tbuckley/cabot-search huggingface dataset:
Authors’ response
Authors: Lauren Sarah Mott, Judy Park, Conor P Murray, Catherine L Gangell, Nicholas H de Klerk, Philip J Robinson, Colin F Robertson, Sarath C Ranganathan, Peter D Sly, Stephen M Stick
Journal: Thorax (2012)

We thank Hochhegger, Irion and Marchiorifor 1 their interest in our manuscript. 2We agree that cumulative radiation dose exposures from chest computed tomography (CT) could be a limiting factor for the use of frequent scans in children with cystic fibrosis, although continuous advances in CT technology are allowing comprehensive assessments of lung structure with increasingly smaller radiation exposures. 3The authors suggest that lung magnetic resonance imaging (MRI) may be an emerging modality with improving temporal and spatial resolution, stating that previous studies demonstrate that MRI is comparable with CT for the detection of structural changes.In fact, these studies were conducted in older children and adults with established structural disease, 4 5 rather than in infants and young children in whom the earliest changes in lung structure occur.As the earliest structural changes due to cystic fibrosis appear to develop in the peripheral airways, 6 a region of the lung that is poorly characterised by lung MRI, both by direct assessment of small airways 7 8 and indirectly by air trapping, 9 the relatively poor ability of lung MRI to accurately assess the peripheral airways is likely to limit its use for assessing airways disease in young children or in mild disease.While lung MRI has an additional ability to assess functional changes, the importance of these in early childhood is not clear.Therefore, at present, the role of lung MRI in assessing mild structural changes due to cystic fibrosis seen in early childhood is uncertain and until lung MRI is established as a feasible and appropriate assessment tool for early structural lung disease, chest CT remains the gold standard in this population, particularly when acknowledging the reducing radiation exposures afforded by technological advances.
Abstract 3652: Coronary Heart Disease Prevention in Women: The Prognostic Significance of Subclinical Atherosclerosis by Carotid Ultrasound
Authors: Kwame O Akosah, Vicki L McHugh, Michelle A Mathiason
Journal: Circulation (2007)

Background : The difficulty of coronary heart disease (CHD) prevention in women is recognized. Reasons include gender disparities in accuracy rates of current diagnostic tests and clinical presentation. Objective : Assess the utility and prognostic significance of carotid atherosclerosis in predicting CHD in women. Methods : Women (n=140) scheduled for elective coronary angiography underwent carotid ultrasound and fasting lipid analysis. Subjects were excluded for age (≥ 65), prior history of CHD, and anti-lipid therapy. Severe coronary artery disease (CAD) was defined as stenosis ≥ 50%. Carotid atherosclerosis was defined as IMT ≥ 1 mm in the main body or focal plaque in the main body or bulb. Subjects were followed for a median of 50 months. Future cardiovascular events (CVEs) were defined as Major (death, MI, and stroke), and Any event (Major, revascularization, and new onset heart failure). Results: 136 women (mean age 53 ± 8) had all data available. 80% (n=108) of subjects were classified as low risk and 1% (n=2) as intermediate risk per Framingham score, with an additional 19% (n=26) having CHD equivalent conditions. Severe CAD was present in 39 (28%) subjects. Carotid atherosclerosis had a sensitivity of 74%, specificity of 49%, and negative predictive value of 83% for CAD. Subjects were categorized into Group 1 (Carotid atherosclerosis, n=79) and Group 2 (no carotid atherosclerosis, n=57). After median follow-up of 50 months, 6 women experienced Major CVEs (Group 1 n = 5; Group 2 n=1). Major event rate for Group 1 was 6.3% vs. 1.8% for Group 2. For Any event, the rates were 22% for Group 1 compared to 9% for Group 2 (p=0.046). The event rates were similar between high-risk (3.8%) and low-risk (3.7%) for Major and 12% vs. 16 % for Any event. Kaplan-Meier survival analysis reveals that women without diagnosis of carotid atherosclerosis enjoyed significantly better event free survival. Negative predictive values for carotid atherosclerosis in predicting angiographic disease, Major events and Any event were 83%, 91% and 98%, respectively. Conclusion : Carotid atherosclerosis predicts CVEs in young to middle-aged women without high-risk clinical scores. Women without diagnosis of carotid atherosclerosis enjoy excellent long-term event free survival.
Micropapillary urothelial carcinoma of the urinary bladder: Early surgery or neoadjuvant chemotherapy?
Authors: I. Ghoneim, A. Stephenson, M. Gong, S. Campbell, A. Fergany
Journal: Journal of Clinical Oncology (2009)

