tbuckley/cabot-search huggingface dataset:
Acute coronary artery occlusion during and after percutaneous transluminal coronary angioplasty. Frequency, prediction, clinical course, management, and follow-up.
Authors: P J de Feyter, M van den Brand, G J Laarman, R van Domburg, P W Serruys, H Suryapranata, G Jaarman
Journal: Circulation (1991)

BACKGROUND Acute coronary artery occlusion after percutaneous transluminal coronary angioplasty (PTCA) continues to remain a serious complication despite significant improvement in operator performance and technological advancements. This retrospective study was performed to ascertain the frequency, predictive variables, management, and outcome of acute coronary artery occlusion. METHODS AND RESULTS The study was based on data from 1,423 consecutive patients who underwent an elective coronary angioplasty between January 1986 and December 1988. Acute coronary artery occlusion occurred in 104 patients (7.3%). Acute occlusion developed during the dilatation procedure in 80 patients (5.6%) and within 24 hours after the procedure in 24 patients (1.7%). Four clinical and 14 angiographic variables predictive for acute coronary artery occlusion were analyzed in these 104 patients with a complicated procedure and were compared with those in 104 representative patients with successful attempts. Multivariate analysis found three independent predictive variables: unstable angina, multivessel disease, and complex lesions. The overall clinical outcome after management of acute coronary artery occlusion including immediate repeat dilatation (95 patients), use of intracoronary streptokinase (34 patients), or autoperfusion catheter (12 patients) was successful (reduction of lumen diameter to less than 50%, no death, no myocardial infarction [MI], and no emergency surgery) in 42 patients (40%), was a failure without major complication in four patients (4%), and was a failure with major complication (death, MI, and emergency surgery) in 58 patients (56%). The overall mortality rate was 6% (six patients), the overall MI rate was 36% (37 patients), and emergency bypass surgery was required in 30% of patients (31 patients). At 6 months' follow-up of 42 patients with successful management, recurrent angina pectoris due to restenosis occurred in 10 patients (24%), and a late MI occurred in one patient (3%). At 6 months' follow-up of 56 survivors with unsuccessful management (development of MI or need for emergency bypass surgery), recurrent angina occurred in nine patients (16%), and cardiac death in two patients (4%). However, the majority of patients in both groups were either symptom free or had mild angina pectoris. CONCLUSION Acute coronary artery occlusion during PTCA is often unpredictable, but its frequency is higher in patients with unstable angina, multivessel disease, and complex lesions. Despite immediate redilatation, use of intracoronary streptokinase, and emergency bypass surgery, PTCA is associated with a high mortality and morbidity.
Incidence and Clinical Complications of Myelodysplastic Syndromes Among United States Medicare Beneficiaries
Authors: Stuart L. Goldberg, Er Chen, Mitra Corral, Amy Guo, Nikita Mody-Patel, Andrew L. Pecora, Marianne Laouri
Journal: Journal of Clinical Oncology (2010)

To determine the incidence and complications of myelodysplastic syndromes (MDS) among Medicare beneficiaries.Retrospective review of 2003 Medicare Standard Analytic Files utilizing International Classification of Diseases for Oncology ninth edition CM code 238.7 to identify new MDS patients, with 3-year follow-up.Among 1,394,343 individuals in Medicare Standard Analytic Files age > or = 65 years, 162 per 100,000 were coded as newly diagnosed MDS during 2003 yielding a calculated 45,000 new cases in the United States Medicare > or = 65 years population. Patients with MDS were older (median age, 77 years), and over-represented by males. Among patients with MDS diagnosed during first quarter of 2003, 73.2% suffered cardiac-related events during 3-year follow-up, which exceeded the Medicare population (54.5%; P < .01) even when age adjusted (odds ratio, 2.10; P < .01). Significant increases in prevalence of diabetes (40.0% v 33.1%), dyspnea (49.4% v 28.5%), hepatic diseases (0.8% v 0.2%), and infections (sepsis: 22.5% v 6.1%) were noted in MDS (all P < .01) compared with the Medicare population. Patients with MDS requiring RBC transfusions had greater prevalence of these comorbidities. Acute myeloid leukemia developed within 3 years in 9.6%, with increased transformation among transfused (24.6%; P < .001). The 3-year Kaplan-Meier age-adjusted survival for MDS was 60.0%, which was significantly lower than the Medicare population (84.7%; hazard ratio, 3.08; P < .001), and mortality was further increased among transfused MDS (P < .01). In 2003, median payment for MDS was $16,181, compared to $1,575 for the Medicare population (P < .001).MDS is a common hematologic malignancy of the elderly, which places patients at risk for comorbid conditions. Transfusion dependency identifies patients with MDS at additional increased risk of organ impairment and shortened survival.
A Novel Tumor Targeting Drug Carrier for Optical Imaging and Therapy
Authors: Rui Li, Ke Zheng, Ping Hu, Zhuo Chen, Shanyong Zhou, Jincan Chen, Cai Yuan, Song Chen, Wei Zheng, En Ma, Fengling Zhang, Jinping Xue, Xueyuan Chen, Mingdong Huang
Journal: Theranostics (2014)

