tbuckley/cabot-search huggingface dataset:
A Panel of Biomarkers Is Associated With Increased Risk of the Presence and Progression of Atherosclerosis in Women With Systemic Lupus Erythematosus
Authors: Maureen McMahon, Brian J. Skaggs, Jennifer M. Grossman, Lori Sahakian, John FitzGerald, Weng Kee Wong, Elaine V. Lourenco, Nagesh Ragavendra, Christina Charles‐Schoeman, Alan Gorn, George A. Karpouzas, Mihaela B. Taylor, Karol E. Watson, Michael H. Weisman, Daniel J. Wallace, Bevra H. Hahn
Journal: Arthritis & Rheumatology (2013)

An increased frequency of atherosclerosis (ATH) in systemic lupus erythematosus (SLE) is well-documented but not fully explained by the presence of traditional cardiac risk factors. Several nontraditional biomarkers, including proinflammatory high-density lipoprotein (piHDL) and leptin, have been individually associated with subclinical ATH in SLE. The aim of this study was to examine whether these and other biomarkers can be combined into a risk profile, the Predictors of Risk for Elevated Flares, Damage Progression, and Increased Cardiovascular Disease in Patients with SLE (PREDICTS), that could be used to better predict future progression of ATH.In total, 210 patients with SLE and 100 age-matched healthy control subjects (all women) participated in this prospective cohort study. The longitudinal presence of carotid plaque and intima-media thickness (IMT) were measured at baseline and followup (mean ± SD 29.6 ± 9.7 months).At followup, carotid plaque was present in 29% of SLE patients. Factors significantly associated with plaque, determined using Salford Predictive Modeling and multivariate analysis, included age ≥48 years (odds ratio [OR] 4.1, P = 0.002), high piHDL function (OR 9.1, P < 0.001), leptin levels ≥34 ng/dl (OR 7.3, P = 0.001), plasma soluble TWEAK levels ≥373 pg/ml (OR 28.8, P = 0.004), and history of diabetes (OR 61.8, P < 0.001). Homocysteine levels ≥12 μmoles/liter were also a predictor. However, no single variable demonstrated an ideal combination of good negative predictive values (NPVs), positive predictive values (PPVs), sensitivity, and specificity. A high-risk PREDICTS profile was defined as ≥3 positive biomarkers or ≥1 positive biomarker plus a history of diabetes; for high-risk SLE patients, the PPV was 64%, NPV was 94%, sensitivity was 89%, and specificity was 79%. In multivariate analysis, SLE patients with the high-risk profile had 28-fold increased odds for the longitudinal presence of plaque (P < 0.001) and increased progression of IMT (P < 0.001).A high-risk PREDICTS score confers 28-fold increased odds of the presence of any current, progressive, or acquired carotid plaque, both in patients with SLE and in control subjects, and is significantly associated with higher rates of IMT progression.
Melkersson-Rosenthal syndrome in childhood: a challenge in differential diagnosis and treatment
Authors: P.E. Ziem, C. Pfrommer, S. Goerdt, C.E. Orfanos, U. Blume-Peytavi
Journal: British Journal of Dermatology (2000)

Facial palsy and orofacial swelling in childhood represent a challenge in differential diagnosis for paediatricians and dermatologists. One possible entity, Melkersson–Rosenthal syndrome (MRS), is a rarity in childhood. We describe a 9-year-old girl with the diagnosis of MRS who had episodic swelling of the upper lip and complete peripheral facial palsy, associated with herpes and recurrent bacterial infections. Therapeutic options for MRS in childhood are limited. Our patient benefited from a 2-month course of prednisolone 1 mg kg−1 daily. We review previously published cases of MRS in childhood, and discuss the differential diagnosis of orofacial swelling and facial palsy as well as treatment options in children.
Plasma c-erbB-2 levels in breast cancer patients: prognostic significance in predicting response to chemotherapy.
Authors: R R Mehta, J H McDermott, T J Hieken, K C Marler, M K Patel, L D Wild, T K Das Gupta
Journal: Journal of Clinical Oncology (1998)

