Fate of biomedical research protocols and publication bias in France: retrospective cohort study

Objectives To describe the fate of protocols approved by the French research ethics committees, a national system created by the French 1988 Huriet-Sérusclat Act; to assess publication bias at a national level.Design Retrospective cohort study.Setting Representative sample of 25/48 French research ethics committees in 1994.Protocols 649 research protocols approved by committees, with follow-up information.Main outcome measures Protocols'' initial characteristics (design, study size, investigator) abstracted from committees'' archives; follow-up information (rates of initiation, completion, and publication) obtained from mailed questionnaire to principal investigators.Results Completed questionnaires were available for 649/976 (69%) protocols. Of these, 581 (90%) studies were initiated, 501/581 (86%) were completed, and 190/501 (38%) were published. Studies with confirmatory results were more likely to be published as scientific papers than were studies with inconclusive results (adjusted odds ratio 4.59, 95% confidence interval 2.21 to 9.54). Moreover, studies with confirmatory results were published more quickly than studies with inconclusive results (hazard ratio 2.48, 1.36 to 4.55).Conclusion At a national level, too many research studies are not completed, and among those completed too many are not published. We suggest capitalising on research ethics committees to register and follow all authorised research on human participants on a systematic and prospective basis.     

Alteration of membrane permeability by amphotericin B

Amphotericin B (AmB) increased unidirectional Na transport and net transcellular sodium movements across the skin of the frog, Rana pipiens, when added to the solution bathing the corium side, but not from the outer epidermal surface. The AmB response was prevented with pretreatment with amiloride, ouabain and mucosal sodium substitution. Alteration in pH markedly reduced the permeability changes induced by AmB. AmB did not interfere with the increase in sodium transport induced by antidiuretic hormone. The present study demonstrates that AmB interacts with the skin of the frog, Rana pipiens, from the corium side specifically increasing transepithelial sodium transport. The increase in transport apparently occurs through the existing sodium pathway.     

Vers une approche physiopathologique des troubles de l’éjaculation

Seminal emission and sperm expulsion are under the control of both the sympathetic and parasympathetic outflows and also of the somatic innervation conveyed by the pudendal nerve. The 2 phases of ejaculation are reflexive with the reflexes handled at the thoraco-lumbar and sacral levels of the spinal cord. Such a spinal organization remains widely unknown. The role of various peripheral neurotransmitters has been evidenced including norepinephrine and acetylcholine and also peptidergic, purinergic i.e. ATP and nitric oxide. Stimulation of the seminal tract afferents play a crucial in the onset of ejaculatory mechanisms. Except for the dorsal nerve of the penis, there is a lack of information concerning these afferents. Several supraspinal centers i.e. hypothalamus, medial amygdala, pons and nucleus paragigantocellularis exert descending and ascending inhibitory and excitatory influences on spinal nuclei controlling emission and expulsion of sperm. Central neurotransmission responsible for this supraspinal control could involve serotonin, oxytocin and norepinephrine. In the light of the available anatomical and neurophysiological data, pathophysiological aspects of ejaculatory disorders are futher discussed. Premature ejaculation could be related to a periheral and central hypersentivity. Most of the other ejaculation abnormalities are likely mainly related to an impairment of the central mechanisms.     

Chromatographic and immunological evidence that chloroplastic and cytosolic pea (Pisum sativum L.) NADP-isocitrate dehydrogenases are distinct isoenzymes

Two NADP-isocitrate dehydrogenase isoenzymes designated as NADP-IDH₁ and NADP-IDH₂ (EC 1.1.1.42) were identified in pea (Pisum sativum) leaf extracts by diethylaminoethylcellulose chromatography. The predominant form was found to be NADP-IDH₁ while NADP-IDH₂ represented only about 4% of the total leaf enzyme activity. These enzymes share few common epitopes as NADP-IDH₂ was poorly recognized by the specific polyclonal antibodies raised against NADP-IDH₁, and as a consequence NADP-IDH₂ does not result from a post-translational modification of NADP-IDH₁. Subcellular fractionation and isolation of chloroplasts through a Percoll gradient, followed by the identification of the associated enzymes, showed that NADP-IDH₁ is restricted to the cytosol and NADP-IDH₂ to the chloroplasts. Compared with the cytosolic isoenzyme, NADP-IDH₂ was more thermolabile and exhibited a lower optimum pH. The data reported in this paper constitute the first report that the chloroplastic NADP-IDH and the cytosolic NADP-IDH are two distinct isoenzymes. The possible functions of the two isoenzymes are discussed.Abbreviations BSA bovine serum albumin - DEAE diethylaminoethyl - NADP-IDH NADP-isocitrate dehydrogenase - NADP-IDH₁ cytosolic NADP-IDH - NADP-IDH₂ chloroplastic NADP-IDH     

