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21.
Ilse C. E. Hendriksen Juliet Mwanga-Amumpaire Lorenz von Seidlein George Mtove Lisa J. White Rasaq Olaosebikan Sue J. Lee Antoinette K. Tshefu Charles Woodrow Ben Amos Corine Karema Somporn Saiwaew Kathryn Maitland Ermelinda Gomes Wirichada Pan-Ngum Samwel Gesase Kamolrat Silamut Hugh Reyburn Sarah Joseph Kesinee Chotivanich Caterina I. Fanello Nicholas P. J. Day Nicholas J. White Arjen M. Dondorp 《PLoS medicine》2012,9(8)
Background
In African children, distinguishing severe falciparum malaria from other severe febrile illnesses with coincidental Plasmodium falciparum parasitaemia is a major challenge. P. falciparum histidine-rich protein 2 (PfHRP2) is released by mature sequestered parasites and can be used to estimate the total parasite burden. We investigated the prognostic significance of plasma PfHRP2 and used it to estimate the malaria-attributable fraction in African children diagnosed with severe malaria.Methods and Findings
Admission plasma PfHRP2 was measured prospectively in African children (from Mozambique, The Gambia, Kenya, Tanzania, Uganda, Rwanda, and the Democratic Republic of the Congo) aged 1 month to 15 years with severe febrile illness and a positive P. falciparum lactate dehydrogenase (pLDH)-based rapid test in a clinical trial comparing parenteral artesunate versus quinine (the AQUAMAT trial, ISRCTN 50258054). In 3,826 severely ill children, Plasmadium falciparum PfHRP2 was higher in patients with coma (p = 0.0209), acidosis (p<0.0001), and severe anaemia (p<0.0001). Admission geometric mean (95%CI) plasma PfHRP2 was 1,611 (1,350–1,922) ng/mL in fatal cases (n = 381) versus 1,046 (991–1,104) ng/mL in survivors (n = 3,445, p<0.0001), without differences in parasitaemia as assessed by microscopy. There was a U-shaped association between log10 plasma PfHRP2 and risk of death. Mortality increased 20% per log10 increase in PfHRP2 above 174 ng/mL (adjusted odds ratio [AOR] 1.21, 95%CI 1.05–1.39, p = 0.009). A mechanistic model assuming a PfHRP2-independent risk of death in non-malaria illness closely fitted the observed data and showed malaria-attributable mortality less than 50% with plasma PfHRP2≤174 ng/mL. The odds ratio (OR) for death in artesunate versus quinine-treated patients was 0.61 (95%CI 0.44–0.83, p = 0.0018) in the highest PfHRP2 tertile, whereas there was no difference in the lowest tertile (OR 1.05; 95%CI 0.69–1.61; p = 0.82). A limitation of the study is that some conclusions are drawn from a mechanistic model, which is inherently dependent on certain assumptions. However, a sensitivity analysis of the model indicated that the results were robust to a plausible range of parameter estimates. Further studies are needed to validate our findings.Conclusions
Plasma PfHRP2 has prognostic significance in African children with severe falciparum malaria and provides a tool to stratify the risk of “true” severe malaria-attributable disease as opposed to other severe illnesses in parasitaemic African children. Please see later in the article for the Editors'' Summary. 相似文献22.
Prof. Renato Meduri Emilio Campos Lucia Scorolli Caterina De Vinci Giancarlo Pizza Dimitri Viza 《Biotherapy》1996,9(1-3):61-66
Recurrent ocular herpes is an insoluble problem for the clinician. As cellular immunity plays an important role in controlling
herpes relapses, and other studies have shown the efficacy of HSV-specific transfer factor (TF) for the treatment of herpes
patients, an open clinical trial was undertaken in 134 patients (71 keratitis, 29 kerato-uveitis, 34 uveitis) suffering from
recurrent ocular herpetic infections. The mean duration of the treatment was 358 days, and the entire follow-up period 189121
before, and 64062 days after TF treatment. The cell-mediated immune response to the viral antigens, evaluated by the lymphocyte
stimulation test (LST) and the leucocyte migration test (LMT) (P<0.001), was significantly increased by the TF treatment.
