tbuckley/cabot-search huggingface dataset:
Genotype-Specific Onset of Arrhythmias in Congenital Long-QT Syndrome
Authors: Hanno L. Tan, Abdennasser Bardai, Wataru Shimizu, Arthur J. Moss, Eric Schulze-Bahr, Takashi Noda, Arthur A. M. Wilde
Journal: Circulation (2006)

The identification of the molecular-genetic substrate underlying the various forms of the congenital long-QT syndrome (LQTS) has sparked studies into possible genotype-phenotype correlations with the aim of developing genotype-tailored therapy. The onset of torsade de pointes (TdP) may differ among LQTS patients, being pause dependent in some but not all. This disparity may point to different arrhythmia mechanisms and may affect therapy strategies. We studied whether the proportion of pause-dependent TdP onset varies among LQTS genotypes.We studied all LQT1 (n=10), LQT2 (n=34), and LQT3 (n=6) patients from 4 centers for whom ECGs of TdP onset were available and analyzed whether pauses preceded TdP onset (first available ECG per patient). Pauses preceded TdP significantly more often in LQT2 (68%) than in LQT1 (0%), and the interval immediately before TdP (pause interval) was significantly longer in LQT2 than in LQT1. The proportion of pause dependence in LQT3 (33%) appeared intermediate, but this group was too small for statistical analysis.Pause dependence of TdP onset is predominant in LQT2 but absent or rare in LQT1. It is suggested that disparities in pause dependence of TdP onset may reflect different arrhythmia mechanisms.
Hereditary colorectal cancer in the general population: from cancer registration to molecular diagnosis
Authors: M P. de Leon, M Pedroni, P Benatti, A Percesepe, C Di Gregorio, M Foroni, G Rossi, M Genuardi, G Neri, F Leonardi, A Viel, E Capozzi, M Boiocchi, L Roncucci
Journal: Gut (1999)

<h3>BACKGROUND</h3> Hereditary non-polyposis colorectal cancer (HNPCC) is one of the most common inherited disorders predisposing to cancer. The genes responsible for the disease have recently been cloned and characterised; their mutations induce a generalised genomic instability which is particularly evident at microsatellite loci (replication error (RER)+ phenotype). <h3>AIMS</h3> To investigate how to select individuals and families in the general population who should be screened for constitutional mutations predisposing to colorectal cancer. <h3>PATIENTS/METHODS</h3> Between 1984 and 1995, 1899 colorectal malignancies in 1831 patients were registered, and in 1721 of these (94%), family trees could be obtained. Patients and families were classified into five categories according to a more or less likely genetic basis: HNPCC; "suspected" HNPCC; juvenile cases; aspecific cancer aggregation; sporadic cases. In 18 families with HNPCC as well as in 18 with suspected HNPCC, microsatellite instability in tumour tissues and constitutional mutations of two DNA mismatch repair genes (<i>MSH2</i> and <i>MLH1</i>) could be evaluated. RER status was studied with five markers (<i>BAT40</i>, <i>D2S123</i>,<i>D18S57</i>, <i>D17S787</i>, and <i>BAT26</i>) in paraffin embedded tissues. Germline mutations of <i>MSH2</i> or<i>MLH1</i> genes were assessed on DNA and RNA extracted from lymphomonocytic cells, using reverse transcription polymerase chain reaction, single strand conformation polymorphism analysis, and direct DNA sequencing. <h3>RESULTS</h3> HNPCC represented 2.6% and suspected HNPCC 4.6% of all registered colorectal neoplasms. Eleven out of 18 HNPCC families (61%) showed microsatellite instability as opposed to four (of 18) suspected HNPCC (22%; p&lt;0.02). Three germline mutations (two in<i>MSH2</i> and one in<i>MLH1</i> gene) were found in three different large HNPCC families, whereas no mutations were detected in suspected HNPCC. <h3>CONCLUSIONS</h3> In this study of cancer genetic epidemiology, data from a tumour registry were analysed and this ultimately led to the identification and selection of families that should be tested for mutator gene mutations. With the use of a population based approach, the incidence of mutations was appreciably lower than previously reported and limited to families with full blown HNPCC. It is possible that in most families with a clinical spectrum of HNPCC (or suspected HNPCC) other DNA mismatch repair genes are involved in the pathogenesis of the disease.
Familial pulmonary alveolar proteinosis caused by mutations in <i>CSF2RA </i>
Authors: Takuji Suzuki, Takuro Sakagami, Bruce K. Rubin, Lawrence M. Nogee, Robert E. Wood, Sarah L. Zimmerman, Teresa Smolarek, Megan K. Dishop, Susan E. Wert, Jeffrey A. Whitsett, Gregory Grabowski, Brenna C. Carey, Carrie Stevens, Johannes C.M. van der Loo, Bruce C. Trapnell
Journal: The Journal of Experimental Medicine (2008)

