The use of conditioned place preference to determine broiler preferences for quantitative or qualitative dietary restriction.

1. Calcium propionate (CAP) may improve the welfare of feed restricted broiler breeders by improving their satiety when included within the feed ration. However, the evidence for this is mixed. 2. This study used a closed economy conditioned place preference (CPP) task and aimed to identify whether broilers (as a model for broiler breeders) preferred an environment associated with quantitative food restriction (QFR) or an environment associated with a diet quality-adjusted by the inclusion of CAP. Birds taught to associate different environments with QFR and ad libitum (AL) access to feed were used to validate the methodology. 3. The two treatment groups were (1) QFR/AL (n = 12) in which birds alternated every 2 d between QFR and ad libitum access to food, and (2) QFR/CAP (n = 12) in which birds alternated every 2 d between QFR and QFR + calcium propionate (increased from 3-9% over the study period). Birds were taught to associate one diet option with vertical stripes and the other with horizontal black and white stripes. Each bird was tested twice for a CPP (once per diet). 4. QFR/AL birds showed a significant preference for the pen associated with ad libitum access to feed, but only when tested hungry (i.e. fed QFR on day of testing). QFR/CAP birds did not show a preference under either hunger state. 5. Reasons for the failure of QFR/CAP birds to show a preference are unclear but could include a lack of preference or failure to learn the task. 6. The existence of state-dependent effects indicates that care is needed in the design of future CPP studies and that the effect of calcium propionate and level of hunger on ability to learn a CPP needs further investigation.

Prosthodontic rehabilitation of hypophosphatasia using dental implants: a review of the literature and two case reports.

There are reports in the literature of the various dental features of hypophosphatasia, especially where it affects the deciduous dentition. The descriptions include both the manifestations of the disorder and the subsequent patterns of tooth loss. There are fewer descriptions of the effects of hypophosphatasia on the permanent dentition and little information on the subsequent prosthodontic management of these patients, particularly in relation to the use of dental implants. The aim of this paper was to review the literature on the dental effects of hypophosphatasia, present two cases and describe how one of those patients, a young adult, was successfully rehabilitated using dental implants. That latter patient's pattern of tooth loss as well as some histological and scanning electron microscopic findings of root cementum from the other case is also described.

Nonclinical aspects of biopharmaceutical development: discussion of case studies at a PhRMA-FDA workshop.

Robust assessments of the nonclinical safety profile of biopharmaceuticals are best developed on a scientifically justified, case-by-case basis, with consideration of the therapeutic molecule, molecular target, and differences/similarities between nonclinical species and humans (ICH S6). Significant experience has been gained in the 10 years ensuing since publication of the ICH S6 guidance. In a PhRMA-FDA-sponsored workshop, "Nonclinical Aspects of Biopharmaceutical Development," industry and US regulatory representatives engaged in exploration of current scientific and regulatory issues relating to the nonclinical development of biopharmaceuticals in order to share scientific learning and experience and to work towards establishing consistency in application of general principles and approaches. The proceedings and discussions of this workshop confirm general alignment of strategy and tactics in development of biopharmaceuticals with regard to such areas as species selection, selection of high doses in toxicology studies, selection of clinical doses, the conduct of developmental and reproductive toxicity (DART) studies, and assessment of carcinogenic potential. However, several important aspects, including, for example, appropriate use of homologues, nonhuman primates, and/or in vitro models in the assessment of risk for potential developmental and carcinogenic effects, were identified as requiring further scientific exploration and discussion.

Radiotherapy dosimetry using a commercial OSL system.

A commercial optically stimulated luminescence (OSL) system developed for radiation protection dosimetry by Landauer, Inc., the InLight microStar reader, was tested for dosimetry procedures in radiotherapy. The system uses carbon-doped aluminum oxide, Al2O3:C, as a radiation detector material. Using this OSL system, a percent depth dose curve for 60Co gamma radiation was measured in solid water. Field size and SSD dependences of the detector response were also evaluated. The dose response relationship was investigated between 25 and 400 cGy. The decay of the response with time following irradiation and the energy dependence of the Al2O3:C OSL detectors were also measured. The results obtained using OSL dosimeters show good agreement with ionization chamber and diode measurements carried out under the same conditions. Reproducibility studies show that the response of the OSL system to repeated exposures is 2.5% (1sd), indicating a real possibility of applying the Landauer OSL commercial system for radiotherapy dosimetric procedures.

