tbuckley/cabot-search huggingface dataset:
People receiving unnecessary treatments: accurate diagnosis is key
Authors: T. Germon, J. Hobart
Journal: BMJ (2015)

We agree that diagnosis drives treatment.1 Clinicians are required to make diagnoses that underpin meaningful discussions about management options, their mechanisms of action, and their potential risks and benefits. However, emphasis needs to be placed on achieving accurate diagnosis rather than identifying “overdiagnosis.”

In our experience lumbar nerve root compression (LNRC) is underdiagnosed, and people with this condition …
Management of video capsule bronchial aspiration
Authors: Matthieu Buscot, Stéphanie Martinez, Jérôme Filippi, Céline Sanfiorenzo, Xavier Hebuterne, Charles-Hugo Marquette
Journal: European Respiratory Journal (2012)

A 74-year old patient with of occult gastrointestinal bleeding was referred for a small bowel exploration using video capsule endoscopy. Medical history revealed left hemiparesis and swallowing disorders as sequels of stroke. A video capsule endoscopy was scheduled after the advice of the ENT specialist.

Within minutes after the capsule ingestion, the patient developed a typical chocking episode. Real-time visualization of the video-endoscopic “bronchial tree” images by the gastroenterologist quickly assisted by the pulmonologist enabled locating the capsule at the level of the main carina / left main bronchus.

Immediate bronchoscopy under general anesthesia allowed the pulmonologist to gently catch the video capsule and to readily place it within the gastro-intestinal tract (stomach). Small bowel exploration could then be perfomed “as scheduled” and revealed duodenal and jejunal angiomas as the source of the bleeding.

Pictures as well as short video sequences of the chocking episode and of the gastro-intestinal placement of the capsule with the bronchoscope are presented.

Based on this experience and on the litterature (about 9 reported cases of tracheo-bronchial video capsule aspiration) two recommendation can be made

§ caution should be taken in patients with swallowing disorders

§ immediate tracking by of the capsule initial path is recommended

The present case also shows that a combined approach (gastroenterologist + pulmonologist) permits to replace the video capsule in the right way during the same procedure.
Mountaineer’s heel
Authors: R M Strauss
Journal: British Journal of Sports Medicine (2004)

Mountaineers are at risk of skin lesions caused by constant boot friction. This is the case of a 35 year old mountaineer who presented with large and deeply ulcerated lesions over the medial aspects of both heels after a two and a half day climb using crampons. A number of factors such as the length of the climb in cold and thin air and the impossibility of removal of the footwear to allow rapid rewarming may have contributed to a more acute presentation of these lesions.
Randomized Phase III Study of Temozolomide Versus Dacarbazine in the Treatment of Patients With Advanced Metastatic Malignant Melanoma
Authors: M.R. Middleton, J.J. Grob, N. Aaronson, G. Fierlbeck, W. Tilgen, S. Seiter, M. Gore, S. Aamdal, J. Cebon, A. Coates, B. Dreno, M. Henz, D. Schadendorf, A. Kapp, J. Weiss, U. Fraass, P. Statkevich, M. Muller, N. Thatcher
Journal: Journal of Clinical Oncology (2000)

PURPOSE: : To compare, in 305 patients with advanced metastatic melanoma, temozolomide and dacarbazine (DTIC) in terms of overall survival, progression-free survival (PFS), objective response, and safety, and to assess health-related quality of life (QOL) and pharmacokinetics of both drugs and their metabolite, 5-(3-methyltriazen-1-yl)imidazole-4-carboximide (MTIC). PATIENTS AND METHODS: Patients were randomized to receive either oral temozolomide at a starting dosage of 200 mg/m 2 /d for 5 days every 28 days or intravenous (IV) DTIC at a starting dosage of 250 mg/m 2 /d for 5 days every 21 days. RESULTS: In the intent-to-treat population, median survival time was 7.7 months for patients treated with temozolomide and 6.4 months for those treated with DTIC (hazards ratio, 1.18; 95% confidence interval [CI], 0.92 to 1.52). Median PFS time was significantly longer in the temozolomide-treated group (1.9 months) than in the DTIC-treated group (1.5 months) (P = .012; hazards ratio, 1.37; 95% CI, 1.07 to 1.75). No major difference in drug safety was observed. Temozolomide was well tolerated and produced a noncumulative, transient myelosuppression late in the 28-day cycle. The most common nonhematologic toxicities were mild to moderate nausea and vomiting, which were easily managed. Temozolomide therapy improved health-related QOL; more patients showed improvement or maintenance of physical functioning at week 12. Systemic exposure (area under the curve) to the parent drug and the active metabolite, MTIC, was higher after treatment with oral temozolomide than after IV administration of DTIC. CONCLUSION: Temozolomide demonstrates efficacy equal to that of DTIC and is an oral alternative for patients with advanced metastatic melanoma.
Monocarboxylate Transporter 4, Associated With the Acidification of Synovial Fluid, Is a Novel Therapeutic Target for Inflammatory Arthritis
Authors: Wataru Fujii, Yutaka Kawahito, Hidetake Nagahara, Yuji Kukida, Takahiro Seno, Aihiro Yamamoto, Masataka Kohno, Ryo Oda, Daigo Taniguchi, Hiroyoshi Fujiwara, Akika Ejima, Tsunao Kishida, Osam Mazda, Eishi Ashihara
Journal: Arthritis & Rheumatology (2015)

