Off-label use of misoprostol for labor induction: a nation-wide survey in Switzerland

Off-label use of drugs is frequent in obstetrical practice. No data however are available about nation-wide off-label use in obstetrics regarding frequency and patient information. The objective of our study was to assess the clinical practice of off-label use of misoprostol for labor induction.

Out of Eastern Africa: defibulation and sexual function in woman with female genital mutilation

Female genital mutilation (FGM) is defined by the World Health Organization (WHO) as all procedures that involve partial or total removal of the female external genitalia and/or injury to the female genital organs for cultural or any other non-therapeutic reasons.

Thymic peptides for treatment of cancer patients

Background Purified thymus extracts (pTE) and synthetic thymic peptides (sTP) are thought to enhance the immune system of cancer patients in order to fight the growth of tumour cells and to resist infections due to immunosuppression induced by the disease and antineoplastic therapy. Objectives To evaluate the effectiveness of pTE and sTP for the management of cancer. Search methods We searched CENTRAL (The Cochrane Library 2010, Issue 3), MEDLINE, EMBASE, AMED, BIOETHICSLINE, BIOSIS, CATLINE, CISCOM, HEALTHSTAR, HTA, SOMED and LILACS (to February 2010). Selection criteria Randomised trials of pTE or sTP in addition to chemotherapy or radiotherapy, or both, compared to the same regimen with placebo or no additional treatment in adult cancer patients. Data collection and analysis Two authors independently extracted data from published trials. We derived odds ratios (OR) from overall survival (OS) and disease-free survival (DFS) rates, tumour response (TR) rates, and rates of adverse effects (AE) related to antineoplastic treatments. We used a random-effects model for meta-analysis. Main results We identified 26 trials (2736 patients). Twenty trials investigated pTE (thymostimulin or thymosin fraction 5) and six trials investigated sTP (thymopentin or thymosin α1). Twenty-one trials reported results for OS, six for DFS, 14 for TR, nine for AE and 10 for safety of pTE and sTP. Addition of pTE conferred no benefit on OS (RR 1.00, 95% CI 0.79 to 1.25); DFS (RR 0.97, 95% CI 0.82 to 1.16); or TR (RR 1.07, 95% CI 0.92 to 1.25). Heterogeneity was moderate to high for all these outcomes. For thymosin α1 the pooled RR for OS was 1.21 (95% CI 0.94 to 1.56, P = 0.14), with low heterogeneity; and 3.37 (95% CI 0.66 to 17.30, P = 0.15) for DFS, with moderate heterogeneity. The pTE reduced the risk of severe infectious complications (RR 0.54, 95% CI 0.38 to 0.78, P = 0.0008; I² = 0%). The RR for severe neutropenia in patients treated with thymostimulin was 0.55 (95% CI 0.25 to 1.23, P = 0.15). Tolerability of pTE and sTP was good. Most of the trials had at least a moderate risk of bias. Authors' conclusions Overall, we found neither evidence that the addition of pTE to antineoplastic treatment reduced the risk of death or disease progression nor that it improved the rate of tumour responses to antineoplastic treatment. For thymosin α1, there was a trend for a reduced risk of dying and of improved DFS. There was preliminary evidence that pTE lowered the risk of severe infectious complications in patients undergoing chemotherapy or radiotherapy.

Determinants of blood pressure in preschool children: the role of parental smoking

Hypertension is the leading risk factor for cardiovascular disease. Although accumulating evidence suggests tracking of blood pressure from childhood into adult life, there is little information regarding the relative contributions of genetic, prenatal, biological, behavioral, environmental, and social determinants to childhood blood pressure.