The total number of relapses was decreased significantly during/after TF treatment, dropping from 832 before, to 89 after
treatment, whereas the cumulative relapse index (RI) dropped, during the same period, from 13.2 to 4.17 (P<0.0001). No side
effects were observed. It is concluded that patients with relapsing ocular herpes can benefit from treatment with HSV-specific
TF. 相似文献
23.
Caterina Crescimanno Jean-Michel Foidart Agns Noël Myriam Polette Erik Maquoi Philippe Birembaut Eugenia Baramova Peter Kaufmann Mario Castellucci 《Experimental cell research》1996,227(2):240
Implantation and placental development are dependent upon trophoblast invasion of the endometrium. While the villous trophoblast does not display invasive behavior, the extravillous cytotrophoblast is highly invasive. By cloning BeWo choriocarcinoma cells, we have isolated two distinct clones that share similarities with villous and extravillous cytotrophoblasts. When cultured at the surface of a type I collagen gel, BeWo MC-1 cells were not invasive, whereas BeWo MC-2 cells rapidly invaded this matrix. When injected subcutaneously in nude mice, BeWo MC-1 cells developed a localized tumor and BeWo MC-2 cells developed larger tumors with micrometastases. Gelatinase A expression and minute amounts of gelatinase B were detected in the parental cell line and in both clones. However, the parental and the BeWo MC-2 cells secreted 5- to 10-fold more gelatinase A than the BeWo MC-1 cells. Laminin and matrigel stimulated the production of gelatinase A in BeWo MC-2 cells. Type I collagen promoted the conversion of the 72-kDa progelatinase A in an active enzyme only in parental BeWo and in BeWo MC-2 cells. These clones provide an interesting model for studying the complex mechanisms regulating implantation as well as the controlled invasiveness during implantation compared to tumor invasion. 相似文献
24.
FOXM1 Transcription Factor: A New Component of Chronic Myeloid Leukemia Stem Cell Proliferation Advantage 下载免费PDF全文
Manuela Mancini Fausto Castagnetti Simona Soverini Elisa Leo Caterina De Benedittis Gabriele Gugliotta Gianantonio Rosti Luana Bavaro Sara De Santis Cecilia Monaldi Margherita Martelli Maria Alessandra Santucci Michele Cavo Giovanni Martinelli 《Journal of cellular biochemistry》2017,118(11):3968-3975
25.
26.
Recombinant Mitochondrial Manganese Containing Superoxide Dismutase Protects Against Ochratoxin A‐Induced Nephrotoxicity 下载免费PDF全文
27.
The extent of whole‐genome copy number alterations predicts aggressive features in primary melanomas 下载免费PDF全文
Greta Gandolfi Caterina Longo Elvira Moscarella Iris Zalaudek Valentina Sancisi Margherita Raucci Gloria Manzotti Mila Gugnoni Simonetta Piana Giuseppe Argenziano Alessia Ciarrocchi 《Pigment cell & melanoma research》2016,29(2):163-175
Recent evidence indicates that melanoma comprises distinct types of tumors and suggests that specific morphological features may help predict its clinical behavior. Using a SNP‐array approach, we quantified chromosomal copy number alterations (CNA) across the whole genome in 41 primary melanomas and found a high degree of heterogeneity in their genomic asset. Association analysis correlating the number and relative length of CNA with clinical, morphological, and dermoscopic attributes of melanoma revealed that features of aggressiveness were strongly linked to the overall amount of genomic damage. Furthermore, we observed that melanoma progression and survival were mainly affected by a low number of large chromosome losses and a high number of small gains. We identified the alterations most frequently associated with aggressive melanoma, and by integrating our data with publicly available gene expression profiles, we identified five genes which expression was found to be necessary for melanoma cells proliferation. In conclusion, this work provides new evidence that the phenotypic heterogeneity of melanoma reflects a parallel genetic diversity and lays the basis to define novel strategies for a more precise prognostic stratification of patients. 相似文献
28.
