Pharmacokinetics of radiopharmaceuticals.

The pharmacokinetics of various radiopharmaceuticals following i.v. administration in mice and rats has been studied and compared. Before injection the radiochemical purity (RP) of the compounds were determined by HPLC and PAGE. In all cases RP-s were higher than 90%. The biodistribution of 99mTc labelled anti CEA IgG was studied in mice bearing human colon carcinoma xenografts. Animals with different tumour weights showed different blood kinetic and tumor uptake. The pilot clinical study of the 99mTc labelled anti melanoma Fab and 111-In-DTPA labelled anti melanoma F(ab')2 showed differences in the pharmacokinetic parameters. (99mTc labelled: comp.A. 84.6%; T1/2:0.6 h, 111-In-labelled: comp.A.: 46%, T1/2 1.5 h.) The various isonitrile derivatives synthetized in our laboratory were labelled with 99mTc and the biodistribution were tested in rats. The kinetic study showed that all the three molecules have different half lives in the heart and liver (T1/2 for heart ranged 5.1-18.6 h, for liver T1/2:1.2-2.5 h). Reversed phase HPLC study of the collected bile showed the 15-100% of injected compounds are metabolized during hepatic excretion. Literature data and our recent observations confirm that the knowledge of pharmacokinetics of radiolabelled compounds both in research, development and clinical practice is of basic importance.     

Aquatic bird densities in two coastal lagoon systems in Chiapas State,Mexico, a preliminary assessment

Six bodies of water in two coastal lagoon systems were investigated in Chiapas State, Mexico between July, 1990 and February, 1991. The size of water bodies ranged from 102.5 to 847.5 ha. Salinity varied seasonally being the lowest in July during the rainy season (1.0) and highest in February (35.8). The waters are hypertrophic with total phosphorus concentrations as high 900 mg m^–3.The number of bird species was the highest in February (N = 9 to 23) and the lowest in July (N = 2 to 15). The majority of birds present are resident species of Mexico but several species of northern birds were present in February (e.g. Lesser Scoup, Osprey, Peregrin Falcon).The number of birds observed in the waterbodies varied during the study period being as high as 2800 Cormorants, 2300 White Pelicans and 681 Limpkins, at a particular time, or expressed in terms of units surface area of each lagoon 8.0, 2.7 and 1.9 individuals per hectare respectively. The daily food requirements of White Pelicans at such a high density is about 4.1 kg ha^–1 d^–1.The hypertrophic state of Cerritos Lagoon allows a sufficient level of production to support such a high food requirement. Considering the limited survey time spent on the lagoons the bird population numbers are probably underestimated.     

Sackville Waterfowl Park,Sackville, New Brunswick,Canada. Baseline characterization,towards long-term monitoring

The Sackville Waterfowl Park, contains a 19 hectare shallow freshwater wetland created by reflooding a saltwater marsh that was drained three centuries ago. Its primary purpose is to provide wetland habitat and wildlife viewing opportunities to tourists and residents. This newly created, eutrophic wetland supports high densities of waterfowl, 2.1 and 3.3 brood ha^–1 in 1991 and 1992 respectively. It is hoped that long term monitoring of the Park's waterfowl population and wetland habitat will contribute to a better understanding of factors controlling breeding waterfowl populations.     

Identification of a major T-cell epitope within VP3 amino acid residues 24 to 37 of Theiler's virus in demyelination-susceptible SJL/J mice.

Intracerebral inoculation of susceptible strains of mice with Theiler's murine encephalomyelitis virus (TMEV) results in a chronic, immunologically mediated demyelinating disease that shares many features with human multiple sclerosis. CD4+ T lymphocytes play a critical role in the pathogenesis of virus-induced demyelinating disease. We have identified a region within amino acid residues 24 to 37 of the VP3 capsid protein of TMEV (VP3(24-37)) that is recognized by T lymphocytes from the demyelination-susceptible SJL/J strain of mice. The T-cell response to VP3(24-37) represents a predominant Th-cell response against the virus from either TMEV-immunized or TMEV-infected SJL/J mice, and viral epitopes VP1(233-250), VP2(74-86), and VP3(24-37) account for most of the Th-cell response to TMEV.     

Temperament and Character in the Child and Adolescent Twin Study in Sweden (CATSS): Comparison to the General Population,and Genetic Structure Analysis

Background

The Child and Adolescent Twin Study in Sweden (CATSS) is an on-going, large population-based longitudinal twin study. We aimed (1) to investigate the reliability of two different versions (125-items and 238-items) of Cloninger''s Temperament and Character Inventory (TCI) used in the CATSS and the validity of extracting the short version from the long version, (2) to compare these personality dimensions between twins and adolescents from the general population, and (3) to investigate the genetic structure of Cloninger''s model.

