tbuckley/cabot-search huggingface dataset:
Influence of Quality of Relationship Between Patient With Melanoma and Partner on Partner-Assisted Skin Examination Education
Authors: Brittney A. Hultgren, Rob Turrisi, Kimberly A. Mallett, Sarah Ackerman, June K. Robinson
Journal: JAMA Dermatology (2015)

Melanoma has a high survival rate if it is detected early. Training patients with early-stage melanoma who are at risk of developing new melanomas to perform skin self-examination (SSE) may improve survival.To examine for whom the intervention works best in a sample composed of dyads of patients with melanoma and skin-check partners who received an SSE intervention vs customary care.For 494 patients with stage 0 to IIB melanoma (mean age, 55 years; 253 [51.2%] females) and their skin-check partners (mean age, 55 years; 280 [56.7%] females), a randomized clinical trial was conducted in ambulatory care dermatologic offices from June 6, 2011, to April 14, 2014. Follow-up assessments were performed at 12 months. Analysis was performed between March 23 and June 25, 2015.Dyads of 494 patients and their partners were randomly assigned to receive the intervention (395 patients) or customary care (control) (99 patients). The main outcome was patient SSE self-efficacy. Partner motivation to assist with SSE and relationship quality (eg, agreeability, activities with partner, and happiness) were assessed for moderation of the influence of the intervention's effect on SSE self-efficacy.Relationship quality, defined by activities with the partner (β = -0.892, SE = 0.432, t = -2.066; P = .001) and happiness (β = -4.586, SE = 2.044, t = -2.24; P = .001), significantly moderated the intervention effects on patients' SSE self-efficacy. In contrast, patient-partner agreeability (β = -0.262, SE = 0.148, t = -1.773; P = .09) and partner motivation (β = -0.328, SE = 1.024, t = -0.320; P = .10) did not significantly moderate the intervention effects on patients' SSE self-efficacy. Differences between the conditions were highest when activities performed with the partner were below average (mean difference, 6.652; P = .001) and when happiness was below average (mean difference, 7.000; P = .001). Although everyone receiving the intervention experienced some benefit, the findings indicate the greatest increases in self-efficacy were observed for those with below-average activities performed with the partner and happiness.The training of patients with melanoma and their partners in early-detection SSE benefited some more than others. Pairs who have low relationship quality, as determined by activities performed with the partner and happiness, may have received the greatest benefits from the training intervention because they were given an activity to perform together.clinicaltrials.gov Identifier: NCT01432860.
Disclosure of Candidate Genes in Acute Myeloid Leukemia With Complex Karyotypes Using Microarray-Based Molecular Characterization
Authors: Frank G. Rücker, Lars Bullinger, Carsten Schwaenen, Daniel B. Lipka, Swen Wessendorf, Stefan Fröhling, Martin Bentz, Simone Miller, Claudia Scholl, Richard F. Schlenk, Bernhard Radlwimmer, Hans A. Kestler, Jonathan R. Pollack, Peter Lichter, Konstanze Döhner, Hartmut Döhner
Journal: Journal of Clinical Oncology (2006)

To identify novel genomic regions of interest in acute myeloid leukemia (AML) with complex karyotypes, we applied comparative genomic hybridization to microarrays (array-CGH), allowing high-resolution genome-wide screening of genomic imbalances.Sixty AML cases with complex karyotypes were analyzed using array-CGH; parallel analysis of gene expression was performed in a subset of cases.Genomic losses were found more frequently than gains. The most frequent losses affected 5q (77%), 17p (55%), and 7q (45%), and the most frequent genomic gains 11q (40%) and 8q (38%). Critical segments could be delineated to genomic fragments of only 0.8 to a few megabase-pairs of DNA. In lost/gained regions, gene expression profiling detected a gene dosage effect with significant lower/higher average gene expression levels across the genes located in the respective regions. Furthermore, high-level DNA amplifications were identified in several regions: 11q23.3-q24.1 (n = 7), 21q22 (n = 6), 11q23.3 (n = 5), 13q12 (n = 3), 8q24 (n = 3), 9p24 (n = 2), 12p13 (n = 2), and 20q11 (n = 2). Parallel analysis of gene expression in critical amplicons displayed overexpressed candidate genes (eg, C8FW and MYC in 8q24).In conclusion, a large spectrum of genomic imbalances, including novel recurring changes in AML with complex karyotypes, was identified using array-CGH. In addition, the combined analysis of array-CGH data with gene expression profiles allowed the detection of candidate genes involved in the pathogenesis of AML.
Silent Victims Children Who Witness Violence
Authors: B M Groves, B Zuckerman, S Marans, D J Cohen
Journal: JAMA (1993)

