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1.
Gilad Horowitz Moran Amit Oded Ben-Ari Ziv Gil Abraham Abergel Nevo Margalit Oren Cavel Oshri Wasserzug Dan M. Fliss 《PloS one》2013,8(12)
Objective
To compare frontal sinus cranialization to obliteration for future prevention of secondary mucocele formation following open surgery for benign lesions of the frontal sinus.Study Design
Retrospective case series.Setting
Tertiary academic medical center.Patients
Sixty-nine patients operated for benign frontal sinus pathology between 1994 and 2011.Interventions
Open excision of benign frontal sinus pathology followed by either frontal obliteration (n = 41, 59%) or frontal cranialization (n = 28, 41%).Main Outcome Measures
The prevalence of post-surgical complications and secondary mucocele formation were compiled.Results
Pathologies included osteoma (n = 34, 49%), mucocele (n = 27, 39%), fibrous dysplasia (n = 6, 9%), and encephalocele (n = 2, 3%). Complications included skin infections (n = 6), postoperative cutaneous fistula (n = 1), telecanthus (n = 4), diplopia (n = 3), nasal deformity (n = 2) and epiphora (n = 1). None of the patients suffered from postoperative CSF leak, meningitis or pneumocephalus. Six patients, all of whom had previously undergone frontal sinus obliteration, required revision surgery due to secondary mucocele formation. Statistical analysis using non-inferiority test reveal that cranialization of the frontal sinus is non-inferior to obliteration for preventing secondary mucocele formation (P<0.0001).Conclusion
Cranialization of the frontal sinus appears to be a good option for prevention of secondary mucocele development after open excision of benign frontal sinus lesions. 相似文献2.
Mohammad R. Islam Razia Khatun Mohammad Khaja Mafij Uddin Md. Siddiqur Rahman Khan Md. Toufiq Rahman Tahmeed Ahmed Sayera Banu 《PloS one》2013,8(7)
Background
From long instances, it is debatable whether three sputum specimens are required for the diagnosis of pulmonary tuberculosis (TB) or TB can be diagnosed effectively using two consecutive sputum specimens. This study was set out to evaluate the significance of examining multiple sputum specimens in diagnosis of TB.Methods
We retrospectively reviewed the acid-fast bacillus (AFB) smear and culture results of three consecutive days’ sputum specimens from 413 confirmed TB patients which were detected as part of a larger active case finding study in Dhaka Central Jail, the largest correctional facility in Bangladesh.Results
AFB was detected from 81% (n = 334) patients, of which 89% (n = 297) were diagnosed from the first and additional 9% (n = 30) were from the second sputum specimen. M. tuberculosis growth was observed for 406 patients and 85% (n = 343) were obtained from the first sputum and additional 10% (n = 42) were from the second one. The third specimen didn’t show significant additional diagnostic value for the detection of AFB by microscopy or growth of the M. tuberculosis.Conclusions
We concluded from our study results that examining two consecutive sputum specimens is sufficient enough for the effective diagnosis of TB. It can also decrease the laboratory workload and hence improve the quality of work in settings with high TB burden like Bangladesh. 相似文献3.
Petra A. Prins Michael F. Hill David Airey Sam Nwosu Prudhvidhar R. Perati Hagai Tavori MacRae F. Linton Valentina Kon Sergio Fazio Uchechukwu K. Sampson 《PloS one》2014,9(1)
Objective
Understanding variations in size and pattern of development of angiotensin II (Ang II)-induced abdominal aortic aneurysms (AAA) may inform translational research strategies. Thus, we sought insight into the temporal evolution of AAA in apolipoprotein (apo)E−/− mice.Approach
A cohort of mice underwent a 4-week pump-mediated infusion of saline (n = 23) or 1500 ng/kg/min of Ang II (n = 85) and AAA development was tracked via in vivo ultrasound imaging. We adjusted for hemodynamic covariates in the regression models for AAA occurrence in relation to time.Results
The overall effect of time was statistically significant (p<0.001). Compared to day 7 of AngII infusion, there was no decrease in the log odds of AAA occurrence by day 14 (−0.234, p = 0.65), but compared to day 21 and 28, the log odds decreased by 9.07 (p<0.001) and 2.35 (p = 0.04), respectively. Hemodynamic parameters were not predictive of change in aortic diameter (Δ) (SBP, p = 0.66; DBP, p = 0.66). Mean total cholesterol (TC) was higher among mice with large versus small AAA (601 vs. 422 mg/ml, p<0.0001), and the difference was due to LDL. AngII exposure was associated with 0.43 mm (95% CI, 0.27 to 0.61, p<0.0001) increase in aortic diameter; and a 100 mg/dl increase in mean final cholesterol level was associated with a 12% (95% CI, 5.68 to 18.23, p<0.0001) increase in aortic diameter. Baseline cholesterol was not associated with change in aortic diameter (p = 0.86).Conclusions
These are the first formal estimates of a consistent pattern of Ang II-induced AAA development. The odds of AAA occurrence diminish after the second week of Ang II infusion, and TC is independently associated with AAA size. 相似文献4.
