tbuckley/cabot-search huggingface dataset:
Cigarette Smoke–induced Emphysema
Authors: Barry W. A. van der Strate, Dirkje S. Postma, Corry-Anke Brandsma, Barbro N. Melgert, Marjan A. Luinge, Marie Geerlings, Machteld N. Hylkema, Anke van den Berg, Wim Timens, Huib A. M. Kerstjens
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Rationale: Little is known about what drives the inflammatory reaction in the development of chronic obstructive lung disease. B cells have been found.Objective: To study the involvement of B cells in the development of emphysema.Methods: The presence of B-cell follicles and their interaction with other cells were investigated in lungs of patients with chronic obstructive pulmonary disease and of smoking mice. B cells were isolated from lymphoid follicles by laser microdissection and analyzed for the presence of immunoglobulin rearrangements and somatic mutations.Main Results: Lymphoid follicles consisting of B cells and follicular dendritic cells with adjacent T cells were demonstrated both in the parenchyma and in bronchial walls of patients with emphysema. A clonal process was observed in all follicles and the presence of ongoing somatic mutations was observed in 75% of the follicles, indicating oligoclonal, antigen-specific proliferation. Similar lymphoid follicles were detected in mice that had developed pulmonary inflammation and progressive alveolar airspace enlargement after smoking. The increase in the number of B-cell follicles was progressive with time and correlated with the increase in mean linear intercept. Specific bacterial or viral nucleic acids could not be detected.Conclusions: B-cell follicles with an oligoclonal, antigen-specific reaction were found in men and mice with emphysema. In mice, the development was progressive with time and correlated with the increase in airspace enlargement. We hypothesize that these B cells contribute to the inflammatory process and/or the development and perpetuation of emphysema by producing antibodies against either tobacco smoke residues or extracellular matrix components.
Metalloproteinase expression and prognosis in soft tissue sarcomas
Authors: M.S. Benassi, G. Gamberi, G. Magagnoli, L. Molendini, P. Ragazzini, M. Merli, F. Chiesa, A. Balladelli, M. Manfrini, F. Bertoni, M. Mercuri, P. Picci
Journal: Annals of Oncology (2001)
Spondylolysis in young tennis players
Authors: A Ruiz-Cotorro, R Balius-Matas, A E Estruch-Massana, J Vilaró Angulo
Journal: British Journal of Sports Medicine (2006)

The general aetiology, diagnosis, and treatment of spondylolysis, a bone defect in the pars interarticularis of the vertebra, are reviewed. A retrospective study of young tennis players diagnosed between 2000 and 2004 with spondylolysis with or without spondylolisthesis, assessed by radiography and planar bone scintigraphy, is described. If the radiographic results were negative, computed tomography was performed. Sixty six cases were evaluated: 53 L5 lesions, eight L4 lesions, two L3 lesions, and one bilateral lesion at the L2 level. Two more lesions at two levels were found (bilateral L5 and unilateral L4 and L3 on the right side). Classification, treatment, and outcome of the cases are reported. A combination of radiography, planar bone scintigraphy, and SPECT is useful for evaluating spondylolysis in tennis players and recommending treatment. Use of a brace did not appear to achieve significant results.
Excitation, conduction, and reflection of impulses in isolated bovine and serum cardiac purkinje fibers.
Authors: J Jalife, G K Moe
Journal: Circulation Research (1981)

When an impulse arrives at an area of impaired conductivity, a slowly rising electrotonic potential may bring the distal tissue to threshold after a delay imposed by the passive electrical properties of the system and by the time-dependent changes of these properties during diastole. This phenomenon can be demonstrated in Purkinje strands in which an area of depressed conductivity has been induced by the impedance of a sucrose gap and can be mimicked by the application of relatively long current pulses of low amplitude. The functional refractory period, defined as the shortest interval between two distal responses both propagated across the gap, was determined by the application of premature stimuli at progressively earlier intervals. The time course of the recovery of excitability as well as the conduction intervals could be varied almost at will by manipulating the electric impedance between proximal and distal ends of the fiber. When the time of activation of the distal end across the gap exceeded the absolute refractory period of the proximal segment, the impulse reflected back as a closely coupled premature beat. Time-dependent changes in the passive electrical properties of the depressed segment may set the conditions for reflection. The results suggest the possibility of reflection as a mechanism for premature beats and demonstrate obligatory shifts in the patterns of premature reentrant activity accompanying changes in basic cycle length. These experiments provide important clues for the distinction between reentrant and parasystolic mechanisms.
Phase I Trial of Large Multivalent Immunogen Derived from Melanoma Lysates in Patients with Disseminated Melanoma
Authors: Malcolm S. Mitchell, June Kan-Mitchell, Philip R. Morrow, Denise Darrah, Vicky E. Jones, Matthew F. Mescher
Journal: Clinical Cancer Research (2004)

