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1.
Heinz Fehrenbach Sebastian Tews Antonia Fehrenbach Matthias Ochs Thorsten Wittwer Thorsten Wahlers Joachim Richter 《Respiratory research》2005,6(1):60
Background
Declining levels of surfactant protein A (SP-A) after lung transplantation are suggested to indicate progression of ischemia/reperfusion (IR) injury. We hypothesized that the previously described preservation-dependent improvement of alveolar surfactant integrity after IR was associated with alterations in intraalveolar SP-A levels.Methods
Using immuno electron microscopy and design-based stereology, amount and distribution of SP-A, and of intracellular surfactant phospholipids (lamellar bodies) as well as infiltration by polymorphonuclear leukocytes (PMNs) and alveolar macrophages were evaluated in rat lungs after IR and preservation with EuroCollins or Celsior.Results
After IR, labelling of tubular myelin for intraalveolar SP-A was significantly increased. In lungs preserved with EuroCollins, the total amount of intracellular surfactant phospholipid was reduced, and infiltration by PMNs and alveolar macrophages was significantly increased. With Celsior no changes in infiltration or intracellular surfactant phospholipid amount occurred. Here, an increase in the number of lamellar bodies per cell was associated with a shift towards smaller lamellar bodies. This accounts for preservation-dependent changes in the balance between surfactant phospholipid secretion and synthesis as well as in inflammatory cell infiltration.Conclusion
We suggest that enhanced release of surfactant phospholipids and SP-A represents an early protective response that compensates in part for the inactivation of intraalveolar surfactant in the early phase of IR injury. This beneficial effect can be supported by adequate lung preservation, as e.g. with Celsior, maintaining surfactant integrity and reducing inflammation, either directly (via antioxidants) or indirectly (via improved surfactant integrity). 相似文献2.
Background
Successful combination antiretroviral therapy (cART) increases levels of CD4+ T-cells, however this increase may not accurately reflect long-term immune recovery since T-cell dysregulation and loss of T-cell homeostasis often persist. We therefore assessed the impact of a decade of effective cART on immune regulation, T-cell homeostasis, and overall T-cell phenotype.Methods
We conducted a retrospective study of 288 HIV+ cART-naïve patients initiating therapy. We identified 86 individuals who received cART for at least a decade, of which 44 consistently maintained undetectable plasma HIV-RNA levels throughout therapy. At baseline, participants were classified into three groups according to pre-treatment CD4+ T-cell counts: Group I (CD4<200 cells/mm3); Group II (CD4: 200–350 cells/mm3); Group III (CD4>350 cells/mm3). Outcomes of interest were: (1) CD4+ T-cell count restoration (CD4>532 cells/mm3); (2) normalization of CD4:CD8 T-cell ratio (1.2–3.3); (3) maintenance of CD3+ T-cell homeostasis (CD3: 65%–85% of peripheral lymphocytes); (4) normalization of the complete T-cell phenotype (TCP).Results
Despite a decade of sustained successful cART, complete T-cell phenotype normalization only occurred in 16% of patients, most of whom had initiated therapy at high CD4+ T-cell counts (>350 cells/mm3). The TCP parameter that was the least restored among patients was the CD4:CD8 T-cell ratio.Conclusions
Failure to normalize the complete T-cell phenotype was most apparent in patients who initiated cART with a CD4+ T-cell count <200 cells/mm3. The impact of this impaired T-cell phenotype on life-long immune function and potential comorbidities remains to be elucidated. 相似文献3.
Miriam E. Koome Joanne O. Davidson Paul P. Drury Sam Mathai Lindsea C. Booth Alistair Jan Gunn Laura Bennet 《PloS one》2013,8(10)
Background and Purpose
Maternal glucocorticoid treatment for threatened premature delivery dramatically improves neonatal survival and short-term morbidity; however, its effects on neurodevelopmental outcome are variable. We investigated the effect of maternal glucocorticoid exposure after acute asphyxia on injury in the preterm brain.Methods
Chronically instrumented singleton fetal sheep at 0.7 of gestation received asphyxia induced by complete umbilical cord occlusion for 25 minutes. 15 minutes after release of occlusion, ewes received a 3 ml i.m. injection of either dexamethasone (12 mg, n = 10) or saline (n = 10). Sheep were killed after 7 days recovery; survival of neurons in the hippocampus and basal ganglia, and oligodendrocytes in periventricular white matter were assessed using an unbiased stereological approach.Results
Maternal dexamethasone after asphyxia was associated with more severe loss of neurons in the hippocampus (CA3 regions, 290±76 vs 484±98 neurons/mm2, mean±SEM, P<0.05) and basal ganglia (putamen, 538±112 vs 814±34 neurons/mm2, P<0.05) compared to asphyxia-saline, and with greater loss of both total (913±77 vs 1201±75/mm2, P<0.05) and immature/mature myelinating oligodendrocytes in periventricular white matter (66±8 vs 114±12/mm2, P<0.05, vs sham controls 165±10/mm2, P<0.001). This was associated with transient hyperglycemia (peak 3.5±0.2 vs. 1.4±0.2 mmol/L at 6 h, P<0.05) and reduced suppression of EEG power in the first 24 h after occlusion (maximum −1.5±1.2 dB vs. −5.0±1.4 dB in saline controls, P<0.01), but later onset and fewer overt seizures.Conclusions
In preterm fetal sheep, exposure to maternal dexamethasone during recovery from asphyxia exacerbated brain damage. 相似文献4.