Artists' advance: decreased upper alpha power while drawing in artists compared with non-artists

Brain mechanisms associated with artistic talents or skills are still not well understood. This exploratory study investigated differences in brain activity of artists and non-artists while drawing previously presented perspective line-drawings from memory and completing other drawing-related tasks. Electroencephalography (EEG) data were analyzed for power in the frequency domain by means of a Fast Fourier Transform (FFT). Low Resolution Brain Electromagnetic Tomography (LORETA) was applied to localize emerging significances. During drawing and related tasks, decreased power was seen in artists compared to non-artists mainly in upper alpha frequency ranges. Decreased alpha power is often associated with an increase in cognitive functioning and may reflect enhanced semantic memory performance and object recognition processes in artists. These assumptions are supported by the behavioral data assessed in this study and complement previous findings showing increased parietal activations in non-artists compared to artists while drawing. However, due to the exploratory nature of the analysis, additional confirmatory studies will be needed.

Pan-histone deacetylase inhibitor panobinostat sensitizes gastric cancer cells to anthracyclines via induction of CITED2

Chemotherapy modestly prolongs survival of patients with advanced gastric cancer, but strategies are needed to increase its efficacy. Histone deacetylase (HDAC) inhibitors modify chromatin and can block cancer cell proliferation and promote apoptosis.

TFAP2E-DKK4 and chemoresistance in colorectal cancer

Chemotherapy for advanced colorectal cancer leads to improved survival; however, predictors of response to systemic treatment are not available. Genomic and epigenetic alterations of the gene encoding transcription factor AP-2 epsilon (TFAP2E) are common in human cancers. The gene encoding dickkopf homolog 4 protein (DKK4) is a potential downstream target of TFAP2E and has been implicated in chemotherapy resistance. We aimed to further evaluate the role of TFAP2E and DKK4 as predictors of the response of colorectal cancer to chemotherapy.

Response of the rat spinal cord to X-ray microbeams

BACKGROUND AND PURPOSE: To quantify the late dose-related responses of the rat cervical spinal cord to X-ray irradiations by an array of microbeams or by a single millimeter beam. MATERIALS AND METHODS: Necks of anesthetized rats were irradiated transversely by an 11mm wide array of 52 parallel, 35μm wide, vertical X-ray microbeams, separated by 210μm intervals between centers. Comparison was made with rats irradiated with a 1.35mm wide single beam of similar X-rays. Rats were killed when paresis developed, or up to 383days post irradiation (dpi). RESULTS: Microbeam peak/valley doses of ≈357/12.7Gy to 715/25.4Gy to an 11mm long segment of the spinal cord, or single beam doses of ≈146-454Gy to a 1.35mm long segment caused foreleg paresis and histopathologically verified spinal cord damage; rats exposed to peak/valley doses up to 253/9Gy were paresis-free at 383dpi. CONCLUSIONS: Whereas microbeam radiation therapy [MRT] for malignant gliomas implanted in rat brains can be safe, palliative or curative, the high tolerance of normal rat spinal cords to similar microbeam exposures justifies testing MRT for autochthonous malignancies in the central nervous system of larger animals with a view to subsequent clinical applications.

Chalcone JAI-51 improves efficacy of synchrotron microbeam radiation therapy of brain tumors

Microbeam radiation therapy (MRT), a preclinical form of radiosurgery, uses spatially fractionated micrometre-wide synchrotron-generated X-ray beams. As MRT alone is predominantly palliative for animal tumors, the effects of the combination of MRT and a newly synthesized chemotherapeutic agent JAI-51 on 9L gliosarcomas have been evaluated. Fourteen days (D14) after implantation (D0), intracerebral 9LGS-bearing rats received either MRT, JAI-51 or both treatments. JAI-51, alone or immediately after MRT, was administered three times per week. Animals were kept up to ∼20 weeks after irradiation or sacrificed at D16 or D28 after treatment for cell cycle analysis. MRT plus JAI-51 increased significantly the lifespan compared with MRT alone (p = 0.0367). JAI-51 treatment alone had no effect on rat survival. MRT alone or associated with JAI-51 induced a cell cycle blockade in G2/M (p < 0.01) while the combined treatment also reduced the proportion of G0/G1 cells. At D28 after irradiation, MRT and MRT/JAI-51 had a smaller cell blockade effect in the G2/M phase owing to a significant increase in tumor cell death rate (<2c) and a proportional increase of endoreplicative cells (>8c). The combination of MRT and JAI-51 increases the survival of 9LGS-bearing rats by inducing endoreduplication of DNA and tumor cell death; further, it slowed the onset of tumor growth resumption two weeks after treatment.

