[The role of the pulmonologist in an armed conflict]. / Place du pneumologue en situation de conflit armé.

INTRODUCTION: Recent news points to the eventuality of an armed conflict on the national territory. STATE OF THE ART: In this situation, pulmonologists will in all likelihood have a major role to assume in caring for the injured, especially insofar as chest damage is a major cause of patient death. PERSPECTIVES: The main injuries that pulmonologists may be called upon to treat stem not only from explosions, but also from chemical, biological and nuclear hazards. In this article, relevant organizational and pedagogical aspects are addressed. Since exhaustiveness on this subject is unattainable, we are proposing training on specific subjects for interested practitioners. CONCLUSION: The resilience of the French health system in a situation of armed conflict depends on the active participation of all concerned parties. With this in mind, it is of prime importance that the pneumological community be sensitized to the potential predictable severity of war-related injuries.

[Autoimmune and inflammatory pathologies associated with systemic scleroderma: Clinical, serological and prognostic profiles. Bi-centric retrospective series in the PACA region]. / Pathologies auto-immunes et inflammatoires associées à la sclérodermie systémique : profils cliniques, sérologiques et pronostiques. Série rétrospective bi-centrique en région PACA.

INTRODUCTION: Systemic sclerosis (SSc) is a rare auto-immune disease, affecting principally women between 40 and 60 years old. It is caracterised by a cutaneous and visceral fibrosis, an alteration of the microvascular network and the presence of autoantibodies. SSc can be associated with another connectivite tissue disease or to other autoimmune diseases, thus defining the overlap syndrome. The goal of our study is to describe these overlap syndromes. METHODS: We have analysed the data of a retrospective and bicentrique cohort, from the internal medicine unit of Hôpital Nord in Marseille and from the internal medicine unit of the Hôpital Sainte-Anne in Toulon, of patients followed for a SSc between January 1st, 2019 and December 1st, 2021. We have collected clinical, imunological features, associated auto-immune and inflammatory diseases with its morbidity and mortality. RESULTS: The cohort included 151 patients including 134 limited cutaneous SSc. Fifty-two (34.4%) patients presented at least one associated auto-immune or inflammatory disease. The association of two connectivite tissue diseases including SSc was found in 24 patients (15.9%), a third with Sjögren's syndrome and a third with autoimmune myositis. The principal associated disease to SSc was the autoimmune thyroiditis found in 17 patients (11.3%). The occurrence of complications (hospitalization, long-term oxygene therapy, death) was not significantly different depending on the existence or not of an overlap syndrom. CONCLUSION: SSc is often associated with other autoimmune diseases. This interrelation between associated pathologies and SSc, modifying sometimes the evolution of SSc, enhances the need of a personalized follow-up.

[Antineutrophil cytoplasmic antibody associated vasculitis: an uncommon side effect of propylthiouracil]. / Vascularite avec anticorps anticytoplasme des polynucléaires neutrophiles: une complication rare du propylthiouracile.

INTRODUCTION: Agranulocytosis or allergic skin reactions are common side effects of antithyroid drugs. Antineutrophil cytoplasmic antibody (ANCA) associated vasculitis is very uncommon. CASE REPORT: We report a 29-year-old woman treated with propylthiouracil for Graves' disease who developed a vasculitic skin involvement. ANCA with antimyeloperoxidase specificity were documented. Symptoms resolved after discontinuation of the drug. CONCLUSION: ANCA associated vasculitis is an unusual complication of propylthiouracil. Prognosis is conditioned by renal and pulmonary involvement.

[Flagellate erythema: an uncommon side effect of bleomycin]. / L'érythème flagellé: une complication rare de la bléomycine.

Bleomycin is a cytotoxic agent used in the treatment of various neoplasias. Its cutaneous adverse effects are diverse. Some of them are rare but specific. We report the case of a 40-year-old man presenting with a non-seminomatous testicular germ cell tumour who developed a flagellate erythema related to a bleomycin administration. Clinical features, histopathology and disease course are presented. This side effect is apparently neither related to the dose nor to the mode of administration of bleomycin. The etiopathogenic mechanism remains unknown.