Arese M Magnifico MC Mastronicola D Altieri F Grillo C Blanck TJ Sarti P 《IUBMB life》2012,64(3):251-258
A novel role of melatonin was unveiled, using immortalized human keratinocyte cells (HaCaT) as a model system. Within a time window compatible with its circadian rhythm, melatonin at nanomolar concentration raised both the expression level of the neuronal nitric oxide synthase mRNA and the nitric oxide oxidation products, nitrite and nitrate. On the same time scale, a depression of the mitochondrial membrane potential was detected together with a decrease of the oxidative phosphorylation efficiency, compensated by glycolysis as testified by an increased production of lactate. The melatonin concentration, ~ nmolar, inducing the bioenergetic effects and their time dependence, both suggest that the observed nitric oxide-induced mitochondrial changes might play a role in the metabolic pathways characterizing the circadian melatonin chemistry. 相似文献
29.
The Influence of Clinical Information in the Histopathologic Diagnosis of Melanocytic Skin Neoplasms
Gerardo Ferrara Zsolt Argenyi Giuseppe Argenziano Rino Cerio Lorenzo Cerroni Arturo Di Blasi Elisa A. A. Feudale Caterina M. Giorgio Cesare Massone Oscar Nappi Carlo Tomasini Carmelo Urso Iris Zalaudek Harald Kittler H. Peter Soyer 《PloS one》2009,4(4)
Background
We tested the relevance of clinical information in the histopathologic evaluation of melanocytic skin neoplasm (MSN).Methods
Histopathologic specimens from 99 clinically atypical MSN were circulated among ten histopathologists; each case had clinical information available in a database with a five-step procedure (no information; age/sex/location; clinical diagnosis; clinical image; dermoscopic image); each step had a histopathologic diagnosis (D1 through D5); each diagnostic step had a level of diagnostic confidence (LDC) ranging from 1 (no diagnostic certainty) to 5 (absolute diagnostic certainty). The comparison of the LDC was employed with an analysis of variance (ANOVA) for repeated measures.Findings
In D1 (no information), 36/99 cases (36.3%) had unanimous diagnosis; in D5 (full information available), 51/99 cases (51.5%) had unanimous diagnosis (p for difference between proportions <0.001). The observer agreement expressed as kappa increased significantly from D1 to D5. The mean LDC linearly increased for each observer from D1 through D5 (p for linear trend <0.001). On average, each histopathologist changed his initial diagnosis in 7 cases (range: 2–23). Most diagnostic changes were in D2 (age/sex/location).Interpretation
The histopathologic criteria for the diagnosis of MSN can work as such, but the final histopathologic diagnosis is a clinically-aided interpretation. Clinical data sometimes reverse the initial histopathologic evaluation. 相似文献30.
Viggiano E Passavanti MB Pace MC Sansone P Spaziano G Viggiano A Aurilio C Monda M Viggiano A Pota V De Luca B De Luca E 《Journal of cellular physiology》2012,227(5):1988-1991
Glutamine (gln) is the most abundant free amino acid in the blood. It is involved in important metabolic and biochemical processes, like cell proliferation and oxidative stress. Previous studies have demonstrated that gln concentration in human plasma decreases in several conditions such as sepsis, ischemia-reperfusion, trauma, major surgery and burn. The aim of the present work was to compare the acute effects of different types of surgical interventions and of anesthetization on blood gln concentration. Plasma samples from 88 subjects (30 males and 58 females) were collected before and after major or minor surgery and the gln concentration was analyzed with high-performance liquid chromatography. The results showed that plasma gln concentration after surgery was lower than pre-surgery values and that in major surgery the decrease of gln was higher than in minor surgery. No significant effect was shown for sex or type of anesthesia. These results demonstrate the importance of a gln supplementation before a surgical intervention and show that the amount of gln supplementation should also be adjusted based on the type of surgery. 相似文献