Supportive therapy for schizophrenia.

BACKGROUND: Supportive therapy is often used in everyday clinical care and in evaluative studies of other treatments. OBJECTIVES: To estimate the effects of supportive therapy for people with schizophrenia. SEARCH STRATEGY: We searched the Cochrane Schizophrenia Group's register of trials (January 2004), supplemented by manual reference searching and contact with authors of relevant reviews or studies. SELECTION CRITERIA: All randomised trials involving people with schizophrenia and comparing supportive therapy with any other treatment or standard care. DATA COLLECTION AND ANALYSIS: We reliably selected studies, quality rated these and extracted data. For dichotomous data, we estimated the relative risk (RR) fixed effect with 95% confidence intervals (CI). Where possible, we undertook intention-to-treat analyses. For statistically significant results, we calculated the number needed to treat/harm (NNT/H). We estimated heterogeneity (I-square technique) and publication bias. MAIN RESULTS: We included 21 relevant studies. We found no significant differences in the primary outcomes between supportive therapy and standard care. There were, however, significant differences favouring other psychological or psychosocial treatments over supportive therapy. These included hospitalisation rates (3 RCTs, n=241, RR 2.12 CI 1.2 to 3.6, NNT 8) but not relapse rates (5 RCTs, n=270, RR 1.18 CI 0.9 to 1.5). We found that the results for general functioning significantly favoured cognitive behavioural therapy compared with supportive therapy in the short (1 RCT, n=70, WMD -9.50 CI -16.1 to -2.9), medium (1 RCT, n=67, WMD -12.6 CI -19.4 to -5.8) and long term (2 RCTs, n=78, SMD -0.50 CI -1.0 to -0.04), but the clinical significance of these findings based on few data is unclear. Participants were less likely to be satisfied with care if receiving supportive therapy compared with cognitive behavioural treatment (1 RCT, n=45, RR 3.19 CI 1.0 to 10.1, NNT 4 CI 2 to 736). The results for mental state and symptoms were unclear in the comparisons with other therapies. No data were available to assess the impact of supportive therapy on engagement with structured activities. AUTHORS' CONCLUSIONS: There are insufficient data to identify a difference in outcome between supportive therapy and standard care. There are several outcomes, including hospitalisation and general mental state, indicating advantages for other psychological therapies over supportive therapy but these findings are based on a few small studies. Future research would benefit from larger trials that use supportive therapy as the main treatment arm rather than the comparator.

Supportive therapy for schizophrenia.

BACKGROUND: Supportive therapy is often used in everyday clinical care and in evaluative studies of other treatments. OBJECTIVES: To estimate the effects of supportive therapy for people with schizophrenia. SEARCH STRATEGY: We searched the Cochrane Schizophrenia Group's register of trials (January 2004), supplemented by manual reference searching and contact with authors of relevant reviews or studies. SELECTION CRITERIA: All randomised trials involving people with schizophrenia and comparing supportive therapy with any other treatment or standard care. DATA COLLECTION AND ANALYSIS: We reliably selected studies, quality rated these and extracted data. For dichotomous data, we estimated the relative risk (RR) fixed effect with 95% confidence intervals (CI). Where possible, we undertook intention-to-treat analyses. For statistically significant results, we calculated the number needed to treat/harm (NNT/H). We estimated heterogeneity (I-square technique) and publication bias. MAIN RESULTS: We included 21 relevant studies. We found no significant differences in the primary outcomes between supportive therapy and standard care. There were, however, significant differences favouring other psychological or psychosocial treatments over supportive therapy. These included hospitalisation rates (3 RCTs, n=241, RR 2.12 CI 1.2 to 3.6, NNT 8) but not relapse rates (5 RCTs, n=270, RR 1.18 CI 0.9 to 1.5). We found that the results for general functioning significantly favoured cognitive behavioural therapy compared with supportive therapy in the short (1 RCT, n=70, WMD -9.50 CI -16.1 to -2.9), medium (1 RCT, n=67, WMD -12.6 CI -19.4 to -5.8) and long term (2 RCTs, n=78, SMD -0.50 CI -1.0 to -0.04), but the clinical significance of these findings based on few data is unclear. Participants were less likely to be satisfied with care if receiving supportive therapy compared with cognitive behavioural treatment (1 RCT, n=45, RR 3.19 CI 1.0 to 10.1, NNT 4 CI 2 to 736). The results for mental state and symptoms were unclear in the comparisons with other therapies. No data were available to assess the impact of supportive therapy on engagement with structured activities. AUTHORS' CONCLUSIONS: There are insufficient data to identify a difference in outcome between supportive therapy and standard care. There are several outcomes, including hospitalisation and general mental state, indicating advantages for other psychological therapies over supportive therapy but these findings are based on a few small studies. Future research would benefit from larger trials that use supportive therapy as the main treatment arm rather than the comparator.