Synchrotron X-ray interlaced microbeams suppress paroxysmal oscillations in neuronal networks initiating generalized epilepsy

Radiotherapy has shown some efficacy for epilepsies but the insufficient confinement of the radiation dose to the pathological target reduces its indications. Synchrotron-generated X-rays overcome this limitation and allow the delivery of focalized radiation doses to discrete brain volumes via interlaced arrays of microbeams (IntMRT). Here, we used IntMRT to target brain structures involved in seizure generation in a rat model of absence epilepsy (GAERS). We addressed the issue of whether and how synchrotron radiotherapeutic treatment suppresses epileptic activities in neuronal networks. IntMRT was used to target the somatosensory cortex (S1Cx), a region involved in seizure generation in the GAERS. The antiepileptic mechanisms were investigated by recording multisite local-field potentials and the intracellular activity of irradiated S1Cx pyramidal neurons in vivo. MRI and histopathological images displayed precise and sharp dose deposition and revealed no impairment of surrounding tissues. Local-field potentials from behaving animals demonstrated a quasi-total abolition of epileptiform activities within the target. The irradiated S1Cx was unable to initiate seizures, whereas neighboring non-irradiated cortical and thalamic regions could still produce pathological oscillations. In vivo intracellular recordings showed that irradiated pyramidal neurons were strongly hyperpolarized and displayed a decreased excitability and a reduction of spontaneous synaptic activities. These functional alterations explain the suppression of large-scale synchronization within irradiated cortical networks. Our work provides the first post-irradiation electrophysiological recordings of individual neurons. Altogether, our data are a critical step towards understanding how X-ray radiation impacts neuronal physiology and epileptogenic processes.

Proteomic changes in the rat brain induced by homogenous irradiation and by the bystander effect resulting from high energy synchrotron X-ray microbeams

Abstract Purpose: To further evaluate the use of microbeam irradiation (MBI) as a potential means of non-invasive brain tumor treatment by investigating the induction of a bystander effect in non-irradiated tissue. Methods: Adult rats were irradiated with 35 or 350 Gy at the European Synchotron Research Facility (ESRF), using homogenous (broad beam) irradiation (HI) or a high energy microbeam delivered to the right brain hemisphere only. The proteome of the frontal lobes were then analyzed using two-dimensional electrophoresis (2-DE) and mass spectrometry. Results: HI resulted in proteomic responses indicative of tumourigenesis; increased albumin, aconitase and triosphosphate isomerase (TPI), and decreased dihydrolipoyldehydrogenase (DLD). The MBI bystander effect proteomic changes were indicative of reactive oxygen species mediated apoptosis; reduced TPI, prohibitin and tubulin and increased glial fibrillary acidic protein (GFAP). These potentially anti-tumourigenic apoptotic proteomic changes are also associated with neurodegeneration. However the bystander effect also increased heat shock protein (HSP) 71 turnover. HSP 71 is known to protect against all of the neurological disorders characterized by the bystander effect proteome changes. Conclusions: These results indicate that the collective interaction of these MBI-induced bystander effect proteins and their mediation by HSP 71, may confer a protective effect which now warrants additional experimental attention.

Clinical scoring system for vulvar lichen sclerosus

Vulvar lichen sclerosus (LS) is a chronic inflammatory and mutilating disease, which goes often undetected for years. Advanced disease severely affects quality of life like sexual disorders and is also associated with an increased risk of vulvar cancer.