Marina Giuliano Mauro Andreotti Giuseppe Liotta Haswell Jere Jean-Baptiste Sagno Martin Maulidi Sandro Mancinelli Ersilia Buonomo Paola Scarcella Maria F. Pirillo Roberta Amici Susanna Ceffa Stefano Vella Leonardo Palombi Maria Cristina Marazzi 《PloS one》2013,8(7)
Background
Optimized preventive strategies are needed to reach the objective of eliminating pediatric AIDS. This study aimed to define the determinants of residual HIV transmission in the context of maternal antiretroviral therapy (ART) administration to pregnant women, to assess infant safety of this strategy, and to evaluate its impact on maternal disease.Methodology/Principal Findings
A total of 311 HIV-infected pregnant women were enrolled in Malawi in an observational study and received a nevirapine-based regimen from week 25 of gestation until 6 months after delivery (end of breastfeeding period) if their CD4+ count was > 350/mm3 at baseline (n = 147), or indefinitely if they met the criteria for treatment (n. 164). Mother/child pairs were followed until 2 years after delivery. The Kaplan-Meier method was used to estimate HIV transmission, maternal disease progression, and survival at 24 months. The rate of HIV infant infection was 3.2% [95% confidence intervals (CI) 1.0-5.4]. Six of the 8 transmissions occurred among mothers with baseline CD4+ count > 350/mm3. HIV-free survival of children was 85.8% (95% CI 81.4-90.1). Children born to mothers with baseline CD4+ count < 350/mm3 were at increased risk of death (hazard ratio 2.6, 95% CI 1.1-6.1). Among women who had stopped treatment the risk of progression to CD4+ count < 350/mm3 was 20.6% (95% CI 9.2-31.9) by 18 months of drug discontinuation.Conclusions
HIV transmission in this cohort was rare however, it occurred in a significative proportion among women with high CD4+ counts. Strategies to improve treatment adherence should be implemented to further reduce HIV transmission. Mortality in the uninfected exposed children was the major determinant of HIV-free survival and was associated to maternal disease stage. Given the considerable proportion of women reaching the criteria for treatment within 18 months of drug discontinuation, life-long ART administration to HIV-infected women should be considered. 相似文献5.
Keertan Dheda Virginia Davids Laura Lenders Teri Roberts Richard Meldau Daphne Ling Laurence Brunet Richard van Zyl Smit Jonathan Peter Clare Green Motasim Badri Leonardo Sechi Surendra Sharma Michael Hoelscher Rodney Dawson Andrew Whitelaw Jonathan Blackburn Madhukar Pai Alimuddin Zumla 《PloS one》2010,5(3)
Background
The accurate diagnosis of TB in HIV-infected patients, particularly with advanced immunosuppression, is difficult. Recent studies indicate that a lipoarabinomannan (LAM) assay (Clearview-TB®-ELISA) may have some utility for the diagnosis of TB in HIV-infected patients; however, the precise subgroup that may benefit from this technology requires clarification. The utility of LAM in sputum samples has, hitherto, not been evaluated.Methods
LAM was measured in sputum and urine samples obtained from 500 consecutively recruited ambulant patients, with suspected TB, from 2 primary care clinics in South Africa. Culture positivity for M. tuberculosis was used as the reference standard for TB diagnosis.Results
Of 440 evaluable patients 120/387 (31%) were HIV-infected. Urine-LAM positivity was associated with HIV positivity (p = 0.007) and test sensitivity, although low, was significantly higher in HIV-infected compared to uninfected patients (21% versus 6%; p<0.001), and also in HIV-infected participants with a CD4 <200 versus >200 cells/mm3 (37% versus 0%; p = 0.003). Urine-LAM remained highly specific in all 3 subgroups (95%–100%). 25% of smear-negative but culture-positive HIV-infected patients with a CD4 <200 cells/mm3 were positive for urine-LAM. Sputum-LAM had good sensitivity (86%) but poor specificity (15%) likely due to test cross-reactivity with several mouth-residing organisms including actinomycetes and nocardia species.Conclusions
These preliminary data indicate that in a high burden primary care setting the diagnostic usefulness of urine-LAM is limited, as a rule-in test, to a specific patient subgroup i.e. smear-negative HIV-infected TB patients with a CD4 count <200 cells/mm3, who would otherwise have required further investigation. However, even in this group sensitivity was modest. Future and adequately powered studies in a primary care setting should now specifically target patients with suspected TB who have advanced HIV infection. 相似文献6.