PURPOSE To determine the significance of plasma c-erbB-2 levels to assess the extent of disease spread and to predict the response to chemotherapy in node-positive breast cancer patients. METHODS We determined plasma levels of c-erbB-2 in 79 stages II and III breast cancer patients who received cyclophosphamide, methotrexate, and flourouracil (CMF)/cyclophosphamide, methotrexate, fluorouracil, vincristine, and prednisone (CMFVP) chemotherapy. All patients had a minimum follow-up of greater than 60 months or until disease recurrence. Plasma samples were obtained before and after chemotherapy. Plasma c-erbB-2 levels were quantified by enzyme-linked immunoassay. c-erbB-2 levels were analyzed in relation to the patients' axillary lymph node status, menopausal status, disease status, disease-free survival (DFS), and steroid receptor status of tumor. RESULTS Plasma c-erbB-2 levels varied widely in breast cancer patients. In general, when all patients were included in the analyses, plasma c-erbB-2 levels before chemotherapy correlated significantly with the number of positive axillary lymph nodes and with postchemotherapy c-erbB-2 levels. No association was observed between pre- or postchemotherapy c-erbB-2 levels and other variables (patients' age at diagnosis, receptor status of the tumor, or disease status). The prognostic significance of different factors (ie, nodal status [one to three v &gt; three positive nodes], menopausal status [pre- v postmenopausal women], estrogen receptor [ER] status [ER+ v ER-], and pre- and postchemotherapy c-erbB-2 levels) in predicting DFS was determined in all study patients. Among the variables examined, nodal status was the strongest predictor of DFS in these patients. The second most significant prognostic marker was postchemotherapy c-erbB-2 level. Prechemotherapy c-erbB-2 levels showed prognostic significance for DFS in a subset of breast cancer patients (ie, patients with &gt; three positive nodes). Patients with greater than three positive lymph nodes and those with greater than 100 fmol/mL of plasma c-erbB-2 levels before therapy had significantly shorter DFS than did those patients with 100 fmol/mL or less c-erbB-2 levels. CONCLUSION In breast cancer patients, determination of c-erbB-2 levels before therapy is an important biomarker to assess the extent of disease spread in the lymph nodes. Postchemotherapy c-erbB-2 levels are also a prognostic indicator for DFS in patients who receive chemotherapy. Finally, in a subgroup of patients with greater than three positive nodes, prechemotherapy c-erbB-2 levels are a prognostic marker for response of patients to standard chemotherapy.
Bronchiolitis Obliterans Syndrome after (Heart–)Lung Transplantation
Authors: JAN HIRSCH, ANDREAS ELSSNER, GERTI MAZUR, KONRAD L. MAIER, IRIS BITTMANN, JÜRGEN BEHR, MARTIN SCHWAIBLMAIR, HERMANN REICHENSPURNER, HEINER FÜRST, JOSEF BRIEGEL, CLAUS VOGELMEIER
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Increased numbers of neutrophils are a common finding in bronchoalveolar lavage fluid (BALF) samples obtained from patients after (heart–)lung transplantation [(H)LTX]. Since proteases and reactive oxygen species secreted by neutrophils are capable of causing substantial damage to the lung tissue if not counterbalanced by the antiprotease and antioxidant screen, we hypothesized that neutrophil products may play a role in the development of obliterative bronchiolitis (OB). A total of 72 BALF samples obtained from 33 patients after (H)LTX were evaluated. Sixteen of these patients were suffering from bronchiolitis obliterans syndrome (BOS) at the time of bronchoalveolar lavage (BAL). As a control, BALF samples from 17 healthy volunteers were analyzed. Anti–neutrophil elastase (NE) activity was quantified by a titration assay. Concentrations of α1-protease inhibitor (API), secretory leukocyte protease inhibitor (SLPI), NE-API complex, and myeloperoxidase (MPO) were measured by ELISA. Oxidized methionine [Met(O)] was quantified by high-performance liquid chromatography (HPLC). Epithelial lining fluid (ELF) from patients suffering from BOS showed significantly increased neutrophil counts, significantly elevated concentrations of NE-API complex and Met(O), and a significant decrease in the concentration of SLPI. Furthermore, a trend toward an increased NE activity and MPO concentration was observed. These findings suggest that neutrophils may be involved in the development of BOS. Hirsch J, Elssner A, Mazur G, Maier KL, Bittmann I, Behr J, Schwaiblmair M, Reichenspurner H, Fürst H, Briegel J, Vogelmeier C for the Munich Lung Transplant Group. Bronchiolitis obliterans syndrome after (heart–)lung transplantation: impaired antiprotease defense and increased oxidant activity.
Comparison of the sensitivity and specificity of the methacholine challenge test and exercise test for the diagnosis of asthma in athletes
Authors: Tatyana Molostova, Malika Mustafina, Alexander Cherniak, Zhanna Naumenko, Ludmila Shogenova, Zaurbek Aisanov
Journal: European Respiratory Journal (2013)

Objective: to compare specificity and sensitivity of the metacholine challenge test (MCT) and exercise challenge test for the diagnosis of bronchial asthma in athletes.

