tbuckley/cabot-search huggingface dataset:
Evidence for increased incidence of dihydropyrimidine dehydrogenase (DPD) deficiency in African Americans compared to Caucasians
Authors: L. K. Mattison, J. Fourie, M. Carpenter, H. Ezzeldin, M. R. Johnson, M. Saif, A. Modak, R. B. Diasio
Journal: Journal of Clinical Oncology (2005)

2004 Background: DPD deficiency is a pharmacogenetic syndrome associated with severe and life-threatening toxicity in cancer patients receiving 5-fluorouracil (5-FU). More than 30 mutations have been reported in the gene (DPYD) which codes for the DPD enzyme. Familial studies have demonstrated that this is an autosomal co-dominantly inherited disorder. While the frequency of DPD deficiency has been reported to be approximately 3–5% in populations composed primarily of Caucasian (CA) volunteers and cancer patients, the incidence in the African American (AA) population remains unknown. Objective: The aim of this study was to compare the range of DPD activity, frequency of DPD deficiency and genotype of AA and CA populations. Methods: DPD enzyme activity was assessed in 91 AA and 87 CA volunteers from the general population using both the 2-13C-uracil breath test (Clin Can Res 10: 2652, 2004; Proc. ASCO 2003, Abstract #494) and DPD radioassay (J Chrom B 696:183, 1998). Differences, reported here, between AAs and CAs were examined for significance by a two-sample t-test (SAS software). All subjects were also genotypically characterized by denaturing high performance liquid chromatography (Anal Biochem 306:63, 2002). Results: AA volunteers had significantly lower mean DPD enzyme activity (mean ± SE: 0.248 ± 0.007) compared to CAs (0.289 ± 0.007; P<0.001). The incidence of DPD deficiency in AAs (7.7%), identified by both DPD radioassay and 2-13C-uracil breath test, was 3-fold higher than in CAs (2.3%). Genotyping of the DPD deficient subjects demonstrated the presence of multiple heterozygous sequence variations in the DPYD gene, several of which have not been described previously. Conclusions: AAs have an increased incidence of DPD deficiency and a lower mean DPD activity compared to CAs, which may predispose them to severe 5-FU-associated toxicity. Overall, these data provide compelling evidence for screening cancer patients, particularly AAs, for low or absent DPD activity prior to 5-FU administration to avoid life-threatening toxicity (CA62164). No significant financial relationships to disclose.
Regulation of macrophage growth responses to colony-stimulating factor-1 by 1,25-dihydroxyvitamin D3.
Authors: A Saini, D J Cohen, B S Ooi
Journal: Journal of the American Society of Nephrology (1995)

1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) has previously been shown to affect the biology of a variety of immune cells, including the functions of macrophages. The effect of the vitamin D metabolite on the proliferative responses of macrophages to the cytokine colony-stimulating factor-1 (CSF-1) has been studied. It was found that this substance was able to suppress the growth responses of macrophages to CSF-1 as assessed by macrophage-tritiated thymidine uptake and also by cell counts. The effect was specific to this vitamin D metabolite because another vitamin D analogue, 25 hydroxyvitamin D3, did not have a similar effect on the responses of such cells to CSF-1. The results yield information on the regulatory role of 1,25(OH)2D3 on macrophage growth. It would appear that this vitamin D metabolite may act as a negative autoregulatory cytokine because it is produced by the macrophage when it is activated. A schema can be envisaged where CSF-1 is delivered to the macrophage to activate it and to cause it to proliferate. In the process, it also secretes 1,25(OH)2D3, which exerts a suppressive action to dampen this response.
Re: Sun Exposure and Mortality From Melanoma
Authors: Richard S. Kalish
Journal: JNCI Journal of the National Cancer Institute (2005)

