Maternal prenatal depression is associated with decreased placental expression of the imprinted gene PEG3.

BACKGROUND: Maternal prenatal stress during pregnancy is associated with fetal growth restriction and adverse neurodevelopmental outcomes, which may be mediated by impaired placental function. Imprinted genes control fetal growth, placental development, adult behaviour (including maternal behaviour) and placental lactogen production. This study examined whether maternal prenatal depression was associated with aberrant placental expression of the imprinted genes paternally expressed gene 3 (PEG3), paternally expressed gene 10 (PEG10), pleckstrin homology-like domain family a member 2 (PHLDA2) and cyclin-dependent kinase inhibitor 1C (CDKN1C), and resulting impaired placental human placental lactogen (hPL) expression. METHOD: A diagnosis of depression during pregnancy was recorded from Manchester cohort participants' medical notes (n = 75). Queen Charlotte's (n = 40) and My Baby and Me study (MBAM) (n = 81) cohort participants completed the Edinburgh Postnatal Depression Scale self-rating psychometric questionnaire. Villous trophoblast tissue samples were analysed for gene expression. RESULTS: In a pilot study, diagnosed depression during pregnancy was associated with a significant reduction in placental PEG3 expression (41%, p = 0.02). In two further independent cohorts, the Queen Charlotte's and MBAM cohorts, placental PEG3 expression was also inversely associated with maternal depression scores, an association that was significant in male but not female placentas. Finally, hPL expression was significantly decreased in women with clinically diagnosed depression (44%, p < 0.05) and in those with high depression scores (31% and 21%, respectively). CONCLUSIONS: This study provides the first evidence that maternal prenatal depression is associated with changes in the placental expression of PEG3, co-incident with decreased expression of hPL. This aberrant placental gene expression could provide a possible mechanistic explanation for the co-occurrence of maternal depression, fetal growth restriction, impaired maternal behaviour and poorer offspring outcomes.

MALDI-MS and NanoSIMS imaging techniques to study cnidarian-dinoflagellate symbioses.

Cnidarian-dinoflagellate photosynthetic symbioses are fundamental to biologically diverse and productive coral reef ecosystems. The hallmark of this symbiotic relationship is the ability of dinoflagellate symbionts to supply their cnidarian host with a wide range of nutrients. Many aspects of this association nevertheless remain poorly characterized, including the exact identity of the transferred metabolic compounds, the mechanisms that control their exchange across the host-symbiont interface, and the precise subcellular fate of the translocated materials in cnidarian tissues. This lack of knowledge is mainly attributed to difficulties in investigating such metabolic interactions both in situ, i.e. on intact symbiotic associations, and at high spatial resolution. To address these issues, we illustrate the application of two in situ and high spatial resolution molecular and ion imaging techniques-matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) and the nano-scale secondary-ion mass spectrometry (NanoSIMS) ion microprobe. These imaging techniques provide important new opportunities for the detailed investigation of many aspects of cnidarian-dinoflagellate associations, including the dynamics of cellular interactions.

Paradoxical reactions during treatment of tuberculosis with extrapulmonary manifestations in HIV-negative patients.

PURPOSE: Tuberculous paradoxical reactions (PR) have been seldom studied in non-immunocompromised patients. We conducted a study to describe the incidence, clinical and biological features, treatment and outcome of PR in human immunodeficiency virus (HIV)-negative patients treated for extrapulmonary tuberculosis (TB) and to identify predictive factors of PR. METHODS: A single-center retrospective study was conducted in consecutive HIV-negative patients presenting with TB with at least one extrapulmonary manifestation who were hospitalized in an internal medicine department between 2000 and 2010. RESULTS: Seventy-six patients were enrolled in the study. Lymphadenitis was the most common extrapulmonary manifestation of tuberculosis among this patient population (72 %). PR occurred in 19 (25 %) patients, mostly involving the lymph nodes (68 %) and lung (16 %), but also the pericardium, pleura, bone, muscle and brain. Median time to PR onset after initiation of anti-TB regimen was 86 days (interquartile range 36-125). Treatment of PR consisted mainly of corticosteroids (47 % of patients) and needle aspiration of PR lymph nodes (31 %). Peripheral lymph node involvement (p = 0.009), lymphopenia (p = 0.03) and anemia (p = 0.002) at presentation were associated with PR occurrence. Outcome was favorable in all patients with PR but one; the latter suffered residual paraplegia. CONCLUSIONS: Paradoxical reactions are frequent in the course of extrapulmonary TB treatment in HIV-negative patients but their outcome is excellent, except in some cases with central nervous system involvement.