Inappropriate bradycardia in Ebola virus disease.

BACKGROUND: As part of French assistance for the outbreak of Ebola virus disease in west Africa, a military treatment center for infected healthcare workers was deployed in Conakry, Guinea. Although some cases of bradycardia have been reported since the first Ebola outbreak, they have never been documented to our knowledge. We studied heart rhythm in patients with Ebola virus disease to analyze inappropriate bradycardia and discuss its mechanism. METHODS: Nine patients who tested positive for Ebola were admitted in March 2015. Baseline clinical data were noted at admission and twice a day during follow-up, and laboratory analyses (with troponin testing) were performed. RESULTS: At admission, patients had no or moderate tachycardia (pulse = 82 ± 27 bpm). Among them, a 32-year-old midwife admitted on her fourth day of symptoms had marked bradycardia: 43 bpm. ECG showed sinus bradycardia with no conduction disturbances or repolarization anomalies; findings were similar for the three other patients with bradycardia (< 60 bpm). During follow-up, her pulse gradually increased, as it did for the other three; all four recovered. DISCUSSION: Despite several factors likely to promote tachycardia, we observed no or only moderate tachycardia in all patients with Ebola. In our study, ECG recorded sinus rhythm, without significant node dysfunction or atrioventricular block. In the absence of any evidence of myocarditis, we discuss the possibility of a central nervous system cause, associated with encephalitis. CONCLUSION: We observed relative or marked bradycardia in our patients infected with Ebola. We hypothesize that its causal mechanism was encephalitis.

The structure of psychosis: latent class analysis of probands from the Roscommon Family Study.

BACKGROUND: The nosologic structure of psychotic illness, still influenced as much by historical as empirical perspectives, remains controversial. METHODS: Latent class analysis was applied to detailed symptomatic and outcome assessments of probands (n=343) with broadly defined schizophrenia and affective illness ascertained from a population-based psychiatric registry in Roscommon County, Ireland. First-degree relatives (n=942) were assessed by personal interview and/or review of hospital record. RESULTS: Six classes were found, all of which bore substantial resemblance to current or historical nosologic constructs. In order of decreasing frequency, they were (1) classic schizophrenia, (2) major depression, (3) schizophreniform disorder, (4) bipolar-schizomania, (5) schizodepression, and (6) hebephrenia. These classes differed on many historical and clinical variables not used in the latent class analysis. Compared with relatives of controls, significantly increased rates of major depression were seen in relatives of depressed and schizodepressed probands. Significantly increased rates of bipolar illness were restricted to relatives of bipolar-schizomanic probands. The risks for schizophrenia and schizophrenia spectrum disorders were significantly increased in relatives of all proband classes except major depression. This increase was moderate for bipolar-schizomanic probands, substantial for schizophrenic, schizophreniform, and schizodepressed probands, and marked for hebephrenic probands. CONCLUSIONS: These results suggest a relatively complex typology of psychotic syndromes consistent neither with a unitary model nor with a Kraepelinian dichotomy. The familial vulnerability to psychosis extends across several syndromes, being most pronounced in those with schizophrenialike symptoms. The familial vulnerability to depressive and manic affective illness is somewhat more specific.

Illicit psychoactive substance use, heavy use, abuse, and dependence in a US population-based sample of male twins.