Methods: 19 athletes (12 M/7 F, mean age 24.8±3.6 yrs) with respiratory symptoms were studied. Lung function with assessment of reversibility to salbutamol (n=19), MCT (n=19) and exercise test on a bicycle ergometer (n=17) were performed. The specificity and sensitivity of the MCT and exercise test were evaluated.

Results: Significant reversibility to salbutamol was found in 5 athletes. The fall in forced expiratory volume in one second (FEV1) following the metacholine inhalation (<8 mg/ml) was more than 20% in 10 athletes. The MCT showed high specificity (100%), high sensitivity (100%) and negative predictive value (100%). At the moderate cut-off value (<4 mg/ml), the MCT had a more low sensitivity (80%) and negative predictive value (82%). Exercise challenge test was negative in all the athletes. The maximal fall in FEV1 during 15 min after exercise was 0.2±2.4%, no significant differences between the group of athletes with asthma and a group of healthy athletes have been identified: 0.3±3.2% vs 0.7±1.5%, p=0.386477.

Conclusion: Assessment of bronchial hyperresponsiveness by a metacholine challenge test is good procedure of diagnosing asthma in athletes. The MCT in athletes with respiratory symptoms had a high specificity and sensitivity. Low sensitivity of the exercise challenge test may result in inefficiency of this method for the diagnosis of bronchial asthma and exercise-induced bronchospasm in athletes.
Potential clinical utilities of prostate cancer risk-associated SNPs
Authors: Jianfeng Xu
Journal: Clinical Cancer Research (2010)

Abstract Prostate cancer (PCa) is the most common solid organ malignancy affecting American men and the second leading cause of cancer related death. Recently, more than 30 PCa risk-associated single nucleotide polymorphisms (SNPs) have been discovered from genome-wide association studies (GWAS). These risk-associated SNPs have been consistently replicated in multiple case-control study populations of European descent. Although each of these SNPs is only moderately associated with PCa risk, a genetic score based on a combination of risk-associated SNPs can be used to identify men at high risk for PCa. However, these results were obtained from case-control studies which have several significant limitations. The validity of these genetic associations, the relative performance of genetic markers for PCa risk prediction compared to existing clinical variables such as PSA, and more importantly, whether genetic markers add value to existing clinical variables, are key questions that need to be addressed in well-controlled prospective studies prior to their consideration for clinical use. In this presentation, I will present the findings of PCa risk prediction using multiple risk-associated SNPs. I will also discuss our effort to assess clinical validity and clinical utility of these genetic markers in the Reduction by DUtasteride of Prostate Cancer Events (REDUCE) study, a large randomized clinical trial. All men in the REDUCE trial had a negative biopsy at baseline and were followed-up for four years, with scheduled not-for-cause (i.e. regardless of PSA levels and other clinical indications) prostate biopsies at years 2 and 4. Therefore, this study design minimizes the potential impact of PSA detection bias on associations between PCa risk and SNPs. In addition, because it is a clinical trial, a number of clinical variables, such as free/total PSA ratio and prostate volume were measured at baseline using a standardized protocol. Therefore, it allows us to compare performance of genetic markers and existing clinical variables in predicting positive prostate biopsy in the same study. Finally, the study design allows us to assess whether genomic-targeted chemoprevention, based on estimated risk from genetic markers, can improve efficacy of chemoprevention. This study represents an important next and critical step towards an assessment of the potential clinical utility of genetic markers.
Impact of etanercept treatment on ultraviolet B-induced inflammation, cell cycle regulation and DNA damage
Authors: T. Gambichler, C. Tigges, A. Dith, M. Skrygan, N. Scola, P. Altmeyer, A. Kreuter
Journal: British Journal of Dermatology (2010)