The purpose of this research was to determine the toxicity and immunological activity of large multivalent immunogen (LMI), a preparation of tumor cell membranes affixed to amorphous silica microbeads, in patients with melanoma.Nineteen patients with metastatic (stage IV) melanoma were entered into the study, of whom 15 received the full 3 months of treatment with LMI. LMI was administered without adjuvant, one-half intradermally (i.d.) and the other half s.c. Because we expected little toxicity, we first treated 2 patients at each dose level, 10-, 30-, or 100-million tumor cell equivalents on weeks 0, 4, and 8, and subsequently randomized the remaining 13 patients to receive treatment with one of those dosage schedules, for a total of 19 patients. Two patients who were registered were found to be ineligible because of brain metastases, and 2 others did not complete the course of treatment for reasons other than toxicity. Thus, 15 patients were fully evaluable. Patients with evidence of a clinical response (at least stable disease at the 12-week checkpoint) had the option of continuing treatment at 4-week intervals. Frequencies of cytolytic T cell precursors against HLA-A2 matched melanoma cells, and delayed-type hypersensitivity to a melanoma cell membrane preparation from a component melanoma cell line were performed to measure immunological efficacy, and serum chemistries and complete blood counts were performed every 2 weeks throughout the study to measure possible toxicity. Computed tomography scans were performed pretreatment and at week 12 to measure possible beneficial effects on known lesions.Eight of the 15 evaluable patients had an increase in cytolytic T-cell precursors during the course of therapy, usually by day 42. No patient had demonstrable delayed-type hypersensitivity to a melanoma membrane preparation before or after treatment. No toxicity of any kind was observed. A degree of clinical effectiveness of LMI was suggested by the elicitation of stable disease in 5 patients at 12 weeks. One patient had >50% regression of a lung nodule but progression of disease to the brain, whereas a second patient had a bona fide partial remission of a 3-cm diameter solitary lung nodule.LMI was nontoxic, improved immunological reactivity to melanoma cells, and showed evidence of clinical effectiveness (shrinkage of tumor) in 1 patient. Additional studies with LMI with added adjuvant materials, in melanoma and other cancers, appear warranted.
Imaging Transgene Activity <i>In vivo</i>
Authors: Terence P.F. Gade, Jason A. Koutcher, William M. Spees, Bradley J. Beattie, Vladimir Ponomarev, Michael Doubrovin, Ian M. Buchanan, Tatiana Beresten, Kristen L. Zakian, H. Carl Le, William P. Tong, Philipp Mayer-Kuckuk, Ronald G. Blasberg, Juri G. Gelovani
Journal: Cancer Research (2008)

Abstract The successful translation of gene therapy for clinical application will require the assessment of transgene activity as a measure of the biological function of a therapeutic transgene. Although current imaging permits the noninvasive detection of transgene expression, the critical need for quantitative imaging of the action of the expressed transgene has not been met. In vivo magnetic resonance spectroscopic imaging (MRSI) was applied to quantitatively delineate both the concentration and activity of a cytosine deaminase–uracil phosphoribosyltransferase (CD-UPRT) fusion enzyme expressed from a transgene. MRSI enabled the generation of anatomically accurate maps of the intratumoral heterogeneity in fusion enzyme activity. We observed an excellent association between the CD-UPRT concentration and activity and the percentage of CD-UPRT+ cells. Moreover, the regional levels of UPRT activity, as measured by imaging, correlated well with the biological affect of the enzyme. This study presents a translational imaging paradigm for precise, in vivo measurements of transgene activity with potential applications in both preclinical and clinical settings. [Cancer Res 2008;68(8):2878–84]
Effect of a Text Messaging Intervention on Influenza Vaccination in an Urban, Low-Income Pediatric and Adolescent Population
Authors: Elyse Olshen Kharbanda
Journal: JAMA (2012)