Human serum albumin (HSA), a naturally abundant protein in blood plasma and tissue fluids, has an extraordinary ligand-binding capacity and is advocated as a drug carrier to facilitate drug delivery. To render it tumor targeting specificity, we generated a recombinant HSA fused with the amino-terminal fragment (ATF) of urokinase, allowing the fusion protein to bind to urokinase receptor (uPAR), which is shown to have a high expression level in many tumors, but not in normal tissues. To test the efficacy of this bifunctional protein (ATF-HSA), a hydrophobic photosensitizer (mono-substituted β-carboxy phthalocyanine zinc, CPZ) was chosen as a cytotoxic agent. A dilution-incubation-purification (DIP) strategy was developed to load the ATF-HSA with this CPZ, forming a 1:1 molecular complex (ATF-HSA:CPZ). We demonstrated that CPZ was indeed embedded inside ATF-HSA at the fatty acid binding site 1 (FA1) of HSA, giving a hydrodynamic radius of 7.5 nm, close to HSA's (6.5 nm). ATF-HSA:CPZ showed high stability and remarkable optical and photophysical properties in aqueous solution. In addition, the molecular complex ATF-HSA:CPZ can bind to recombinant uPAR in vitro and uPAR on tumor cell surfaces, and was efficient in photodynamic killing of tumor cells. The tumor-killing potency of this molecular complex was further demonstrated in a tumor-bearing mouse model at a dose of 0.080 μmol / kg, or 0.050 mg CPZ / kg of mouse body weight. Using fluorescent molecular tomography (FMT), ATF-HSA:CPZ was shown to accumulate specifically in tumors, and importantly, such tumor retention was higher than that of HSA:CPZ. Together, these results indicate that ATF-HSA:CPZ is not only an efficient tumor-specific cytotoxic agent, but also an useful tumor-specific imaging probe. This bifunctional protein ATF-HSA can also be used as a drug carrier for other types of cytotoxic or imaging agents to render them specificity for uPAR-expressing tumors.
The effect of etanercept on anti-cyclic citrullinated peptide antibodies and rheumatoid factor in patients with rheumatoid arthritis
Authors: Horng-An Chen, Kuan-Chia Lin, Chun-Hsiung Chen, Hsien-Tzung Liao, Hon-Pin Wang, Hsiao-Ning Chang, Chang-Youh Tsai, Chung-Tei Chou
Journal: Annals of the Rheumatic Diseases (2005)

<b>Objective:</b> To evaluate the changes in anti-cyclic citrullinated peptide antibodies (anti-CCP) and rheumatoid factor (RF) following etanercept treatment in patients with rheumatoid arthritis. <b>Methods:</b> The study included 90 patients with rheumatoid arthritis who failed treatment with disease modifying antirheumatic drugs (DMARDs). All patients were allowed to continue treatment with DMARDs; 52 of them received etanercept as a twice weekly 25 mg subcutaneous injection for three months, and the others did not. Serum samples were collected at baseline and one month intervals during the treatment course. The serum levels of anti-CCP and RF were tested by enzyme linked immunosorbent assay and nephelometry, respectively. <b>Results:</b> At baseline, 45 of the 52 etanercept treated patients (86.5%) and 32 of the 38 controls (84.2%) were positive for anti-CCP. Tests for RF were positive in 78.9% and 84.2% of patients with or without etanercept treatment, respectively. The serum levels of anti-CCP and RF decreased significantly after a three month etanercept treatment (p = 0.007 and p = 0.006, respectively). The average decrease from baseline calculated for each individual patient in the etanercept treated group was 31.3% for anti-CCP and 36% for RF. The variation in anti-CCP was positively correlated with the variation in disease activity, swollen and tender joint counts, RF, and C reactive protein. <b>Conclusions:</b> Etanercept combined with DMARDs leads to a much greater decrease than DMARDs alone in the serum levels of anti-CCP and RF in rheumatoid arthritis, compatible with a reduction in clinical disease activity.
THE DIFFERING SURVIVAL OF NORMAL AND SENSITIZED SPLEEN CELLS TRANSFERRED TO ALLOGENEIC HOSTS
Authors: Brack G. Hattler, Michael Schlesinger, D. Bernard Amos
Journal: The Journal of Experimental Medicine (1964)