e16007 Background: Micropapillary bladder carcinoma is a rare variant of urothelial carcinoma (UC) of the urinary bladder. As a particularly aggressive variant, patients are often urged to undergo up-front radical cystectomy. Though data is scarce on the treatment outcomes of patients with this entity, we present the case for neoadjuvant chemotherapy as opposed to early cystectomy in the setting of clinically localized micropapillary UC. Methods: A review of records of all patients evaluated at our institution for UC was conducted to identify micropapillary UC of the bladder over the period from 2000–2007. A total of 24 cases were found, and were evaluated for preoperative pathology and clinical stage, treatment course, pathological stage and cancer specific survival. Results: Mean patient age was 67.9 years with 19 males and 5 females. Twenty-one (87.5%) patients had clinically organ confined micropapillary UC at the time of diagnosis, three had minimally enlarged lymph nodes on pelvic CAT scans. Half of our patients had BCG refractory high grade non-muscle invasive UC. Twenty-two patients (91.67%) were offered radical cystectomy as first line management. Extended lymph node dissection was performed in eleven patients (45.83%). Final pathologic examination diagnosed metastatic lymph node involvement in 20 patients (83.33%), with 4 patients (20%) having positive LN outside the standard (pelvic) template of dissection. A stage upgrade was noticed in 95.23% of cases. Median cancer specific survival was 13 months. Survival at one year was 44% and 50% at 2years, with only one patient alive at 5 years. Conclusions: Our results suggest that clinically localized micropapillary UC is often metastatic to LN at the time of presentation. This setting of frequent systemic disease should encourage standard neoadjuvant chemotherapy rather than early surgical management for these patients. Extended LN dissection is warranted in these cases due to the high incidence of nodal involvement outside the standard template. No significant financial relationships to disclose.
A combination of capecitabine and thalidomide in patients with hepatocellular carcinoma
Authors: W. Jeong, H. G. Chun, D. Cer, V. Sekhri, L. Kim-Schluger, D. Wolf
Journal: Journal of Clinical Oncology (2006)

4142 Background: Based on the single-agent efficacies observed in phase II trials (Cancer 2004;101:578–586 and Cancer 2005;103:749–755), a pilot trial with a combination of oral capecitabine and thalidomide has been conducted in patients with unresectable, recurrent or metastatic hepatocellular carcinoma (HCC) to evaluate its efficacy and toxicity. Methods: The regimen consisted of capecitabine at a dose of 750 mg/m 2 po bid for 14 days every 3 weeks and thalidomide at 400 mg po bed time. Eligibility criteria included histological diagnosis of HCC, measurable disease, no prior systemic therapy, age ≥18 years, ECOG performance score (PS) of ≤2, adequate hematological, hepatic and gastrointestinal functions, no metabolic encephalopathy, and informed consent. Results: A total of 29 patients have been accrued. Two patients had never received the protocol therapy due to rapid deterioration of clinical condition after registration. Twenty-seven have been treated according to the protocol. Patient characteristics included median (range) age -60 (48–77) years; male -24; median ECOG PS -1; cirrhosis -22; hepatitis C antibody -19; hepatitis B surface antigen -4; hemochromatosis -1; extrahepatic metastasis -5. Eight patients were not evaluable for response since they received less than 2 cycles of protocol therapy. Five patients had grade 3 but asymptomatic, transient hyperbilirubinemia. Three patients had grade 1 hand-foot syndrome. Three patients had excessive somnolence which required a reduction of thalidomide dose to 200 mg. Among 19 patients evaluable for response (received ≥ 3 cycles of capecitabine), 1 patient had complete response for 5 months (Time to progression [TTP] -7 months), 4 had partial responses (TTP -2.5, 5.0, 6.0, &amp; 7.0 months) and 4 had stable diseases for ≥ 3 months. Conclusions: This result suggests clinical efficacy of the combination of oral capecitabine and thalidomide, at given doses and schedules, with acceptable safety profile in patients with HCC (Supported by a grant from Celgene Corporation). No significant financial relationships to disclose.
Die normale und pathologische Physiologie der Milz
Authors: Ernst Lauda
Journal: JAMA (1934)

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
Aberrant indoleamine 2,3 dioxygenase (IDO) expression is present in pediatric patients with Hodgkin's lymphoma
Authors: A. H. Shahlaee, S. Z. Al-Quran, W. Hou, C. Schwartz, D. H. Munn
Journal: Journal of Clinical Oncology (2007)