Carsten Schleh Christian Mühlfeld Karin Pulskamp Andreas Schmiedl Matthias Nassimi Hans D Lauenstein Armin Braun Norbert Krug Veit J Erpenbeck Jens M Hohlfeld 《Respiratory research》2009,10(1):90
Background
Pulmonary surfactant reduces surface tension and is present at the air-liquid interface in the alveoli where inhaled nanoparticles preferentially deposit. We investigated the effect of titanium dioxide (TiO2) nanosized particles (NSP) and microsized particles (MSP) on biophysical surfactant function after direct particle contact and after surface area cycling in vitro. In addition, TiO2 effects on surfactant ultrastructure were visualized.Methods
A natural porcine surfactant preparation was incubated with increasing concentrations (50-500 μg/ml) of TiO2 NSP or MSP, respectively. Biophysical surfactant function was measured in a pulsating bubble surfactometer before and after surface area cycling. Furthermore, surfactant ultrastructure was evaluated with a transmission electron microscope.Results
TiO2 NSP, but not MSP, induced a surfactant dysfunction. For TiO2 NSP, adsorption surface tension (γads) increased in a dose-dependent manner from 28.2 ± 2.3 mN/m to 33.2 ± 2.3 mN/m (p < 0.01), and surface tension at minimum bubble size (γmin) slightly increased from 4.8 ± 0.5 mN/m up to 8.4 ± 1.3 mN/m (p < 0.01) at high TiO2 NSP concentrations. Presence of NSP during surface area cycling caused large and significant increases in both γads (63.6 ± 0.4 mN/m) and γmin (21.1 ± 0.4 mN/m). Interestingly, TiO2 NSP induced aberrations in the surfactant ultrastructure. Lamellar body like structures were deformed and decreased in size. In addition, unilamellar vesicles were formed. Particle aggregates were found between single lamellae.Conclusion
TiO2 nanosized particles can alter the structure and function of pulmonary surfactant. Particle size and surface area respectively play a critical role for the biophysical surfactant response in the lung. 相似文献7.
Cheng-Sheng Wang Lian-Jun Du Ming-Jue Si Qi-Hua Yin Liang Chen Min Shu Fei Yuan Xiao-Chun Fei Xiao-Yi Ding 《PloS one》2013,8(8)
Objectives
The purpose of our study is to investigate whether diffusion-weighted imaging (DWI) is useful for monitoring the therapeutic response after neoadjuvant chemotherapy in osteosarcoma of long bones.Materials and methods
Conventional magnetic resonance imaging (MRI) and DWI were obtained from 35 patients with histologically proven osteosarcomas. MR examinations were performed in all patients before and after 4 courses of preoperative neoadjuvant chemotherapy. Apparent diffusion coefficients (ADC) were measured. The degree of tumor necrosis was assessed macroscopically and histologically by two experienced pathologists after operation. Student’s t test was performed for testing changes in ADC value. Pearson’s correlation coefficient was used to estimate the correlation between necrosis rate and post- neoadjuvant chemotherapy ADC values. P<0.05 was considered to denote a significant difference.Results
The difference of the whole osteosarcoma between pre- neoadjuvant chemotherapy ADC value (1.24±0.17×10−3 mm2/s) and post- (1.93±0.39×10−3 mm2/s) was significant difference (P<0.01). Regarding in patients with good response, the post- neoadjuvant chemotherapy values were significantly higher than the pre- neoadjuvant chemotherapy values (P<0.01). The post- neoadjuvant chemotherapy ADC value in patients with good response was higher than that of poor response (t = 8.995, P<0.01). The differences in post- neoadjuvant chemotherapy ADC between viable (1.03±0.17×10−3 mm2/s) and necrotic (2.38±0.25×10−3 mm2/s) tumor was highly significant (t = 23.905, P<0.01). A positive correlation between necrosis rates and the whole tumor ADC values (r = 0.769, P<0.01) was noted, but necrosis rates were not correlated with the ADC values of necrotic (r = −0.191, P = 0.272) and viable tumor areas (r = 0.292, P = 0.089).Conclusions
DWI can identify residual viable tumor tissues and tumor necrosis induced by neoadjuvant chemotherapy in osteosarcoma. The ADC value can directly reflect the degree of tumor necrosis, and it is useful to evaluate the preoperative neoadjuvant chemotherapy response in patients with osteosarcoma. 相似文献8.
