The neuropathology of septic shock

The neuropathological correlates of encephalopathy and autonomic dysfunction in septic shock are unclear. We performed post mortem analysis of 5 brain areas susceptible to ischemia and 5 autonomic nuclei (AN) in 23 patients who had died in our intensive care unit (ICU) from septic shock and 8 dying from non-septic shock as well as 5 controls who had died suddenly from extracranial injury. Proinflammatory cytokine (IL1-beta and TNF-alpha) and inducible nitric oxide synthase (iNOS) expression was assessed by immunocytochemistry. Abnormalities in septic shock were: hemorrhages (26%), hypercoagulability syndrome (9%), micro-abscesses (9%), multifocal necrotizing leukoencephalopathy (9%) and ischemia (100%). The incidence of cerebral hemorrhage or hypercoagulability syndrome was not related to clotting disturbances. The intensity of ischemia within susceptible areas was the same in both ICU groups, but more pronounced in the autonomic centers of septic patients (P < 0.0001). Neuronal apoptosis assessed using anti-caspase 3 immunocytochemistry and in situ end labeling was more pronounced in the autonomic nuclei of septic patients. (P < 0.0001). TNF-alpha expression did not differ between groups but vascular iNOS expression assessed by immunocytochemistry was higher in sepsis (P<0.0001) and correlated with autonomic center neuronal apoptosis (P < 0.02). We conclude that septic shock is associated with diffuse cerebral damage and specific autonomic neuronal apoptosis which may be due to circulating factors particularly iNOS.     

Allele variations in the OCA2 gene (pink-eyed-dilution locus) are associated with genetic susceptibility to melanoma

The occuloalbinism 2 (OCA2) gene, localized at 15q11, encodes a melanosomal transmembrane protein that is involved in the most common form of human occulo-cutaneous albinism, a human genetic disorder characterized by fair pigmentation and susceptibility to skin cancer. We wondered whether allele variations at this locus could influence susceptibility to malignant melanoma (MM). In all, 10 intragenic single-nucleotide polymorphisms (SNPs) were genotyped in 113 patients with melanomas and in 105 Caucasian control subjects with no personal or family history of skin cancer. By comparing allelic distribution between cases and controls, we show that MM and OCA2 are associated (p value=0.030 after correction for multiple testing). Then, a recently developed strategy, the 'combination test' enabled us to show that a combination formed by two SNPs was most strongly associated to MM, suggesting a possible interaction between intragenic SNPs. In addition, the role of OCA2 on MM risk was also detected using a logistic model taking into account the presence of variants of the melanocortin 1 receptor gene (MC1R, a key pigmentation gene) and all pigmentation characteristics as melanoma risk factors. Our data demonstrate that a second pigmentation gene, in addition to MC1R, is involved in genetic susceptibility to melanoma.     

Polymer incompatibility study of a polystyrene network contaminated by linear polyisoprene chains

The present paper deals with the study of anionic polystyrene (PS) networks containing linear polyisoprene (PI) chains. Special attention was devoted to the problem of the compatibility of such a system, depending on the molecular weight M?_w (weight average) or M?_n (number average) of the chains in the polymeric network and the number average molecular weight M?_n of the linear polyisoprene chains. For that purpose, three different methods were used: diffusion of a concentrated linear polyisoprene solution into the polymeric network, “in situ” polymerization of isoprene inside the polystyrene network, and crosslinking of “living” polystyrene in a linear polyisoprene solution.     

ARCHITECT® urine-neutrophil gelatinase-associated lipocalin (u-NGAL) assay as new prognostic marker for clear cell Renal Cell Carcinoma (ccRCC) (preliminary results)

International Urology and Nephrology - Biomarkers for the diagnosis and monitoring treatment response of kidney cancer are urgently needed. Neutrophil gelatinase-associated lipocalin (NGAL) is a...     