BACKGROUND: In order to develop informed approaches to prevention and treatment of illicit psychoactive substance use, abuse, and dependence, we need to understand the sources of individual differences in risk. METHODS: In personal interviews with 1198 male-male twin pairs (708 monozygotic and 490 dizygotic) ascertained from a population-based registry, we assessed lifetime use, heavy use, and abuse of and dependence on cannabis, sedatives, stimulants, cocaine, opiates, and hallucinogens. Twin resemblance was assessed by probandwise concordance, odds ratio, tetrachoric correlations, and biometrical model fitting. RESULTS: Twin resemblance for substance use, heavy use, abuse, and dependence was substantial, and consistently greater in monozygotic than in dizygotic twins. For any drug use and for cannabis and hallucinogen use, model fitting suggested that twin resemblance was due to both genetic and familial-environmental factors. Twin resemblance for sedative, stimulant, cocaine, and opiate use, however, was caused solely by genetic factors. With 2 exceptions (cocaine abuse and stimulant dependence), twin resemblance for heavy use, abuse, and dependence resulted from only genetic factors, with heritability of liability usually ranging from 60% to 80%. No consistent evidence was found for violations of the equal environment assumption. CONCLUSIONS: In accord with prior results in studies of women, the family environment plays a role in twin resemblance for some forms of substance use in men. However, twin resemblance for heavy use, abuse, and dependence in men is largely caused by genetic factors, and heritability estimates are high.

Causal relationship between stressful life events and the onset of major depression.

OBJECTIVE: Stressful life events are associated with the onset of episodes of major depression. However, exposure to stressful life events is influenced by genetic factors, and these factors are correlated with those that predispose to major depression. The aim of this study was to clarify the degree to which stressful life events cause major depression. METHOD: The authors assessed the occurrence of 15 classes of stressful life events and the onset of DSM-III-R major depression over a 1-year period in female twins ascertained from a population-based registry. The sample contained 24,648 person-months and 316 onsets of major depression. Stressful life events were individually rated on contextual threat and dependence (the degree to which the stressful life event could have resulted from the respondent's behavior). The nature of the relationship between stressful life events and major depression was tested by 1) discrete-time survival analysis examining the relationship between dependence and the depressogenic effect of stressful life events and 2) a co-twin control analysis. RESULTS: While independent stressful life events were significantly associated with onsets of depression, when level of threat was controlled, the association was significantly stronger for dependent events. The odds ratio for onset of major depression in the month of a stressful life event was 5.64 in all subjects, 4.52 within dizygotic pairs, and 3.58 within monozygotic pairs. CONCLUSIONS: Stressful life events have a substantial causal relationship with the onset of episodes of major depression. However, about one-third of the association between stressful life events and onsets of depression is noncausal, since individuals predisposed to major depression select themselves into high-risk environments.

Longitudinal population-based twin study of retrospectively reported premenstrual symptoms and lifetime major depression.

OBJECTIVE: While family and twin studies suggest that retrospectively reported premenstrual symptoms are heritable, these studies have not accounted for the unreliability of such measures. In addition, we know little about the relationship of the familial risk factors for premenstrual symptoms and major depression. METHOD: Lifetime major depression and premenstrual-related tiredness, sadness, and irritability were assessed twice over 6 years in 1,312 menstruating female twins ascertained from a population-based twin register. A twin-measurement model--which permits estimation of the etiologic roles of genetic and environmental factors with correction for errors of measurement or short-term temporal fluctuations--was applied to these data. RESULTS: A single premenstrual symptom factor was found that was moderately stable over time. The best-fitting twin-measurement model estimated the heritability of the stable component of premenstrual symptoms at 56% and showed no impact of family-environmental factors. A bivariate twin-measurement model estimated that the genetic and environmental risk factors for lifetime major depression contributed only modestly to the etiology of premenstrual syndrome. No evidence was found for significant biases in the twin method. CONCLUSIONS: Retrospectively reported premenstrual-related symptoms of depression and anxiety are moderately stable over time and, when correction is made for this level of stability, substantially heritable. The genetic and environmental risk factors for these premenstrual symptoms and lifetime major depression are not closely related.

Sibling correlation of deficit syndrome in the Irish study of high-density schizophrenia families.