Noam Nissan Talia Golan Edna Furman-Haran Sara Apter Yael Inbar Arie Ariche Barak Bar-Zakay Yuri Goldes Michael Schvimer Dov Grobgeld Hadassa Degani 《PloS one》2014,9(12)
Purpose
To develop a diffusion-tensor-imaging (DTI) protocol that is sensitive to the complex diffusion and perfusion properties of the healthy and malignant pancreas tissues.Materials and Methods
Twenty-eight healthy volunteers and nine patients with pancreatic-ductal-adenocacinoma (PDAC), were scanned at 3T with T2-weighted and DTI sequences. Healthy volunteers were also scanned with multi-b diffusion-weighted-imaging (DWI), whereas a standard clinical protocol complemented the PDAC patients’ scans. Image processing at pixel resolution yielded parametric maps of three directional diffusion coefficients λ1, λ2, λ3, apparent diffusion coefficient (ADC), and fractional anisotropy (FA), as well as a λ1-vector map, and a main diffusion-direction map.Results
DTI measurements of healthy pancreatic tissue at b-values 0,500 s/mm2yielded: λ1 = (2.65±0.35)×10−3, λ2 = (1.87±0.22)×10−3, λ3 = (1.20±0.18)×10−3, ADC = (1.91±0.22)×10−3 (all in mm2/s units) and FA = 0.38±0.06. Using b-values of 100,500 s/mm2 led to a significant reduction in λ1, λ2, λ3 and ADC (p<.0001) and a significant increase (p<0.0001) in FA. The reduction in the diffusion coefficients suggested a contribution of a fast intra-voxel-incoherent-motion (IVIM) component at b≤100 s/mm2, which was confirmed by the multi-b DWI results. In PDACs, λ1, λ2, λ3 and ADC in both 0,500 s/mm2 and 100,500 s/mm2 b-values sets, as well as the reduction in these diffusion coefficients between the two sets, were significantly lower in comparison to the distal normal pancreatic tissue, suggesting higher cellularity and diminution of the fast-IVIM component in the cancer tissue.Conclusion
DTI using two reference b-values 0 and 100 s/mm2 enabled characterization of the water diffusion and anisotropy of the healthy pancreas, taking into account a contribution of IVIM. The reduction in the diffusion coefficients of PDAC, as compared to normal pancreatic tissue, and the smaller change in these coefficients in PDAC when the reference b-value was modified from 0 to 100 s/mm2, helped identifying the presence of malignancy. 相似文献9.
Kenneth K. Poon Bich N. Dang Jessica A. Davila Christine Hartman Thomas P. Giordano 《PloS one》2013,8(3)
Objective
Little is known about the treatment outcomes of undocumented Hispanic immigrants with HIV infection. We sought to compare the treatment outcomes of undocumented and documented patients 12-months after entering HIV care.Methods
We conducted a retrospective cohort study of antiretroviral-naive patients 18 years and older attending their first visit at Thomas Street Health Center in Houston, Texas, between 1/1/2003 and 6/30/2008. The study population of 1,620 HIV-infected adults included 186 undocumented Hispanic, 278 documented Hispanic, 986 Black, and 170 White patients. The main outcome measures were retention in care (quarter years with at least one completed HIV primary care provider visit) and HIV suppression (HIV RNA <400 copies/mL), both measured 12-months after entering HIV care.Results
Undocumented Hispanic patients had lower median initial CD4 cell count (132 cells/mm3) than documented Hispanic patients (166 cells/mm3; P = 0.186), Black patients (226 cells/mm3; P<0.001), and White patients (264 cells/mm3; P = 0.001). However, once in care, undocumented Hispanic patients did as well or better than their documented counterparts. One year after entering HIV care, undocumented Hispanics achieved similar rates of retention in care and HIV suppression as documented Hispanic and White patients. Of note, black patients were significantly less likely to have optimal retention in care (adjusted odds ratio [aOR] 0.65, CI = 0.45–0.94) or achieve HIV suppression (aOR 0.32, CI = 0.17–0.61) than undocumented Hispanics.Conclusions
Undocumented Hispanic persons with HIV infection enter care with more advanced disease than documented persons, suggesting testing and/or linkage to care efforts for this difficult-to-reach population need intensification. Once diagnosed, however, undocumented Hispanics have outcomes as good as or better than other racial/ethnic groups. Safety net providers for undocumented immigrants are vital for maintaining individual and public health. 相似文献10.