[Hypo-uricemia in the syndrome of inappropriate secretion of antidiuretic hormone: A prospective study]. / Utilité diagnostique de l'hypo-uricémie dans l'hyponatrémie par sécrétion inadéquate d'hormone antidiurétique.

PURPOSE: Hypo-uricemia is still considered as a hallmark of the syndrome of inappropriate secretion of antidiuretic hormone. METHODS: We analyzed prospectively 98 hospitalized patients with hyponatremia (≤135 mmol/L), excluding those receiving diuretic treatment. Gold standard for the syndrome of inappropriate secretion of antidiuretic hormone combined plasma hypoosmolality, inappropriately concentrated urine, and normal volemia. RESULTS: A final diagnosis of inappropriate secretion of antidiuretic hormone was obtained in 55 patients. They were significantly hypo-uricemic (188 µmol/L [153-245], median [interquartile range]) versus 241 µmol/L, [179-333]; p<0,02) but hypo-uricemia (≤240 µmol/L) performed poorly as a diagnostic test: 71 % sensitivity, 53 % specificity. Positive and negative likelihood ratios were 1,67 and 0,49, respectively. CONCLUSIONS: The syndrome of inappropriate secretion of antidiuretic hormone is associated with a lower plasma uric acid concentration, but in routine clinical practice, contrary to what has been previously published, this difference is insufficient for hypouricemia to discriminate reliably between the syndrome of inappropriate secretion of antidiuretic hormone and other causes of hyponatremia.

[Thrombocytopenia associated with iron deficiency: a rare differential diagnosis of auto-immune thrombocytopenic purpura]. / Thrombopénie ferriprive : un diagnostic différentiel rare du purpura thrombopénique auto-immun.

INTRODUCTION: Iron deficiency is typically associated with microcytic anemia and thrombocytosis. It is a very uncommon cause of thrombocytopenia. CASE REPORT: A 17-year-old female presented with marked fatigue and dyspnea on exertion. Review of systems was only remarkable for abundant menstruations during the past two years. The hemogram revealed a profound microcytic anemia (4.4 g/dL, mean corpuscular volume [MCV] 49 fL) and a thrombocytopenia (33 G/L). Marked iron deficiency was also present: ferritinemia <3 µg/L. Investigations did not find any cause of iron deficiency anemia other than excessive menstrual loss. Bone marrow examination showed an increase number of megakaryocytes, compatible with an immune thrombocytopenia purpura. Iron supplementation completely normalized the platelet count within 48 hours. CONCLUSION: Iron affects thrombopoiesis. Because the number of megakaryocytes may then increase in the bone marrow, "iron deficiency thrombocytopenia" may be falsely diagnosed as immune thrombocytopenic purpura, leading to inappropriate corticosteroid therapy. Iron supplementation is the appropriate treatment of iron deficiency thrombocytopenia and allowed a rapid correction of the platelet count in all the 24 cases that have been previously reported with sufficient detail to be analyzed in the literature.

[Prospective evaluation of the relevance of prescribing antibiotic combinations in an internal medicine department]. / Evaluation prospective de la pertinence des associations d'antibiotiques en médecine interne.