Objective Synovial fluid pH is decreased in patients with rheumatoid arthritis (RA); however, the underlying mechanisms are unclear. We undertook this study to examine the mechanism by which synovial fluid pH is regulated and to explore the possibility of a therapeutic strategy by manipulating this mechanism. Methods We determined the pH and lactate concentration in synovial fluid from 16 RA patients. Cultured synovial fibroblasts (SFs) from the inflamed joints of 9 RA patients (RASFs) were examined for the expression of ion transporters that regulate intracellular and extracellular pH. The ion transporter up‐regulated in RASF lines was then suppressed in RASFs by small interfering RNA (siRNA), and the effect of transfection on viability and proliferation was investigated. Finally, we examined the therapeutic effect of electrotransfer of monocarboxylate transporter 4 (MCT4)–specific siRNA into the articular synovium of mice with collagen‐induced arthritis (CIA). Results Synovial fluid pH correlated inversely with both the Disease Activity Score in 28 joints using the C‐reactive protein level and the synovial fluid lactate levels. RASFs exhibited up‐regulated transcription of MCT4 messenger RNA. MCT4 exported intracellular lactate into the extracellular space. RASFs had significantly higher MCT4 protein levels than did SFs from patients with osteoarthritis. Knockdown of MCT4 induced intrinsic apoptosis of RASFs, thereby inhibiting their proliferation. Moreover, electrotransfer of MCT4‐specific siRNA into the articular synovium of mice with CIA significantly reduced the severity of arthritis. Conclusion RA activity correlated with decreased synovial fluid pH. This may be due to increased MCT4 expression in RASFs. Silencing MCT4 induced apoptosis in RASFs and reduced the severity of CIA, suggesting that MCT4 is a potential therapeutic target for inflammatory arthritis.
Urban living is a risk factor for allergic sensitization among adults in northern Sweden
Authors: Katja Warm, Sigrid Sundberg, Anne Lindberg, Bo Lundbäck, Eva Rönmark
Journal: European Respiratory Journal (2012)

Aim : To assess prevalence and risk factors for allergic sensitization based on skin prick test (SPT) and specific IgE in adults.

Methods : In 2009 a random sample of 737 adults in ages 20-69 years was invited for examinations including SPT and blood sampling for specific IgE. SPT with ten common airborne allergens were performed in 463 subjects aged 20-60 years. A wheal ≥3 mm was considered as a positive reaction. Blood samples for specific IgE were collected in 692 subjects, and specific IgE was analyzed for the same allergens as tested in the SPT. An elevated level of specific IgE was defined as ≥0.35 IU/ml.

Results : In general, the prevalence of allergic sensitization based on SPT and specific IgE, respectively, yielded similar results. The prevalence of any positive SPT was 39% versus 35% for any elevated IgE, p=0.23. The prevalence of sensitization to cat and dog was significantly lower based on IgE compared to SPT, while sensitization to other allergens showed almost identical figures irrespectively of method used. The risk factor analyses based on SPT and IgE, respectively, yielded similar results. The prevalence decreased significantly by increasing age. Having a family history of rhinitis (OR 3.1 95% CI 2.0-4.8 for any positive SPT, OR 2.7, 95% CI 1.8-4.0) and urban living (OR 1.7, 95% CI 1.1-2.7 for any positive SPT and OR 1.5, 95% CI 1.0-2.3) were significant risk factors for allergic sensitization.