Farah Idali Jan Wahlstr?m Benita Dahlberg Mohsen Khademi Tomas Olsson Anders Eklund Johan Grunewald 《Respiratory research》2009,10(1):42
Background
Activated T helper (Th)-1 pulmonary CD4+ cells and their mediators are essential for the inflammation and granulomatous process in sarcoidosis. Recently, T-cell immunoglobulin and mucin domain (TIM) molecules were suggested to be important regulators of immune function. In this study, we wanted to investigate whether TIM molecules could play a role in sarcoidosis.Methods
We used real-time polymerase chain reaction to investigate the differential gene expression of TIM-1 and TIM-3 as well as a few Th1 and Th2 cytokines (IL-2, IFN-γ, IL-4, IL-5 and IL-13) in CD4+ T cells isolated from bronchoalveolar lavage fluid (BALF) of patients (n = 28) and healthy controls (n = 8). Using flow cytometry, we were also able to analyse TIM-3 protein expression in 10 patients and 6 healthy controls.Results
A decreased TIM-3 mRNA (p < 0.05) and protein (p < 0.05) expression was observed in patients, and the level of TIM-3 mRNA correlated negatively with the CD4/CD8 T cell ratio in BALF cells of patients. Compared to a distinct subgroup of patients i.e. those with Löfgren''s syndrome, BALF CD4+ T cells from non- Löfgren''s patients expressed decreased mRNA levels of TIM-1 (p < 0.05). mRNA expression of IL-2 was increased in patients (p < 0.01) and non-Löfgren''s patients expressed significantly higher levels of IFN-γ mRNA (p < 0.05) versus patients with Löfgren''s syndrome.Conclusion
These findings are the first data on the expression of TIM-1 and TIM-3 molecules in sarcoidosis. The reduced TIM-3 expression in the lungs of patients may result in a defective T cell ability to control the Th1 immune response and could thus contribute to the pathogenesis of sarcoidosis. The down-regulated TIM-1 expression in non-Löfgren''spatients is in agreement with an exaggerated Th1 response in these patients. 相似文献11.
12.
Jieqing Chen Wei Li Xiaojie Huang Caiping Guo Ran Zou Qiuying Yang Hongwei Zhang Tong Zhang Hui Chen Hao Wu 《PloS one》2013,8(7)
Objective
To evaluate the correlation of total lymphocyte count (TLC) and CD4 cell count and the suitability of TLC as a surrogate marker for CD4 cell count of HIV-infected patients in China.Methods
Usefulness of TLC as a surrogate marker for a CD4 cell count <350 cells/mm3 for HIV-positive patients in China was evaluated by 977 pairs of TLC and CD4 cell count from 977 outpatients. The result was then validated by a literature review which was conducted on 9 relevant articles. Further investigation using the 977 pairs of TLC and CD4 cell count data was done to determine a TLC threshold for predicting a CD4 cell count <500 cells/mm3. Correlation and receiver operating characteristic (ROC) analysis were performed for both CD4 cell counts, and the sensitivity and specificity were computed.Results
Good correlation was noted between TLC and CD4 count (r = 0.60, 95% CI, 0.56–0.64). TLC obtained a relatively high diagnostic performance (area under ROC curve, 0.80) for predicting a CD4 cell count <350 cells/mm3, with a sensitivity of 0.65 (95% CI, 0.61–0.68) and a specificity of 0.80 (95% CI, 0.75–0.85) at the TLC threshold of 1570 cells/mm3. The literature review suggested that for a CD4 cell count <350 cells/mm3, the optimal TLC threshold was 1500 cells/mm3, which was similar to the figure presented in this observational study. As for predicting a CD4 cell count <500 cells/mm3, TLC obtained a high diagnostic performance (area under ROC curve, 0.82) as well with a sensitivity of 0.70 (95% CI, 0.67–0.73) and a specificity of 0.80 (95% CI, 0.73–0.87).Conclusions
When considering the antiretroviral therapy for HIV-infected Chinese individuals, total lymphocyte count can be considered as an inexpensive and easily available surrogate marker for predicting two clinically important thresholds of CD4 count of 350 cells/mm3 and 500 cells/mm3. 相似文献13.