Normal and isoimmune C(3)H and C57BL spleen cells were transferred intravenously into normal and irradiated allogeneic recipients and the fate of the donor cells determined by differential cytotoxicity and radioautographic techniques. It was found that spleen cells sensitized against their prospective recipients could be identified in the host's spleen for 1 day, whereas normal donor cells survived 2 to 3 days. Spleen cells presensitized with an indifferent antigen had survival times similar to normal donor cells. Irradiation of the recipients prior to cell transfer eliminated any difference in survival times between normal and presensitized donor cells in allogeneic hosts. It is concluded that the host plays an important role in the rapid destruction of spleen cells presensitized against host antigens. Experiments in which sensitized and normal C57BL spleen cells were mixed and transferred into normal C(3)H mice indicated that as little as 5 to 10 per cent of the donor cell population need be sensitized for the entire mixture to behave as if it were obtained from a sensitized animal, as shown by its elimination in the 1-day interval.
Probe-level estimation improves the detection of differential splicing in Affymetrix exon array studies
Authors: Essi Laajala, Tero Aittokallio, Riitta Lahesmaa, Laura L Elo
Journal: Genome biology (2009)

Abstract The recent advent of exon microarrays has made it possible to reveal differences in alternative splicing events on a global scale. We introduce a novel statistical procedure that takes full advantage of the probe-level information on Affymetrix exon arrays when detecting differential splicing between sample groups. In comparison to existing ranking methods, the procedure shows superior reproducibility and accuracy in distinguishing true biological findings from background noise in high agreement with experimental validations.
Cannabinoids reduce ErbB2-driven breast cancer progression through Akt inhibition
Authors: María M Caffarel, Clara Andradas, Emilia Mira, Eduardo Pérez-Gómez, Camilla Cerutti, Gema Moreno-Bueno, Juana M Flores, Isabel García-Real, José Palacios, Santos Mañes, Manuel Guzmán, Cristina Sánchez
Journal: Molecular Cancer (2010)

ErbB2-positive breast cancer is characterized by highly aggressive phenotypes and reduced responsiveness to standard therapies. Although specific ErbB2-targeted therapies have been designed, only a small percentage of patients respond to these treatments and most of them eventually relapse. The existence of this population of particularly aggressive and non-responding or relapsing patients urges the search for novel therapies. The purpose of this study was to determine whether cannabinoids might constitute a new therapeutic tool for the treatment of ErbB2-positive breast tumors. We analyzed their antitumor potential in a well established and clinically relevant model of ErbB2-driven metastatic breast cancer: the MMTV-neu mouse. We also analyzed the expression of cannabinoid targets in a series of 87 human breast tumors.Our results show that both Delta9-tetrahydrocannabinol, the most abundant and potent cannabinoid in marijuana, and JWH-133, a non-psychotropic CB2 receptor-selective agonist, reduce tumor growth, tumor number, and the amount/severity of lung metastases in MMTV-neu mice. Histological analyses of the tumors revealed that cannabinoids inhibit cancer cell proliferation, induce cancer cell apoptosis, and impair tumor angiogenesis. Cannabinoid antitumoral action relies, at least partially, on the inhibition of the pro-tumorigenic Akt pathway. We also found that 91% of ErbB2-positive tumors express the non-psychotropic cannabinoid receptor CB2.Taken together, these results provide a strong preclinical evidence for the use of cannabinoid-based therapies for the management of ErbB2-positive breast cancer.
Vitamin D status in patients with bullous pemphigoid
Authors: S. Tukaj, E. Schmidt, A. Recke, R.J. Ludwig, D. Zillikens, C. Tukaj, M. Kasperkiewicz
Journal: British Journal of Dermatology (2012)

