[Complete molar pregancy with development of non-metastatic persistent trophoblastic diseaseA case report, reflection of rules of care and decision-making processes Forensic responsibility and the position of doctor in the general gynecologic and obstetric outpatient practice]. / Mola hydatidosa completa s prechodem do nemetastázující perzistující trofoblastické nemociKazuistika, poucení a úvaha nad pravidly dispenzarizace a rozhodovacích mechanismu Forenzní zodpovednost a postavení spádového gynekologa.

OBJECTIVE: To define the forensic responsibility and the position of doctor in the general gynecologic and obstetric outpatient practice in care of the complete molar pregancy. DESIGN: Case report and review article. SETTING: General gynecologic and obstetric outpatient practice Velké Mezirící; Sanatorium REPROMEDA, Centre of reproductive medicine and preimplantation genetics, Brno; Histopatology department of Hospital Jihlava. CASE REPORT: The changing clinical presentation of complete molar pregnancy with development of non-metastatic gestational trophoblastic disease: management. Subsequent early pregnancies outcome following complete hydatiform molar pregnancy. DISCUSSION: Discussed are the forensic responsibility and the position of doctor in the general gynecologic and obstetric outpatient practice with the collaboration of Trophoblastic Disease Center based on the detail expert knowledges: rules of care and decision-making processes and potential controversies, the pitfalls of the histopathologic diagnosis, the genetics of complete hydatiform mole: new lights on a disease, outpatient follow-up and possibility and the risks of the subsequent pregnancy. CONCLUSION: The conclusion is trying to guide quickly a doctor in the general gynecologic and obstetric outpatient practice in the decision-making processes through the crossings of any situation of the complete molar pregnancy and outpatient follow-up, alternatively with the collaboration of Trophoblastic Disease Center.

Getting our house in order: an audit of the registration and publication of clinical trials supported by the National Institute for Health Research Oxford Biomedical Research Centre and the Musculoskeletal Biomedical Research Unit.

OBJECTIVES: To audit the proportion of clinical trials that had been publically registered and, of the completed trials, the proportion published. SETTING: 2 major research institutions supported by the National Institute of Health Research (NIHR). PRIMARY AND SECONDARY OUTCOME MEASURES: The proportion of trials reporting results within 12 months, 24 months and 'ever'. Factors associated with non-publication were analysed using logistic regression. INCLUSION CRITERIA: Phases 2-4 clinical trials identified from internal documents and publication lists. RESULTS: In total, 286 trials were identified. We could not find registration for 4 (1.4%) of these, all of which were completed and published. Of the trials with a registered completion date pre-January 2015, just over half (56%) were published, and half of these were published within 12 months (36/147, 25%). For some trials, information on the public registers was found to be out-of-date and/or inaccurate. No clinical trial characteristics were found to be significantly associated with non-publication. We have produced resources to facilitate similar audits elsewhere. CONCLUSIONS: It was feasible to conduct an internal audit of registration and publication in 2 major research institutions. Performance was similar to, or better than, comparable cohorts of trials sampled from registries. The major resource input required was manually seeking information: if all registry entries were maintained, then almost the entire process of audit could be automated--and routinely updated--for all research centres and funders.

[Status of bone mineral density after the long-standing application of contraception Depo-Provera]. / Stav kostní minerální denzity po mnohaleté aplikaci antikoncepce Depo-Provery.