Management of lower urinary tract fibroepithelial polyps in children

IntroductionFibroepithelial polyps (FEP) of the lower urinary tract are relatively common in adults but rare in children, with fewer than 250 cases reported in the literature to date.ObjectiveThe aim of this study was to address the experience of FEP management in children.Study designA retrospective multicenter review was undertaken in children with defined FEP of the lower urinary tract managed between 2008 and 2018. The data at 18 pediatric surgery centers were collected. Their demographic, radiological, surgical, and pathological information were reviewed.ResultsA total of 33 children (26 boys; 7 girls) were treated for FEP of the lower urinary tract at 13 centers. The most common presentation was urinary outflow as hematuria (41%), acute urinary retention (25%), dysuria (19%), or urinary infections (28%). A prenatal diagnosis was made for three patients with hydronephrosis. Almost all of the children (94%) underwent ultrasound imaging of the urinary tract as the first diagnostic examination, 23 (70%) of them also either had an MRI (15%), cystourethrography (25%), computerized tomography (6%), or cystoscopy (45%). Two of these children (6%) had a biopsy prior to the surgery. The median preoperative delay was 7.52 (range: 1–48) months. Most of the patients were treated endoscopically, although four (12.1%) had open surgery and two (6.1%) had an additional incision for specimen extraction. The median hospital stay was 1.5 (range: 1–10) days. There were no recurrences and no complications after a median follow-up of 13 (range: 1–34) months.DiscussionThe main limitation of our study is the retrospective design, although it is the largest one for this pathology.ConclusionThis series supports sonography as the most suitable diagnosis tool before endoscopy to confirm the diagnosis and to perform the resection for most FEP in children. This report confirms the recognized benign nature in the absence of recurrences.Level of EvidenceLevel V.     

Changes in humoral immune response after SARS-CoV-2 infection in liver transplant recipients compared to immunocompetent patients

The protective capacity and duration of humoral immunity after SARS-CoV-2 infection are not yet understood in solid organ transplant recipients. A prospective multicenter study was performed to evaluate the persistence of anti-nucleocapsid IgG antibodies in liver transplant recipients 6 months after coronavirus disease 2019 (COVID-19) resolution. A total of 71 liver transplant recipients were matched with 71 immunocompetent controls by a propensity score including variables with a well-known prognostic impact in COVID-19. Paired case–control serological data were also available in 62 liver transplant patients and 62 controls at month 3 after COVID-19. Liver transplant recipients showed a lower incidence of anti-nucleocapsid IgG antibodies at 3 months (77.4% vs. 100%, p < .001) and at 6 months (63.4% vs. 90.1%, p < .001). Lower levels of antibodies were also observed in liver transplant patients at 3 (p = .001) and 6 months (p < .001) after COVID-19. In transplant patients, female gender (OR = 13.49, 95% CI: 2.17–83.8), a longer interval since transplantation (OR = 1.19, 95% CI: 1.03–1.36), and therapy with renin–angiotensin–aldosterone system inhibitors (OR = 7.11, 95% CI: 1.47–34.50) were independently associated with persistence of antibodies beyond 6 months after COVID-19. Therefore, as compared with immunocompetent patients, liver transplant recipients show a lower prevalence of anti-SARS-CoV-2 antibodies and more pronounced antibody levels decline.     

Cryptococcus neoformans capsule structure evolution in vitro and during murine infection

Cryptococcus neoformans capsule structure modifications after prolonged in vitro growth or in vivo passaging have been reported previously. However, nothing is known about the dynamics of these modifications or about their environmental specificities. In this study, capsule structure modifications after mouse passaging and prolonged in vitro culturing were analyzed by flow cytometry using the glucuronoxylomannan-specific monoclonal antibody E1. The capsule structures of strains recovered after 0, 1, 8, and 35 days were compared by using the level of E1-specific epitope expression and its cell-to-cell heterogeneity within a given cell population. In vitro, according to these parameters, the diversity of the strains was higher on day 35 than it was initially, suggesting the absence of selection during in vitro culturing. In contrast, the diversity of the strains recovered from the brain tended to decrease over time, suggesting that selection of more adapted strains had occurred. The strains recovered on day 35 from the spleen and the lungs had different phenotypes than the strains isolated from the brain of the same mouse on the same day, thus strongly suggesting that there is organ specificity for C. neoformans strain selection. Fingerprinting of the strains recovered in vitro and in vivo over time confirmed that genotypes evolved very differently in vitro and in vivo, depending on the environment. Overall, our results suggest that organ-specific selection can occur during cryptococcosis.     