The relationship between sun exposure and melanoma mortality and risk of lymphoma was explored in two recent articles and a related editorial ( 1 – 3 ) . Unfortunately, the discussion in the related editorial ( 1 ) was not supported by the data presented. The study by Berwick et al. ( 2 ) demonstrated, within the limits of a retrospective study, that patients with melanoma have a better prognosis if they had previous extensive sun exposure. The indices of sun exposure refl ected many years of exposure dating to youth and did not relate to exposure in the interval after diagnosis of melanoma. No data on vitamin D levels were provided. The data strongly suggested that melanomas induced by intense sun exposure have a more benign behavior than those not induced by intense sun exposure. This is the most direct explanation for increased survival from melanomas arising in patients with a history of intense sun exposure and is analogous to experience with other sun-induced cancers. Squamous cell carcinomas of the skin induced by sun have a much better prognosis than squamous cell cancers arising in scars. This relationship between melanoma survival and sun exposure may explain the stable melanoma mortality rate despite an increase in incidence in sun – induced melanoma and has consequences for public health. Data in the article by Smedby et al. ( 3 ) suggest that participants who had extensive sun exposure had a decreased lymphoma risk compared with participants with less sun exposure. However, there was an exception for patients with a prior history of skin cancer. Thus, lymphoma risk was elevated in patients with skin cancer plus extensive sun exposure and decreased in patients with extensive sun exposure without skin cancer. This difference in risk cannot be explained by vitamin D levels because vitamin D levels should also be elevated in patients with extensive sun exposure and skin cancer. The data suggest that suninduced skin cancer is simply a marker for a decreased ability to handle carcinogenic insult. The skin cancer data confl ict with a direct link between sun exposure and lymphoma risk or a role for vitamin D. This problem with the analysis, which attributed the results to vitamin D levels, is not without consequences because it would lead to the recommendation that people increase their exposure to a carcinogen.
Influence of fungal colonization on 6-minute-walk test disance in patients with hypersensitivity pneumonitis
Authors: Ilya Sivokozov, Olga Lovacheva, Elena Shergina, Natalya Makaryants, Eugene Shmelev
Journal: European Respiratory Journal (2013)

Background. Fungal antigens sensibilization is a known cause of hypersensitivity pneumonitis (HP). Nevertheless, the role of fungal colonization in respiratory tract on clinics and prognosis of HP is still unclear.  Aim. To assess the influense of fungal colonization on excercise tolerance in HP.  Methods. 79 pts with morphologically proven HP were enrolled. Mean age 48,8 yrs, males 33. In all cases during work-up BAL was performed with PCR test on DNA of Aspergillus and Candida fungi, as also as PFT and 6MWT. Data were analyzed using Mann-Whitney test.  Results. Fungi were detected in 21/79 (27%) pts. The were no difference between PCR-positive and negative groups for Aspergillus in PFT, but there was significant difference for sPO2 before and after 6MWT (94,1 and 90 %; 91 and 88% respectively, p 0.05). Detection of Candida in BAL did not impact on HP.  Conclusion. Fungal colonization with Aspergillus worsens excercise tolerance in HP patients, whereas Candida doesn9t impact on HP.
Management of a Patient With Electrical Storm
Authors: Laurent M. Haegeli, Paolo Della Bella, Corinna B. Brunckhorst
Journal: Circulation (2016)

C linical Case: A 53-year-old male patient was referred to our center for the management of severe electrical storm (ES).The patient experienced 76 appropriate shocks within 30 minutes delivered from his implantable cardioverter-defibrillator as a result of recurrent ventricular tachycardia (VT) occurring just after retiring to his hotel room at the end of an uneventful business meeting.The implantable cardioverter-defibrillator was implanted 16 years ago when the patient presented with syncope and had inducible VT at an electrophysiological study.Coronary artery disease was ruled out at that time with coronary angiography.However, the systolic function of the left ventricle was moderately impaired, with an ejection fraction of 38% measured by echocardiography, which also revealed regional wall motion abnormalities.This nonischemic cardiomyopathy was attributed to remote myocarditis.When presenting with ES, the patient was admitted at first to the intensive care unit of the local university hospital.A 12-lead ECG showed monomorphic VT of 188 bpm (Figure 1A).Ventricular tachyarrhythmia was stabilized acutely by sequential drug application of β-blockers, amiodarone, and lidocaine as well as sedation followed by endotracheal intubation under general anesthesia.After the initial cooling-down phase, the patient was transferred to our center for further management.To prevent more episodes of ES and to avoid long-term use of amiodarone with the risk of potentially severe adverse effects, catheter ablation was performed.
Evidence for spending millions on deworming schoolchildren is inadequate, report says
Authors: Nigel Hawkes
Journal: BMJ (2015)