Primary pulmonary alveolar proteinosis (PAP) is a rare syndrome characterized by accumulation of surfactant in the lungs that is presumed to be mediated by disruption of granulocyte/macrophage colony-stimulating factor (GM-CSF) signaling based on studies in genetically modified mice. The effects of GM-CSF are mediated by heterologous receptors composed of GM-CSF binding (GM-CSF-Rα) and nonbinding affinity-enhancing (GM-CSF-Rβ) subunits. We describe PAP, failure to thrive, and increased GM-CSF levels in two sisters aged 6 and 8 yr with abnormalities of both GM-CSF-Rα–encoding alleles (CSF2RA). One was a 1.6-Mb deletion in the pseudoautosomal region of one maternal X chromosome encompassing CSF2RA. The other, a point mutation in the paternal X chromosome allele encoding a G174R substitution, altered an N-linked glycosylation site within the cytokine binding domain and glycosylation of GM-CSF-Rα, severely reducing GM-CSF binding, receptor signaling, and GM-CSF–dependent functions in primary myeloid cells. Transfection of cloned cDNAs faithfully reproduced the signaling defect at physiological GM-CSF concentrations. Interestingly, at high GM-CSF concentrations similar to those observed in the index patient, signaling was partially rescued, thereby providing a molecular explanation for the slow progression of disease in these children. These results establish that GM-CSF signaling is critical for surfactant homeostasis in humans and demonstrate that mutations in CSF2RA cause familial PAP.
Preoperative Evaluation of the Patient With Hypertension
Authors: Lee A. Fleisher
Journal: JAMA (2002)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Relationship Between the Size and Margin Status of Ductal Carcinoma In Situ of the Breast and Residual Disease
Authors: L. Cheng, N. K. Al-Kaisi, F. Gebrail, R. R. Shenk, N. H. Gordon, A. Y. Liu
Journal: JNCI Journal of the National Cancer Institute (1997)

Background: For women with ductal carcinoma in situ (DCIS) of the breast who have been treated with breast-conserving surgery, the usefulness of size and surgical margin status (i.e., presence or absence of disease at the point of excision) as prognostic factors for predicting residual disease has not been well established. This study was conducted to determine more clearly the relationship between size and margin status of mammary DCIS to residual disease. Methods: The pathology records of 232 consecutive patients with mammary DCIS who had been initially treated with lumpectomy at the University Hospitals of Cleveland were retrospectively reviewed. The size of the DCIS and the surgical margins of lumpectomy were analyzed. Residual disease was defined as the persistence of DCIS in the re-excision and/or mastectomy specimens. Results: Residual disease was found in 15 of 101 patients with DCIS of less than 1.0 cm in longest dimension, in 27 of 96 patients with DCIS of 1.0–2.4 cm in size, and in 24 of 35 patients with DCIS of greater than or equal to 2.5 cm in size ( P <.001). Residual disease was found in 30 of 77 patients with DCIS and positive margins, in 11 of 59 patients with DCIS and close margins (⩽1 mm), and in 10 of 73 patients with DCIS and negative margins (>1 mm) ( P = .001). In multivariate analysis, the occurrence of residual disease was associated with large tumor size (i.e., ⩾2.5 cm) (odds ratio [OR] = 7.7; 95% confidence interval [CI] = 3.13–20.00; two-sided P = .0001) and with positive margin status (OR = 2.2; 95% CI = 1.02–4.55; two-sided P = .04). Conclusions: The size and margin status of DCIS each were found to be independent predictors of residual disease.
Finding the missing millions with COPD - Does it work?
Authors: Rehan Mustafa, Fiona Bates, Angela Charlesworth, Tina Stallard, Rosie Watts, Joan Summersgill, Cindy Lightowler
Journal: European Respiratory Journal (2012)

Introduction 

Many COPD patients do not receive a diagnosis until it is relatively advanced. It is estimated that for every one patient that has been diagnosed there are four that are not known to the health service. In conjunction with World COPD Day in 2011, our COPD Outreach team promoted this event by performing spirometry on patients, staff and visitors at the main hospital entrance, to raise public awareness and to find the 'missing millions'.