Funding sources: this study was supported by a grant from the Medical University of Gdansk (ST‐59). Conflicts of interest: none declared. Madam, Epidemiological studies have suggested that serum levels of the main circulating form of vitamin D, 25‐hydroxyvitamin D3 [25(OH)D], correlate with the disease activity of patients with various chronic inflammatory disorders. Interaction with the immune system is a well‐established, nonclassical effect of vitamin D, and accumulating evidence from experimental studies indicates that vitamin D and its analogues have immunomodulatory and anti‐inflammatory effects.1 Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering skin disease, and is characterized by autoantibodies to the hemidesmosomal constituents BP180 and BP230. Detection of circulating IgG autoantibodies against the immunodominant region of BP180 (BP180 NC16A) facilitates diagnosis of BP, and monitoring of these autoantibodies is useful in the assessment of the efficacy of treatment, as they correlate with disease activity.2 In a recent report, Marzano et al.3 presented data on vitamin D serum levels in active and untreated patients with BP (n = 15) and pemphigus vulgaris (n = 13). They observed that 25(OH)D levels were reduced approximately twofold in both of these autoimmune bullous diseases compared with controls.
Simultaneous Purifying Selection on the Ancestral MC1R Allele and Positive Selection on the Melanoma-Risk Allele V60L in South Europeans
Authors: Conrado Martínez-Cadenas, Saioa López, Gloria Ribas, Carlos Flores, Oscar García, Arrate Sevilla, Isabel Smith-Zubiaga, Maider Ibarrola-Villaba, Maria del Mar Pino-Yanes, Jesús Gardeazabal, Dolores Boyano, Alicia García de Galdeano, Neskuts Izagirre, Concepción de la Rúa, Santos Alonso
Journal: Molecular Biology and Evolution (2013)

In humans, the geographical apportionment of the coding diversity of the pigmentary locus melanocortin-1 receptor (MC1R) is, unusually, higher in Eurasians than in Africans. This atypical observation has been interpreted as the result of purifying selection due to functional constraint on MC1R in high UV-B radiation environments. By analyzing 3,142 human MC1R alleles from different regions of Spain in the context of additional haplotypic information from the 1000 Genomes (1000G) Project data, we show that purifying selection is also strong in southern Europe, but not so in northern Europe. Furthermore, we show that purifying and positive selection act simultaneously on MC1R. Thus, at least in Spain, regions at opposite ends of the incident UV-B radiation distribution show significantly different frequencies for the melanoma-risk allele V60L (a mutation also associated to red hair and fair skin and even blonde hair), with higher frequency of V60L at those regions of lower incident UV-B radiation. Besides, using the 1000G south European data, we show that the V60L haplogroup is also characterized by an extended haplotype homozygosity (EHH) pattern indicative of positive selection. We, thus, provide evidence for an adaptive value of human skin depigmentation in Europe and illustrate how an adaptive process can simultaneously help to maintain a disease-risk allele. In addition, our data support the hypothesis proposed by Jablonski and Chaplin (Human skin pigmentation as an adaptation to UVB radiation. Proc Natl Acad Sci U S A. 2010;107:8962–8968), which posits that habitation of middle latitudes involved the evolution of partially depigmented phenotypes that are still capable of suitable tanning.
Effect of polyethylene glycol electrolyte balanced solution on patients with acute colonic pseudo obstruction after resolution of colonic dilation: a prospective, randomised, placebo controlled trial
Authors: S N Sgouros
Journal: Gut (2005)