Conclusion : A similar sensitization pattern was observed when assessing the prevalence of allergic sensitization by SPT and specific IgE, respectively. Young age, a family history of allergic rhinitis and urban living were significant risk factors for allergic sensitization among adults.
Prefrontal Cortical Dysfunction in Depression Determined by Wisconsin Card Sorting Test Performance
Authors: Elisha P. Merriam, Michael E. Thase, Gretchen L. Haas, Matcheri S. Keshavan, John A. Sweeney
Journal: American Journal of Psychiatry (1999)

OBJECTIVE: Neuroimaging studies have demonstrated reduced prefrontal cortical blood flow and metabolism in depression, but the neurobehavioral significance of these observations is not yet established. METHOD: The Wisconsin Card Sorting Test, a widely used neuropsychological index of prefrontal cortical function, was administered to 79 patients with major depression who had been unmedicated for at least 28 days, to 47 patients with schizophrenia who had never received antipsychotic medication, and to 61 healthy comparison subjects. RESULTS: Depressed patients demonstrated significant deficits on multiple Wisconsin Card Sorting Test measures compared with healthy individuals. These deficits were correlated with the severity of depression and were less severe than those demonstrated by patients with schizophrenia. CONCLUSIONS: These results provide neuropsychological evidence for significant prefrontal cortical dysfunction in depression.
Diagnostic Accuracy of Digital Screening Mammography With and Without Computer-Aided Detection
Authors: Constance D. Lehman, Robert D. Wellman, Diana S. M. Buist, Karla Kerlikowske, Anna N. A. Tosteson, Diana L. Miglioretti
Journal: JAMA Internal Medicine (2015)

After the US Food and Drug Administration (FDA) approved computer-aided detection (CAD) for mammography in 1998, and the Centers for Medicare and Medicaid Services (CMS) provided increased payment in 2002, CAD technology disseminated rapidly. Despite sparse evidence that CAD improves accuracy of mammographic interpretations and costs over $400 million a year, CAD is currently used for most screening mammograms in the United States.To measure performance of digital screening mammography with and without CAD in US community practice.We compared the accuracy of digital screening mammography interpreted with (n = 495 818) vs without (n = 129 807) CAD from 2003 through 2009 in 323 973 women. Mammograms were interpreted by 271 radiologists from 66 facilities in the Breast Cancer Surveillance Consortium. Linkage with tumor registries identified 3159 breast cancers in 323 973 women within 1 year of the screening.Mammography performance (sensitivity, specificity, and screen-detected and interval cancers per 1000 women) was modeled using logistic regression with radiologist-specific random effects to account for correlation among examinations interpreted by the same radiologist, adjusting for patient age, race/ethnicity, time since prior mammogram, examination year, and registry. Conditional logistic regression was used to compare performance among 107 radiologists who interpreted mammograms both with and without CAD.Screening performance was not improved with CAD on any metric assessed. Mammography sensitivity was 85.3% (95% CI, 83.6%-86.9%) with and 87.3% (95% CI, 84.5%-89.7%) without CAD. Specificity was 91.6% (95% CI, 91.0%-92.2%) with and 91.4% (95% CI, 90.6%-92.0%) without CAD. There was no difference in cancer detection rate (4.1 in 1000 women screened with and without CAD). Computer-aided detection did not improve intraradiologist performance. Sensitivity was significantly decreased for mammograms interpreted with vs without CAD in the subset of radiologists who interpreted both with and without CAD (odds ratio, 0.53; 95% CI, 0.29-0.97).Computer-aided detection does not improve diagnostic accuracy of mammography. These results suggest that insurers pay more for CAD with no established benefit to women.
Regulatory T-lymphocytes in peripheral blood of never smoking patients with COPD
Authors: Aliaksei Kadushkin, Anatoliy Tahanovich, Tatiana Shman
Journal: European Respiratory Journal (2013)

