured tilapia hepatocytes. (c) 2007 Elsevier B.V. All rights reserved.

Effects of 2,3,7,8-TCDD and benzo[a]pyrene on modulating vitellogenin expression in primary culture of crucian carp (Carassius auratus) hepatocytes

Vitellogenin (Vtg) is the precursor of yolk protein. Its expression and secretion are estrogen-regulated and are crucial for oocyte maturation. An in vitro xenoestrogen screening model was established by measuring Vtg induction in cultured primary hepatocytes from crucian carp. Vtg production was detected by biotin-avidin sandwich ELISA method while Vtg and cytochrome P4501A1 (CYP1A1) mRNA induction were measured by semi- quantitative PCR-primer dropping technique. Vtg and Vtg mRNA were dose-dependently induced by diethylstilbestrol (DES, 0.2-200 ng/mL) in hepatocytes of crucian carp. Co-treatment of the DES-induced hepatocytes with either 2,3,7,8-TCDD (TCDD, 0.1-4 pg/mL) or benzo[a]pyrene (B[a]P, 5-1000 ng/mL) resulted in a reduction of Vtg production and an increment of CYP1A1 mRNA expression both in a dose dependent manner, indicating the anti-estrogenic effects of the compounds. However, at lower tested concentrations, TCDD (0.1, 0.2 pg/mL), B[a]P (5 ng/mL) seemed to have a potentiating effect on Vtg expression and secretion, although by their own these compounds had no observable estrogenic effect on Vtg induction. Tamoxifen (a selective estrogen receptor modulators, 1 nmol/L-1 mumol/L), and P-naphtho-flavone (beta-NF, an aryl hydrocarbon receptor inducing compounds, 2.5-1000 ng/mL) also were employed to study the possible interactions in DES-induced Vtg expression. In co-treatment of the DES-induced hepatocytes with beta-NF or tamoxifen, the decrease in Vtg production did parallel induction of CYP1A1 for beta-NF, but tamoxifen inhibited Vtg induction did not parallel induced CYP1A1 expression in all test concentrations. On the contrary, it was found that in co-treatment of the TCDD-induced hepatocytes with DES, TCDD induced CYP1A1 mRNA production was inhibited by DES also. These results implicated a possible cross talk between estrogen receptor- and aryl hydrocarbon receptor-mediated pathways in the hepatocytes.

on quadratic bent functions in polynomial forms

In this correspondence, we construct some new quadratic bent functions in polynomial forms by using the theory of quadratic forms over finite fields. The results improve some previous work. Moreover, we solve a problem left by Yu and Gong in 2006.

An exploration of the positive and negative relationships associated with the development of asthma and atopic disorders in primary school children in Cork

Childhood asthma, allergic rhinitis and eczema are complex heterogenic chronic inflammatory allergic disorders which constitute a major burden to children, their families. The prevalence of childhood allergic disorders is increasing worldwide and merely rudimentary understanding exists regarding causality, or the influence of the environment on disease expression. Phase Three of the International Study of Asthma and Allergy in Childhood (ISAAC) reported that Irish adolescents had the 4th highest eczema and rhinoconjunctivitis prevalence and 3rd highest asthma prevalence in the world. There are no ISAAC data pertaining to young Irish children. In 2002, Sturley reported a high prevalence of current asthma in Cork primary school children aged 6-9 years. This thesis comprises of three cross-sectional studies which examined the prevalence of and associations with childhood allergy and a quasi-retrospective cohort study which observed the natural history of allergy from 6-9 until 11-13 years. Although not part of ISAAC, data was attained by parentally completed ISAAC-based questionnaires, using the ISAAC protocol. The prevalence, natural history and risk factors of childhood allergy in Ireland, as described in this thesis, echo those in worldwide allergy research. The variations of prevalence in different populations worldwide and the recurring themes of associations between childhood allergy and microbial exposures, from farming environments and/or gastrointestinal infections, as shown in this thesis, strengthen the mounting evidence that microbial exposure on GALT may hold the key to the mechanisms of allergy development. In this regard, probiotics may be an area of particular interest in allergy modification. Although their effects in relation to allergy, have been investigated now for several years, our knowledge of their diversity, complex functions and interactions with gut microflora, remain rudimentary. Birth cohort studies which include genomic and microbiomic research are recommended in order to examine the underlying mechanisms and the natural course of allergic diseases.