OBJECTIVE: The deficit syndrome is a subtype of schizophrenia characterized by primary and enduring negative features of psychopathology. It appears to reflect a distinct subtype within the syndrome of schizophrenia. Little is known about the familial or genetic aspects of the deficit syndrome. The purpose of this study was to determine whether deficit versus nondeficit subtypes are correlated in sibling pairs affected with schizophrenia. METHOD: The present study was based on the Irish Study of High-Density Schizophrenia Families. From the earlier study the authors selected a subset of patients who were members of sibling pairs in which both siblings had been diagnosed with "core" schizophrenia, which included schizophrenia, simple schizophrenia, and schizoaffective disorder with poor outcome. The Schedule for the Deficit Syndrome was used to make deficit versus nondeficit diagnoses, which were based on chart examinations by reviewers blind to sibling status. This method resulted in 65 patients being diagnosed with the deficit syndrome and 401 patients diagnosed as nondeficit (prevalence=13.9%). This group included 347 full sibling pairs, which were analyzed for resemblance with respect to deficit versus nondeficit subtype by means of logistic regression. RESULTS: Deficit versus nondeficit subtypes were significantly correlated in sibling pairs concordant for core schizophrenia. CONCLUSIONS: Familial factors contribute significantly to whether a person has the deficit subtype of schizophrenia. This familial contribution could be genetic or environmental.

Differences in locomotor activity across the lifespan of Drosophila melanogaster.

The identification of differential patterns of change across the lifespan in quantitative traits is of abiding interest in the biological and gerontological research communities. These differential phenotypic patterns in complex systems illuminate developmental processes and form the foundation for the identification of putative biomarkers of aging. The goal of the present study was to explore changes in locomotor activity through the lifespan of Drosophila melanogaster. A replicated serial cross-sectional sampling design was used to test activity in five genetically independent inbred strains at 7, 14, 21, 28, 35, and 42 days of age. Differences were observed in activity level across ages and strains, suggesting that patterns of activity throughout the lifespan of D. melanogaster are influenced by genetic factors. Observed sex differences in change in activity level indicate that the aging processes may proceed differently in males and females.

Multivariate assessment of factors influencing illicit substance use in twins from female-female pairs.

Although familial factors have been shown to influence drug use, abuse, and dependence, little is known about the common and specific factors that influence polysubstance use and misuse. Our objective was to assess whether there are genetic and environmental factors specific to each substance or whether there are factors that predispose an individual to use of illicit substances in general. Twins from female-female pairs from the Virginia Twin Registry were interviewed by phone to assess lifetime nonmedical use of cannabis, sedatives, stimulants, cocaine, opiates, and hallucinogens. Multivariate, biometrical model-fitting was applied to the data using the Mx computer package. In the best-fitting model, use of all classes of drugs was influenced by a single general genetic factor (common to all substances) and a general familial environmental factor. The magnitude of influence of the general genetic factor ranged from 3% of the variance for opiates to 59% of the variance for cannabis. Some differences were seen from the univariate results, indicating some of the parameter estimates were unstable due to small numbers of concordant pairs. However, generalizations could be made. In women, the substances examined share genetic and familial environmental factors which contribute to the vulnerability to use. Degree of influence of the factors differs for the substances examined. However, no specific genetic or familial environmental factors were found to contribute significantly to use of any of the illicit substances.

Family characteristics of deficit and nondeficit schizophrenia in the Roscommon Family Study.

Studies of course, treatment response, biological correlates, and environmental risk factors have suggested that the deficit syndrome of schizophrenia defines a meaningful subgroup within schizophrenia. Probands from the Roscommon Family Study who met criteria for schizophrenia or simple schizophrenia were categorized into deficit (N=22) and nondeficit (N=111). Within schizophrenia, the lifetime prevalence of the deficit syndrome was 16.5%; the percentage of males was 91% compared to 63% in the nondeficit group. The first-degree relatives of deficit probands had a significantly greater social isolation than the relatives of nondeficit probands, despite significantly less severe dysphoria and psychotic-like symptoms. The risk of schizophrenia was 1.75 times greater in the families of deficit compared to nondeficit probands. There were no significant differences in the adjusted morbid risk for nonaffective psychosis, affective disorder, or alcoholism. These results provide further evidence that the deficit syndrome is a marker of a group of patients with clinical and neurobiological characteristics that distinguish them from the rest of schizophrenia. The deficit syndrome may be a useful phenotype in genetic linkage studies.