Background.  Regulatory T-lymphocytes (Treg) play an important role in systemic inflammation, however their role in chronic obstructive pulmonary disease (COPD) is uncertain.   Objective.  The objective of this study was the evaluation of Treg defined as CD4+CD25+CD127- cells in never smoking COPD patients, and their comparison with COPD smokers, asymptomatic smokers and healthy non-smokers.   Methods.  The analysis of lymphocytes subtypes was performed using three-colour flow cytometry method. We examined 21 non-smokers and 20 smokers with respiratory symptoms and moderate to severe airflow limitation, 20 healthy non-smokers, 21 healthy smokers.   Results.  The percentage of CD4+CD25+CD127- lymphocytes was significantly higher in non-smoking COPD subjects compared with non-smoking healthy control subjects (median value was 6.0% versus 4.5%, respectively, p   Conclusion:  The results of this study support the possible role of Treg not related to smoking in the systemic inflammation in COPD. Smoking aggravates changes in the percentage of Treg induced by disease in COPD smokers.
Perlecan heparan sulfate deficiency impairs pulmonary vascular development and attenuates hypoxic pulmonary hypertension
Authors: Y.-T. Chang, C.-N. Tseng, P. Tannenberg, L. Eriksson, K. Yuan, V. A. de Jesus Perez, J. Lundberg, M. Lengquist, I. R. Botusan, S.-B. Catrina, P.-K. Tran, U. Hedin, K. Tran-Lundmark
Journal: Cardiovascular Research (2015)

Excessive vascular cell proliferation is an important component of pulmonary hypertension (PH). Perlecan is the major heparan sulfate (HS) proteoglycan in the vascular extracellular matrix. It binds growth factors, including FGF2, and either restricts or promotes cell proliferation. In this study, we have explored the effects of perlecan HS deficiency on pulmonary vascular development and in hypoxia-induced PH. In normoxia, Hspg2Δ3/Δ3 mice, deficient in perlecan HS, had reduced pericytes and muscularization of intra-acinar vessels. Pulmonary angiography revealed a peripheral perfusion defect. Despite these abnormalities, right ventricular systolic pressure (RVSP) and myocardial mass remained normal. After 4 weeks of hypoxia, increases in the proportion of muscularized vessels, RVSP, and right ventricular hypertrophy were significantly less in Hspg2Δ3/Δ3 compared with wild type. The early phase of hypoxia induced a significantly lower increase in fibroblast growth factor receptor-1 (FGFR1) protein level and receptor phosphorylation, and reduced pulmonary artery smooth muscle cell (PASMC) proliferation in Hspg2Δ3/Δ3. At 4 weeks, FGF2 mRNA and protein were also significantly reduced in Hspg2Δ3/Δ3 lungs. Ligand and carbohydrate engagement assay showed that perlecan HS is required for HS–FGF2–FGFR1 ternary complex formation. In vitro, proliferation assays showed that PASMC proliferation is reduced by selective FGFR1 inhibition. PASMC adhesion to fibronectin was higher in Hspg2Δ3/Δ3 compared with wild type. Perlecan HS chains are important for normal vascular arborization and recruitment of pericytes to pulmonary vessels. Perlecan HS deficiency also attenuates hypoxia-induced PH, where the underlying mechanisms involve impaired FGF2/FGFR1 interaction, inhibition of PASMC growth, and altered cell–matrix interactions.
M13 Bacteriophage and Adeno‐Associated Virus Hybrid for Novel Tissue Engineering Material with Gene Delivery Functions
Authors: So Young Yoo, Hyo‐Eon Jin, Dong Shin Choi, Masae Kobayashi, Yohan Farouz, Sky Wang, Seung‐Wuk Lee
Journal: Advanced Healthcare Materials (2015)

A novel hybrid phage carrying genes from prokaryotic M13 phage and eukaryotic adeno-associated viruses can be used as a tissue engineering material with gene delivery functions. The filamentous shape of the resulting hybrid phage easily forms nanofibrous matrices, which can support cellular growth in tissue culture conditions and deliver the target programmed gene information into the target cells.
Longitudinal Intestinal Lengthening and Tailoring: Results in 20 Children
Authors: A Bianchi
Journal: Journal of the Royal Society of Medicine (1997)

