Insuffisance rénale severe sur maladie des emboles de cholestérol: controverses thérapeutiques revisitées [Severe renal insufficiency secondary to renal cholesterol emboli: therapeutical options revisited]

Disseminated cholesterol crystal embolism is observed in elderly men with severe atherosclerosis. This syndrome may be triggered by arterial catheterizations, major vascular surgery, thrombolytic and/or anticoagulation treatment. Cutaneous signs, subacute renal insufficiency, a marked inflammatory syndrome and eosinophilia are common. Immunologic testing is normal except for hypocomplementaemia. The diagnosis may be confirmed by biopsy (skin, gastrointestinal or renal), and/or by a fundoscopic examination. The treatment consists in withdrawing all form of anticoagulation, proscribing vascular surgery and arterial catheterization, prescribing aspirin and statins, and controlling arterial blood pressure. Corticosteroids may be given in refractory cases. The prognosis of cholesterol crystal embolism is poor but may be improved by statins.

Existential questionings during the pretransplantation period: A qualitative phenomenological study

Background: Transplantation improves quality of life (kidney transplantation), and saves lives (heart, lung or liver transplantation), but few qualitative studies have explored existential questionings before transplantation. Methods: In this phenomenological qualitative study, patients registered for kidney (n¼30), liver (n¼11), lung (n¼15), or heart (n¼15) transplantation participated in a semi-structured interview. Findings: The following aspects were discussed: The dilemma of choice, the evaluation process, the endorsement of the ''good candidate's role'', the modification of objects, time and space perception, the co-existence of life and death, and the challenge of the body integrity and of the person's identity. Transplantation generates paradoxical situations, and challenges the person's life values. Discussion: Anxiety and distress may arise with awareness of existential questionings and the co-existence different worlds' life values. Transplantation further generates a broader societal and ethical debate as how to accompany existential questionings in a pragmatic medical environment.

Documenting a time-bound, circular view of hierarchies: a microanalysis of parent-infant dyadic interaction.

This article presents a new theory that separates the levels of communication and relates them circularly, namely, by separating time from space/meaning variables. Documenting this proposition requires sequential microdescriptions--a far-out project in the field of family therapy. In an extensive study of clinical and nonclinical families, starting with available microanalytic data on nonverbal parent-infant dialogue, distinct time organizations have been found to modify the degree of circularity between the levels of interaction according to the observed types of engagement, that is, consensual, conflictual, and paradoxical. The double description of the dyad as a totality versus the dyad as a framing/developing organization imparts crucial information on how development proceeds in dyadic, co-evolutive systems, and presumably in larger ones too. In this perspective, a model is elaborated and then applied to a case description in our therapeutic consultation.

Sex differences in patients receiving anticoagulant therapy for venous thromboembolism.

In patients with venous thromboembolism (VTE), the outcome during the course of anticoagulant therapy may differ according to the patient's sex. We used the RIETE (Registro Informatizado Enfermedad TromboEmbólica) database to compare the rate of VTE recurrences, major bleeding, and mortality due to these events according to sex.As of August 2013, 47,499 patients were enrolled in RIETE, of whom 24,280 (51%) were women. Women were older, more likely presented with pulmonary embolism (PE), and were more likely to have recent immobilization but less likely to have cancer than men. During the course of anticoagulation (mean duration: 253 d), 659 patients developed recurrent deep vein thrombosis (DVT), 576 recurrent PE, 1368 bled, and 4506 died. Compared with men, women had a lower rate of DVT recurrences (hazard ratio [HR]: 0.78; 95% confidence interval [CI]: 0.67-0.91), a similar rate of PE recurrences (HR: 0.98; 95% CI: 0.83-1.15), a higher rate of major bleeding (HR: 1.21; 95% CI: 1.09-1.35), and higher mortality due to PE (HR: 1.24; 95% CI: 1.04-1.47). On multivariable analysis, any influence of sex on the risk for recurrent DVT (HR: 0.88; 95% CI: 0.75-1.03), major bleeding (HR: 1.10; 95% CI: 0.98-1.24), or fatal PE (HR: 1.01; 95% CI: 0.84-1.22) was no longer statistically significant.In conclusion, women had fewer DVT recurrences and more bleeds than men during the course of anticoagulation. These differences were not due to sex, but very likely to other patient characteristics more common in female patients and differences in treatment choice.