Human platelets after their contact with influenza virus activate the complement system in autologous serum

Guinea pig erythrocytes that have been exposed to influenza virus activate the alternative pathway through virus-induced desialation of the cells. Neuraminidase treatment of rabbit platelets enhance their clearancein vivo. Washed human platelets were labeled with⁵¹Cr exposed to Influenza virus, and resuspended in autologous serum that had been dialyzed against Veronal-buffered saline containing Ca⁺⁺ and Mg⁺⁺ (VBS⁺⁺), VBS containing 8 mM EGTA and 2 mM Mg⁺⁺ (VBS-MgEGTA) or VBS containing 20 mM EDTA (VBS-EDTA) for 60 min at 37°C. Three per cent⁵¹Cr release and no complement consumption were observed in VBS-EDTA serum. In contrast, 6%⁵¹Cr release with 37 and 54% decrease in C3 and B hemolytic activities respectively occurred in VBS-MgEGTA serum and 14%⁵¹Cr release with 50% decrease in C2 hemolytic activity occurred in VBS⁺⁺ serum. These results suggest that influenza virus may alter the platelet surface in such a way that both complement pathways might be recruited and the cells be lyzed in autologous serum.The human complement system is activated by a number of viruses and virus-infected cells through antibody-dependent and independent mechanisms. Guinea pig erythrocytes that have been treated with influenza virus are lyzed in human serum through activation of the classical and of the alternative pathways: activation of the alternative pathway is dependent on an acquired resistance of the cell-bound C3 amplification convertase to control mechanisms that are directly related to desialation of the cells by viral neuraminidase [1]. Since,in vivo, clearance of desialated platelets is enhanced in animal models and since human platelets do not express the C3b receptor-associated inhibitory activity of the complement system, we investigated whether human platelets, after contact with influenza virus, acquire the ability to activate complement in autologous serum.     

Testing a new health indicator: Using avoidable causes of death and life expectancy for Spain between 1975–1986

The concept of avoidable cause of death serves as the basis for measuring the quality and diversity of a health care system. In this study the authors propose a new way to use this kind of mortality by combining with the concept of life expectancy to obtain what they call life expectancy free of avoidable mortality (LEFAM).This indicator was 76.9 in 1986 in Spain while life expectancy was 75.83. If these deaths were avoidable there would be a gain of 1.09 years per person born. There is an important difference between the would-be male gain of 1.76 years and the would-be female gain of 0.6. In the ecological study, LEFAM would better explain the year to year changes of the resources in the health sector, measured in terms of the human resources (R = 0.96), the hospital beds per thousand persons (R = –0.86), and would also increase the relation with other health indicators such as infant mortality rate (R = –0.98) and mortality rate (R = 0.59) as compared with life expectancy alone.     

Contractile proteins in human fetoplacental vessels

OBJECTIVE: Our purpose was to compare the protein isoform composition of the contractile apparatus at different levels of the fetoplacental vessel musculature et term.STUDY DESIGN: Umbilical, chorionic, and stem villi vessel protein extracts were run on one- and two-dimensional gel electrophoresis; previously characterized human myometrium proteins were used as the smooth muscle proteins of reference.RESULTS: Fetoplacental vessel musculature exhibited a high ratio. The presence, in varying quantities, of myosin heavy chain and actin isoforms of smooth muscle type in the different vessels reflected their degree of differentiation. The presence of nonmuscle protein isoforms, particularly in stem villi vessels, indicated a certain degree of immaturity.CONCLUSIONS: The presence of smooth muscle contractile protein isoforms indicates that fetoplacental vessel musculature is highly differentiated. Regional modulation of fetoplacental blood flow could be, in part, the result of local differences in contractile apparatus protein composition.