THE CRISIS of violence in the United States has expanded to include more than the traditional emphasis on the victim and perpetrator. We would like to bring attention to a previously underrecognized group of victims in this public health epidemic: the children who witness the violence. These usually silent, indirect victims show no physical sign of harm and are commonly overlooked. In urban pediatric practices, clinicians increasingly are told that their young patients hear gunshots outside their homes, witness shootings on the playground, or have a family member (often an older sibling) involved with violence. Recent studies support this. One of every 10 children attending Boston (Mass) City Hospital pediatric primary care clinic witnessed a shooting or stabbing before the age of 6 years,<sup>1</sup>half in the home, half on the streets. The average age of the children in this study was 2.7 years. A survey of elementary-school-aged children
Reduced peripheral conversion of thyroxine to triiodothyronine in patients with hepatic cirrhosis.
Authors: S Nomura, C S Pittman, J B Chambers, M W Buck, T Shimizu
Journal: Journal of Clinical Investigation (1975)

The role of liver in the peripheral conversion of thyroxine (T4) to triiodothyronine (T3) was studied in normal subjects and patients with alcoholic liver disease by measurement of thyrotrophin (TSH) and total and free T4 and T3 in randomand serial serum samples. Also, T4 to T3 conversion rates and T3 disposal rates were compared by noncompartmental analysis. While the mean total serum T4 values were similar for the two groups, 8.6 and 8.1 mug/kl, the mean free T4 value was significantly higher in the cirrhotic patients (3.3 ng/dl) than in the normal subjects (2.1 ng/dl, P less than 0.001). The mean serum T3 value, 85 ng/dl, was significantly reduced in the hepatic patients as compared to a mean serum T3 value of 126 ng/dl in the normal subjects (P less than 0.001), while the free T3 value was 0.28 ng/dl in both groups. The reduction of the serum total and free T3 values were closely correlated with the degree of liver damage, as indicated by elevation of serum bilirubin (r equal -0.547) and reduction of serum albumin (r equal 0.471). The mean serum TSH level was 3.1 muU/ml in the normals and 7.1 muU/ml in the cirrhotic aptients ( less than 0.001). 15% of the hepatic patients had serum TSH values above 10 muU/ml, which, however, did not correlate with any of the four liver function tests studied. Serial blood sampling from two convalescing patients with alcoholic hepatitis showed a gradual normalization of serum TSH and T3 levels as the liver function improved. After oral T4 administration, 0.25 mg/day for 10 days, three of four cirrhotic patients studied failed to raise their serum T3 values. The mean T4 to T3 conversion rate of seven normal subjects was 35.7%. The mean T4 to T3 conversion rate of four cirrhotic patients studied was significantly reduced to 15.6% (P less than 0.001). The mean disposal rates of T4 and T3 of the normal subjects were 114 and 34 mug/day, respectively. The ratio of T4 disposal to T3 disposal was 3.5. In contrast, the mean T4 disposal rate, 82 mug/day, and the mean T3 disposal rate, 10 mug/day, were both reduced in the cirrhotic patients. Their ratio of T4 disposal to T3 disposal was 7.9. These findings suggest that impairment of T4 conversion in patients with advanced hepatic cirrhosis may lead to reduced T3 production and lowered serum T3 level. Therefore, the liver is one of the major sites of T4 conversion to T3.
Meta-Analysis: Obesity and the Risk for Gastroesophageal Reflux Disease and Its Complications
Authors: Howard Hampel, Neena S. Abraham, Hashem B. El-Serag
Journal: Annals of Internal Medicine (2005)