Dominique J. Pepper Kevin Rebe Chelsea Morroni Robert J. Wilkinson Graeme Meintjes 《PloS one》2009,4(2)
Background
Clinical deterioration on drug therapy for tuberculosis is a common cause of hospital admission in Africa. Potential causes for clinical deterioration in settings of high HIV-1 prevalence include drug resistant Mycobacterium tuberculosis (M.tb), co-morbid illnesses, poor adherence to therapy, tuberculosis associated-immune reconstitution inflammatory syndrome (TB-IRIS) and subtherapeutic antitubercular drug levels. It is important to derive a rapid diagnostic work-up to determine the cause of clinical deterioration as well as specific management to prevent further clinical deterioration and death. We undertook this study among tuberculosis (TB) patients referred to an adult district level hospital situated in a high HIV-1 prevalence setting to determine the frequency, reasons and outcome for such clinical deterioration.Method
A prospective observational study conducted during the first quarter of 2007. We defined clinical deterioration as clinical worsening or failure to stabilise after 14 or more days of antitubercular treatment, resulting in hospital referral. We collected data on tuberculosis diagnosis and treatment, HIV-1 status and antiretroviral treatment, and investigated reasons for clinical deterioration as well as outcome.Results
During this period, 352 TB patients met inclusion criteria; 296 were admitted to hospital accounting for 17% of total medical admissions (n = 1755). Eighty three percent of TB patients (291/352) were known to be HIV-1 co-infected with a median CD4 count of 89cells/mm3 (IQR 38–157). Mortality among TB patients admitted to hospital was 16% (n = 48). The median duration of hospital admission was 9.5 days (IQR 4–18), longer than routine in this setting (4 days). Among patients in whom HIV-1 status was known (n = 324), 72% of TB patients (n = 232) had an additional illness to tuberculosis; new AIDS defining illnesses (n = 80) were the most frequent additional illnesses (n = 208) in HIV-1 co-infected patients (n = 291). Rifampin-resistant M.tb (n = 41), TB-IRIS (n = 51) and drug resistant bacterial infections (n = 12) were found in 12%, 14% and 3.4% of the 352 cases, respectively.Interpretation
In our setting, new AIDS defining illnesses, drug resistant M.tb and other drug resistant bacteria are important reasons for clinical deterioration in HIV-1 co-infected patients receiving antitubercular treatment. HIV-1 co-infected patients may be at increased risk of acquiring nosocomial drug resistant pathogens because profound immune suppression results in co-morbid illnesses that require prolonged inpatient admissions. Routine infection control is essential and needs to be strengthened in our setting. 相似文献5.