Current studies indicate that treatment with tumour necrosis factor (TNF)-α blockers plus ultraviolet (UV) B phototherapy results in higher relative Psoriasis Area and Severity Index reduction as compared with TNF-α monotherapy.This study aimed to investigate the acute impact of etanercept on UVB-induced inflammation, cell cycle regulation and DNA damage.Eleven subjects diagnosed with psoriasis who fulfilled the indication criteria for etanercept treatment were studied. A healthy skin site on the upper back was treated with UVB at 2 minimal erythema doses (MED). After 1, 24 and 72 h punch biopsies were taken from this site. Following the 72 h biopsy etanercept 50 mg was administered subcutaneously. After 48 h, 2 MED was given on healthy skin adjacent to previously treated skin sites. Again, after 1, 24 and 72 h punch biopsies were taken from this site. UVB- as well as UVB plus etanercept-treated skin was assessed by means of colorimetry and immunohistochemical studies for caspase 3, cyclin D(1), interleukin-12, Ki-67, p16, p53, survivin, thymine dimers and TNF-α.Erythema formation did not differ significantly between UVB- and UVB plus etanercept-treated sites. Comparisons between UVB- and UVB plus etanercept-treated sites at a given time (1, 24, 72 h) did not result in significant differences in immunoreactivity of the markers investigated, except for cyclin D(1), p53 and survivin. Immunoreactivity of cyclin D(1) and p53 was significantly decreased in UVB plus etanercept-treated sites at 24 h. Survivin expression was significantly higher in UVB plus etanercept-treated skin as compared with UVB monotherapy.Our data indicate that combined treatment with broadband UVB and TNF-α blockers might increase the risk of photocarcinogenesis by influencing apoptotic as well as antiapoptotic pathways.
Randomized Trial of a Slow-Release Versus a Standard Formulation of Cytarabine for the Intrathecal Treatment of Lymphomatous Meningitis
Authors: Michael J. Glantz, Suzanne LaFollette, Kurt A. Jaeckle, William Shapiro, Lode Swinnen, Jack R. Rozental, Surasak Phuphanich, Lisa R. Rogers, John C. Gutheil, Tracy Batchelor, David Lyter, Marc Chamberlain, Bernard L. Maria, Charles Schiffer, Rifaat Bashir, David Thomas, Wayne Cowens, Stephen B. Howell
Journal: Journal of Clinical Oncology (1999)

To evaluate the efficacy and safety of a slow-release formulation of cytarabine (DepoCyt; Chiron Corp, Emeryville, CA, and Skye Pharma, Inc, San Diego, CA) that maintains cytotoxic concentrations of cytarabine (ara-C) in the CSF of most patients for more than 14 days.Twenty-eight patients with lymphoma and a positive CSF cytology were randomized to receive DepoCyt 50 mg once every 2 weeks or free ara-C 50 mg twice a week for 1 month. Patients whose CSF cytology converted to negative and who did not have neurologic progression received an additional 3 months of consolidation therapy and then 4 months of maintenance therapy. All patients received dexamethasone 4 mg orally bid on days 1 through 5 of each 2-week cycle.The response rate was 71% for DepoCyt and 15% for ara-C on an intent-to-treat basis (P =.006). All of the patients on the DepoCyt arm but only 53% of those on the ara-C arm were able to complete the planned 1-month induction therapy regimen. Time to neurologic progression and survival trend in favor of DepoCyt (median, 78.5 v 42 days and 99.5 v 63 days, respectively; P >.05). DepoCyt treatment was associated with an improved mean change in Karnofsky performance score at the end of induction (P =.041). The major adverse events on both arms were headache and arachnoiditis, which were often caused by the underlying disease.DepoCyt injected once every 2 weeks produced a high response rate and a better quality of life as measured by Karnofsky score relative to that produced by free ara-C injected twice a week.
Effects of Deletion of the<i>Matrix Metalloproteinase 9</i>Gene on Development of Murine Thoracic Aortic Aneurysms
Authors: John S. Ikonomidis, John R. Barbour, Zainab Amani, Robert E. Stroud, Amanda R. Herron, David M. McClister, Sarah E. Camens, Merry L. Lindsey, Rupak Mukherjee, Francis G. Spinale
Journal: Circulation (2005)