OBJECTIVE: The objective of this study was to assess bone mineral density (BMD) on a cohort of women who used depot medroxyprogesterone acetate (DMPA) (Depo-Provera) contraception uninterruptedly between 3 and 10 years. DESIGN: Retrospective study with review of the literature. SETTINGS: Office gynecology Velké Mezirící; Osteocentrum Brno; Department of Obstetrics and Gynecology, Hospital Nové Mesto na Morave. METHODS: The study included 21 healthy women aged between 26 and 43 years (the mean age 31 years) who started long-term continual application of depot medroxyprogesterone acetate (DMPA) in contraception (Depo-Provera) (the mean time of using 7 years, range 3-10 years). The women underwent lumbar spine, hip, femoral neck and forearm BMC (g) (bone mass content), BMD (g/cm2)(bone mass density), T-score, PR (%) (peak reference), Z-score, AM (%)(age matched) evaluation using Hologic dual-energy X-ray absorptiometry. Age of women, time of application of Depo-Provera and body mass index (BMI) were collected. Randomly from this cohort of users DMPA (n = 11) were determined levels of serum folicle stimulating hormone (FSH) and estradiol (E2), mostly shortly before next application of DMPA. RESULTS: At average 7 years of treatment, as compared to baseline, the mean BMD of DMPA users was in total lumbar spine AM (age matched) 96.48%, total hip AM 100%, femoral neck AM 97.62%, total forearm (radius+ulna) AM 99.81%. Concentrations of serum estradiol varied from 94.3-294 pmol/l (25.7-80.1 pg/ml) with average level 190.3 pmol/l(51.9 pg/ml), seen in the early follicular phase. CONCLUSION: There are probably several reasons, but not at least, why mean bone loss even after long use of DMPA is low. The loss of BMD is more pronounced during the first 2 years of use DMPA and its fall subsequently gradually stabilises due to new balance between extrinsic and intrinsic factors that influence bone resorption and formation. After the two years bone loss in DMPA users nears under 1% per year and practically copies level of physiological bone loss. Another hypothetical compensation mechanisms of bone remodelling in the hypoestrogenic time during DMPA use may be reason of higher levels of BMD 4-5 years after discontinuing the use of contraceptive injections than that of nonusers (rebound phenomenon).

Regulation of online pharmacies: a case for cooperative federalism.

Ms. Zeman examines the regulatory challenges and responses arising from online pharmacies. In particular, Ms. Zeman discusses the roles taken by the States' attorney general offices, the States' legislatures, and the pharmaceutical industry itself, to ensure protection for those consumers seeking health care via the Internet.

Self--administered cough cardiopulmonary resuscitation (c-CPR) in patients threatened by MAS events of cardiovascular origin.

Sudden cardiac death caused by cardiac arrhythmia's or asystolies in patients with coronary heart disease can often be avoided if resuscitation is administered immediately, preferably before the patient loses consciousness. In cases when rapid help is not available usually death occurs. We have studied a method of cardiopulmonary resuscitation (CPR) which can be self--administered by patients trained in recognizing imminent arrival of life-threatening Morgani Adams Stokes (MAS) events. The recent study comprised the three methods of investigation in three separate groups of patients: the first group underwent invasive procedures (20 pts), the second non invasive Doppler studies (31 pts) and the third in-and outhospital clinical observations (115 pts). The results indicate that evoked coughing can effectively prevent fainting and maintaining consciousness until conventional CPR help becomes available.

Characterization of covalent adriamycin-DNA adducts.

Adriamycin is a popular antineoplastic agent whose ability to form covalent adducts with DNA has been correlated to cellular apoptosis (programmed cell death) in tumor models. We have isolated and purified this adduct formed under oxido-reductive (Fenton) conditions in Tris buffer. We show by homo- and heteronuclear NMR spectroscopy that the covalent Adriamycin-DNA adduct is structurally equivalent to that resulting from direct reaction with formaldehyde. Covalent linkage of the drug to one of the DNA strands confers remarkable stability to the duplex, indicated by a 162-fold reduction in the rate of strand displacement compared with the complex with noncovalently bound drug. Glyceraldehyde also engenders covalent Adriamycin-DNA complexes, providing a possible relevant biological context for in vivo adduct formation.

Simultaneous determination of helical unwinding angles and intrinsic association constants in ligand-DNA complexes: the interaction between DNA and calichearubicin B.

We present a helical unwinding assay for reversibly binding DNA ligands that uses closed circular DNA, topoisomerase I (Topo I), and two-dimensional agarose gel electrophoresis. Serially diluted Topo I relaxation reactions at constant DNA/ligand ratio are performed, and the resulting apparent unwinding of the closed circular DNA is used to calculate both ligand unwinding angle (phi) and intrinsic association constant (Ka). Mathematical treatment of apparent unwinding is formally analogous to that of apparent extinction coefficient data for optical binding titrations. Extrapolation to infinite DNA concentration yields the true unwinding angle of a given ligand and its association constant under Topo I relaxation conditions. Thus this assay delivers simultaneous structural and thermodynamic information describing the ligand-DNA complex. The utility of this assay has been demonstrated by using calichearubicin B (CRB), a synthetic hybrid molecule containing the anthraquinone chromophore of (DA) and the carbohydrate domain of calicheamicin gamma1I. The unwinding angle for CRB calculated by this method is -5. 3 +/- 0.5 degrees. Its Ka value is 0.20 x 10(6) M-1. For comparison, the unwinding angles of ethidium bromide and DA have been independently calculated, and the results are in agreement with canonical values for these compounds. Although a stronger binder to selected sites, CRB is a less potent unwinder than its parent compound DA. The assay requires only small amounts of ligand and offers an attractive option for analysis of DNA binding by synthetic and natural compounds.