9531 Background: Indoleamine 2,3 dioxygenase (IDO) is a tryptophan-catabolizing enzyme capable of inducing local immunosuppression and systemic tolerance. IDO activity, as measured by serum levels of tryptophan (TRP) and kynurenine (KYN), has been shown to portend a worse prognosis in several different malignancies. Additionally, IDO expression in tumor draining lymph nodes predicts a worst outcome in patients with malignant melanoma making IDO a potential target for therapeutic intervention. To date, no studies have evaluated the expression pattern of IDO in the setting of pediatric Hodgkin Disease. Methods: 20 cases of pediatric Hodgkin Disease (2 stage I, 11 stage II, 2 stage III and 5 stage IV), treated on Children's Oncology Group trials were studied. Paraffin-embedded tumor tissues and matching pre- and post-chemotherapy sera were obtained via the Cooperative Human Tissue Network (CHTN). Immunohistochemical studies were performed on sections of paraffin-embedded tissues to evaluate aberrant IDO expression and secondary serum KYN/TRP changes were analyzed. Results: Tumor tissues from 17/20 patients (85%) were positive for IDO. Two cases showed no expression and one was not evaluable due to tissue necrosis. Morphologically several cell types were noted to express IDO including eosinophils, dendritic cells and large cells, some of which are bi-nucleated, possibly consistent with Reed-Sternberg cells and variants. The mean serum KYN/TRP ratio was elevated pre-chemotherapy in comparison to post therapy levels (P value=0.0043 by Wilcoxon sign rank test). Conclusions: This pilot data demonstrates that aberrant IDO expression is a common finding in pediatric Hodgkin Disease, and that the potential immunomodulatory role of IDO expression in the context of Hodgkin Disease needs to be further studied. These data warrant further prospective evaluation in a larger cohort of patients to determine the clinical applicability of this observation. No significant financial relationships to disclose.
The future for mental health in primary health care programs
Authors: Richard C. Morrill
Journal: American Journal of Psychiatry (1978)

Our largely separate mental health system has developed in relationship to a health care system oriented toward specialization and solo practice. Now the health care system is moving in the direction of primary care and group and organizational practice. New forms of mental health delivery are needed to maximize the potential of these new health care programs for mental health services. The author describes these new integrated programs which bring mental health providers into the primary health care programs for direct services as well as consultation. Issues discussed include mutual roles, changes in services, the referral process, and provider relationships. The advantages of such integrated programs include decreased stigma, increased prevention through earlier detection and referral, increased family orientation, greater coordination of care, and less duplication.
Prediction of response to Gefitinib in NSCLC by EGFR protein expression is increased by a novel antibody and the use of AQUA technology.
Authors: B. Reyna Asuncion, K. Yoshida, J. Ranger-Moore, Jamie Zhao, Murry W Wynes, Céline Mascaux, William Powell, N. Ikeda, Fred R Hirsch, Yasufumi Kato
Journal: Journal of Thoracic Oncology (2010)
Maximizing the Impact of Training Initiatives for Health Professionals in Low-Income Countries: Frameworks, Challenges, and Best Practices
Authors: Corrado Cancedda, Paul E. Farmer, Vanessa Kerry, Tej Nuthulaganti, Kirstin W. Scott, Eric Goosby, Agnes Binagwaho
Journal: PLoS Medicine (2015)

Points• Historically, the impact of many health professional training initiatives in low-income countries has been limited by narrow focus on a small set of diseases, inefficient utilization of donor funding, inadequate scale up, insufficient emphasis on the acquisition of practical skills, poor alignment with local priorities, and lack of coordination.• Fortunately, several innovative training initiatives have emerged over the past five years in sub-Saharan Africa.
Why are doctors so unhappy?
Authors: P A West
Journal: BMJ (2001)

Editor—As an economist who has spent the past 30 years looking at health care all round the world, may I suggest that frustration and perhaps boredom play a part in the anger of doctors and contribute to their unhappiness, as described by Smith in his editorial?1 This is aside from what I accept are genuine conflicts between levels of public funding and clinical aspirations to help patients. Looking at other professions, I note that people advance through their careers, their work changes, and they build teams and grow their businesses. Some stay in single practice, but many move into management, with changes periodically in their working life.

Similarly, economists like me have a wide range of research and travel as part of our work, and we manage teams on a diversity of projects. I have no idea what I will be doing in September this year, but I am confident that it will be interesting. Contrast these professional lives with those of doctors. General practitioners may have opportunities to develop their management skills but in an environment where the management structures and self employed status of colleagues make this far from easy. And someone has to see the patients each week. Consultants have more of the variety and team building mentioned, but, again, their work plans look very much the same—year in, year out—to the outsider. This leads me to my conclusion.

Might the calibre of people recruited to medicine be too high for the job, not necessarily for the technical elements but for the pattern of work once general practitioner or consultant status is reached? Is a degree of frustration inevitable given doctors' abilities and the relative consistency of the job beyond the age of 30 or 35? Are many years of clinical practice consistent with the job enrichment that able people may want as their career develops?
A randomized phase 2 study of the thrombospondin-mimetic peptide ABT-510 in patients with advanced soft tissue sarcoma (STS)
Authors: L. H. Baker, G. D. Demetri, D. S. Mendelson, E. K. Rowinsky, E. M. McKeegan, R. A. Knight, D. M. Carlson, M. Lobell
Journal: Journal of Clinical Oncology (2005)