Cardenolides in nectar may be more than a consequence of allocation to other plant parts: a phylogenetic study of Asclepias

The primary function of secondary plant metabolites is thought to be defence against herbivores. The frequent occurrence of these same noxious compounds in floral nectar, which functions primarily to attract pollinators, has been seen as paradoxical. Although these compounds may have an adaptive purpose in nectar, they may also occur as a nonadaptive consequence of chemical defence in other plant parts. If nectar chemistry reflects physiological constraints or passive leakage from other tissues, we expect that the identity and relative concentration of nectar cardenolides to be correlated with those of other plant parts; in contrast, discordant distributions of compounds in nectar and other tissues may suggest adaptive roles in nectar. We compared the concentrations and identities of cardenolides in the nectar, leaves and flowers of 12 species from a monophyletic clade of Asclepias. To measure putative toxicity of nectar cardenolides, we then examined the effects of a standard cardenolide (digoxin) on the behaviour of bumblebees, a common generalist pollinator of Asclepias. We found that the average cardenolide concentrations in nectar, leaves and flowers of the 12 Asclepias species were positively correlated as predicted by nonadaptive hypotheses. However, significant differences in the identities and concentrations of individual cardenolides between nectar and leaves suggest that the production or allocation of cardenolides may be independently regulated at each plant part. In addition, cardenolide concentrations in leaves and nectar exhibited no phylogenetic signal. Surprisingly, bumblebees did not demonstrate an aversion to digoxin-rich nectar, which may indicate that nectar cardenolides have little effect on pollination. Although the idea that discordant patterns of secondary metabolites across tissue types may signal adaptive functions is attractive, there is evidence to suggest constraint contributes to nectar secondary chemistry. Further work testing the ecological impacts of such patterns will be critical in determining the functional significance of nectar cardenolides

Occult lung infarction may induce false interpretation of 18F-FDG PET in primary staging of pulmonary malignancies.

PURPOSE: The aim of the present report is to describe abnormal (18)F-fluorodeoxyglucose (FDG) accumulation patterns in the pleura and lung parenchyma in a group of lung cancer patients in whom lung infarction was present at the time of positron emission tomography (PET). METHODS: Between November 2002 and December 2003, a total of 145 patients (102 males, 43 females; age range 38-85 years) were subjected to whole-body FDG PET for initial staging (n=117) or restaging (n=11) of lung cancer or for evaluation of solitary pulmonary nodules (n=17). Of these patients, 24 displayed abnormal FDG accumulation in the lung parenchyma that was not consistent with the primary lesion under investigation (ipsilateral n=12, contralateral n=9 or bilateral n=3). Without correlative imaging, this additional FDG uptake would have been considered indeterminate in differential diagnosis. RESULTS: Of the 24 patients who were identified as having such lesions, six harboured secondary tumour nodules diagnosed as metastases, while in three the diagnosis of a synchronous second primary lung tumour was established. Additionally, nine patients were identified as having post-stenotic pneumonia and/or atelectasis (n=6) or granulomatous lung disease (n=3). In the remaining six (4% of all patients), a diagnosis of recent pulmonary embolism that topographically matched the additional FDG accumulation (SUV(max) range 1.4-8.6, mean 3.9) was made. Four of these six patients were known to have pulmonary embolism, and hence false positive interpretation was avoided by correlating the PET findings with those of the pre-existing diagnostic work-up. The remaining two patients were harbouring small occult infarctions that mimicked satellite nodules in the lung periphery. Based on histopathological results, the abnormal FDG accumulation in these two patients was attributed to the inflammatory reaction and tissue repair associated with the pathological cascade of pulmonary embolism. CONCLUSION: In patients with pulmonary malignancies, synchronous lung infarction may induce pathological FDG accumulation that can mimic active tumour manifestations. Identifying this potential pitfall may allow avoidance of false positive FDG PET interpretation.