Evaluation of the relative amount of specific gaba-benzodiazepine receptor mrna after injection of total poly(A+)-rna into xenopus oocytes

GABA-benzodiazepine receptor-chloride channel complexes have been detected by electrophysiological recording in Xenopus oocytes previously injected with messenger RNA extracted either from optic lobes of chick embryos or from adult rat hippocampi. The ability of the oocyte to correctly translate exogenous messengers was used to develop a routine method which could allow a quantitative evaluation of specific mRNA coding for GABA-benzodiazepine receptor proteins following an injection of a fixed amount of total poly(A+)-RNA. The conditions of the validation of this method have been determined.     

Comparative effects of four surfactants on growth,contraction and adhesion of cultured human fibroblasts

A range of surfactants, including the anionic sodium dodecyl sulfate, the cationic cetyltrimethylammonium bromide and the nonionics octylphenoxy polyethoxyethanol (Triton X100) and polyoxyethylene 20 sorbitan monoleate (Tween 80) was studied for effects on proliferation, contractibility and attachment of cultured human fibroblasts. Only ionic surfactants exhibited a stimulatory effect on fibroblast proliferation, whereas all the surfactants tested increased the contraction of collagen gels containing fibroblasts, with the greatest effect from the non-ionic surfactants. This activity was not correlated with an increase of cell population or cell attachment within the collagenous matrix. The activity of the surfactants was seen only at levels close to their LD₅₀ values and in a narrow range of concentrations. Thus, we consider that they are the result of the so-called hormesis phenomenon.Abbreviations CTAB cetyltrimethyl-ammonium bromide - FCS fetal calf serum - LD₁₀₀ dose lethal to 100% of exposed - MCD maximal contraction dose - PDL population doubling level - SDS sodium dodecyl sulfate     

Subculture of rabbit articular chondrocytes within a collagen gel: growth and analysis of differentiation

Primary cultures of rabbit articular chondrocytes have been subcultured within three-dimensional (3D) collagen gels. Under these conditions, the cells remained viable and divided, but with a lower proliferation rate than that observed in control monolayer cultures. Flow cytometric analysis of progression of the cells into the cell cycle has confirmed and extended these findings. Also the cellular volume was decreased in 3D-culture, being in the same range as thein vivo size of cartilage cells. Specific staining for proteoglycans and type II collagen immunolocalization on sections of gels showed the expression of differentiated phenotypes and revealed the accumulation of these matrix components in the immediate surroundings of the cells. The use of Ultroser G (a serum substitute) improved the conditions for 3D- culture of rabbit articular chondrocytes.     

Protein Synthesis Linked to Respiration and Phosphorylation in Intact Euglena Mitochondria

Highly purified condensed mitochondria obtained from bleachedmutant. W₁₀BSmL of Euglena gracilis Klebs var bacillaris Coriincorporate [³⁵S]methionine into protein when fortified withmalate, ADP, Mg²⁺, phosphate and a sucrose osmoticum. Twentyto twenty-five polypeptide bands were found to be labeled inorganello when the labeled protein was subjected to sodium dodecylsulfatepolyacrylamide gel electrophoresis. Methionine incorporation,but not respiration or oxidative phosphorylation, was blockedby chloramphenicol and other 70S ribosomal translation inhibitorsbut cycloheximide and ribonuclease were without effect. Inhibitorsof electron transport and uncouplers of oxidative phosphorylationwere excellent inhibitors of protein synthesis. Thus, thesemitochondrial preparations carry out protein synthesis in organellothat is linked to respiration and oxidative phosphorylation. ¹Present address: VA Hospital Outpatient Clinic, 17 Court St.,Boston, MA 02115, U.S.A. ²Present address: Laboratories de Microbiologia e Inmunologia,Universidad Catolica de Chile, Casilla 114-D, Santiago, Chile. ³Present address: Botany Department, University of Massachusetts,Amherst, MA 01003, U.S.A. (Received June 17, 1985; Accepted October 28, 1985)