Limited studies have assessed the resting 12-lead electrocardiogram (ECG) as a screening test in intermediate risk populations. We evaluated whether a panel of common ECG parameters are independent predictors of mortality risk in a prospective cohort of participants with CKD. The Chronic Renal Insufficiency Cohort (CRIC) study enrolled 3939 participants with eGFR&lt;70 ml/min per 1.73 m<sup>2</sup> from June 2003 to September 2008. Over a median follow-up of 7.5 years, 750 participants died. After adjudicating the initial 497 deaths, we identified 256 cardiovascular and 241 noncardiovascular deaths. ECG metrics were independent risk markers for cardiovascular death (hazard ratio, 95% confidence interval): PR interval ≥200 ms (1.62, 1.19–2.19); QRS interval 100–119 ms (1.64, 1.20–2.25) and ≥120 ms (1.75, 1.17–2.62); corrected QT (QTc) interval ≥450 ms in men or ≥460 ms in women (1.72, 1.19–2.49); and heart rate 60–90 beats per minute (1.21, 0.89–1.63) and ≥90 beats per minute (2.35, 1.03–5.33). Most ECG measures were stronger markers of risk for cardiovascular death than for all-cause mortality or noncardiovascular death. Adding these intervals to a comprehensive model of cardiorenal risk factors increased the C-statistic for cardiovascular death from 0.77 to 0.81 (<i>P</i>&lt;0.001). Furthermore, adding ECG metrics to the model adjusted for standard risk factors resulted in a net reclassification of 12.1% (95% confidence interval 8.1%–16.0%). These data suggest common ECG metrics are independent risk factors for cardiovascular death and enhance the ability to predict death events in a population with CKD.
Abstract 17576: Readmission for Stroke and Quality of Care Among Patients Hospitalized With Transient Ischemic Attack (TIA): Findings From Get With the Guidelines (GWTG)-Stroke
Authors: Emily C O'Brien, Xin Zhao, Gregg C Fonarow, Eric E Smith, Lee H Schwamm, Deepak L Bhatt, Ying Xian, Jeffrey L Saver, Mathew J Reeves, Eric D Peterson, Adrian F Hernandez
Journal: Circulation (2013)

Background: Patients with TIA are at increased risk for recurrent stroke, yet there is variation in the quality of care that may reduce this risk. We examined the association between receipt of TIA...
Patupilone for the treatment of recurrent/progressive brain metastases in patients (pts) with non-small cell lung cancer (NSCLC): An open-label phase II study
Authors: L. E. Abrey, P. Wen, R. Govindan, H. Reimers, J. R. Rigas, H. I. Robins, E. Allen-Freda, B. Gao, J. Ko, A. Johri
Journal: Journal of Clinical Oncology (2008)

2033 Background: Preclinical data have shown that patupilone, a novel microtubule stabilizer, crosses the intact blood brain barrier in mice, rats and dogs and has antitumor activity in brain tumor models. This study evaluates patupilone's efficacy in NSCLC pts with brain metastases and progression after chemotherapy, surgery and/or radiation to the brain. Methods: This open-label, single-arm, multicenter, phase II, Simon 2-stage (St) study (25 pts per St) uses a multinomial design (response (R), early progression (EP)). Primary efficacy endpoints were a combination of EP (PD or death before cycle 1 Day 21) and R (progression free at 9 wks). Criteria to proceed to St 2 were >3 R and <11 EP in 25 pts. Eligible pts had confirmed NSCLC and ≥1 recurrent, measurable intracranial lesion ≥2 cm. Patupilone was given as 10 mg/m2 in a single 20-min IV infusion every 3 wks. Results: So far, 25 pts in St I and 2 pts in St II (median age 62 yrs, range 40–74, 59% male) have received 78 cycles (median 2 cycles). All pts received prior radiotherapy and 10/27 (37%) had prior chemotherapy for the brain. Karnofsky status in 25/27 ≥70% and in 2/27 <70%. Common G1/2 adverse events (AEs) were as follows: diarrhea 59%, nausea 19%, fatigue and peripheral neuropathy, each 11%. There were 21 G3 AEs (44%); 10 were related to study drug (diarrhea in 6). Eight G4 AEs (19%) were not related and 1 G4 AE (colitis) was suspected. Investigator reported efficacy data from St 1 (n=25) showed 8 responders (median duration of response 192 days, range 191–273); 7 had stable disease, 9 EP and assessment was unknown in 1 pt. Investigator reported median progression free survival is 1.2 mos. Three of the responding patients continued ≥8 cycles. Conclusions: The study met the statistical criteria to proceed to St 2. Proof of concept of patupilone activity in human brain metastases has been reached. These results warrant further investigation of patupilone as a treatment for CNS metastases from NSCLC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis Novartis Novartis AstraZeneca, Aventis, Eli Lilly, Genentech™ BioOncology, Pfizer Merck, Novartis
Mutational Landscape of Aggressive Prostate Tumors in African American Men
Authors: Karla J. Lindquist, Pamela L. Paris, Thomas J. Hoffmann, Niall J. Cardin, Rémi Kazma, Joel A. Mefford, Jeffrey P. Simko, Vy Ngo, Yalei Chen, Albert M. Levin, Dhananjay Chitale, Brian T. Helfand, William J. Catalona, Benjamin A. Rybicki, John S. Witte
Journal: Cancer Research (2016)