PURPOSE: To assess the relevance of antibiotic combinations according to available recommendations. METHODS: Prospective monocentric study of 12-month duration in the department of internal medicine of a teaching hospital. All antibiotic combinations were assessed taking into account the infection type, the involved bacteria, the antibiotic nature, dosage and duration of treatment. A scientific committee classified each combination antibiotic therapy as: (1) in agreement with existing recommendations; (2) adapted to the antibiogram in the absence of available recommendations; (3) irrelevant but with no adverse clinical outcome for the patient; (4) irrelevant with potential adverse clinical outcome for the patient. RESULTS: Among 87 antibiotic combinations prescribed, 67 (77%) agreed with available recommendations. The percentages of irrelevant combinations with and without potential adverse clinical outcome for the patient were 7% (six cases) and 16% (14 cases), respectively. Reasons for non-conformity included: (1) prescription of combination therapy while monotherapy could have been sufficient or antibiotic therapy was unjustified (14 cases); (2) prescribed antibiotics not adapted to antibiogram (three cases); (3) prescribed antibiotics not effective on the most likely bacteria when treatment of infection was empirical (three cases). The rate of prescription appropriateness was 97% when the mobile microbiology team had interfered with the decision, versus 53% (p<0.001) when it had not. CONCLUSION: Seventy-seven percent of antibiotic combinations were appropriate and agreed with available recommendations. The advice of a microbiology team markedly improves this rate.

[Nonbacterial thrombotic endocarditis and gastric carcinoma]. / Endocardite marastique et adénocarcinome gastrique.

We report a 74-year-old woman with acute heart failure and recurrent ischemic strokes as the presenting features of a nonbacterial thrombotic endocarditis complicating a gastric adenocarcinoma. The treatment only allowed a few months remission. Diagnosis of nonbacterial thrombotic endocarditis is rarely obtained while the patient is alive. Coagulation abnormalities due to the tumoral process are responsible of the valvular thrombotic process. Anticoagulation with heparin is recommended. Valvular surgery remains controversial.

[Workshop to teach elderly patients how to get up from the ground: pilot prospective assessment in a hospital department of internal medicine]. / Apprentissage de la technique pour se relever du sol chez des patients âgés hospitalisés. Etude prospective en médecine interne.

BACKGROUND: Falls occur frequently among the elderly and often lead to hospitalization. Even if uninjured, some of them cannot get up again, and prolonged time on the floor and failed efforts to get up can cause complications. Training methods and exercises for getting up from the floor exist but have not been evaluated. METHODS: We set up a training course to teach elderly patients to get up from the ground and assessed it over the short term by a prospective observational study of 29 patients over 3 months. Each week, a group training session took place, followed 2-9 days later by an individual assessment conducted according to a written protocol. RESULTS: Of the 29 patients (16% of those older than 65 years admitted to our internal medicine department during this period) who received the training, 24 (80%) underwent the subsequent evaluation. Training was effective: before training, only 2 of 29 assessable patients were able to get up on their own, while at the reassessment, 11 of 24 succeeded (p=0.003). Significant improvement was observed for the first two-and most difficult-steps of the maneuver: rolling over from a supine to a prone position (p=0.003), and then moving up into a quadrupedal position (getting up onto all four limbs) (p=0.006). The only variable that appeared to predict a poor result was a Mini Mental Status (MMS) score lower than 26/30. CONCLUSION: Teaching elderly patients how to get up from the floor can be accomplished in an inpatient internal medicine department and appears to be effective in the short term. Although further studies involving more patients followed for a longer period are required to confirm and assess the actual benefits, this training is safe and can be recommended.

[Blood pressure control after a one year follow-up in high risk subject screened in occupational medicine]. / Contrôle de la pression artérielle après un suivi d'un an chez des sujets ia haut risque cardiovasculaire dépistés en médecine du travail.