IMELY VACCINATION IS THE CORnerstone of influenza prevention through vaccination of susceptible populations before illness becomes epidemic in communities. 1The effectiveness of the influenza vaccine in children and adolescents ranges from 66% to 95%, depending on age, vaccine type, and season. 2,3Despite the availability of effective vaccines, influenza infection results in an estimated 31 million outpatient visits, 226 000 hospitalizations, and 36 000 deaths annually, 4,5 along with a high burden of cost from direct medical expenses and days lost from work. 5 Children and adolescents aged 6 months to 18 years are at increased risk for influenza morbidity and mortality, and influenza is one of the most common causes of hospitalization in children and adolescents. 1,4Schoolaged children and adolescents also serve as an important reservoir, transmitting influenza to those at highest risk for severe disease.
Nutritional support of malnourished lactose intolerant African patients.
Authors: S J O'Keefe, J K Adam, E Cakata, S Epstein
Journal: Gut (1984)

The effectiveness of two commonly available liquid diets was assessed in 40 severely malnourished black African patients. All patients were shown to have normal xylose absorption. The diets were given according to the manufacturer's recommendations. One diet was lactose containing (LC diet) (150 g/d) and high protein (112 g/d), the other normal protein and lactose free (LF diet) (protein 67 g/d), total energy content being similar. Patients were randomly divided into two equal groups and allocated (blind) to one of the diets. Tolerance and nitrogen balance were assessed over two three day periods on half and then full strength formulations. Severe intolerant symptoms were observed in 50% of patients on half strength and 94% of patients on full strength lactose containing diet with evidence of malabsorption of fluid, nitrogen, and fat. Despite high stool nitrogen losses (3.75 +/- 1.04 g/d), however, positive nitrogen balance was achieved in most patients receiving the full strength LC formulation. On the other hand, the full strength LF diet was generally well tolerated and was associated with significantly lower faecal losses and positive nitrogen balance. The results indicate that high density lactose containing liquid formulae are poorly tolerated by severely malnourished black African patients, while lactose free formulae containing approximately 10 g nitrogen/d are well tolerated and result in positive nitrogen balance.
Lung function and clinical outcome in postpolio patients: a prospective cohort study during 11 years
Authors: B Midgren
Journal: European Respiratory Journal (1997)

The object of this investigation was to prospectively study the annual decline in lung function in a cohort of postpolio patients, and to determine the usefulness of initial lung function tests in the prediction of a subsequent poor outcome. Cross-sectional data were analysed in 55 patients from the total cohort of 350 survivors of poliomyelitis in our admission area of 550,000 inhabitants. Longitudinal data (&gt; 5 yrs, average 8.9 yrs) were available for 31 patients. Seventeen of the patients had a poor outcome (13 were started on domiciliary artificial ventilation and five died from respiratory failure; with one overlap). At the time of entry to the study (on average 4.3 years before the poor outcome), these patients had a lower vital capacity (VC) (43 vs 65% of predicted; p &lt; 0.01) and arterial oxygen tension (Pa,O2) (9.9 vs 11 kPa; p &lt; 0.05) and a higher arterial carbon dioxide tension (Pa,CO2) (6.0 vs 5.0 kPa; p &lt; 0.01). They also had a more rapid increase in Pa,CO2 (0.3 vs 0.03 kPa.yr-1; p &lt; 0.01), but the difference in decline in VC (40 vs 30 mL.yr-1) was not significant. Initial VC &lt; 50% of predicted and/or Pa,CO2 &gt; 6 kPa was associated with a poor prognosis. In conclusion, annual decline in vital capacity was not abnormally rapid but annual increase in arterial carbon dioxide tension was higher in patients with a poor outcome. Initial determination of vital capacity and initial and repeated blood gas analysis appear to be useful in identifying high-risk postpolio patients.
Difference in the risk of serious infections in patients with rheumatoid arthritis treated with adalimumab, infliximab and etanercept: results from the Dutch Rheumatoid Arthritis Monitoring (DREAM) registry
Authors: Sanne A A van Dartel, Jaap Fransen, Wietske Kievit, Marcel Flendrie, Alfons A den Broeder, H Visser, A Hartkamp, Mart A F J van de Laar, Piet L C M van Riel
Journal: Annals of the Rheumatic Diseases (2012)