An examination of the genetic relationship between bipolar and unipolar illness in an epidemiological sample.

In an epidemiologic sample of female-female twin pairs, we previously reported analyses of lifetime major depression. Because lifetime mania was not assessed, we could not differentiate unipolar from bipolar illness. Having completed such an evaluation in this sample, we now examine three questions: (i) does removing bipolar cases from our cohort substantially alter estimates for the heritability of major depression?; (ii) does our epidemiologic data support a familial relationship between major depression and mania?; and (iii) do our results for major depression and mania suggest that the two disorders are caused by the same underlying liability? We find that (i) the heritability of major depression declines only trivially if cases with a history of mania are removed; (ii) mania in one twin predicts major depression in her cotwin-suggesting a familial/genetic relationship between major depression and mania; and (iii) a multiple threshold model fits our data well, consistent with the hypothesis that unipolar and bipolar disorders are points on a continuum of a single liability of illness. The validity of these results are tempered by the small number of bipolar cases detected, as expected from the low base rate of mania in general population samples.

Genetic selection disrupts stability of mouse brain weight development.

Fuller Brain Weight Selection lines are well differentiated for 42-day brain weight and a high degree of genetic homogeneity for trait-relevant genes is indicated. Using these lines, random bred descendants of the foundation population and an inbred line, biometrical analysis of brain growth from birth to 23 days was attempted. While strain means differ as expected, within and between litter variances for genetically heterogeneous mice were typically no greater than for more genetically homogeneous selected lines. Possible explanations involving gestational age, intra-uterine and postnatal competition and ontogenetic buffering are discussed.

[Ischemic stroke as the first manifestation of Wegener's granulomatosis]. / Une manifestation inaugurale inhabituelle de la granulomatose de Wegener : l'accident vasculaire cérébral ischémique.

The most characteristic clinical manifestations of Wegener's granulomatosis are upper and lower respiratory tract and renal involvement. The central nervous system manifestations are uncommon and occur usually late in the course of the disease. We report a 48-year-old man who presented with an ischemic stroke as the first manifestation of Wegener's granulomatosis. Wegener's granulomatosis should be considered in the differential diagnosis of ischemic stroke even in the absence of extraneurological involvement.

[Etiology and prognosis of highly elevated C-reactive protein levels (≥500 mg/L): a retrospective study about 168 measures in a series of 113 patients]. / Profil étiologique et pronostique des valeurs extrêmes (≥500 mg/L) de protéine C-réactive : étude rétrospective de 168 valeurs chez 113 patients.

PURPOSE: The C-reactive protein (CRP) is a useful inflammatory marker with a rapid kinetics during the inflammatory process. The objective of this study was to determine the etiology and prognosis of extremely elevated CRP values greater or equal to 500 mg/L. METHODS: We performed an exhaustive retrospective study from January 2004 to July 2009, in a general hospital, of all patients with a CRP value above 500 mg/L, admitted in all clinical departments. Clinical data were collected by a single observer using a standardized questionnaire. RESULTS: One hundred and sixty-eight CRP values greater or equal to 500 mg/L were identified amongst 106,758 tests (0.16%) corresponding to 113 patients: 51% were men and their mean age was 59.5 years. Mean CRP value was 561 mg/L (500-772). An immunocompromised condition was observed in 52% of the patients. All but 13 patients presented an infectious disease. Microbiological analysis of the infected patients identified 59 Gram-positive cocci (20 Staphylococcus spp., 35 Streptococcus spp. including 21 Streptococcus pneumoniae), two Gram-negative cocci, 48 Gram-negative bacilli (including 19 Escherichia coli), three Gram-positive bacilli, 16 fungal infections, one viral infection. Site of infection was respiratory in 63%, urinary in 17% and abdominal in 16%. At day 30, mortality rate was 27% and only 41% of the patients were discharged at home. CONCLUSION: CRP value above 500 mg/L is highly related to bacterial infections, without over-representation of a given microorganism. One-month mortality is high (27%).