Aims and Objectives 

To raise public awareness of COPD and to detect people with undiagnosed COPD.

Method 

The day was advertised in the Trust Talking Point and the Trust Press release. Flyers were posted around the hospital. 4 stands were set up in the main atrium of the JCUH, with spirometers and COPD nurse specialists to perform spirometry. Volunteers completed a questionnaire focussing on their smoking history, symptoms of COPD, history of comorbidities and contraindications to performing spirometry. Individuals with abnormal spirometry were provided a letter for their primary care physicians, to undergo repeat testing or further investigations if appropriate.

Results 

Out of the 75 volunteers tested, only 9% (n=7) were noted to have abnormal spirometry results. 5% (n=4) of the volunteers had a prior history of air flow obstruction. Therefore only 4% (n=3) of the volunteers screened were found to have abnormal recordings.

Conclusion 

Random screening doesn't capture a large population of people with abnormal spirometry. Screening needs to be more selective e.g.individuals over the age of 35 with a smoking history or symptoms suggestive of COPD. Where our screening did raise awareness of COPD within the general public, it didn't diagnose a large number of people with COPD.
Disparities in Stage at Diagnosis, Treatment, and Survival in Nonelderly Adult Patients With Cancer According to Insurance Status
Authors: Gary V. Walker, Stephen R. Grant, B. Ashleigh Guadagnolo, Karen E. Hoffman, Benjamin D. Smith, Matthew Koshy, Pamela K. Allen, Usama Mahmood
Journal: Journal of Clinical Oncology (2014)

The purpose of this study was to determine the association of insurance status with disease stage at presentation, treatment, and survival among the top 10 most deadly cancers using the SEER database.A total of 473,722 patients age 18 to 64 years who were diagnosed with one of the 10 most deadly cancers in the SEER database from 2007 to 2010 were analyzed. A Cox proportional hazards model was used for multivariable analyses to assess the effect of patient and tumor characteristics on cause-specific death.Overall, patients with non-Medicaid insurance were less likely to present with distant disease (16.9%) than those with Medicaid coverage (29.1%) or without insurance coverage (34.7%; P < .001). Patients with non-Medicaid insurance were more likely to receive cancer-directed surgery and/or radiation therapy (79.6%) compared with those with Medicaid coverage (67.9%) or without insurance coverage (62.1%; P < .001). In a Cox regression that adjusted for age, race, sex, marital status, residence, percent of county below federal poverty level, site, stage, and receipt of cancer-directed surgery and/or radiation therapy, patients were more likely to die as a result of their disease if they had Medicaid coverage (hazard ratio [HR], 1.44; 95% CI, 1.41 to 1.47; P < .001) or no insurance (HR, 1.47; 95% CI, 1.42 to 1.51; P < .001) compared with non-Medicaid insurance.Among patients with the 10 most deadly cancers, those with Medicaid coverage or without insurance were more likely to present with advanced disease, were less likely to receive cancer-directed surgery and/or radiation therapy, and experienced worse survival.
No increase in the prevalence of asthma, allergies, and atopic sensitisation among children in Germany: 1992-2001
Authors: I K Zollner
Journal: Thorax (2005)