Goetz Bosse Ferdinand Mtatifikolo Wiltrud Abels Christian Strosing Jan-Philipp Breuer Claudia Spies 《PloS one》2013,8(6)
Introduction
Outcome assessment is the standard for evaluating the quality of health services worldwide. In this study, outcome has been divided into immediate and final outcome. Aim was to compare an intervention hospital with a Continuous Quality Improvement approach to a control group using benchmark assessments of immediate outcome indicators in surgical care. Results were compared to final outcome indicators.Method
Surgical care quality in six hospitals in Tanzania was assessed from 2006–2011, using the Hospital Performance Assessment Tool. Independent observers assessed structural, process and outcome quality using checklists based on evidence-based guidelines. The number of surgical key procedures over the benchmark of 80% was compared between the intervention hospital and the control group. Results were compared to Case Fatality Rates.Results
In the intervention hospital, in 2006, two of nine key procedures reached the benchmark, one in 2009, and four in 2011. In the control group, one of nine key procedures reached the benchmark in 2006, one in 2009, and none in 2011. Case Fatality Rate for all in-patients in the intervention hospital was 5.5% (n = 12,530) in 2006, 3.5% (n = 21,114) in 2009 and 4.6% (n = 18,840) in 2011. In the control group it was 3.1% (n = 17,827) in 2006, 4.2% (n = 13,632) in 2009 and 3.8% (n = 17,059) in 2011.Discussion
Results demonstrated that quality assurance improved performance levels in both groups. After the introduction of Continuous Quality Improvement, performance levels improved further in the intervention hospital while quality in the district hospital did not. Immediate outcome indicators appeared to be a better steering tool for quality improvement compared to final outcome indicators. Immediate outcome indicators revealed a need for improvement in pre- and postoperative care.Conclusion
Quality assurance programs based on immediate outcome indicators can be effective if embedded in Continuous Quality Improvement. Nevertheless, final outcome indicators cannot be neglected. 相似文献6.
Tao Zhang Huimei Chen Shaoshan Liang Dacheng Chen Chunxia Zheng Caihong Zeng Haitao Zhang Zhihong Liu 《PloS one》2014,9(11)
Background
Thrombotic microangiopathy (TMA) in the kidney is a histopathologic lesion that occurs in a number of clinical settings and is often associated with poor renal prognosis. The standard test for the diagnosis of TMA is the renal biopsy; noninvasive parameters such as potential biomarkers have not been developed.Methods
We analyzed routine parameters in a cohort of 220 patients with suspected TMA and developed a diagnostic laboratory panel by logistic regression. The levels of candidate markers were validated using an independent cohort (n = 46), a cohort of systemic lupus erythematosus (SLE) (n = 157) and an expanded cohort (n = 113), as well as 9 patients with repeat biopsies.Results
Of the 220 patients in the derivation cohort, 51 patients with biopsy-proven TMA presented with a worse renal prognosis than those with no TMA (P = 0.002). Platelet and L-lactate dehydrogenase (LDH) levels showed an acceptable diagnostic value of TMA (AUC = 0.739 and 0.756, respectively). A panel of 4 variables - creatinine, platelets, ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats 13) activity and LDH - can effectively discriminate patients with TMA (AUC = 0.800). In the validation cohort, the platelet and LDH levels and the 4-variable panel signature robustly distinguished patients with TMA. The discrimination effects of these three markers were confirmed in patients with SLE. Moreover, LDH levels and the 4-variable panel signature also showed discrimination values in an expanded set. Among patients undergoing repeat biopsy, increased LDH levels and panel signatures were associated with TMA status when paired evaluations were performed. Importantly, only the 4-variable panel was an independent prognostic marker for renal outcome (hazard ratio = 3.549; P<0.001).Conclusions
The noninvasive laboratory diagnostic panel is better for the early detection and prognosis of TMA compared with a single parameter, and may provide a promising biomarker for clinical application. 相似文献7.