Background Tumour necrosis factor (TNF)-inhibiting therapy increases the risk of serious infections in rheumatoid arthritis (RA). However, it is not clear whether this risk differs between TNF inhibitors. Objective To analyse whether the risk of serious infections in patients with RA treated with an anti-TNF inhibitor is different for adalimumab, infliximab and etanercept. Methods Data from the Dutch RA monitoring registry were used. Incidence rates were calculated from the observed number of first serious infections and follow-up time up to 5 years. A Cox proportional hazards model with time-to-first-serious infection was used to estimate risk differences among the anti-TNF treatment groups, with correction for confounders. Results The unadjusted incidence rate of a first serious infection in patients with RA per 100 patient-years was 2.61 (95% CI 2.21 to 3.00) for adalimumab, 3.86 (95% CI 3.33 to 4.40) for infliximab and 1.66 (95% CI 1.09 to 2.23) for etanercept. Age, year of starting anti-TNF therapy, comorbidities at baseline and disease activity score 28 over time were included as confounders. No difference in risk for serious infections was found between adalimumab and infliximab with an adjusted HR (adjHR) of 0.90 (95% CI 0.55 to 1.48). The risk of serious infections was significantly lower in etanercept than in both infliximab (adjHR=0.49 (95% CI 0.29 to 0.83)) and adalimumab (adjHR=0.55 (95% CI 0.44 to 0.67)). Conclusions The risk of serious infections in patients with RA treated with adalimumab or infliximab was similar, while the risk of serious infections in patients with RA treated with etanercept was lower than with both adalimumab and infliximab.
Modification of <i>BRCA1</i>-Associated Breast and Ovarian Cancer Risk by <i>BRCA1</i>-Interacting Genes
Authors: Timothy R. Rebbeck, Nandita Mitra, Susan M. Domchek, Fei Wan, Tara M. Friebel, Teo V. Tran, Christian F. Singer, Muy-Kheng Maria Tea, Joanne L. Blum, Nadine Tung, Olufunmilayo I. Olopade, Jeffrey N. Weitzel, Henry T. Lynch, Carrie L. Snyder, Judy E. Garber, Antonis C. Antoniou, Susan Peock, D. Gareth Evans, Joan Paterson, M. John Kennedy, Alan Donaldson, Huw Dorkins, Douglas F. Easton, Wendy S. Rubinstein, Mary B. Daly, Claudine Isaacs, Heli Nevanlinna, Fergus J. Couch, Irene L. Andrulis, Eitan Freidman, Yael Laitman, Patricia A. Ganz, Gail E. Tomlinson, Susan L. Neuhausen, Steven A. Narod, Catherine M. Phelan, Roger Greenberg, Katherine L. Nathanson
Journal: Cancer Research (2011)

Inherited BRCA1 mutations confer elevated cancer risk. Recent studies have identified genes that encode proteins that interact with BRCA1 as modifiers of BRCA1-associated breast cancer. We evaluated a comprehensive set of genes that encode most known BRCA1 interactors to evaluate the role of these genes as modifiers of cancer risk. A cohort of 2,825 BRCA1 mutation carriers was used to evaluate the association of haplotypes at ATM, BRCC36, BRCC45 (BRE), BRIP1 (BACH1/FANCJ), CTIP, ABRA1 (FAM175A), MERIT40, MRE11A, NBS1, PALB2 (FANCN), RAD50, RAD51, RAP80, and TOPBP1, and was associated with time to breast and ovarian cancer diagnosis. Statistically significant false discovery rate (FDR) adjusted P values for overall association of haplotypes (P(FDR)) with breast cancer were identified at ATM (P(FDR) = 0.029), BRCC45 (P(FDR) = 0.019), BRIP1 (P(FDR) = 0.008), CTIP (P(FDR) = 0.017), MERIT40 (P(FDR) = 0.019), NBS1 (P(FDR) = 0.003), RAD50 (P(FDR) = 0.014), and TOPBP1 (P(FDR) = 0.011). Haplotypes at ABRA1 (P(FDR) = 0.007), BRCC45 (P(FDR) = 0.016 and P(FDR) = 0.005 in two haplotype blocks), and RAP80 (P(FDR) < 0.001) were associated with ovarian cancer risk. Overall, the data suggest that genomic variation at multiple loci that encode proteins that interact biologically with BRCA1 are associated with modified breast cancer and ovarian cancer risk in women who carry BRCA1 mutations.
No changes in the distribution of organisms responsible for septic arthritis over a 20 year period
Authors: J J Dubost
Journal: Annals of the Rheumatic Diseases (2002)