Background: The association of body mass index and gastroesophageal reflux disease (GERD), including its complications (esophagitis, Barrett esophagus, and esophageal adenocarcinoma), is unclear. Purpose: To conduct a systematic review and meta-analysis to estimate the magnitude and determinants of an association between obesity and GERD symptoms, erosive esophagitis, Barrett esophagus, and adenocarcinoma of the esophagus and of the gastric cardia. Data Sources: MEDLINE search between 1966 and October 2004 for published full studies. Study Selection: Studies that provided risk estimates and met criteria on defining exposure and reporting outcomes and sample size. Data Extraction: Two investigators independently performed standardized search and data abstraction. Unadjusted and adjusted odds ratios for individual outcomes were obtained or calculated for each study and were pooled by using a random-effects model. Data Synthesis: Nine studies examined the association of body mass index (BMI) with GERD symptoms. Six of these studies found statistically significant associations. Six of 7 studies found significant associations of BMI with erosive esophagitis, 6 of 7 found significant associations with esophageal adenocarcinoma, and 4 of 6 found significant associations with gastric cardia adenocarcinoma. In data from 8 studies, there was a trend toward a dose–response relationship with an increase in the pooled adjusted odds ratios for GERD symptoms of 1.43 (95% CI, 1.158 to 1.774) for BMI of 25 kg/m2 to 30 kg/m2 and 1.94 (CI, 1.468 to 2.566) for BMI greater than 30 kg/m2. Similarly, the pooled adjusted odds ratios for esophageal adenocarcinoma for BMI of 25 kg/m2 to 30 kg/m2 and BMI greater than 30 kg/m2 were 1.52 (CI, 1.147 to 2.009) and 2.78 (CI, 1.850 to 4.164), respectively. Limitations: Heterogeneity in the findings was present, although it was mostly in the magnitude of statistically significant positive associations. No studies in this review examined the association between Barrett esophagus and obesity. Conclusion: Obesity is associated with a statistically significant increase in the risk for GERD symptoms, erosive esophagitis, and esophageal adenocarcinoma. The risk for these disorders seems to progressively increase with increasing weight.
Tumor Cell–Derived and Macrophage-Derived Cathepsin B Promotes Progression and Lung Metastasis of Mammary Cancer
Authors: Olga Vasiljeva, Anna Papazoglou, Achim Krüger, Harald Brodoefel, Matvey Korovin, Jan Deussing, Nicole Augustin, Boye S. Nielsen, Kasper Almholt, Matthew Bogyo, Christoph Peters, Thomas Reinheckel
Journal: Cancer Research (2006)

Abstract Proteolysis in close vicinity of tumor cells is a hallmark of cancer invasion and metastasis. We show here that mouse mammary tumor virus–polyoma middle T antigen (PyMT) transgenic mice deficient for the cysteine protease cathepsin B (CTSB) exhibited a significantly delayed onset and reduced growth rate of mammary cancers compared with wild-type PyMT mice. Lung metastasis volumes were significantly reduced in PyMT;ctsb+/−, an effect that was not further enhanced in PyMT;ctsb−/− mice. Furthermore, lung colonization studies of PyMT cells with different CTSB genotypes injected into congenic wild-type mice and in vitro Matrigel invasion assays confirmed a specific role for tumor-derived CTSB in invasion and metastasis. Interestingly, cell surface labeling of cysteine cathepsins by the active site probe DCG-04 detected up-regulation of cathepsin X on PyMT;ctsb−/− cells. Treatment of cells with a neutralizing anti-cathepsin X antibody significantly reduced Matrigel invasion of PyMT;ctsb−/− cells but did not affect invasion of PyMT;ctsb+/+ or PyMT;ctsb+/− cells, indicating a compensatory function of cathepsin X in CTSB-deficient tumor cells. Finally, an adoptive transfer model, in which ctsb+/+, ctsb+/−, and ctsb−/− recipient mice were challenged with PyMT;ctsb+/+ cells, was used to address the role of stroma-derived CTSB in lung metastasis formation. Notably, ctsb−/− mice showed reduced number and volume of lung colonies, and infiltrating macrophages showed a strongly up-regulated expression of CTSB within metastatic cell populations. These results indicate that both cancer cell–derived and stroma cell–derived (i.e., macrophages) CTSB plays an important role in tumor progression and metastasis. (Cancer Res 2006; 66(10): 5242-50)
Defective epithelial barrier function in asthma
Authors: Chang Xiao, Sarah M. Puddicombe, Sarah Field, Joel Haywood, Victoria Broughton-Head, Ilaria Puxeddu, Hans Michael Haitchi, Elizabeth Vernon-Wilson, David Sammut, Nicole Bedke, Catherine Cremin, Jody Sones, Ratko Djukanović, Peter H. Howarth, Jane E. Collins, Stephen T. Holgate, Phillip Monk, Donna E. Davies
Journal: Journal of Allergy and Clinical Immunology (2011)
Identification of GP2, the major zymogen granule membrane glycoprotein, as the autoantigen of pancreatic antibodies in Crohn's disease
Authors: D. Roggenbuck, G. Hausdorf, L. Martinez-Gamboa, D. Reinhold, T. Buttner, P. R. Jungblut, T. Porstmann, M. W. Laass, J. Henker, C. Buning, E. Feist, K. Conrad
Journal: Gut (2009)