Jeannine D. Rinderknecht Simone M. Goldinger Sima Rozati Jivko Kamarashev Katrin Kerl Lars E. French Reinhard Dummer Benedetta Belloni 《PloS one》2013,8(3)
Purpose
Vemurafenib is a potent inhibitor of V600 mutant BRAF with significant impact on progression-free and overall survival in advanced melanoma. Cutaneous side effects are frequent. This single-center observational study investigates clinical and histological features of these class-specific cutaneous adverse reactions.Patients and Methods
Patients were all treated with Vemurafenib 960 mg b.i.d. within local ethic committees approved clinical trials. All skin reactions were collected and documented prospectively. Cutaneous reactions were classified by reaction pattern as phototoxic and inflammatory, hair and nail changes, keratinocytic proliferations and melanocytic disorders.Results
Vemurafenib was well tolerated, only in two patients the dose had to be reduced to 720 mg due to arthralgia. 26/28 patients (93%) experienced cutaneous side effects. Observed side effects included UVA dependent photosensitivity (n = 16), maculopapular exanthema (n = 14), pruritus (n = 8), folliculitis (n = 5), burning feet (n = 3), hair thinning (mild alopecia) (n = 8), curly hair (n = 2) and nail changes (n = 2). Keratosis pilaris and acanthopapilloma were common skin reactions (n = 12/n = 13), as well as plantar hyperkeratosis (n = 4), keratoacanthoma (n = 5) and invasive squamous cell carcinoma (n = 4). One patient developed a second primary melanoma after more than 4 months of therapy (BRAF and RAS wild type).Conclusion
Vemurafenib has a broad and peculiar cutaneous side effect profile involving epidermis and adnexa overlapping with the cutaneous manifestations of genetic diseases characterized by activating germ line mutations of RAS (RASopathy). They must be distinguished from allergic drug reaction. Regular skin examination and management by experienced dermatologists as well as continuous prophylactic photo protection including an UVA optimized sun screen is mandatory. 相似文献8.
Alexandre Wullschleger Viktoria Kapina Nicolas Molnarfi Delphine S. Courvoisier J?rg D. Seebach Marie-Laure Santiago-Raber Denis F. Hochstrasser Patrice H. Lalive 《PloS one》2013,8(8)
Background
Interleukin (IL)-6 is recognised as an important cytokine involved in inflammatory diseases of the central nervous system (CNS).Objective
To perform a large retrospective study designed to test cerebrospinal fluid (CSF) IL-6 levels in the context of neurological diseases, and evaluate its usefulness as a biomarker to help discriminate multiple sclerosis (MS) from other inflammatory neurological diseases (OIND).Patients and Methods
We analyzed 374 CSF samples for IL-6 using a quantitative enzyme-linked immunosorbent assay. Groups tested were composed of demyelinating diseases of the CNS (DD, n = 117), including relapsing-remitting MS (RRMS, n = 65), primary progressive MS (PPMS, n = 11), clinically isolated syndrome (CIS, n = 11), optic neuritis (ON, n = 30); idiopathic transverse myelitis (ITM, n = 10); other inflammatory neurological diseases (OIND, n = 35); and non-inflammatory neurological diseases (NIND, n = 212). Differences between groups were analysed using Kruskal−Wallis test and Mann−Whitney U-test.Results
CSF IL-6 levels exceeded the positivity cut-off of 10 pg/ml in 18 (51.4%) of the 35 OIND samples, but in only three (3.9%) of the 76 MS samples collected. CSF IL-6 was negative for all NIND samples tested (0/212). IL-6 cut-off of 10 pg/ml offers 96% sensitivity to exclude MS.Conclusion
CSF IL-6 may help to differentiate MS from its major differential diagnosis group, OIND. 相似文献9.
10.
Kim E. Kortekaas C. Arnoud Meijer Jan Willem Hinnen Ronald L. Dalman Baohui Xu Jaap F. Hamming Jan H. Lindeman 《PloS one》2014,9(12)
Background
Independent of their blood pressure lowering effect, ACE inhibitors are thought to reduce vascular inflammation. The clinical relevance of this effect is unclear with the current knowledge. Abdominal aortic aneurysms (AAA) are characterized by a broad, non-specific inflammatory response, and thus provide a clinical platform to evaluate the anti-inflammatory potential of ACE inhibitors.Methods and Results
Eleven patients scheduled for open AAA repair received ramipril (5 mg/day) during 2–4 weeks preceding surgery. Aortic wall samples were collected during surgery, and compared to matched samples obtained from a biobank. An anti-inflammatory potential was evaluated in a comprehensive analysis that included immunohistochemistry, mRNA and protein analysis. A putative effect of ACE inhibitors on AAA growth was tested separately by comparing 18-month growth rate of patients on ACE inhibitors (n = 82) and those not taking ACE inhibitors (n = 204). Ramipril reduces mRNA expression of multiple pro-inflammatory cytokines such as IL-1β, IL-6, IL-8, TNF -α, Interferon-, and MCP-1, as well as aortic wall IL-8 and MCP-1 (P = 0.017 and 0.008, respectively) protein content. The is followed by clear effects on cell activation that included a shift towards anti-inflammatory macrophage (M2) subtype. Evaluation of data from the PHAST cohort did not indicate an effect of ACE inhibitors on 18-month aneurysm progression (mean difference at 18 months: −0.24 mm (95% CI: −0.90–0.45, P = NS).Conclusions
ACE inhibition quenches multiple aspects of vascular inflammation in AAA. However, this does not translate into reduced aneurysm growth.Trial Registration
Nederlands Trial Register 1345. 相似文献11.