C. Scott Mahan Maria Walusimbi Denise F. Johnson Christina Lancioni Edwin Charlebois Joyce Baseke Keith A. Chervenak Roy D. Mugerwa Diane V. Havlir Harriet Mayanja-Kizza Christopher C. Whalen W. Henry Boom for the Uganda-Case Western Research Collaboration 《PloS one》2010,5(2)
Background
Both HIV and TB cause a state of heightened immune activation. Immune activation in HIV is associated with progression to AIDS. Prior studies, focusing on persons with advanced HIV, have shown no decline in markers of cellular activation in response to TB therapy alone.Methodology
This prospective cohort study, composed of participants within a larger phase 3 open-label randomized controlled clinical trial, measured the impact of TB treatment on immune activation in persons with non-advanced HIV infection (CD4>350 cells/mm3) and pulmonary TB. HIV load, CD4 count, and markers of immune activation (CD38 and HLA-DR on CD4 and CD8 T cells) were measured prior to starting, during, and for 6 months after completion of standard 6 month anti-tuberculosis (TB) therapy in 38 HIV infected Ugandans with smear and culture confirmed pulmonary TB.Results
Expression of CD38, and co-expression of CD38 and HLA-DR, on CD8 cells declined significantly within 3 months of starting standard TB therapy in the absence of anti-retroviral therapy, and remained suppressed for 6 months after completion of therapy. In contrast, HIV load and CD4 count remained unchanged throughout the study period.Conclusion
TB therapy leads to measurable decreases in immune activation in persons with HIV/TB co-infection and CD4 counts >350 cells/mm3. 相似文献14.
So Nishimura Naoyoshi Nagata Takuro Shimbo Naoki Asayama Junichi Akiyama Norio Ohmagari Hirohisa Yazaki Shinichi Oka Naomi Uemura 《PloS one》2013,8(3)
Background
Candidia esophagitis (CE) is an AIDS-defining condition, usually occurring in individuals with low CD4 counts of <200 cells/µL. Endoscopy is a valuable definitive diagnostic method for CE but may not be indicated for asymptomatic patients or for those with high CD4 counts or without oral candidiasis. This study assessed such patients to clarify the factors associated with CE and its severity on endoscopy in the highly active antiretroviral therapy (HAART) era.Methodology/ Principal Findings
A total of 733 HIV-infected patients who underwent upper gastrointestinal (GI) endoscopy were analyzed. Sexual behavior, CD4+ count, HIV-RNA viral load (VL), history of HAART, GI symptoms, GI diseases, and oral candidiasis were assessed. Endoscopic severity of CE was classified as mild (Kodsi''s grade I/II) or severe (grade III/IV). Of the 733 subjects, 62 (8.46%) were diagnosed with CE (mild, n = 33; severe, n = 29). Of them, 56.5% (35/62) had no GI symptoms, 30.6% (19/62) had CD4 + ≥200 cells/μL, and 55.3% (21/38) had no oral candidiasis. Univariate analysis found lower CD4+ counts, higher HIV VL, and no history of HAART to be significantly associated with CE. With lower CD4+ counts and higher HIV VL, CE occurrence increased significantly (P<0.01 for trend in odds). Multivariate analysis showed low CD4+ counts and high HIV VL to be independently associated with CE. Of the severe CE patients, 55.2% (16/29) had no GI symptoms and 44.4% (8/18) had no oral candidiasis. Median CD4+ counts in severe cases were significantly lower than in mild cases (27 vs. 80; P = 0.04).Conclusions
Low CD4+ counts and high HIV VL were found to be factors associated with CE, and advanced immunosuppression was associated with the development of severity. Endoscopy is useful as it can detect CE, even severe CE, in patients without GI symptoms, those with high CD4 counts, and those without oral candidiasis. 相似文献15.