Method

Reliability and correlation analyses were conducted for both TCI versions, 2,714 CATSS-twins were compared to 631 adolescents from the general population, and the genetic structure was investigated through univariate genetic analyses, using a model-fitting approach with structural equation-modeling techniques based on same-sex twin pairs from the CATSS (423 monozygotic and 408 dizygotic pairs).

Results

The TCI scores from the short and long versions showed comparable reliability coefficients and were strongly correlated. Twins scored about half a standard deviation higher in the character scales. Three of the four temperament dimensions (Novelty Seeking, Harm Avoidance, and Persistence) had strong genetic and non-shared environmental effects, while Reward Dependence and the three character dimensions had moderate genetic effects, and both shared and non-shared environmental effects.

Conclusions

Twins showed higher scores in character dimensions compared to adolescents from the general population. At least among adolescents there is a shared environmental influence for all of the character dimensions, but only for one of the temperament dimensions (i.e., Reward Dependence). This specific finding regarding the existence of shared environmental factors behind the character dimensions in adolescence, together with earlier findings showing a small shared environmental effects on character among young adults and no shared environmental effects on character among adults, suggest that there is a shift in type of environmental influence from adolescence to adulthood regarding character.     

Completeness of Reporting of Patient-Relevant Clinical Trial Outcomes: Comparison of Unpublished Clinical Study Reports with Publicly Available Data

Background

Access to unpublished clinical study reports (CSRs) is currently being discussed as a means to allow unbiased evaluation of clinical research. The Institute for Quality and Efficiency in Health Care (IQWiG) routinely requests CSRs from manufacturers for its drug assessments.Our objective was to determine the information gain from CSRs compared to publicly available sources (journal publications and registry reports) for patient-relevant outcomes included in IQWiG health technology assessments (HTAs) of drugs.

Methods and Findings

We used a sample of 101 trials with full CSRs received for 16 HTAs of drugs completed by IQWiG between 15 January 2006 and 14 February 2011, and analyzed the CSRs and the publicly available sources of these trials. For each document type we assessed the completeness of information on all patient-relevant outcomes included in the HTAs (benefit outcomes, e.g., mortality, symptoms, and health-related quality of life; harm outcomes, e.g., adverse events). We dichotomized the outcomes as “completely reported” or “incompletely reported.” For each document type, we calculated the proportion of outcomes with complete information per outcome category and overall.We analyzed 101 trials with CSRs; 86 had at least one publicly available source, 65 at least one journal publication, and 50 a registry report. The trials included 1,080 patient-relevant outcomes. The CSRs provided complete information on a considerably higher proportion of outcomes (86%) than the combined publicly available sources (39%). With the exception of health-related quality of life (57%), CSRs provided complete information on 78% to 100% of the various benefit outcomes (combined publicly available sources: 20% to 53%). CSRs also provided considerably more information on harms. The differences in completeness of information for patient-relevant outcomes between CSRs and journal publications or registry reports (or a combination of both) were statistically significant for all types of outcomes.The main limitation of our study is that our sample is not representative because only CSRs provided voluntarily by pharmaceutical companies upon request could be assessed. In addition, the sample covered only a limited number of therapeutic areas and was restricted to randomized controlled trials investigating drugs.

Conclusions

In contrast to CSRs, publicly available sources provide insufficient information on patient-relevant outcomes of clinical trials. CSRs should therefore be made publicly available. Please see later in the article for the Editors'' Summary     

Nutrient enrichment increased species richness of leaf litter fungal assemblages in a tropical forest

Microbial communities play a major role in terrestrial ecosystem functioning, but the determinates of their diversity and functional interactions are not well known. In this study, we explored leaf litter fungal diversity in a diverse Panama lowland tropical forest in which a replicated factorial N, P, K and micronutrient fertilization experiment of 40 × 40 m plots had been ongoing for nine years. We extracted DNA from leaf litter samples and used fungal‐specific amplification and a 454 pyrosequencing approach to sequence two loci, the nuclear ribosomal internal transcribed spacer (ITS) region and the nuclear ribosomal large subunit (LSU) D1 region. Using a 95% sequence similarity threshold for ITS1 spacer recovered a total of 2523 OTUs, and the number of unique ITS1 OTUs per 0.5–1.0 g leaf litter sample ranged from 55 to 177. Ascomycota were the dominant phylum among the leaf litter fungi (71% of the OTUs), followed by Basidiomycota (26% of the OTUs). In contrast to our expectations based on temperate ecosystems, long‐term addition of nutrients increased, rather than decreased, species richness relative to controls. Effect of individual nutrients was more subtle and seen primarily as changes in community compositions especially at lower taxonomic levels, rather than as significant changes in species richness. For example, plots receiving P tended to show a greater similarity in community composition compared to the other nutrient treatments, the +PK, +NK and +NPK plots appeared to be more dominated by the Nectriaceae than other treatments, and indicator species for particular nutrient combinations were identified.