<b>Background:</b> From 1970 to 1990 increasing rates of asthma and allergic sensitisation were observed in several countries. The aim of this study was to investigate time trends in the prevalence of asthma and allergic sensitisation among school children in Germany between 1992 and 2001. <b>Methods:</b> Parental reports of asthma, hay fever, and wheezing and measurements of specific serum IgE antibodies were investigated in six serial cross sectional surveys of 9–11 year old school children in three study areas in south west Germany. <b>Results:</b> A total of 6762 school children of mean age 10 years (mean participation rate 77.9%) took part in the investigation in the three study areas. Over the 9 year study period no increase in the prevalence of current wheezing and asthma was observed. In addition, the prevalence of atopic sensitisation remained unchanged during the observation period. <b>Conclusions:</b> These data, using parental reports and objective measures of allergy, suggest that there has been no further increase in the prevalence of asthma and atopy since 1992. The epidemic may thus have reached a plateau.
Blastomycosis in Patients with the Acquired Immunodeficiency Syndrome
Authors: Peter G. Pappas, John C. Pottage, William G. Powderly, Victoria J. Fraser, Charles W. Stratton, Stacey McKenzie, Tapper Michael L., Herman Chmel, Frank C. Bonebrake, Raymond Blum, Robert W. Shafer, Coleman King, William E. Dismukes
Journal: Annals of Internal Medicine (1992)

To describe the clinical, demographic, radiographic, diagnostic, and therapeutic aspects of blastomycosis in patients with the acquired immunodeficiency syndrome (AIDS).A retrospective survey.Ten university medical centers and community hospitals, six in geographic areas endemic for Blastomyces dermatitidis, and four outside the endemic area.We identified 15 patients with blastomycosis and positive serologic test results for human immunodeficiency virus (HIV).A diagnosis of blastomycosis was based on a positive culture (14 patients) or typical histopathologic features (one patient) for B. dermatitidis in clinical specimens.Twelve of 15 patients had a previous or concomitant AIDS-defining illness at the time of diagnosis of blastomycosis, and only one patient had a CD4 lymphocyte count of greater than 200 cells/mm3. Two patterns of disease emerged: localized pulmonary involvement (seven patients), and disseminated or extrapulmonary blastomycosis (eight patients). Central nervous system involvement was common (40%). Six patients died within 21 days of presentation with blastomycosis, including four patients with disseminated and two with fulminant pulmonary disease. Among the nine patients who survived longer than 1 month, all received amphotericin B as initial antifungal therapy, and most received subsequent therapy with ketoconazole. Only two of these nine patients died with evidence of progressive blastomycosis.Blastomycosis is a late and frequently fatal infectious complication in a few patients with AIDS. In these patients, overwhelming disseminated disease including involvement of the central nervous system is common, and it is associated with a high early mortality. Initial therapy with amphotericin B is appropriate in patients with AIDS and presumptive blastomycosis.
Effect of Elemental Diet on Mucosal Immunopathology and Clinical Symptoms in Type 1 Refractory Celiac Disease
Authors: R OLAUSSEN, A LOVIK, S TOLLEFSEN, P ANDRESEN, M VATN, T DELANGE, J BRATLIE, P BRANDTZAEG, I FARSTAD, K LUNDIN
Journal: Clinical Gastroenterology and Hepatology (2005)
Neuropsychologic Impact of Standard-Dose Systemic Chemotherapy in Long-Term Survivors of Breast Cancer and Lymphoma
Authors: T. A. Ahles
Journal: Journal of Clinical Oncology (2002)

PURPOSE: The primary purpose of this study was to compare the neuropsychologic functioning of long-term survivors of breast cancer and lymphoma who had been treated with standard-dose systemic chemotherapy or local therapy only. PATIENTS AND METHODS: Long-term survivors (5 years postdiagnosis, not presently receiving cancer treatment, and disease-free) of breast cancer or lymphoma who had been treated with systemic chemotherapy (breast cancer: n = 35, age, 59.1 ± 10.7 years; lymphoma: n = 36, age, 55.9 ± 12.1 years) or local therapy only (breast cancer: n = 35, age, 60.6 ± 10.5 years; lymphoma: n = 22, age, 48.7 ± 11.7 years) completed a battery of neuropsychologic and psychologic tests (Center for Epidemiological Study–Depression, Spielberger State-Trait Anxiety Inventory, and Fatigue Symptom Inventory). RESULTS: Multivariate analysis of variance, controlling for age and education, revealed that survivors who had been treated with systemic chemotherapy scored significantly lower on the battery of neuropsychologic tests compared with those treated with local therapy only (P < .04), particularly in the domains of verbal memory (P < .01) and psychomotor functioning (P < .03). Survivors treated with systemic chemotherapy were also more likely to score in the lower quartile on the Neuropsychological Performance Index (39% v 14%, P < .01) and to self-report greater problems with working memory on the Squire Memory Self-Rating Questionnaire (P < .02). CONCLUSION: Data from this study support the hypothesis that systemic chemotherapy can have a negative impact on cognitive functioning as measured by standardized neuropsychologic tests and self-report of memory changes. However, analysis of the Neuropsychological Performance Index suggests that only a subgroup of survivors may experience long-term cognitive deficits associated with systemic chemotherapy.
Cells and Molecules that Regulate B Lymphopoiesis in Bone Marrow
Authors: P W Kincade, G Lee, C E Pietrangeli, S I Hayashi, J M Gimble
Journal: Annual Review of Immunology (1989)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
Critical Points When Using Vectors
Authors: Frank C. Detterbeck
Journal: Journal of Clinical Oncology (2009)