Soluble cell adhesion molecules in gingival crevicular fluid in periodontal health and disease.

BACKGROUND: Cell adhesion molecules (CAMs) are cell surface proteins involved in the binding of cells to each other, to endothelial cells, or to the extracellular matrix. The soluble forms of CAMs (sCAMs) are thought to be produced by proteolytic cleavage from the cell surface and are shed into the gingival crevicular fluid (GCF). The aim of this study was to investigate whether sCAMs, sICAM-1, sVCAM-1, and sE-Selectin were present in GCF in both periodontal health and disease and to examine their relationship with periodontal inflammation. METHODS: GCF was collected from a clinically healthy, a gingivitis, and a periodontitis site in 29 subjects with chronic periodontitis and from a single clinically healthy site in 22 subjects without chronic periodontitis. The volume of GCF was measured and each sample was analyzed for sCAMs by enzyme-linked immunosorbent assay (ELISA). The effect of treatment (oral hygiene instruction, scaling and root planing) on the levels of sCAMs in each site of the diseased group was also investigated. RESULTS: Statistically significant differences (P < 0.05) were found between the levels of sVCAM-1 in periodontal health and disease. These results indicate that changes in the levels of sCAMs may be a sensitive indicator to differentiate healthy sites from those with periodontitis. Statistically significant changes in the levels of sICAM-1 were recorded after treatment (P < 0.05). CONCLUSIONS: Further studies are required to establish if these potential biomarkers will enable the identification of those sites most at risk for disease progression and also evaluate the response to treatment, thereby playing a preventive role in the pathogenesis of periodontal disease.

The water-equivalence of phantom materials for 90Sr-90Y beta particles.

Intravascular brachytherapy requires that the dose be specified within millimeters of the source. High dose gradients near brachytherapy sources require that the source-detector distance be accurately known for dosimetry purposes. Solid phantoms can be designed to accommodate these stringent requirements. This study reports dosimeter readings from 90Sr-90Y sources measured in water, A150, polystyrene and in an epoxy-based water-equivalent plastic. Measurements showed that while A150 and the epoxy-based plastic agreed well with water when the surface of the source contacted the detector housing, the relative response in the phantoms decreased with increasing depth in phantom, falling to approximately 0.55 those of water at a depth of 5 mm. Readings in polystyrene were within 4% of those in water between 1 and 2 mm depth. However, while polystyrene followed water more closely than the other two materials, at greater depths the relative response in polystyrene to water varied from 0.65 to 1.34. When the density of the materials is accounted for, the relative response in A150 is nearly constant with increasing areal density. Furthermore, the response in A150 shows the closest agreement with that in water of any of the solid materials for higher areal densities. For values below 0.3 g/cm2, polystyrene shows the closest agreement with water.

Identification of urinary metabolites of isoprene in rats and comparison with mouse urinary metabolites.