OBJECTIVE: To identify factors predicting the success or the failure of intervention on blood pressure in a population estimated at high risks. METHODS: The program "Coeur 2001" has analysed the absolute cardiovascular risk (ACVR Framingham) in 107 371 voluntary French railways employees. In the company, were considered at high risk (HR), subjects for whom risk was > or = to the 95th percentile of the distribution of the observed ACVR by age range: ACVR > or = 4.5% before 35 years, 12% between 35 and 45 years and 19% beyond 45 years, i.e. a total of 4 190 subjects. These subjects were warned about their risk and advised to choose and consult a physician. A two-year follow up was planned. Identical data (risk factors, ACVR, type of management and therapies) were collected during the first consultation with the occupational physician (T0), one year later (T1) and two years later (T2). RESULTS: Our work concerned 2376 employees at HR, consulting at T1. At T1, 54% of subjects were in the hight risk group (SHR) [48% when BP at T1 was < 140/90 mmHg and 62% when the BP was > or = 140/90 mmHg]. The mean decrease of the systolic BP (SBP) was 4 mmHg in the whole sample, 7.7 mmHg in subjects with normalised ACVR, and it remained stable in the group still at HR (-0.7 mmHg). At T0, blood pressure (BP) was > or = 140/90 mmHg in 55.8% of the patients and 38.4 at T1. This high BP was associated with higher frequency of diabetes (14 vs 7%) and overweight (BMI > or =30 kg/m2; 32.8 vs 19.7%). The percentage of treated hypertensive subjects had increased from 35 to 62% but one third of uncontrolled hypertensive subjects was treated by mono therapies at T1. CONCLUSION: To keep BP under control is a difficult task in routine medicine. At T1, despite a more aggressive treatment, 38% of subjects at high risk were still hypertensive subjects.

What's in a risk factor? "He who strikes the ball".

A major aim of epidemiology is to explore the prognosis and aetiology of diseases, in order to improve treatment and prevention. To avoid misleading interpretations of observed associations between a modifier and the occurrence of a disease, the all-purpose idiom "risk factor" should be replaced by 3 locutions with narrower meanings: a risk marker is a modifier which is associated (correlated) with disease prevalence (case-control studies) or incidence (cohort studies); a risk marker truly becomes a risk factor if its experimental correction (intervention studies) does improve the disease incidence or prognosis; a risk factor is promoted to the rank of cause if it is proved to be necessary (sine qua non) for the occurrence of the disease. A more rigorous vocabulary avoids premature claims for unsubstantiated treatments or preventions, and helps defining sound priorities in aetiological research.

Transient down-regulation of L-type Ca(2+) channel and dystrophin expression after balloon injury in rat aortic cells.

OBJECTIVE: Migration and proliferation of arterial smooth muscle cells are critical responses during restenosis after balloon angioplasty. We investigated the changes in the expression of Ca(2+) channels and dystrophin, two determinants of contraction, after balloon injury of rat aortas. METHODS: Proliferation and migration of aortic myocytes were triggered in vivo by the passage of an inflated balloon catheter in the aortas of 12-week-old male Wistar rats. We used the whole-cell patch clamp technique to investigate Ba(2+) currents (I(Ba)) through Ca(2+) channels in single cells freshly isolated from media and neointima at various times after injury (days 2, 7, 15, 30 and 45). RESULTS: No T-type Ca(2+) channel current was recorded in any cell at any time. In contrast, a dihydropyridine (DHP)-sensitive L-type I(Ba)was recorded consistently in the media of intact aorta. After aortic injury, I(Ba) decreased dramatically (at days 2 and 7) but recovered over time to reach normal amplitude on days 30 and 45. In the neointima, I(Ba) was absent on day 15 but also increased gradually over time as observed at days 30 and 45. The use of a specific antibody directed against the L-type Ca(2+) channel alpha(1C) subunit showed, both by immunostaining and by Western blotting, no expression of the Ca(2+) channel protein on day 15. Parallel immunodetection of dystrophin showed that this marker of the contractile phenotype of SMCs was also not detectable at this stage in neointimal cells. Both proteins were re-expressed at days 45 and 63. Balloon injury induces a transient down-regulation of I(Ba) in arterial cells. CONCLUSIONS: Cell dedifferentiation and proliferation in vivo abolish the expression of L-type Ca(2+) channels and dystrophin in neointimal cells. These changes may be critical in the regulation of Ca(2+) homeostasis and, thereby, contraction of the arterial SMCs during restenosis following angioplasty.