Background— The matrix metalloproteinases (MMPs) contribute to cardiovascular remodeling, and MMPs, such as the gelatinases ( MMP-9 and MMP-2 ), have been identified in thoracic aortic aneurysmal (TAA) tissue, but a cause-effect relationship has not been clearly established. Accordingly, this study examined TAA progression in mice devoid of the MMP-9 gene. Methods and Results— The descending thoracic aortas of wild-type (WT) FVB (n =17) and MMP-9 gene knockout (KO, n =11) mice were exposed to 0.5 mol/L of CaCl 2 for 15 minutes with terminal studies performed at 4 weeks. Aortic lumen diameter was measured using video micrometry at baseline and at 4 weeks (TAA) followed by aortic tissue analysis. In WT mice, aortic diameter increased by 138±5% at 4 weeks ( P &lt;0.05), consistent with TAA formation. In the KO mice, aortic diameter increased from baseline by 120±4% ( P &lt;0.05) but was attenuated from WT TAA values ( P &lt;0.05). Gelatin zymography performed on TAA segments confirmed the absence of MMP-9 in the KO mice but a &gt;8-fold relative increase in the active form of MMP-2 compared with WT ( P &lt;0.05). Despite this, MMP-2 activity was relatively increased ( P &lt;0.05) and colocalized to smooth muscle cell actin in a differential pattern favoring medial distruction in the WT TAA compared with the KO TAA segments. Conclusions— These results demonstrate that MMP-9 gene deletion attenuated TAA formation despite an increase in the zymographic levels of MMP-2 . These unique findings suggest that an interaction between these 2 MMPs is necessary to facilitate TAA progression.
Age at First Birth and the Risk of Epithelial Ovarian Cancer&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Carlo La Vecchia, Adriano Decarli, Silvia Franceschi, Michela Regallo, Gianni Tognoni
Journal: JNCI Journal of the National Cancer Institute (1984)

The relationships between age at first birth, parity, and the risk of ovarian cancer were evaluated in a case-control study of 272 women with histologically confirmed epithelial ovarian cancer and 544 age-matched controls with a spectrum of acute conditions unrelated to any of the established or potential risk factors for ovarian cancer. Late age at first birth was associated with increased risk: Compared to women who first had a child before the age of 22 years, the relative risks (RR) for those who first gave birth at ages 22-24, 25-27, and 28 or more were 2.7, 3.2, and 4.0, respectively. Nulliparous women showed increased RR (3.9) comparable to the RR among women who first bore a child at age 25 or more, regardless of the number of births. The elevated risk associated with later age at first birth was not accounted for by low parity. The risk of ovarian cancer, as expected, increased with decreasing parity: RR estimates for women having 5 or more, 3 or 4, and 1 or 2 children and for nulliparae were 1.0, 1.7, 1.9, and 2.6, respectively. However, the inverse association between parity and ovarian cancer could be accounted for largely by the importance of age at first birth, because when adjustment was made for that variable, the RR for 3 or 4 and 1 or 2 children decreased to 1.3 and 1.2, respectively. Thus the results of the present study show a strong independent effect of age at first birth on the risk of epithelial ovarian cancer, whereas the association with parity can be explained largely or totally in terms of a high correlation between total parity and age at first birth. The pattern of ovarian cancer risk that emerges from this study, therefore, is similar to the epidemiology of breast cancer. General evidence on this issue from various other studies, however, is rather controversial, and similar analysis of other data-sets would be useful.
Review of the Comparative Pharmacology and Clinical Activity of Cisplatin and Carboplatin
Authors: Ronald S. Go, Alex A. Adjei
Journal: Journal of Clinical Oncology (1999)

To review the pharmacodynamics, pharmacokinetics, toxicities, and relative clinical activities of cisplatin and carboplatin. Through a search of the MEDLINE database, we identified phase III clinical trials and pharmacologic studies comparing cisplatin and carboplatin published in the English language medical literature from January 1966 to December 1997.Prospective randomized trials comparing cisplatin to carboplatin were identified for ovarian (n = 12), germ cell (n = 4), non-small-cell lung (n = 1), small-cell lung (n = 3), and head and neck (n = 4) cancers. Carboplatin and cisplatin were equally effective in suboptimally debulked ovarian cancer and extensive-stage small-cell lung cancer. One study each showed a trend toward better survival in favor of cisplatin for patients with optimally debulked ovarian and limited-stage small-cell lung cancers. These results were, however, based on subset analyses. In germ cell tumors, carboplatin was inferior because of lower relapse-free survival rates. Cisplatin produced superior response rates and survival in head and neck cancers. There are no published randomized phase III studies of bladder, cervical, endometrial, and esophageal cancers.Carboplatin does not possess equivalent activity to cisplatin in all platinum-sensitive tumors. Carboplatin can replace cisplatin in chemotherapy regimens for suboptimally debulked ovarian cancer. Two ongoing studies will address the same question in optimally debulked disease. Carboplatin can also be substituted for cisplatin in the treatment of non-small-cell and extensive-stage small-cell lung cancers. Its role in limited-stage small-cell lung cancer needs to be investigated further. Carboplatin is inferior to cisplatin in germ cell, head and neck, and esophageal cancers. Randomized studies are needed to determine whether carboplatin has equivalent efficacy to cisplatin in bladder, cervical, and endometrial cancers.