I read with interest the article by Zhu et al 1 of using support vector machines to identify prognostic classifiers for stage IB non-small-cell lung cancer (NSCLC).This is an interesting technique, and the authors have done a lot of work.However, I am worried that the study design has two significant flaws.3][4][5][6][7][8] The other 40% to 45% of deaths are due to such things as cardiovascular diseases and new primary cancers.This means that factors predictive of death for any reason cannot be interpreted as an indication to give adjuvant chemotherapy.The poor prognostic classifiers may be indicating that the patients should have their cholesterol lowered, or have a colonoscopy, and so on.It would be much better to do an analysis looking for markers of a poor risk of lung cancer recurrence.Many, if not most, articles discussing the prognosis of stage I NSCLC make the mistake of equating the lack of survival with lung cancer death.For most of these articles, however, it is merely an erroneous or deliberately misleading statement, perhaps in order to play on the fear of recurrence.In Zhu et al, 1 however, it seems to me this mistake results in a fundamental flaw of the study, not just a misleading statement.Second, the training and validation sets of patients are from two different time periods.Ideally, the training set should be picked randomly from the total sample, and the validation done in the remaining patients.Why was the study not done this way?Having said this, it is likely that the use of different cohorts of patients (from different time periods) would make the correlation between the training and validation cohort worse; the fact that it was good suggests that the effect of the different time periods was not so great.Along these lines, I am confused by the contradiction between the statement that the study involved a total of 148 consecutive patients, and the later statement that it involved 73 randomly selected patients between 1990 and 1998 and 75 randomly selected patients between 1998 and 2005. 1 It doesn't make sense to randomly select all of the patients.It seems to me they were selected by time period, and not randomly.Can this be clarified?
Neutrophil elastase associated with alveolar macrophages from older volunteers.
Authors: T Betsuyaku, A Yoshioka, M Nishimura, K Miyamoto, T Kondo, Y Kawakami
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

We focused on the role of neutrophil elastase (NE) in alveolar macrophages (AMs), and evaluated the esterolytic activity using an NE-sensitive substrate, methoxysuccinyl-alanyl-alanyl-prolyl-valyl paranitroanilide (MEOSAAPVNA) in AMs from 36 older healthy volunteers (61 +/- 2 yr mean age +/- standard error) and examined the relationship to chronic effects of cigarette smoking and also to the presence of low attenuation areas (LAAs) on the computed tomographic (CT) scans. The AMs from the subjects with LAAs showed significantly higher activity than those from the current smokers without LAA (1.16 +/- 0.40 versus 0.34 +/- 0.07 nM, respectively, p < 0.05). Although the study of inhibitory profile revealed that the esterolytic activity could not be attributed to NE alone, the NE activity seemed to dominate in AMs at least from some who had higher esterolytic activity. We then examined the releasability of NE from cultured AMs in 10 subjects. The immunologic NE complex with alpha 1-protease inhibitor (alpha 1-PI) was released significantly higher in the LAA(+) group than in the LAA(-) group (17.4 +/- 6.5 versus 1.8 +/- 0.6 micrograms/L, respectively, p < 0.05). These data suggest that NE in AMs may play a role in the development of emphysematous changes in susceptible smokers.