Role of immune and angiogenic markers in the pathology of endometriosis

Background: Endometriosis is an estrogen-dependent, pro-inflammatory, pro-angiogenic condition that affects 5 to 10% of women of reproductive age. Its defining feature is the presence of endometrium-like tissue in sites outside the uterine cavity, primarily on the pelvic peritoneum and ovaries. The main clinical features are chronic pain, pain during intercourse and infertility. In patients with endometriosis, inflammatory and immune responses, angiogenesis and apoptosis are altered in favour of the survival and replenishment of endometriotic tissue. These basic pathological processes depend on the excessive formation of estrogen and prostaglandins. Recently, new cellular and molecular mechanisms for the resolution of inflammation have been discovered, revealing key roles for lipid mediators such as lipoxins, resolvins and protectins. It is possible that disequilibrium in the expression of these molecules exists in endometriosis. Objective: To compare the expression of two proteins involved in the synthe sis and in the function of lipid mediators; the Arachidonate 15-lipoxygenase (ALOXI5), implicated in the synthesis of lipoxins A4 and B4 and the Formyl peptide receptor 1 (FPRLI), the specific receptor for Lipoxin A4 and B4, between women who suffer from endometriosis and a control group. We wish to demonstrate the cellular localisation of these two molecules and to investigate if their expression is alteted in this pathology. Methods and Materials Using immunohistochemistry we will compare ALOXI5 and FPRLI staining, in endometrium, normal peritoneum and endometriotic lesions. The samples are being collected in the department of Gynaecology and Obstetrics at the Centre Hospitalier Universitaire Lausanne (CHUV). Women attending the department for laparoscopic investigation of pain/infertility, suspected endometriosis or for a hysterectomy, are invited to participate. Approval of the ethics committee (Commission d'Ethique de la recherché clinique) was obtained in March 2009. Clinical samples will only be obtained from subjects having consented. Expected results and interpretation: No published studies investigating the expression of these two molecules in endometriotic lesions exist. A better understanding of the mechanisms underlying this disease will result in the development of new medical therapies and new diagnostic tests, with the aim of ameliorating the quality of life of endometriosis patients.

Associations of short-term particle and noise exposures with markers of cardiovascular and respiratory health among highway maintenance workers

BACKGROUND: Highway maintenance workers are constantly and simultaneously exposed to traffic-related particle and noise emissions, and both have been linked to increased cardiovascular morbidity and mortality in population-based epidemiology studies. OBJECTIVES: We aimed to investigate short-term health effects related to particle and noise exposure. METHODS: We monitored 18 maintenance workers, during as many as five 24-hour periods from a total of 50 observation days. We measured their exposure to fine particulate matter (PM2.5), ultrafine particles, noise, and the cardiopulmonary health endpoints: blood pressure, pro-inflammatory and pro-thrombotic markers in the blood, lung function and fractional exhaled nitric oxide (FeNO) measured approximately 15 hours post-work. Heart rate variability was assessed during a sleep period approximately 10 hours post-work. RESULTS: PM2.5 exposure was significantly associated with C-reactive protein and serum amyloid A, and negatively associated with tumor necrosis factor α. None of the particle metrics were significantly associated with von Willebrand factor or tissue factor expression. PM2.5 and work noise were associated with markers of increased heart rate variability, and with increased HF and LF power. Systolic and diastolic blood pressure on the following morning were significantly associated with noise exposure after work, and non-significantly associated with PM2.5. We observed no significant associations between any of the exposures and lung function or FeNO. CONCLUSIONS: Our findings suggest that exposure to particles and noise during highway maintenance work might pose a cardiovascular health risk. Actions to reduce these exposures could lead to better health for this population of workers.

Octopus Standard Automated Perimetry, Pulsar Perimetry, Moorfields Motion Displacement Test and Heidelberg Retinal Tomography in Glaucoma Detection - A Comparison of Diagnostic Accuracy

Purpose: To investigate the accuracy of 4 clinical instruments in the detection of glaucomatous damage. Methods: 102 eyes of 55 test subjects (Age mean = 66.5yrs, range = [39; 89]) underwent Heidelberg Retinal Tomography (HRTIII), (disc area<2.43); and standard automated perimetry (SAP) using Octopus (Dynamic); Pulsar (TOP); and Moorfields Motion Displacement Test (MDT) (ESTA strategy). Eyes were separated into three groups 1) Healthy (H): IOP<21mmHg and healthy discs (clinical examination), 39 subjects, 78 eyes; 2) Glaucoma suspect (GS): Suspicious discs (clinical examination), 12 subjects, 15 eyes; 3) Glaucoma (G): progressive structural or functional loss, 14 subjects, 20 eyes. Clinical diagnostic precision was examined using the cut-off associated with the p<5% normative limit of MD (Octopus/Pulsar), PTD (MDT) and MRA (HRT) analysis. The sensitivity, specificity and accuracy were calculated for each instrument. Results: See table Conclusions: Despite the advantage of defining glaucoma suspects using clinical optic disc examination, the HRT did not yield significantly higher accuracy than functional measures. HRT, MDT and Octopus SAP yielded higher accuracy than Pulsar perimetry, although results did not reach statistical significance. Further studies are required to investigate the structure-function correlations between these instruments.