Sara Lodi Martin Fisher Andrew Phillips Andrea De Luca Jade Ghosn Ruslan Malyuta Robert Zangerle Santiago Moreno Philippe Vanhems Faroudy Boufassa Marguerite Guiguet Kholoud Porter for CASCADE Collaboration in EuroCoord 《PloS one》2013,8(11)
Background
The risk/benefit of initiating ART in primary HIV infection (PHI) is unclear. The benefits are more likely to outweigh the risks in patients with severe PHI. An accepted definition of severe PHI is, however, lacking.Methods
CASCADE patients with HIV test interval <6 months were classified as severe and non-severe PHI based on whether the following traits were recorded in the first 6 months following seroconversion: severe specific pre-defined symptoms, central nervous system-implicated illness, and ≥1, ≥2 CD4<350 (and <500) cells/mm3. For each definition, we used Kaplan-Meier curves and Cox survival models to compare time to AIDS/death, censoring at the earlier of last clinic visit or 1/1/1997, when combination antiretroviral therapy (cART) became available.Results
Among 1108 included patients mostly males (85%) infected through sex between men (71%), 366 were diagnosed with AIDS/died. The risk of AIDS/death was significantly higher for individuals with severe symptoms, those with ≥1 CD4<350 cells/mm3 or ≥2 CD4 <500 cells/mm3 in the first 6 months [aHR (95% confidence interval) 2.1 (1.4,3.2), 2.0 (1.5,2.7), and 2.3, (1.5–3.5) respectively]. Median [interquantile range] survival for patients with ≥2, ≥1 and no CD4<350 cells/mm3 within 6 months of seroconversion was 3.9 [2.7,6.5], 5.4 [4.5,8.4] and 8.1 [4.3,10.3] years, respectively. The diagnosis of CNS-implicated symptoms was rare and did not appear to be prognostic.Conclusion
One CD4 count <350 or two <500 cells/mm3 within 6 months of seroconversion and/or severe illness in PHI may be useful early indicators of individuals at high risk of disease progression. 相似文献16.
J. Mocco Aqeela Afzal Saeed Ansari Annemarie Wolfe Kenneth Caldwell E S. Connolly Edward W. Scott 《PloS one》2014,9(1)
Background
Hematopoietic stem cells mobilize to the peripheral circulation in response to stroke. However, the mechanism by which the brain initiates this mobilization is uncharacterized.Methods
Animals underwent a murine intraluminal filament model of focal cerebral ischemia and the SDF1-A pathway was evaluated in a blinded manner via serum and brain SDF1-A level assessment, Lin−/Sca1+ cell mobilization quantification, and exogenous cell migration confirmation; all with or without SDF1-A blockade.Results
Bone marrow demonstrated a significant increase in Lin−/Sca1+ cell counts at 24 hrs (272±60%; P<0.05 vs sham). Mobilization of Lin−/Sca1+ cells to blood was significantly elevated at 24 hrs (607±159%; P<0.05). Serum SDF1-A levels were significant at 24 hrs (Sham (103±14), 4 hrs (94±20%, p = NS) and 24 hrs (130±17; p<0.05)). Brain SDF1-A levels were significantly elevated at both 4 hrs and 24 hrs (113±7 pg/ml and 112±10 pg/ml, respectively; p<0.05 versus sham 76±11 pg/ml). Following administration of an SDF1-A antibody, Lin−/Sca1+ cells failed to mobilize to peripheral blood following stroke, despite continued up regulation in bone marrow (stroke bone marrow cell count: 536±65, blood cell count: 127±24; p<0.05 versus placebo). Exogenously administered Lin−/Sca1+ cells resulted in a significant reduction in infarct volume: 42±5% (stroke alone), versus 21±15% (Stroke+Lin−/Sca1+ cells), and administration of an SDF1-A antibody concomitant to exogenous administration of the Lin−/Sca1+ cells prevented this reduction. Following stroke, exogenously administered Lin−/Sca1+ FISH positive cells were significantly reduced when administered concomitant to an SDF1-A antibody as compared to without SDF1-A antibody (10±4 vs 0.7±1, p<0.05).Conclusions
SDF1-A appears to play a critical role in modulating Lin−/Sca1+ cell migration to ischemic brain. 相似文献17.