Xin Yang Yong Zhou Chao Liu Xiang Gao Anxin Wang Yuming Guo Wen Li Xingquan Zhao Wannian Liang 《PloS one》2014,9(4)
Background and Purpose
This study aimed to explore the possible association of plasma total homocysteine with carotid plaque stability.Methods
A cross-sectional study was conducted from 2010 to 2011. A stratified random sample of 2,919 Chinese participants aged 40 years or older was enrolled. Plasma total homocysteine levels were measured and carotid plaques were evaluated by ultrasonography. Logistic regression model was used to analyze the association of homocysteine levels to the progression of carotid plaque development, while adjusting for demographics and vascular risk factors.Results
The mean level of plasma homocysteine in the subjects was 14.9 µmol/l. Along with increase in homocysteine level, the risk of advanced carotid plaque elevated (odds ratio = 1.28; 95% confidence interval = 1.09–1.51) after adjusting for age, sex, and other potential confounders. Stratified by sex, higher homocysteine level was strongly associated with advanced carotid plaque in men (OR = 1.41; 95% confidence interval = 1.17–1.70), but not in women.Conclusion
The findings suggest that plasma level of homocysteine may be associated with advanced carotid plaque, which constitutes high risks of stroke, in male Chinese adults. 相似文献12.
Yvan Devaux Melanie Vausort Gerry P. McCann Dominic Kelly Olivier Collignon Leong L. Ng Daniel R. Wagner Iain B. Squire 《PloS one》2013,8(8)
Background
Prediction of clinical outcome after acute myocardial infarction (AMI) is challenging and would benefit from new biomarkers. We investigated the prognostic value of 4 circulating microRNAs (miRNAs) after AMI.Methods
We enrolled 150 patients after AMI. Blood samples were obtained at discharge for determination of N-terminal pro-brain natriuretic peptide (Nt-proBNP) and levels of miR-16, miR-27a, miR-101 and miR-150. Patients were assessed by echocardiography at 6 months follow-up and the wall motion index score (WMIS) was used as an indicator of left ventricular (LV) contractility. We assessed the added predictive value of miRNAs against a multi-parameter clinical model including Nt-proBNP.Results
Patients with anterior AMI and elevated Nt-proBNP levels at discharge from the hospital were at high risk of subsequent impaired LV contractility (follow-up WMIS>1.2, n = 71). A combination of the 4 miRNAs (miR-16/27a/101/150) improved the prediction of LV contractility based on clinical variables (P = 0.005). Patients with low levels of miR-150 (odds ratio [95% confidence interval] 0.08 [0.01–0.48]) or miR-101 (0.19 [0.04–0.97]) and elevated levels of miR-16 (15.9 [2.63–95.91]) or miR-27a (4.18 [1.36–12.83]) were at high risk of impaired LV contractility. The 4 miRNA panel reclassified a significant proportion of patients with a net reclassification improvement of 66% (P = 0.00005) and an integrated discrimination improvement of 0.08 (P = 0.001).Conclusion
Our results indicate that panels of miRNAs may aid in prognostication of outcome after AMI. 相似文献13.