Isoprene, a major commodity chemical used in production of polyisoprene elastomers, has been shown to be carcinogenic in rodents. Similar to findings for the structurally related compound butadiene, mice are more susceptible than rats to isoprene-induced toxicity and carcinogenicity. Although differences in uptake, and disposition of isoprene in rats and mice have been described, its in vivo biotransformation products have not been characterized in either species. The purpose of these studies was to identify the urinary metabolites of isoprene in Fischer 344 rats and compare these metabolites with those formed in male B6C3F1 mice. After i.p. administration of 64 mg [14C]isoprene/kg to rats and mice, isoprene was excreted unchanged in breath ( approximately 50%) or as urinary metabolites ( approximately 32%). In rats isoprene was primarily excreted in urine as 2-hydroxy-2-methyl-3-butenoic acid (53%), 2-methyl-3-buten-1,2-diol (23%), and the C-1 glucuronide conjugate of 2-methyl-3-buten-1,2-diol (13%). These metabolites are consistent with preferential oxidation of isoprene's methyl-substituted vinyl group. No oxidation of the unsubstituted vinyl group was observed. In addition to the isoprene metabolites found in rat urine, mouse urine contained numerous other isoprene metabolites with a larger percentage (25%) of total urinary radioactivity associated with an unidentified, polar fraction than in the rat (7%). Unlike butadiene, there was no evidence that glutathione conjugation played a significant role in the metabolism of isoprene in rats. Because of the unidentified metabolites in mouse urine, involvement of glutathione in the metabolism of isoprene in mice cannot be delineated.

A survey of continuing dental education in the South and Mid-West Region of the Postgraduate Medical and Dental Board.

This paper presents the data from the analysis of Feedback Questionnaires obtained from dentists who attended Continuing Education Courses run by the Postgraduate Medical and Dental Board, South & Mid-West Region from 1992 to 1994. The implications of the findings are discussed.

A survey of continuing dental education in the South and Mid-West Region of the Postgraduate Medical and Dental Board.

This paper presents the data from the analysis of Feedback Questionnaires obtained from dentists who attended Continuing Education Courses run by the Postgraduate Medical and Dental Board, South & Mid-West Region form 1992 to 1994. The implications of the findings are discussed.

Carcinogenicity of 2',3'-dideoxycytidine in mice.

2',3'-dideoxycytidine (ddC) is a synthetic pyrimidine nucleoside analogue approved for treatment of HIV-positive patients. Previous studies indicated that ddC has the potential to cause thymic lymphoma in C57BL/6 x C3H F1 (hereafter called B6C3F1) mice. In this study, we evaluated the carcinogenic potential of ddC in two different mouse models. B6C3F1 hybrid mice carry ecotropic endogenous proviral sequences that may be activated to cause lymphoma, whereas NIH Swiss mice lack proviral sequences that can be expressed. The mice were treated with ddC by gavage at 500 and 1000 mg/kg/day for up to 6 months (human dose, 2.25 mg/day) and evaluated for toxicity, plasma levels of ddC, and pathological changes. Lymphocyte cell markers from the thymic lymphomas were assessed by immunophenotyping. Expression of p53 protein was evaluated using immunohistochemical staining. Treatment-related thymic lymphomas were present in both mouse models with a higher incidence in NIH Swiss than in B6C3F1 mice. The lymphomas were more prevalent in females than in males of both mouse models. Most mice with thymic lymphoma died during the course of the study. In addition to the thymus, lymphoma was often present in lymph nodes, spleen, and other organs. Lymphomas arose more frequently in mice that lack endogenous ecotropic retroviral sequences and thus were not due to activation of endogenous provirus. During the third month of the study, a few NIH Swiss mice that died had granulosa cell tumors of the ovary. Treatment-related but reversible thymic atrophy was observed in both mouse models. There was a very high correlation between the internal dose of ddC and the incidence of thymic lymphoma in both mouse models. Most of the lymphocytes from control thymuses and ddC-induced lymphomas were positive for Thy-1.2 (pan-T), heat stable antigen, and CD4 and CD8 markers, with no marked differences in the lymphocyte markers of the tumors between sexes or dose groups. p53 protein was detected in only 20% (23/115) of the ddC-induced lymphomas with mostly minimal expression in scattered cells. Because ddC induced lymphomas in two different mouse models, the potential carcinogenic risk should be considered in long-term treatment of HIV-positive patients, especially children and adolescent patients treated with ddC.