<h3>Backround and aims:</h3> The aetiopathogenesis of Crohn’s disease, an inflammatory bowel disease (IBD), is not yet fully understood. Autoimmune mechanisms are thought to play a role in the development of Crohn’s disease, but the target antigens and the underlying pathways have not been sufficiently identified. <h3>Methods:</h3> Based on data from immunoblotting and matrix-assisted laser desorption ionisation time-of-flight (MALDI-TOF) mass spectrometry, the major antigenic target of pancreatic autoantibodies (PABs), which are specific for Crohn’s disease, was identified. Specificity of autoantibody reactivity was confirmed by enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence (IIF) using purified rat and human recombinant GP2 synthesised in transiently transfected mammalian HEK 293 cells. Real-time polymerase chain reaction (rt-PCR) and IIF were used to detect mRNA and antigen localisation in human colon biopsies. <h3>Results:</h3> The major zymogen granule membrane glycoprotein 2 (GP2) was identified as the autoantigen of PABs in Crohn’s disease. PAB-positive sera from patients with Crohn’s disease (n = 42) displayed significantly higher IgG reactivity to rat GP2 in ELISA than either PAB-negative sera (n = 31), or sera from patients with ulcerative colitis (n = 49), or sera from blood donors (n = 69) (p&lt;0.0001, respectively). Twenty-eight (66%) and 18 (43%) of 42 PAB-positive sera demonstrated IgG and IgA reactivity to human recombinant GP2 in IIF, respectively. Patients with PAB-negative Crohn’s disease (n = 31) were not reactive. GP2 mRNA transcription was significantly higher in colon biopsies from patients with Crohn’s disease (n = 4) compared to patients with ulcerative colitis (n = 4) (p = 0.0286). Immunochemical staining confirmed GP2 expression in human colon biopsies from patients with Crohn’s disease. <h3>Conclusion:</h3> Anti-GP2 autoantibodies constitute novel Crohn’s disease-specific markers, the quantification of which could significantly improve the serological diagnosis of IBD. The expression of GP2 in human enterocytes suggests an important role for anti-GP2 response in the pathogenesis of Crohn’s disease.
Sodium excretion in advanced cirrhosis: Effect of expansion of central blood volume and suppression of plasma aldosterone
Authors: Kathleen M. Nicholls, Michael D. Shapiro, Rudiger Kluge, Hsaio-Min Chung, Daniel G. Bichet, Robert W. Schrier
Journal: Hepatology (1986)

Sodium excretion in 13 patients with decompensated cirrhosis was measured under baseline conditions of water loading (n = 13) and during conditions designed to improve effective blood volume including: head–out water immersion alone (n = 13); norepinephrine infusion alone (n = 6), and combined norepinephrine and head–out water immersion (n = 6). All 13 patients were in positive sodium balance under baseline conditions, with a mean plasma aldosterone concentration of 78.7 ± 15.6 ng per dl. In only four patients was plasma aldosterone less than 50 ng per dl. During head–out water immersion alone, 5 patients achieved negative sodium balance and, in all 5, plasma aldosterone was less than 50 ng per dl (mean = 23.0 ± 5.3 ng per dl). However, the mean plasma aldosterone during head–out water immersion in the eight patients who remained in positive sodium balance during this maneuver was 64.0 ± 11.9 ng per dl (p &lt; 0.01). During norepinephrine alone, positive sodium balance was maintained in all patients, and plasma aldosterone was not significantly different from baseline. Combining norepinephrine and head–outwater immersion resulted in the largest and most consistent negative sodium balance. The mean plasma aldosterone concentration was decreased significantly (78.7 ± 15.6 to 32.6 ± 9.9) ng per dl (p &lt; 0.05). Regardless of the maneuver performed, nopatient in whom aldosterone exceeded 50 ng per dl achieved negative sodium balance. Furthermore, only in those studies utilizing head–out water immersion, with or without norepinephrine, was negative sodium balance seen. The results, therefore, suggest that expansion of central blood volume with suppression of plasma aldosterone overcomes sodium avidity in decompensated cirrhosis.
Natural History of Male Psychological Health, XIV: Relationship of Mood Disorder Vulnerability to Physical Health
Authors: G E Vaillant
Journal: American Journal of Psychiatry (1998)