Prostate cancer is the most frequently diagnosed and second most fatal nonskin cancer among men in the United States. African American men are two times more likely to develop and die of prostate cancer compared with men of other ancestries. Previous whole genome or exome tumor-sequencing studies of prostate cancer have primarily focused on men of European ancestry. In this study, we sequenced and characterized somatic mutations in aggressive (Gleason ≥7, stage ≥T2b) prostate tumors from 24 African American patients. We describe the locations and prevalence of small somatic mutations (up to 50 bases in length), copy number aberrations, and structural rearrangements in the tumor genomes compared with patient-matched normal genomes. We observed several mutation patterns consistent with previous studies, such as large copy number aberrations in chromosome 8 and complex rearrangement chains. However, TMPRSS2-ERG gene fusions and PTEN losses occurred in only 21% and 8% of the African American patients, respectively, far less common than in patients of European ancestry. We also identified mutations that appeared specific to or more common in African American patients, including a novel CDC27-OAT gene fusion occurring in 17% of patients. The genomic aberrations reported in this study warrant further investigation of their biologic significant role in the incidence and clinical outcomes of prostate cancer in African Americans. Cancer Res; 76(7); 1860-8. ©2016 AACR.
Cyclosporine (CSP) or CSP plus methylprednisolone for graft-versus-host-disease prophylaxis in patients with high-risk lymphohemopoietic malignancies: long-term follow-up of a randomized trial
Authors: H. Joachim Deeg, Mary E. D. Flowers, Wendy Leisenring, Frederick R. Appelbaum, Paul J. Martin, Rainer F. Storb
Journal: Blood (2000)
Pharmacy Expenditures for Children With Serious Chronic Illness
Authors: James H. Ruble, Diana I. Brixner
Journal: JAMA (2016)

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
The diagnostic value of serum levels of VEGF, bFGF and endostatin in patients with liver cancer
Authors: A. Nikopoulou, P. Makrantonakis, M. Karamouzis, P. Nikolaidis, J. Agorastos, A. Nikopoulos, E. Giannoulis
Journal: Journal of Clinical Oncology (2007)

21133 Background: : Aim of this study is to evaluate the diagnostic value of serum levels of vascular endothelial growth factor ( VEGF ), basic fibroblast growth factor ( bFGF ) and Endostatin in patients with primary hepatocellular carcinoma ( PHC ) and in patients with metastatic liver disease ( MLD ). Methods: Eighty participants were included in this study and divided into three groups. Exclusion criteria were history of myocardial infraction, stroke, diabetic retinopathy, rheumatoid arthritis, psoriatic arthritis, pregnancy, trauma and recent surgical treatment. In group A were included 20 normal controls (NC), in group B 30 patients with PHC and in group C 30 patients with MLD. The concentrations of VEGF, bFGF and Endostatin in serum were measured by using enzyme like immunosorbent assay kits (Quantikine R&amp;D systems Inc., Mineapolis.MN). Results: Results are shown in table . In patients with PHC there was a positive correlation between the serum level of VEGF and tumor size (r=0.517, p=0.08), between the serum level of VEGF and platelets number (r=0.573, p=0.003) and between the serum level of VEGF and the serum level of a-fetoprotein (r=0.478, p=0.029). In patients with PHC sensitivity of VEGF, bFGF and Endostatin was found 60%, 54% and 23% respectively. In patients with MLD sensitivity of VEGF, bFGF and Endostatin was found 73%, 73% and 27.5% respectively. However, both in patients with PHC and with MLD specificity of VEGF, bFGF and Endostatin were found 95%, 95% and 100% respectively. Conclusions: Angiogenic factors VEGF, bFGF and Endostatin can distinguish normal controls from patients with liver cancer. Serum levels of VEGF are related to the size of the tumor in patients with PHC. Serum VEGF, bFGF and Endostatin could be useful tumor markers in the diagnosis of PHC and MLD because of their high specificity. The significant correlation of VEGF with a- fetoprotein indicates its importance as a marker in diagnosis of PHC. [Table: see text] No significant financial relationships to disclose.
Hematopoietic Clonal Dominance and Evolutionary Pattern Of JAK2V617F Allele Burden In Polycythemia Vera Patients
Authors: Anna Angona, Alberto Alvarez-Larrán, Beatriz Bellosillo, Luz Martínez-Avilés, Laura Camacho, Concepcion Fernández-Rodríguez, Silvia Pairet, Raquel Longarón, Agueda Ancochea, Carlos Besses
Journal: Blood (2013)
Feasibility and tolerability of multimodality treatment of locally advanced rectal cancer, particularly in elderly patients in a community cancer center.
Authors: N. Agnihotri, A. Chiba, Y. Huang, B. Donahue, M. I. Chorost, Y. Xu
Journal: Journal of Clinical Oncology (2010)