To assess changes in the distribution and resistance of the pathogens responsible for septic arthritis over a 20 year period in patients admitted to the same hospital unit.Retrospective study of the hospital records of patients admitted between 1979 and 1998 for septic arthritis with positive microbiological diagnosis after blood or joint cultures, or both.303 cases of septic arthritis were studied, 141 in the period 1979-88 and 162 in the period 1989-98. The incidence between the first and second period did not vary significantly for the staphylococci (67% v. 63%), streptococci (16% v. 20%), and Gram negative bacilli (7% v. 10%). Tuberculous infections decreased from 9% to 4% (p<0.04). No gonococci were isolated in the second 10 year period. Among the staphylococcal species, there was an increase in the number of coagulase negative staphylococci (10 cases v. 21, p<0.05) between the two periods. There was no significant difference in the frequency of occurrence of methicillin resistant pathogens (12.6% v. 16.6%). The number of streptococcal B infections increased (2 v. 10 cases), and beta-lactamine resistant pneumococci emerged. In the second 10 year period, patients were older and were more likely to have co-existing disease, particularly tumoral growth, and less commonly were receiving dialysis. Localisation of joint infection was comparable except for an increase in prosthetic knee infections.The distribution and sensitivity of pathogens causing septic arthritis changed little over a 20 year period.
Automated quantitation of indexes of coronary lesion complexity. Comparison between patients with stable and unstable angina.
Authors: S J Kalbfleisch, M J McGillem, S B Simon, S F DeBoe, I M Pinto, G B Mancini
Journal: Circulation (1990)

Analysis of lesion morphology is becoming increasingly important in the study of coronary artery disease. Lesion irregularity has been shown to be one of the most important predictive features for development of myocardial infarction. Most studies to date have used only qualitative assessments of morphology and are thus subject to variability and lack of standardization inherent in subjective visual inspection. We describe a new approach that allows quantitation of lesion morphology. Fifty-nine patients with unstable angina and 17 patients with stable angina were compared. Five morphometric parameters were tested (peaks per centimeter, summed maximum error per centimeter, integrated error per centimeter, number of major features per centimeter, and scaled edge length ratio), four of which were significantly different between the two groups and indicated greater lesion complexity in unstable compared with stable angina patients. No correlation was found between the parameters tested and the degree of luminal narrowing, showing the method's independence from traditional assessments of lesion severity. Excellent intraobserver and interobserver reproducibility was found for all of the parameters. This technique provides a more rigorous approach for analysis of lesion morphology than has previously been available, may provide a method for premorbid detection of high-risk lesions amenable to interventional therapy, and is especially well suited to detect subtle changes in lesion morphology after therapeutic interventions because the parameters are derived on a continuous scale and are not categorical.
Noninvasive Magnetic Resonance Thermography of Recurrent Rectal Carcinoma in a 1.5 Tesla Hybrid System
Authors: Johanna Gellermann, Waldemar Wlodarczyk, Bert Hildebrandt, Hildegard Ganter, Anett Nicolau, Beate Rau, Wolfgang Tilly, Horst Fähling, Jacek Nadobny, Roland Felix, Peter Wust
Journal: Cancer Research (2005)

Abstract To implement noninvasive thermometry, we installed a hybrid system consisting of a radiofrequency multiantenna applicator (SIGMA-Eye) for deep hyperthermia (BSD-2000/3D) integrated into the gantry of a 1.5 Tesla magnetic resonance (MR) tomograph Symphony. This system can record MR data during radiofrequency heating and is suitable for application and evaluation of methods for MR thermography. In 15 patients with preirradiated pelvic rectal recurrences, we acquired phase data sets (25 slices) every 10 to 15 minutes over the treatment time (60-90 minutes) using gradient echo sequences (echo time = 20 ms), transformed the phase differences to MR temperatures, and fused the color-coded MR-temperature distributions with anatomic T1-weighted MR data sets. We could generate one complete series of MR data sets per patient with satisfactory quality for further analysis. In fat, muscle, water bolus, prostate, bladder, and tumor, we delineated regions of interest (ROI), used the fat ROI for drift correction by transforming these regions to a phase shift zero, and evaluated the MR-temperature frequency distributions. Mean MR temperatures (TMR), maximum TMR, full width half maximum (FWHM), and other descriptors of tumors and normal tissues were noninvasively derived and their dependencies outlined. In 8 of 15 patients, direct temperature measurements in reference points were available. We correlated the tumor MR temperatures with direct measurements, clinical response, and tumor features (volume and location), and found reasonable trends and correlations. Therefore, the mean TMR of the tumor might be useful as a variable to evaluate the quality and effectivity of heat treatments, and consequently as optimization variable. Feasibility of noninvasive MR thermography for regional hyperthermia has been shown and should be further investigated.