Increased mitochondrial superoxide dismutase activity in Parkinson's disease but not amyotrophic lateral sclerosis motor cortex.

Oxidative stress may contribute to the neurodegenerative process in amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD). Motor cortex in PD is not affected and its inclusion in studies of free radical involvement in ALS pathogenesis could help elucidate whether oxidative stress is disease specific or a more widespread phenomenon present in the neurodegeneration. We have measured cytosolic and mitochondrial isoforms of superoxide dismutase (SOD), antioxidant enzymes involved in primary defence against free radical damage, in motor cortex of six patients with sporadic form of ALS (SALS), eight with PD and eight normal control subjects. We have found no difference in the activities of cytosolic and mitochondrial SOD between SALS and control motor cortex. Mitochondrial SOD activity in PD motor cortex was, however, significantly higher than in SALS and control motor cortex whereas activity of cytosolic SOD was lower than in two other groups although the differences were not statistically significant. Our findings indicate the presence of an altered antioxidant defence system in PD but not ALS upper motor neurons, suggesting that oxidative stress may be a widespread phenomenon in PD.

Ciliary neurotrophic factor receptor expression in spinal cord and motor cortex in amyotrophic lateral sclerosis.

Ciliary neurotrophic factor (CNTF) is known to rescue motor neurones in animal models of injury and neurodegeneration and we have recently described regional changes of CNTF protein levels in spinal cord from patients with sporadic motor neurone disease of the amyotrophic lateral sclerosis (ALS) type. However, information is lacking about the CNTF receptor in this condition. We have therefore studied mRNA levels for the alpha subunit of the CNTF receptor (CNTFR alpha) and for CNTF itself in postmortem spinal cord and cerebral cortex in patients with sporadic ALS and matched controls. We report that in the spinal cord of ALS patients there is a marked increase in the hybridisation signal for CNTFR alpha subunit mRNA overlying motor neurones. In contrast, very little mRNA for CNTFR alpha subunit was found in the motor cortex and no differences were seen between ALS and controls. We were unable to detect any hybridisation signal for CNTF mRNA. Our findings provide evidence for regional differences in CNTF receptor expression in upper- and lower-motor neurones in ALS.

Synthesis and biological activity of fluorescent yeast pheromones.

The mating pheromones of Saccharomyces cerevisiae and derivatives of these pheromones have been synthesized and tested for biological activity in a solution-phase assay. The effects of native alpha-factor and a-factor on the growth of target cells in these assays were identical. A derivative of alpha-factor in which the amino terminus was modified with the fluorescent probe, 6-amino-N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)hexanoyl, was only slightly less active than the unmodified pheromone. Derivatives of a-factor that contain various alkyl groups in place of the farnesyl moiety of the native pheromone were also synthesized and tested for biological activity. A derivative in which the farnesyl moiety is substituted with an unbranched decyl group exhibited activity identical to that of the natural pheromone, whereas a derivative that contains an unbranched pentyl group exhibited significantly lower biological activity than native a-factor. The derivatives of a-factor have in addition been modified to incorporate 6-amino-N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) at the terminus of the alkyl chains. A derivative with the probe attached to a decyl chain displayed activity similar to that of the native pheromone, whereas the same modification on a pentyl chain produced a derivative with very low activity. The fluorescence spectra of the modified alpha-factor and a-factors were measured in methanol, aqueous solution, and aqueous solution containing phospholipid vesicles. The fluorescence of the probes depends on the environment of the pheromones and can be used to monitor the association of the pheromones with the lipid bilayer.

Regional changes of ciliary neurotrophic factor and nerve growth factor levels in post mortem spinal cord and cerebral cortex from patients with motor disease.