Longitudinal intestinal lengthening and tailoring (LILT) is increasingly favoured as a treatment for short-bowel syndrome. In a personal series, 20 children underwent LILT between 1982 and 1997. There was negligible morbidity (hemiloop anastomotic stenosis in 2) and no operative mortality. At a mean follow-up of 6.4 years overall survival was 45%, and certain features were clearly related to outcome. Survivors had &gt;40cm of residual small bowel (commonly jejunum) and had little hepatic dysfunction despite parenteral nutrition of similar time and nature as non-survivors. Children who did not survive had &lt; 40 cm of residual small bowel and developed early lethal hepatic dysfunction of unclear aetiology. Outcome did not seem to be influenced by the presence of the ileocaecal valve or the length of residual colon. Children born with short-bowel should be offered LILT at an early stage when still in good physical condition, so as to avoid liver-damaging intraluminal stasis and bacterial translocation and to enhance intestinal adaptation and hepatoprotective factors.
An open-label, single arm, phase II study of IV weekly (days 1 and 8) topotecan in combination with carboplatin (day 1) every 21 days as second-line therapy in subjects with platinum-sensitive relapsed ovarian cancer: First stage results
Authors: P. E. Schwartz, P. G. Rose, B. J. Monk, D. Provencher, B. Dharan, P. Legenne, L. J. Sherman
Journal: Journal of Clinical Oncology (2008)

16518 Background: A phase I clinical trial of IV weekly topotecan (T) in combination with carboplatin (C) for recurrent ovarian cancer (OC) showed less toxicity than the daily X 5 T with C schedule, and comparable activity. Methods: Eligible subjects were ≥18 years, had relapsed platinum-sensitive epithelial OC, measurable disease, ECOG PS ≤ 2, and adequate bone marrow, hepatic and renal function. T at 2.5 mg/m2 (D1and D8) with C at AUC5 (D1) q 21 days was the maximum tolerated dose based on dose-finding portion of study. Intent to treat (ITT) population, defined as all subjects who received at least one dose of study medication, was used in the analysis. The primary endpoint was response rate (RR), defined as the percentage of ITT subjects who achieved a complete or partial tumor response (WHO Criteria). A two-stage Green and Dahlberg design was used to evaluate the hypotheses (Ho: RR ≤30% vs Ha: RR ≥50%) at 90% power and 5% type 1 error. Thirty subjects were to be enrolled in Stage 1. If there were 9 or more responders, an additional 25 subjects were to be enrolled in Stage 2 for a total of 55. RR was summarized using exact binomial confidence limits. Results: 30 subjects, median age: 63 (39–77); PS 0/1/2 (73%; 20%; 7%) were enrolled in Stage 1. One CR and 9 PRs (10/30; ORR 33%; [95 % CI: 17.9, 54.3]), 9/30 (30%) stable disease, 5/30 (17%) progressive disease and 6/30 (20%) not evaluable (NE). Of the 6 subjects that were NE, 1 withdrew consent and 5 (17%) discontinued within the 1st 2 cycles due to neutropenia (gr 2–4) and/or thrombocytopenia (gr 2–3). Conclusions: IV Weekly T 2.5 mg/m2 with C at AUC5 combination shows promising activity in relapsed OC in this Stage 1 portion. Stage 2 of the study is currently enrolling. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline
Unexpected Serious Toxicity With Chemotherapy and Antiangiogenic Combinations: Time to Take Stock!
Authors: Gavin M. Marx, Christopher B. Steer, Peter Harper, Nick Pavlakis, Olivier Rixe, David Khayat
Journal: Journal of Clinical Oncology (2002)

Article Tools EDITORIALS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.6.1446 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11896090 Unexpected Serious Toxicity With Chemotherapy and Antiangiogenic Combinations: Time to Take Stock! Gavin M. MarxxGavin M. MarxSearch for articles by this author , Christopher B. SteerxChristopher B. SteerSearch for articles by this author , Peter HarperxPeter HarperSearch for articles by this author , Nick PavlakisxNick PavlakisSearch for articles by this author , Olivier RixexOlivier RixeSearch for articles by this author , David KhayatxDavid KhayatSearch for articles by this author Show More Guys Hospital, London, United Kingdom, Royal North Shore Hospital, Sydney, Australia, Salpetriere Hospital, Paris, France https://doi.org/10.1200/JCO.2002.20.6.1446 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical Oncology
<i>Evening (Landscape in Brilliant Colors)</i>
Authors: Jeanette M. Smith
Journal: JAMA (2015)

life of Russian painter Nikolai Nedashkovsky was a light that burned briefly but brightly, leaving behind work of creative inventiveness and use of color, revealing an imaginative world that perhaps transcended the time and place in which it was wrought.Indeed, the following would be noted about the artist and his work: "Another adventurer in the realm of chromatic landscape is Nikolai Nedashkovsky.… [H]is canvases relate to the new school, wherein the actual landscape is expressed in pure color and significant form that tell of its eternal verities rather than its passing mood.His brush is brave and his results show an understanding that is yet formative but progressive.