Tsutomu Tamada Naoki Kanomata Teruki Sone Yoshimasa Jo Yoshiyuki Miyaji Hiroki Higashi Akira Yamamoto Katsuyoshi Ito 《PloS one》2014,9(5)
Objective
The objective of our study was to investigate tumor conspicuity and the discrimination potential for tumor aggressiveness on diffusion-weighted magnetic resonance imaging (DW-MRI) with high b value at 3-T.Materials and Methods
The institutional review board approved this study and waived the requirement for informed consent. A total of 50 patients with prostate cancer (69 cancer foci; 48 in the PZ, 20 in the TZ, and one in whole prostate) who underwent multiparametric prostate MRI including DW-MRI (b values: 0, 1000 s/mm2 and 0, 2000 s/mm2) on a 3-T system were included. Lesion conspicuity score (LCS) using visual assessment (1 = invisible for surrounding normal site; 2 = slightly high intensity; 3 = moderately high; and 4 = very high) and tumor-normal signal intensity ratio (TNR) were assessed, and apparent diffusion coefficient (ADC, ×10−3 mm2/s) of the tumor regions and normal regions were measured.Results
Mean LCS and TNR at 0, 2000 s/mm2 was significantly higher than those at 0, 1000 s/mm2 (p<0.001 for both). In addition, ADC at both 0, 1000 and 0, 2000 s/mm2 was found to distinguish intermediate or high risk cancer with Gleason score ≥7 from low risk cancer with Gleason score ≤6 (p<0.001 for both). Furthermore, ADC of tumor regions correlated with Gleason score at both 0, 1000 s/mm2 (ρ = −0.602; p<0.001) and 0, 2000 s/mm2 (ρ = −0.645; p<0.001).Conclusions
For tumor conspicuity and characterization of prostate cancer on DW-MRI of 3-T MRI, b = 0, 2000 s/mm2 is more useful than b = 0, 1000 s/mm2. 相似文献18.
Aim
We have previously shown that lithium treatment immediately after hypoxia-ischemia (HI) in neonatal rats affords both short- and long-term neuroprotection. The aim of this study was to evaluate possible therapeutic benefits when lithium treatment was delayed 5 days, a time point when most cell death is over.Methods
Eight-day-old male rats were subjected to unilateral HI and 2 mmol/kg lithium chloride was injected intraperitoneally 5 days after the insult. Additional lithium injections of 1 mmol/kg were administered at 24 h intervals for the next 14 days. Brain injury was evaluated 12 weeks after HI. Serum cytokine measurements and behavioral analysis were performed before sacrificing the animals.Results
Brain injury, as indicated by tissue loss, was reduced by 38.7%, from 276.5±27.4 mm3 in the vehicle-treated group to 169.3±25.9 mm3 in the lithium-treated group 12 weeks after HI (p<0.01). Motor hyperactivity and anxiety-like behavior after HI were normalized by lithium treatment. Lithium treatment increased neurogenesis in the dentate gyrus as indicated by doublecortin labeling. Serum cytokine levels, including IL-1α, IL-1β, and IL-6, were still elevated as late as 5 weeks after HI, but lithium treatment normalized these cytokine levels.Conclusions
Delayed lithium treatment conferred long-term neuroprotection in neonatal rats after HI, and this opens a new avenue for future development of treatment strategies for neonatal brain injury that can be administered after the acute injury phase. 相似文献19.
Kraft P Benz PM Austinat M Brede ME Schuh K Walter U Stoll G Kleinschnitz C 《PloS one》2010,5(12):e15106
Background
Stroke-induced brain edema formation is a frequent cause of secondary infarct growth and deterioration of neurological function. The molecular mechanisms underlying edema formation after stroke are largely unknown. Vasodilator-stimulated phosphoprotein (VASP) is an important regulator of actin dynamics and stabilizes endothelial barriers through interaction with cell-cell contacts and focal adhesion sites. Hypoxia has been shown to foster vascular leakage by downregulation of VASP in vitro but the significance of VASP for regulating vascular permeability in the hypoxic brain in vivo awaits clarification.Methodology/Principal Findings
Focal cerebral ischemia was induced in Vasp−/− mice and wild-type (WT) littermates by transient middle cerebral artery occlusion (tMCAO). Evan''s Blue tracer was applied to visualize the extent of blood-brain-barrier (BBB) damage. Brain edema formation and infarct volumes were calculated from 2,3,5-triphenyltetrazolium chloride (TTC)-stained brain slices. Both mouse groups were carefully controlled for anatomical and physiological parameters relevant for edema formation and stroke outcome. BBB damage (p<0.05) and edema volumes (1.7 mm3±0.5 mm3 versus 0.8 mm3±0.4 mm3; p<0.0001) were significantly enhanced in Vasp−/− mice compared to controls on day 1 after tMCAO. This was accompanied by a significant increase in infarct size (56.1 mm3±17.3 mm3 versus 39.3 mm3±10.7 mm3, respectively; p<0.01) and a non significant trend (p>0.05) towards worse neurological outcomes.Conclusion
Our study identifies VASP as critical regulator of BBB maintenance during acute ischemic stroke. Therapeutic modulation of VASP or VASP-dependent signalling pathways could become a novel strategy to combat excessive edema formation in ischemic brain damage. 相似文献20.
Natsuko Nagaoka Jost B. Jonas Kei Morohoshi Muka Moriyama Noriaki Shimada Takeshi Yoshida Kyoko Ohno-Matsui 《PloS one》2015,10(10)