"We do have space in Lausanne. We have a large cemetery": The non-controversy of a non-existent Muslim burial ground

In the context of the administration of spaces assigned by municipalities for the burial of the dead, this article provides a critical analysis of the techniques for the governance of political collectives of citizens implemented by public authorities. More broadly, this article shows how funerary practices (i.e. the social practices surrounding death-the rituals, the legislation, etc.) can be used to develop a critical reading of the social relations that structure the social production of space. To this end, the authors use the conceptual tools provided by critical legal geography to explore the controversy surrounding the development of a 'carré confessionnel' (denominational area) within the Bois-de-Vaux Cemetery in Lausanne, Switzerland. Here, a focus on the techniques that allow 'nomosphere' technicians to convene a subset of the citizens within the public space reveals the administration of cemeteries as a means of governance, a method for mobilising bodies and a paradoxical means of managing flux.

Dominant PRPF31 Mutations Are Hypostatic to a Recessive CNOT3 Polymorphism in Retinitis Pigmentosa: A Novel Phenomenon of "Linked Trans-Acting Epistasis".

Mutations in PRPF31 are responsible for autosomal dominant retinitis pigmentosa (adRP, RP11 form) and affected families show nonpenetrance. Differential expression of the wildtype PRPF31 allele is responsible for this phenomenon: coinheritance of a mutation and a higher expressing wildtype allele provide protection against development of disease. It has been suggested that a major modulating factor lies in close proximity to the wildtype PRPF31 gene on Chromosome 19, implying that a cis-acting factor directly alters PRPF31 expression. Variable expression of CNOT3 is one determinant of PRPF31 expression. This study explored the relationship between CNOT3 (a trans-acting factor) and its paradoxical cis-acting nature in relation to RP11. Linkage analysis on Chromosome 19 was performed in mutation-carrying families, and the inheritance of the wildtype PRPF31 allele in symptomatic-asymptomatic sibships was assessed-confirming that differential inheritance of wildtype chromosome 19q13 determines the clinical phenotype (P < 2.6 × 10(-7) ). A theoretical model was constructed that explains the apparent conflict between the linkage data and the recent demonstration that a trans-acting factor (CNOT3) is a major nonpenetrance factor: we propose that this apparently cis-acting effect arises due to the intimate linkage of CNOT3 and PRPF31 on Chromosome 19q13-a novel mechanism that we have termed "linked trans-acting epistasis."

Distribution of artifactual gas on post-mortem multidetector computed tomography (MDCT).

PURPOSE: We investigated the incidence and distribution of post-mortem gas detected with multidetector computed tomography (MDCT) to identify factors that could distinguish artifactual gas from cardiac air embolism. MATERIAL AND METHODS: MDCT data of 119 cadavers were retrospectively examined. Gas was semiquantitatively assessed in selected blood vessels, organs, and body spaces (82 total sites). RESULTS: Seventy-four of the 119 cadavers displayed gas (62.2%; CI 95% 52.8-70.9), and 56 (75.7%) displayed gas in the heart. Most gas was detected in the hepatic parenchyma (40%), right heart (38% ventricle, 35% atrium), inferior vena cava (30% infrarenally, 26% suprarenally), hepatic veins (26% left, 29% middle, 22% right), and portal spaces (29%). Male cadavers displayed gas more frequently than female cadavers. Gas was detected 5-84 hours after death; therefore, the post-mortem interval could not reliably predict gas distribution (rho = 0.719, p < 0.0001). We found that a large amount of putrefaction-generated gas in the right heart was associated with aggregated gas bubbles in the hepatic parenchyma (sensitivity = 100%, specificity = 89.7%). In contrast, gas in the left heart (sensitivity = 41.7%, specificity = 100%) or in periumbilical subcutaneous tissues (sensitivity = 50%, specificity = 96.3%) could not predict gas due to putrefaction. CONCLUSION: This study is the first to show that the appearance of post-mortem gas follows a specific distribution pattern. An association between intracardiac gas and hepatic parenchymal gas could distinguish between post-mortem-generated gas and vital air embolism. We propose that this finding provides a key for diagnosing death due to cardiac air embolism.

Absence of the fourth cranial nerve in congenital Brown syndrome.