Conservative therapy for patients with acute colonic pseudo obstruction (Ogilvie's syndrome) may be successful initially but relapses are common. The aim of the present study was to evaluate the effect of polyethylene glycol (PEG) electrolyte balanced solution on the relapse rate of the syndrome after initial resolution with neostigmine or endoscopic decompression.The study was performed on 30 consecutive patients who presented with abdominal distension and radiographic evidence of colonic dilation, with a caecal diameter > or = 10 cm, that resolved conservatively. Patients then were randomised to receive daily 29.5 g of PEG (n = 15) or similar placebo (n = 15). Patients were monitored daily for a seven day period for stool and flatus evacuations, and colonic diameter on abdominal radiographs. Administration of the test solutions and assessment of patient symptoms and x rays were performed in a blinded fashion. A caecal diameter > or = 8 cm with a concomitant > or =10% increase after initial successful therapeutic intervention was considered as a relapse and these patients, after a second therapeutic intervention, were eligible to receive open label PEG.Twenty five patients received neostigmine as the initial therapeutic intervention which resulted in resolution of colonic dilation in 88% of cases. Eight patients had successful endoscopic decompression. Five (33.3%) patients in the placebo group had recurrent caecal dilation compared with none in the PEG group (p = 0.04). Therapy with PEG resulted in a significant increase in stool and flatus evacuations (p = 0.001 and 0.032, respectively) as well as in a significant decrease in the diameter of caecum, ascending and transverse colon, and abdominal circumference (p = 0.017, 0.018, 0.014, and 0.008, respectively).Administration of PEG in patients with Ogilvie's syndrome after initial resolution of colonic dilation may increase the sustained response rate after initial therapeutic intervention.
Association of Loss-of-Function Mutations in the &lt;emph type="ital"&gt;ABCA1&lt;/emph&gt; Gene With High-Density Lipoprotein Cholesterol Levels and Risk of Ischemic Heart Disease
Authors: Ruth Frikke-Schmidt, Børge G. Nordestgaard, Maria C. A. Stene, Amar A. Sethi, Alan T. Remaley, Peter Schnohr, Peer Grande, Anne Tybjærg-Hansen
Journal: JAMA (2008)

Low levels of high-density lipoprotein (HDL) cholesterol are inversely related to cardiovascular risk. Whether this is a causal effect is unclear.To determine whether genetically reduced HDL cholesterol due to heterozygosity for 4 loss-of-function mutations in ABCA1 cause increased risk of ischemic heart disease (IHD).Three studies of white individuals from Copenhagen, Denmark, were used: the Copenhagen City Heart Study (CCHS), a 31-year prospective general population study (n = 9022; 28 heterozygotes); the Copenhagen General Population Study (CGPS), a cross-sectional general population study (n = 31,241; 76 heterozygotes); and the Copenhagen Ischemic Heart Disease Study (CIHDS), a case-control study (n = 16,623; 44 heterozygotes). End points in all 3 studies were recorded during the period of January 1, 1976, through July 9, 2007.Levels of HDL cholesterol in the general population, cellular cholesterol efflux, and the association between IHD and HDL cholesterol and genotype.Heterozygotes vs noncarriers for 4 ABCA1 mutations (P1065S, G1216V, N1800H, R2144X) had HDL cholesterol levels of 41 mg/dL (interquartile range, 31-50 mg/dL) vs 58 mg/dL (interquartile range, 46-73 mg/dL), corresponding to a reduction in HDL cholesterol of 17 mg/dL (P < .001). A 17-mg/dL lower HDL cholesterol level in the CCHS was associated with a multifactorially adjusted hazard ratio for IHD of 1.70 (95% confidence interval [CI], 1.57-1.85). However, for IHD in heterozygotes vs noncarriers, the multifactorially adjusted hazard ratio was 0.67 (95% CI, 0.28-1.61; 1741 IHD events) in the CCHS, the multifactorially adjusted odds ratio was 0.82 (95% CI, 0.34-1.96; 2427 IHD events) in the CGPS, and the multifactorially adjusted odds ratio was 0.86 (95% CI, 0.32-2.32; 2498 IHD cases) in the CIHDS. The corresponding odds ratio for IHD in heterozygotes vs noncarriers for the combined studies (n = 41,961; 6666 cases; 109 heterozygotes) was 0.93 (95% CI, 0.53-1.62).Lower plasma levels of HDL cholesterol due to heterozygosity for loss-of-function mutations in ABCA1 were not associated with an increased risk of IHD.
Isolated chylopericardium due to mediastinal lymphangiomatous hamartoma;.
Authors: R E Jenner, H Oo
Journal: Thorax (1975)

Isolated chylopericardium is a rare cause of pericardial effusion. Intrapericardial chyle was first noticed by Hasebroek (1888) at necropsy. Twenty years ago Groves and Effler (1954) first reported a clinical case of isolated chylopericardium. The present case is similar to theirs in several respects, and is the nineteenth case to be reported. To our knowledge this is the first British report of an isolated chylopericardium and is the fourth case of isolated chylopericardium due to a mediastinal lymphangiomatous hamartoma to be successfully treated.