Chato Taher Jana de Boniface Abdul-Aleem Mohammad Piotr Religa Johan Hartman Koon-Chu Yaiw Jan Frisell Afsar Rahbar Cecilia S?derberg-Naucler 《PloS one》2013,8(2)
Background
Breast cancer is a leading cause of death among women worldwide. Increasing evidence implies that human cytomegalovirus (HCMV) infection is associated with several malignancies. We aimed to examine whether HCMV is present in breast cancer and sentinel lymph node (SLN) metastases.Materials and Methods
Formalin-fixed paraffin-embedded tissue specimens from breast cancer and paired sentinel lymph node (SLN) samples were obtained from patients with (n = 35) and without SLN metastasis (n = 38). HCMV immediate early (IE) and late (LA) proteins were detected using a sensitive immunohistochemistry (IHC) technique and HCMV DNA by real-time PCR.Results
HCMV IE and LA proteins were abundantly expressed in 100% of breast cancer specimens. In SLN specimens, 94% of samples with metastases (n = 34) were positive for HCMV IE and LA proteins, mostly confined to neoplastic cells while some inflammatory cells were HCMV positive in 60% of lymph nodes without metastases (n = 35). The presence of HCMV DNA was confirmed in 12/12 (100%) of breast cancer and 10/11 (91%) SLN specimens from the metastatic group, but was not detected in 5/5 HCMV-negative, SLN-negative specimens. There was no statistically significant association between HCMV infection grades and progesterone receptor, estrogen receptor alpha and Elston grade status.Conclusions
The role of HCMV in the pathogenesis of breast cancer is unclear. As HCMV proteins were mainly confined to neoplastic cells in primary breast cancer and SLN samples, our observations raise the question whether HCMV contributes to the tumorigenesis of breast cancer and its metastases. 相似文献14.
Nathella Pavan Kumar Rathinam Sridhar Luke E. Hanna Vaithilingam V. Banurekha Thomas B. Nutman Subash Babu 《PloS one》2014,9(10)
Background
Circulating T follicular helper (Tfh) cells represent a distinct subset of CD4+ T cells and are important in immunity to infections. Although they have been shown to play a role in experimental models of tuberculosis infection, their role in human tuberculosis remains unexplored.Aims/Methodology
To determine the distribution of circulating Tfh cells in human TB, we measured the frequencies of Tfh cells ex vivo and following TB - antigen or polyclonal stimulation in pulmonary TB (PTB; n = 30) and latent TB (LTB; n = 20) individuals, using the markers CXCR5, PD-1 and ICOS.Results
We found that both ex vivo and TB - antigen induced frequencies of Tfh cell subsets was significantly lower in PTB compared to LTB individuals. Similarly, antigen induced frequencies of Tfh cells expressing IL-21 was also significantly lower in PTB individuals and this was reflected in diminished circulating levels of IL-21 and IFNγ. This was not accompanied by diminished frequencies of activated or memory B cell subsets. Finally, the diminution in frequency of Tfh cells in PTB individuals was dependent on IL-10, CTLA-4 and PD-L1 in vitro.Conclusions
Thus, PTB is characterized by adiminution in the frequency of Tfh cell subsets. 相似文献15.
Aim
Sustained virologic response (SVR) can be attained with boceprevir plus peginterferon alfa and ribavirin (PR) in up to 68% of patients, and short duration therapy is possible if plasma HCV RNA levels are undetectable at treatment week 8 (TW8 response). We have developed predictive models for SVR, and TW8 response using data from boceprevir clinical trials.Methods
Regression models were built to predict TW8 response and SVR. Separate models were built for TW8 and SVR using baseline variables only, and compared to models with baseline variables plus HCV RNA change after 4 weeks of PR (TW4 delta). Predictive accuracy was assessed by c-statistics, calibration curves, and decision curve analyses. Nomograms were developed to create clinical decision support tools. Models were externally validated using independent data.Results
The models that included TW4 delta produced the best discrimination ability. The predictive factors for TW8 response (n = 856) were TW4 delta, race, platelet count and ALT. The predictive factors for SVR (n = 522) were TW4 delta, HCV-subtype, gender, BMI, RBV dose and platelet count. The discrimination abilities of these models were excellent (C-statistics = 0.88, 0.80 respectively). Baseline models for TW8 response (n = 444) and SVR (n = 197) had weaker discrimination ability (C-statistic = 0.76, 0.69). External validation confirmed the predictive accuracy of the week 4 models.Conclusions
Models incorporating baseline and treatment week 4 data provide excellent prediction of TW8 response and SVR, and support the clinical utility of the lead-in phase of PR. The nomograms are suitable for point-of-care use to inform individual patient and physician decision-making. 相似文献16.