PURPOSE: To elucidate the aetiology of congenital Brown syndrome. METHODS: Four consecutive patients diagnosed with unilateral congenital Brown syndrome had a comprehensive standardized ocular motility examination. Any compensatory head posture was measured. Brain magnetic resonance imaging (MRI) with regard for the IV cranial nerve (CN) was performed in all patients. Orbital MRI was performed in 2/4 patients, with images acquired in eight directions of gaze and superior oblique (SO) muscle areas compared. RESULTS: CN IV could not be identified bilaterally in two patients, but was absent only on the side of the Brown syndrome in the two other patients. On the normal side, orbital MRI revealed a smaller SO muscle area in upgaze than in downgaze, demonstrating normal actions of this muscle. On the side of the Brown syndrome, the SO area remained the same in upgaze and in downgaze and approximately symmetric to the area of SO in downgaze on the normal side. CONCLUSIONS: These cases add further anatomical support to the theory of paradoxical innervation in congenital Brown syndrome. CN IV was absent in two patients on the side of the Brown syndrome, but without muscle hypoplasia. SO muscle size did not vary in up- and downgaze, which we interpreted as a sign of constant innervation through branches of CN III.

Low postseroconversion CD4 count and rapid decrease of CD4 density identify HIV+ fast progressors.

CD4 expression in HIV replication is paradoxical: HIV entry requires high cell-surface CD4 densities, but replication requires CD4 down-modulation. However, is CD4 density in HIV+ patients affected over time? Do changes in CD4 density correlate with disease progression? Here, we examined the role of CD4 density for HIV disease progression by longitudinally quantifying CD4 densities on CD4+ T cells and monocytes of ART-naive HIV+ patients with different disease progression rates. This was a retrospective study. We defined three groups of HIV+ patients by their rate of CD4+ T cell loss, calculated by the time between infection and reaching a CD4 level of 200 cells/microl: fast (<7.5 years), intermediate (7.5-12 years), and slow progressors (>12 years). Mathematical modeling permitted us to determine the maximum CD4+ T cell count after HIV seroconversion (defined as "postseroconversion CD4 count") and longitudinal profiles of CD4 count and density. CD4 densities were quantified on CD4+ T cells and monocytes from these patients and from healthy individuals by flow cytometry. Fast progressors had significantly lower postseroconversion CD4 counts than other progressors. CD4 density on T cells was lower in HIV+ patients than in healthy individuals and decreased more rapidly in fast than in slow progressors. Antiretroviral therapy (ART) did not normalize CD4 density. Thus, postseroconversion CD4 counts define individual HIV disease progression rates that may help to identify patients who might benefit most from early ART. Early discrimination of slow and fast progressors suggests that critical events during primary infection define long-term outcome. A more rapid CD4 density decrease in fast progressors might contribute to progressive functional impairments of the immune response in advanced HIV infection. The lack of an effect of ART on CD4 density implies a persistent dysfunctional immune response by uncontrolled HIV infection.

Activities of fluconazole, caspofungin, anidulafungin, and amphotericin B on planktonic and biofilm Candida species determined by microcalorimetry.

We investigated the activities of fluconazole, caspofungin, anidulafungin, and amphotericin B against Candida species in planktonic form and biofilms using a highly sensitive assay measuring growth-related heat production (microcalorimetry). C. albicans, C. glabrata, C. krusei, and C. parapsilosis were tested, and MICs were determined by the broth microdilution method. The antifungal activities were determined by isothermal microcalorimetry at 37°C in RPMI 1640. For planktonic Candida, heat flow was measured in the presence of antifungal dilutions for 24 h. Candida biofilm was formed on porous glass beads for 24 h and exposed to serial dilutions of antifungals for 24 h, and heat flow was measured for 48 h. The minimum heat inhibitory concentration (MHIC) was defined as the lowest antifungal concentration reducing the heat flow peak by ≥50% (≥90% for amphotericin B) at 24 h for planktonic Candida and at 48 h for Candida biofilms (measured also at 24 h). Fluconazole (planktonic MHICs, 0.25 to >512 μg/ml) and amphotericin B (planktonic MHICs, 0.25 to 1 μg/ml) showed higher MHICs than anidulafungin (planktonic MHICs, 0.015 to 0.5 μg/ml) and caspofungin (planktonic MHICs, 0.125 to 0.5 μg/ml). Against Candida species in biofilms, fluconazole's activity was reduced by >1,000-fold compared to its activity against the planktonic counterparts, whereas echinocandins and amphotericin B mainly preserved their activities. Fluconazole induced growth of planktonic C. krusei at sub-MICs. At high concentrations of caspofungin (>4 μg/ml), paradoxical growth of planktonic C. albicans and C. glabrata was observed. Microcalorimetry enabled real-time evaluation of antifungal activities against planktonic and biofilm Candida organisms. It can be used in the future to evaluate new antifungals and antifungal combinations and to study resistant strains.