Ciliary neurotrophic factor (CNTF) rescues motor neurons in animal models of injury and neurodegeneration, and disruption of the mouse CNTF gene results in motor neuron degeneration in mature adults. Glial cells increase nerve growth factor (NGF) expression in neuropathological conditions, and the sensory system can be affected in the amyotrophic lateral sclerosis (ALS) type of motor neuronic disease. We therefore studied CNTF and NGF levels in post mortem spinal cord and cerebral cortex from patients with ALS and matched controls. We report a marked decrease of CNTF in the ventral horn of spinal cord in ALS, with no change in cerebral motor cortex. In contrast, NGF levels were decreased in ALS cerebral motor cortex, where the corticospinal tract originates, but increased in the lateral column of spinal cord, which includes the region of corticospinal tract degeneration in ALS. Both CNTF and NGF levels were decreased in ALS dorsal spinal cord.

Excitatory amino acids, free radicals and the pathogenesis of motor neuron disease.

The cause of motor neuron disease (MND) remains unknown, but the pathogenic involvement of excitatory amino acid (EAA) neurotransmitters and related exogenous compounds has been proposed. We discuss current concepts of the mechanisms of action of EAAs and the evidence for links between these neurotransmitters and free radical hypotheses of neuronal damage. These concepts are especially pertinent following reports of mutations in the gene encoding the free radical scavenging enzyme, copper-zinc superoxide dismutase, in familial MND. New approaches to treatment are suggested by advances in understanding of the disease.

Methohexitone antagonises kainate and epileptiform activity in rat neocortical slices.

Using a grease-seal technique on cortical slices, methohexitone (10-316 microM) dose dependently and reversibly reduced depolarising responses to kainate more than those to alpha-amino-3-hydroxy-4-isoxazolepropionate (AMPA) and N-methyl-D-aspartate (NMDA). The respective pA2 values were 4.9 +/- 0.07, 3.6 +/- 0.03 and 4.0 +/- 0.05 whereas, for 6-nitro,7-sulphamoylbenz[F]quinoxalinedione (NBQX), they were 5.8 +/- 0.06, 6.7 +/- 0.05 and < 4.0. Methohexitone was also more effective than NBQX in reducing the spontaneous epileptiform activity occurring in these cortical slices. Thus 10 and 20 microM of this short-acting barbiturate reduced afterpotentials and burst frequencies respectively by about 50% whereas NBQX 10 microM only reduced burst frequency by some 15%. The results are discussed with respect to a putative methohexitone- and kainate-sensitive autoreceptor which facilitates presynaptic glutamate release.

Pharmacological characterization of non-NMDA subtypes of glutamate receptor in the neonatal rat hemisected spinal cord in vitro.

1. A grease-gap technique was used to record depolarizing responses to alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA), kainate and N-methyl-D-aspartate (NMDA) in the hemisected spinal cord of the neonatal rat. The pharmacology of non-NMDA subtypes of glutamate receptor was investigated with the novel quinoxalinedione, 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo (F)-quinoxaline (NBQX) and with a series of barbiturates. 2. NBQX antagonized AMPA- and kainate-, but not NMDA- induced depolarizations. The near parallel shifts of the major part of the dose-response curves for AMPA and kainate by NBQX gave pA2 values (+/- s.e.) of 6.7 +/- 0.2 and 6.8 +/- 0.2 respectively, consistent with a common site of action for these two agonists. 3. Below the 50% level at which these pA2 values were calculated, however, an NBQX-resistant plateau was seen within the kainate, but not the AMPA, dose-response curve. 4. In decreasing order of potency, methohexitone, secobarbitone, thiopentone, pentobarbitone and phenobarbitone preferentially reduced kainate-, rather than AMPA- and NMDA-, induced depolarizations. Methohexitone was also the most selective with IC50S against kainate, AMPA and NMDA of 31 +/- 7, 172 +/- 47 and greater than 200 microM respectively. 5. The NBQX-resistant plateau seen within the kainate dose-response curve was reduced by methohexitone. Kainate antagonism by methohexitone was not reduced by 50 microM picrotoxin. 6. We conclude that, while mixed agonist actions may hamper demonstration of antagonist selectivity, depolarizations induced by the non-NMDA ionotropic agonists, AMPA and kainate, are mediated in part via distinct receptors.