OBJECTIVE: A 55-year prospective study attempted to determine the antecedents and consequences of positive mental and physical health in adult men. A substudy was conducted to look at the late-life physical health of men selected to be as unlike men with major depressive disorder as possible. METHOD: Of 237 men selected for health and followed since college, 64 undistressed men had never used mood-altering drugs or consulted a psychiatrist before the age of 50. The health at age 70 of these 64 men was compared with that of 20 men classified as depressed at age 70, 109 men classified as neither healthy nor depressed at age 70, and 44 men classified as having alcohol dependence or abuse at age 70. RESULTS: At age 70, the 64 undistressed men enjoyed significantly better health than the 109 men in the intermediate group. Only three (5%) of the 64 undistressed men were dead or disabled by age 70, compared with 30 (28%) of the 109 men in the intermediate group and nine (45%) of the 20 depressed men. The mean age of the subjects' maternal grandfathers at death also significantly differentiated the three groups. The differences in longevity among the three groups could not be explained by personality disorder, by cigarette, dietary, or alcohol abuse, or by longevity of the subjects' other first-degree ancestors. CONCLUSIONS: These findings lend support to the hypothesis that risk of affective disorder may lie along a continuum. At one extreme may be men with stable lifestyles, a lifelong resistance to mood disorder, and unusually good physical health in late life. At the other extreme of the continuum may be men with vulnerability to mood disorder and accelerated physical aging. (Am J Psychiatry 1998; 155:184–191)
My most informative mistake
Authors: Lampis C Stavrinou
Journal: BMJ (2008)

Medicine will always come down to one thing: a doctor or two puzzling out what might be wrong with a patient. Experience, common assumptions, and human nature can guide them but can just as easily lead them astray.

One of the errors that greatly influenced my clinical practice concerned a middle aged man admitted with acute paraplegia. His symptoms had started only 12 hours before admission and included lower back pain, paralysis, and urinary retention. Clinical examination revealed leg weakness, diminished sensation below the T8 …
Combined Treatment With Exercise Training and Acarbose Improves Metabolic Control and Cardiovascular Risk Factor Profile in Subjects With Mild Type 2 Diabetes
Authors: Henrik Wagner, Marie Degerblad, Anders Thorell, Jonas Nygren, Agneta Ståhle, Jeanette Kuhl, Torkel B. Brismar, John Öhrvik, Suad Efendic, Peter N. Båvenholm
Journal: Diabetes Care (2006)

The effect of exercise training and acarbose on glycemic control, insulin sensitivity, and phenotype was investigated in mild type 2 diabetes.Sixty-two men and women with type 2 diabetes were randomized to 12 weeks of structured exercise training with or without acarbose treatment or to acarbose alone. Glycemic control was determined by HbA(1c) (A1C), insulin sensitivity (M value) by euglycemic-hyperinsulinemic clamp, and regional fat distribution by computerized tomography and dual X-ray absorptiometry. Physical fitness was determined as maximal oxygen uptake (Vo(2max)). All investigations were performed before and after the intervention.Forty-eight subjects completed the study. Exercise improved M value by 92% (P = 0.017) and decreased total and truncal fat (P = 0.002, 0.001) and systolic blood pressure (P = 0.01) but had no significant effect on Vo(2max) or A1C level. The combination of exercise and acarbose significantly decreased fasting plasma glucose, A1C, lipids, and diastolic blood pressure and increased Vo(2max), whereas effects on M value and body composition were comparable with that of exercise alone. Acarbose alone had no significant effect on either M value or A1C but decreased systolic (P = 0.001) and diastolic blood pressure (P = 0.001) and fasting proinsulin level (P = 0.009). Multiple regression analysis showed that addition of acarbose to exercise improved glycemic control.In subjects with mild type 2 diabetes, exercise training improved insulin sensitivity but had no effect on glycemic control. The addition of acarbose to exercise, however, was associated with significant improvement of glycemic control and possibly cardiovascular risk factors.