Jambes lourdes, insuffisance veineuse des membres inférieurs et hormonothérapie substitutive [Heavy legs, venous insufficiency of the legs and hormone substitution therapy]

The effects of estrogens and gestagens on veins and circulation have been studied since prescription of these hormones as oral contraception and description of related thromboembolic events. The identification of different receptors and the description of these receptors in venous walls have helped to understand some hormonal effects. However, the actual knowledge remains insufficient to explain the complexity of the actions of hormones on venous function. The distribution, the density and the receptor types vary with age, gender, hormonal status and vascular bed. Gestagens mainly reduce the tone of venous walls, whereas estrogens have various effects. Between 25% and 50% of European adults and even 80% or more in some risk groups complain about heavy legs, with or without chronic venous insufficiency. The number of women to whom hormonal substitution is or could be prescribed increases along with aging of populations and the better understanding of potential benefits. The need for a better understanding of vascular effects of sexual hormones is growing, since the incidence of chronic venous insufficiency of the legs increases with age. The life prognosis will not be affected by a deterioration of a chronic venous insufficiency. In contrast, the quality of life, morbidity and the cost of treatment will be expected to change. In addition, thromboembolic events have to be considered, as has been shown in recent studies. These findings outline the need for further studies on the relation between hormones and venous function and for some caution when prescribing hormonal substitution.

Well-being and the frailty process in later life: an evaluation of the effectiveness of downward social comparison

This article, which is based on a longitudinal study conducted with a cohort ofoctogenarians, examines downward social comparison and its effectiveness as an adjustment mechanism during the frailty process. First of all, a paradoxical stability of subjective well-being is to be observed: it remains stable over five years notwithstanding the general decline in health. Next, an analysis based on individual health trajectories reveals that downward social comparison is associated with the maintenance of a stable level of well-being, whereas, when it is not associated with well-being, the latter tends to vary.

Development and validation of a postmortem radiological alteration index: the RA-Index.

This study aimed to derive an index quantifying the state of alteration of cadavers by quantifying the presence of gas in the body using postmortem multidetector computed tomography (MDCT) imaging, and to validate the index by defining its sensitivity and specificity. The RA (radiological alteration)-index was derived from postmortem MDCT data from 118 nontraumatically deceased people. To validate the index, 100 additional scanned bodies (50 % traumatically deceased) were retrospectively examined by two independent observers. Presence of gas at 82 sites was assessed by a radiologist, whereas a forensic pathologist only investigated the seven sites used for the RA-index. The RA-index was highly correlated to the overall presence of gas in all 82 sites (R(2) = 0.98 in the derivation set and 0.85 in the validation set). Semiquantitative evaluation of gas presence in each site showed moderate reliability (Cohen's kappa range, 0.41-0.78); nevertheless, the overall RA-index was very reliable (ICC(2,1) = 0.95; 95 % CI 0.92-0.96). Examiner using the RA-index detected heart cavities full of gas with a sensitivity of 100 % (95 % CI 51.7-100) and a specificity of 98.8 % (92.6-99.9). We conclude that determining the presence of gas at seven sites is a valid means to measure the distribution of gas due to cadaveric alteration in the entire body. The RA-index is rapid, easy-to-use, and reliable for nonexperienced users, and it is a valid method to suspect the normal presence of gas from cadaveric alteration. MDCT can be used to screen for gas embolism and to give indications for gas composition analysis (gas chromatography).