Systematic identification of genomic markers of drug sensitivity in cancer cells.

Clinical responses to anticancer therapies are often restricted to a subset of patients. In some cases, mutated cancer genes are potent biomarkers for responses to targeted agents. Here, to uncover new biomarkers of sensitivity and resistance to cancer therapeutics, we screened a panel of several hundred cancer cell lines--which represent much of the tissue-type and genetic diversity of human cancers--with 130 drugs under clinical and preclinical investigation. In aggregate, we found that mutated cancer genes were associated with cellular response to most currently available cancer drugs. Classic oncogene addiction paradigms were modified by additional tissue-specific or expression biomarkers, and some frequently mutated genes were associated with sensitivity to a broad range of therapeutic agents. Unexpected relationships were revealed, including the marked sensitivity of Ewing's sarcoma cells harbouring the EWS (also known as EWSR1)-FLI1 gene translocation to poly(ADP-ribose) polymerase (PARP) inhibitors. By linking drug activity to the functional complexity of cancer genomes, systematic pharmacogenomic profiling in cancer cell lines provides a powerful biomarker discovery platform to guide rational cancer therapeutic strategies.

Diagnostic yield of short-term video-EEG monitoring for epilepsy and PNESs: a European assessment.

INTRODUCTION: Although long-term video-EEG monitoring (LVEM) is routinely used to investigate paroxysmal events, short-term video-EEG monitoring (SVEM) lasting <24 h is increasingly recognized as a cost-effective tool. Since, however, relatively few studies addressed the yield of SVEM among different diagnostic groups, we undertook the present study to investigate this aspect. METHODS: We retrospectively analyzed 226 consecutive SVEM recordings over 6 years. All patients were referred because routine EEGs were inconclusive. Patients were classified into 3 suspected diagnostic groups: (1) group with epileptic seizures, (2) group with psychogenic nonepileptic seizures (PNESs), and (3) group with other or undetermined diagnoses. We assessed recording lengths, interictal epileptiform discharges, epileptic seizures, PNESs, and the definitive diagnoses obtained after SVEM. RESULTS: The mean age was 34 (±18.7) years, and the median recording length was 18.6 h. Among the 226 patients, 127 referred for suspected epilepsy - 73 had a diagnosis of epilepsy, none had a diagnosis of PNESs, and 54 had other or undetermined diagnoses post-SVEM. Of the 24 patients with pre-SVEM suspected PNESs, 1 had epilepsy, 12 had PNESs, and 11 had other or undetermined diagnoses. Of the 75 patients with other diagnoses pre-SVEM, 17 had epilepsy, 11 had PNESs, and 47 had other or undetermined diagnoses. After SVEM, 15 patients had definite diagnoses other than epilepsy or PNESs, while in 96 patients, diagnosis remained unclear. Overall, a definitive diagnosis could be reached in 129/226 (57%) patients. CONCLUSIONS: This study demonstrates that in nearly 3/5 patients without a definitive diagnosis after routine EEG, SVEM allowed us to reach a diagnosis. This procedure should be encouraged in this setting, given its time-effectiveness compared with LVEM.

Association between conventional risk factors and different ultrasound-based markers of atherosclerosis at carotid and femoral levels in a middle-aged population.

Ultrasound detection of sub-clinical atherosclerosis (ATS) may help identify individuals at high cardiovascular risk. Most studies evaluated intima-media thickness (IMT) at carotid level. We compared the relationships between main cardiovascular risk factors (CVRF) and five indicators of ATS (IMT, mean and maximal plaque thickness, mean and maximal plaque area) at both carotid and femoral levels. Ultrasound was performed on 496 participants aged 45-64 years randomly selected from the general population of the Republic of Seychelles. 73.4 % participants had ≥ 1 plaque (IMT thickening ≥ 1.2 mm) at carotid level and 67.5 % at femoral level. Variance (adjusted R2) contributed by age, sex and CVRF (smoking, LDL-cholesterol, HDL-cholesterol, blood pressure, diabetes) in predicting any of the ATS markers was larger at femoral than carotid level. At both carotid and femoral levels, the association between CVRF and ATS was stronger based on plaque-based markers than IMT. Our findings show that the associations between CVRF and ATS markers were stronger at femoral than carotid level, and with plaque-based markers rather than IMT. Pending comparison of these markers using harder cardiovascular endpoints, our findings suggest that markers based on plaque morphology assessed at femoral artery level might be useful cardiovascular risk predictors.

Eosinophilie sanguine: quel bilan, quel cheminement diagnostique [Peripheral blood eosinophilia: diagnostic value and further assessment].

Although not specific, an increased in peripheral blood eosinophils may contribute substantially to the diagnosis of numerous infectious, allergic and inflammatory diseases. The scope of this article is to detail pathologies associated with peripheral eosinophilia by order of frequency and to guide further investigations.

Inflammatory markers and blood pressure: sex differences and the effect of fat mass in the CoLaus Study.