Biologically-based models of dioxin pharmacokinetics.

Significant advances have been made in the development of physiologically-based models of dioxin pharmacokinetics (PBPK) in the last 5-6 years. These models incorporate explicit descriptions of biological factors which determine tissue dosimetry of dioxin and include some description of dioxin-mediated pharmacodynamic events. Biological determinants of dioxin disposition include fat solubility, specific and inducible binding in the liver, diffusion-limited tissue distribution and metabolic elimination. PBPK models have been successfully used to predict the dose and time-dependent chemical disposition and protein induction properties of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) over a wide variety of experimental data sets with rodents. The models have also been extended to describe the disposition of a brominated dioxin, 2,3,7,8-tetrabromodibenzo-p-dioxin. As these quantitative descriptions of disposition are more fully refined, particularly with regard to pharmacodynamic descriptions of dioxin-mediated alterations in gene expression, more accurate predictions of tissue dosimetry and tissue responses will be performed across dose, species and related polyhalogenated aromatic hydrocarbons. Accurate, mechanistic dosimetry models will facilitate biologically-based approaches to the human risk assessment of these important and ubiquitous environmental contaminants.

A comparison of the attitudes of dentists and the public to periodontal health in Ireland.

The Irish National Gum Health Campaign began in 1989 and consisted of three stages. A questionnaire was sent to all dentists on the Irish Dental Register regarding their perception of their patients' knowledge of periodontal health and disease. In addition a postgraduate programme was established for dentists to learn a soft tissue screening programme based on the CPITN method but termed the Basic Periodontal Examination. Finally public attitudes were assessed by questionnaire and the results compared. The public had a far greater awareness of periodontal disease than the dentists had perceived. Overall the Campaign showed encouraging results primarily through the raising of awareness in both the dental profession and the public of the importance of periodontal health.

Photochemistry of DNA using 193 nm excimer laser radiation.

Photoproducts in double-stranded DNA induced by 193 nm radiation have been investigated. Double-stranded, supercoiled pBR322 DNA in buffered aqueous solution was exposed to varying fluences of 193 nm radiation from an ArF excimer laser. The quantum yields for formation of cyclobutylpyrimidine dimers, frank strand breaks and alkali labile sites were calculated from the conversion of supercoiled (Form I) DNA to relaxed (Form II) DNA after treatment with Micrococcus luteus dimer-specific endonuclease, no treatment, or treatment with alkali and heat, respectively. The quantum yields were 1.65 (+/- 0.03) X 10(-3) for pyrimidine dimers, 9.4 (+/- 3.2) X 10(-5) for frank strand breaks and 9.6 (+/- 3.6) X 10(-5) for alkali labile sites. The quantum yields for pyrimidine dimers and strand breaks and alkali labile sites were not affected by 10 nM mannitol. The relative quantum yields for these DNA photoproducts induced by 193 nm radiation differed markedly from those produced by 254 nm radiation.

Diabetes mellitus and periodontal disease in an Irish population.

The prevalence of periodontitis was studied in a population of 157 insulin dependent diabetes mellitus patients aged 8-78 years attending the outpatients diabetic clinic of a large general hospital in Cork, Ireland. Every third diabetic patient attending the clinic was selected for examination. The dental parameters measured were plaque index (PI), gingivitis index (GI), periodontal pocket depth (PD) and periodontal attachment loss (PAL). Diabetic control was measured by estimating percentage haemoglobin glycolysation (% Hb Alc) known duration of diabetes (KDD) and insulin dependence. It was found that none of the diabetic measurements showed any consistent pattern in relation to any of the periodontal measurements. The findings are in agreement with other studies which suggest that no significant correlation between diabetic parameters and periodontal disease can be demonstrated. When the diabetic patient suffered periodontitis it was due to factors (such as genetic predisposition) other than impaired glucose metabolism.