Seung-Hyun Kim Bo-Young Cho Hyunna Choi Eun-Soon Shin Young-Min Ye Jong-Eun Lee Hae-Sim Park 《PloS one》2014,9(12)
Background
Two common clinical syndromes of acetylsalicylic acid (aspirin) hypersensitivity, aspirin-exacerbated respiratory disease (AERD) and aspirin-exacerbated cutaneous disease (AECD), were subjected to a genome-wide association study to identify strong genetic markers for aspirin hypersensitivity in a Korean population.Methods
A comparison of SNP genotype frequencies on an Affymetrix Genome-Wide Human SNP array of 179 AERD patients and 1989 healthy normal control subjects (NC) revealed SNPs on chromosome 6 that were associated with AERD, but not AECD. To validate the association, we enrolled a second cohort comprising AERD (n = 264), NC (n = 238) and disease-control (aspirin tolerant asthma; ATA, n = 387) groups.Results
The minor genotype frequency (AG or AA) of a particular SNP, rs3128965, in the HLA-DPB1 region was higher in the AERD group compared to the ATA or NC group (P = 0.001, P = 0.002, in a co-dominant analysis model, respectively). Comparison of rs3128965 alleles with the clinical features of asthmatics revealed that patients harboring the A allele had increased bronchial hyperresponsiveness to inhaled aspirin and methacholine, and higher 15-HETE levels, than those without the A allele (P = 0.039, 0.037, and 0.004, respectively).Conclusions
This implies the potential of rs3128965 as a genetic marker for diagnosis and prediction of the AERD phenotype. 相似文献17.
Lennart Nilsson Wouter G. Wieringa Gabija Pundziute Marcus Gjerde Jan Engvall Eva Swahn Lena Jonasson 《PloS one》2014,9(9)
Background
Elevations in soluble markers of inflammation and changes in leukocyte subset distribution are frequently reported in patients with coronary artery disease (CAD). Lately, the neutrophil/lymphocyte ratio has emerged as a potential marker of both CAD severity and cardiovascular prognosis.Objectives
The aim of the study was to investigate whether neutrophil/lymphocyte ratio and other immune-inflammatory markers were related to plaque burden, as assessed by coronary computed tomography angiography (CCTA), in patients with CAD.Methods
Twenty patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) and 30 patients with stable angina (SA) underwent CCTA at two occasions, immediately prior to coronary angiography and after three months. Atherosclerotic plaques were classified as calcified, mixed and non-calcified. Blood samples were drawn at both occasions. Leukocyte subsets were analyzed by white blood cell differential counts and flow cytometry. Levels of C-reactive protein (CRP) and interleukin(IL)-6 were measured in plasma. Blood analyses were also performed in 37 healthy controls.Results
Plaque variables did not change over 3 months, total plaque burden being similar in NSTE-ACS and SA. However, non-calcified/total plaque ratio was higher in NSTE-ACS, 0.25(0.09–0.44) vs 0.11(0.00–0.25), p<0.05. At admission, levels of monocytes, neutrophils, neutrophil/lymphocyte ratios, CD4+ T cells, CRP and IL-6 were significantly elevated, while levels of NK cells were reduced, in both patient groups as compared to controls. After 3 months, levels of monocytes, neutrophils, neutrophil/lymphocyte ratios and CD4+ T cells remained elevated in patients. Neutrophil/lymphocyte ratios and neutrophil counts correlated significantly with numbers of non-calcified plaques and also with non-calcified/total plaque ratio (r = 0.403, p = 0.010 and r = 0.382, p = 0.024, respectively), but not with total plaque burden.Conclusions
Among immune-inflammatory markers in NSTE-ACS and SA patients, neutrophil counts and neutrophil/lymphocyte ratios were significantly correlated with non-calcified plaques. Data suggest that these easily measured biomarkers reflect the burden of vulnerable plaques in CAD. 相似文献18.