Several studies have reported high levels of inflammatory biomarkers in hypertension, but data coming from the general population are sparse, and sex differences have been little explored. The CoLaus Study is a cross-sectional examination survey in a random sample of 6067 Caucasians aged 35-75 years in Lausanne, Switzerland. Blood pressure (BP) was assessed using a validated oscillometric device. Anthropometric parameters were also measured, including body composition, using electrical bioimpedance. Crude serum levels of interleukin-6 (IL-6), tumor necrosis factor α (TNF-α) and ultrasensitive C-reactive protein (hsCRP) were positively and IL-1β (IL-1β) negatively (P<0.001 for all values), associated with BP. For IL-6, IL-1β and TNF-α, the association disappeared in multivariable analysis, largely explained by differences in age and body mass index, in particular fat mass. On the contrary, hsCRP remained independently and positively associated with systolic (β (95% confidence interval): 1.15 (0.64; 1.65); P<0.001) and diastolic (0.75 (0.42; 1.08); P<0.001) BP. Relationships of hsCRP, IL-6 and TNF-α with BP tended to be stronger in women than in men, partly related to the difference in fat mass, yet the interaction between sex and IL-6 persisted after correction for all tested confounders. In the general population, the associations between inflammatory biomarkers and rising levels of BP are mainly driven by age and fat mass. The stronger associations in women suggest that sex differences might exist in the complex interplay between BP and inflammation.

Gene flow among wild and domesticated almond species: insights from chloroplast and nuclear markers

Hybridization has played a central role in the evolutionary history of domesticated plants. Notably, several breeding programs relying on gene introgression from the wild compartment have been performed in fruit tree species within the genus Prunus but few studies investigated spontaneous gene flow among wild and domesticated Prunus species. Consequently, a comprehensive understanding of genetic relationships and levels of gene flow between domesticated and wild Prunus species is needed. Combining nuclear and chloroplastic microsatellites, we investigated the gene flow and hybridization among two key almond tree species, the cultivated Prunus dulcis and one of the most widespread wild relative Prunus orientalis in the Fertile Crescent. We detected high genetic diversity levels in both species along with substantial and symmetric gene flow between the domesticated P. dulcis and the wild P. orientalis. These results were discussed in light of the cultivated species diversity, by outlining the frequent spontaneous genetic contributions of wild species to the domesticated compartment. In addition, crop-to-wild gene flow suggests that ad hoc transgene containment strategies would be required if genetically modified cultivars were introduced in the northwestern Mediterranean.

Hand exposure in diagnostic nuclear medicine with 18F- and 99mTc-labelled radiopharmaceuticals - Results of the ORAMED project

Workers performing preparation and administration of radiopharmaceuticals in NM departments are likely to receive high local skin doses to the hands which may even surpass the dose limit of 500 mSv whenever radiation protection standards are insufficient. A large measurement campaign was organised within the framework of the ORAMED project to determine the dose distribution across the hands received during preparation and administration of 18F- and 99mTc-labelled radiopharmaceuticals. The final data, collected over almost 3 years, include 641 measurements from 96 workers in 30 NM departments from 6 European countries. Results have provided levels of reference doses for the considered standard NM diagnostic procedures (mean maximum normalised skin dose of 230 μSv/GBq, 430 μSv/GBq, 930 μSv/GBq and 1200 μSv/GBq for the administration of 99mTc, preparation of 99mTc, administration of 18F and preparation of 18F, respectively). Finger dose was analysed as a function of the potential parameters of influence showing that shielding is the most efficient means of radiation protection to reduce skin dose. An appropriate method for routine monitoring of the extremities is also proposed: the base of the index finger of the non-dominant hand is a suitable position to place the ring dosemeter, with its sensitive part oriented towards the palm side; its reading may be multiplied by a factor of 6 to estimate the maximum local skin dose. Finally, results were compared to earlier published data, which correspond mostly to individual works with a reduced number of workers and measurements.

Diagnostic et traitement de l'instabilité rotulienne [Diagnosis and treatment of patellar instability].

Patellar instability concerns mostly young and active patients. Because of the condition's multifactorial origin, knowledge about the risk factors of patella instability and the biomechanics of the femoropatellar joint are necessary to understand this disorder. Most of the patellar dislocations are spontaneously reduced. Only the patient's history, clinical examination and appropriate imaging lead to the correct diagnosis. If haemarthrosis is present, MRI is recommended to rule out concomitant injuries. A traumatic patellar dislocation without history of prior dislocation is treated conservatively. Surgical treatment is indicated in presence of intra-articular injury or for recurrent dislocations. The surgical procedure should correct the different factors of patella instability identified by preoperative analysis.

Carences en vitamine B12 et fer: du diagnostic au suivi [Vitamin B12 and iron deficiencies: from diagnostic to follow-up].

Vitamin B12 and iron deficiencies are common problems in consultations of general internal medicine. They cause different symptoms that can be non-specific. This article makes it possible, from a clinical frame of reference, to answer the following questions: What value of vitamin B12 should we consider a "deficiency", and what is the role of methylmalonate? What is the role of vitamin B12 oral supplements? How should we interpret values of ferritine? How should iron deficiency be investigated? What is the place of intravenous iron administration?