9013 Background: ABT-510 is a 9-amino acid peptide that mimics the antiangiogenic activity of the naturally occurring protein, thrombospondin-1. In phase 1, ABT-510 was tolerated at doses up to 260 mg by subcutaneous injection (SC) per day. The pharmacokinetic target of 100 ng/mL for >3 hours was achieved at doses ≥20 mg daily. 15 patients with STS were included, with one confirmed partial response and 4 additional patients with stable disease >6 months. A phase 2 study evaluating the activity of ABT-510 in patients with relapsed or refractory STS has completed accrual. Methods: 88 patients with locally advanced or metastatic STS were randomized to receive 20 mg ABT-510 QD or 100 mg ABT-510 BID SC. Dosing is continuous. The primary endpoint of the study is progression-free survival (PFS); secondary endpoints include response rate, overall survival, and performance status. Tumor progression (by RECIST) is assessed every 8 wks. Circulating endothelial cells (CECs) are evaluated at baseline, 4 wks, then every 8 weeks. Safety is evaluated at every visit. Patients may remain on study until tumor size increases by 50% from baseline if there is clinical benefit and no other therapeutic options exist. Results: 44 men and 44 women were enrolled; 19 are active. The median age was 53 years (range 23–79); the baseline ECOG Performance Score for all patients was 0 or 1. Preliminary data for patients with prior cytotoxic chemotherapy (n=57) indicate a 6-month progression-free rate (PFR) of 34.4% (95% CI=18.2, 50.6) and without prior cytotoxic chemotherapy (n=25), 35.0% (95% CI=12.9, 57.2). No confirmed partial responses have been observed. Therapy was extremely well tolerated. Injection site reactions were the most frequently observed adverse event. Blinded data suggest a correlation of CEC concentration with duration of therapy; analysis is ongoing. Conclusions: The PFR seen in patients treated with ABT-510 exceeds the 14% rate reported for active drugs in STS by the EORTC and is suggestive of drug activity. Given the excellent safety profile and known antiangiogenic properties of ABT-510, further study is warranted for its use in the treatment of STS as a single-agent therapy or in combination with other active drugs. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Abbott Laboratories Abbott Laboratories Abbott Laboratories Abbott Laboratories
Enzastaurin a protein kinase Cbeta-selective inhibitor, inhibits the growth of SCLC and NSCLC cell lines
Authors: E. Nakajima, B. Helfrich, D. Chan, Z. Zhang, F. R. Hirsch, V. Chen, D. Ma, P. A. Bunn
Journal: Journal of Clinical Oncology (2006)

13138 Background: PKCβ is a member of the PKC family of serine-threonine protein kinases involved in tumor cell proliferation and apoptosis. Inhibition of PKCs induced differentiation and enhanced chemotherapy. PKCβ activation is required for tumor-induced angiogenesis. The PKCβ-selective inhibitor enzastaurin, originally developed as an antiangiogenic agent, inhibited tumor cell proliferation in prostate, colon and glioblastoma cell lines in vitro. In NSCLC lines, enhanced phosphorylation and altered PKC expression was demonstrated. In SCLC lines specific PKC isoforms were associated with cisplatin resistance. Methods: The growth inhibitory effects of enzastaruin were evaluated by 6-day MTT assays; the cell cycle effects by FACS analysis; the effects on downstream phophorylated signaling molecules by western blotting. Results: Enzastaurin inhibited the growth of 11 SCLC lines (IC50s 3–10 μM) and 4 NSCLC cell lines (IC50s 3–10 μM). An increase of 7–31% of cells in the G2/M phase of the cell cycle compared to untreated control was observed following 48 hour exposure to the IC50 dose of enzastaurin in both SCLC and NSCLC cell lines. PKCβ has been shown to phosphorylate both GSK3β and Akt. A 24-hour IC50 enzastaurin exposure significantly reduced phosphorylation of GSK3β (Ser9) in both SCLC and NSCLC lines. No changes were observed in phospho-AKT (Thr308) in either SCLC or NSCLC cell lines. Phospho-ribosomal protein S6 (Ser240/244) was also reduced in both SCLC and NSCLC cell lines. Potential synergy was studied between enzastaurin and pemetrexed in SCLC and NSCLC lines and the results were analyzed using the Calcusyn Program by Chou and Talalay. Synergistic (CI &lt;1) to additive interactions were observed between pemetrexed (IC20–70) and enzastaurin (≤ IC50) in both SCLC lines (N = 3) and NSCLC lines (N = 2). Conclusions: We conclude that enzastaruin produces in vitro growth inhibition of SCLC and NSCLC cell lines through inhibition of GSK3β ser9 phosphorylation and has synergistic growth inhibition with pemetrexed. [Table: see text]
Geschlechtsentstehung und willkürliche Geschlechtsbestimmung
Authors: Edwin Kramer
Journal: JAMA (1934)

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