Jasper V. Been Sizzle F. Vanterpool Jasmijn D. E. de Rooij G. Ingrid J. G. Rours René F. Kornelisse Martien C. J. M. van Dongen Christel J. A. W. van Gool Ronald R. de Krijger Peter Andriessen Luc J. I. Zimmermann Boris W. Kramer 《PloS one》2012,7(10)
Background
Histological chorioamnionitis (HC) is an intrauterine inflammatory process highly associated with preterm birth and adverse neonatal outcome. HC is often clinically silent and diagnosed postnatally by placental histology. Earlier identification could facilitate treatment individualisation to improve outcome in preterm newborns.Aim
Develop a clinical prediction rule at birth for HC and HC with fetal involvement (HCF) in preterm newborns.Methods
Clinical data and placental pathology were obtained from singleton preterm newborns (gestational age ≤32.0 weeks) born at Erasmus UMC Rotterdam from 2001 to 2003 (derivation cohort; n = 216) or Máxima MC Veldhoven from 2009 to 2010 (validation cohort; n = 206). HC and HCF prediction rules were developed with preference for high sensitivity using clinical variables available at birth.Results
HC and HCF were present in 39% and 24% in the derivation cohort and in 44% and 22% in the validation cohort, respectively. HC was predicted with 87% accuracy, yielding an area under ROC curve of 0.95 (95%CI = 0.92–0.98), a positive predictive value of 80% (95%CI = 74–84%), and a negative predictive value of 93% (95%CI = 88–96%). Corresponding figures for HCF were: accuracy 83%, area under ROC curve 0.92 (95%CI = 0.88–0.96), positive predictive value 59% (95%CI = 52–62%), and negative predictive value 97% (95%CI = 93–99%). External validation expectedly resulted in some loss of test performance, preferentially affecting positive predictive rather than negative predictive values.Conclusion
Using a clinical prediction rule composed of clinical variables available at birth, HC and HCF could be predicted with good test characteristics in preterm newborns. Further studies should evaluate the clinical value of these rules to guide early treatment individualisation. 相似文献19.
Khalid M. Alkharfy Nasser M. Al-Daghri Paul M. Vanhoutte Soundararajan Krishnaswamy Aimin Xu 《PloS one》2012,7(10)
Background
Elevated serum level of retinol-binding protein 4 (RBP4) has been associated with obesity-related co-morbidities including insulin resistance, dyslipidemia and hypertension.Objectives
The present study examined the relationship between serum level of RBP4 and various risk factors related to cardiovascular disease (CVD) in men and women.Methods
284 subjects (139 males, 145 females), grouped into healthy (n = 60), obese diabetes (n = 60), non-obese diabetes (n = 60), obese non-diabetes (n = 60) and patients with CVD (n = 44), were assessed for anthropometric and biochemical parameters related to obesity, diabetes and CVD. In addition, serum levels of several adipokines, including fatty acid binding protein 4 (FABP4) and lipocalin 2 (LCN2) and RBP4 were measured using specific immunoassays.Results
Serum RBP4 level correlated significantly with principal component derived from known risk factors of CVD (β = 0.20±0.06, P = 0.002). Significance of this correlation was limited to women (β = 0.20±0.06, P = 0.002) and it persisted even after adjusting for BMI (β = 0.19±0.06, P = 0.002). Overall (n = 284) serum RBP4 values significantly correlated with FABP4 (R = 0.19, p = 0.001). Serum FABP4 level of CVD subjects was significantly higher than healthy control (P = 0.001) and non-obese diabetes (P = 0.04) groups, but this difference was attributable to differences in BMI. Serum LCN2 level correlated well with RBP4 (R = 0.15, P = 0.008) and FABP4 (R = 0.36, P<0.001), but did not differ significantly between CVD and other groups.Conclusions
Results of this study indicate a significant correlation between serum RBP4 and various established risk factors for CVD and suggest RBP4 may serve as an independent predictor of CVD in women. 相似文献20.