e14090 Background: Preoperative chemoradiation followed by surgery is the current recommended treatment for locally advanced rectal cancer. We aim to review our community cancer center experience with this approach, with attention to feasibility, toxicity, EUS staging accuracy, and elderly patient tolerance. Methods: A chart review was performed on all consecutive patients treated in cancer center between 08/01/2005 and 12/31/2009, with T3 or Any T, N+ disease. Results: 47 patients were treated with multidisciplinary evaluation, and EUS staging. 6 patients had surgery first due to bleeding (2), obstruction (1) and patient preference (3), while 41 patients underwent neoadjuvant treatment. The median radiation dose was 50.4 Gy in 28 fractions of 1.8 Gy daily; 14 (34%) and 25 (60.9%) patients received continuous infusion (CIV) 5-FU and capecitabine chemotherapy respectively. There were 29 males, 12 females; with ages from 35 to 86, median = 63 years, 10 (24.3%) patients were more than 75 years old. All 41 patients went on to surgery. Pathological CR was seen in 10 patients (24.3%). 4 patients (9.7%) were upstaged from N- by EUS to pN+ disease. Adjuvant chemotherapy with capecitabine or FOLFOX or 5-FU was administered in 38 (92%) patients, while 3 patients declined treatment. Toxicity and treatment intensity by age groups is described in the Table. Median follow was 11 months and all patients are alive with 2 (4.87% ) local recurrences. Conclusions: Neoadjuvant chemoradiation with CIV 5-FU or capecitabine with EUS staging and multimodality planning is feasible in the community setting, producing 24.3% pCR rate consistent with randomized trial data. 92% of patients, particularly 70% of elderly patients, were able to complete trimodality treatment. Definitive EUS under staging is seen in only 4 (9.7%) cases. Neoadjuvant chemoradiation of locally advanced rectal cancer should be a standard practice in the community. N Hematologic Skin GI Any grade 3 Delay/dose reduction in chemotherapy Delay/dose reduction in radiation Refusal of adjuvant treatment Group A <75y 31 11 (35.4%) 27 (87%) 24 (77%) 4 (12.9%) 6 0 0 Group B > 75 10 3 (30%) 9 (90%) 8 (80%) 3 (30%) 1 2 3 No significant financial relationships to disclose.
Tumor-Bound Immunoglobulin in Human Gynecologic Cancers<xref ref-type="fn" rid="FN2">2</xref>
Authors: J P McCoy, D E Hofheinz, A B Ng, S Nordqvist, H G Haines
Journal: JNCI Journal of the National Cancer Institute (1979)

By the use of Immunofluorescence techniques, Immunoglobulin of the IgG class was consistently found In touch preparations and in frozen sections of squamous cell carcinomas of the uterine cervix (both keratinizing and nonkeratinizing) and in an adenosquamous cell carcinoma of the cervix, an adenocarcinoma of the cervix, a mixed mesodermal-uterine tumor, and a uterine adenocarcinoma metastasized to the ovaries. Trace amounts of IgM were found in 1 squamous cell carcinoma and in 1 adenocarcinoma of the cervix. Except for 1 tumor specimen consisting primarily of infiltrating lymphocytes that stained positive for human IgG, IgM, IgA, and C3, the tumors were consistently negative for IgA and C3. Specimens made from normal cervical tissue were uniformly negative for all immunoglobulins and complement. Positive staining for human IgG could be eliminated by incubation of the tumor preparations with unconjugated goat antihuman IgG before the preparations were stained with fluorescein isothiocyanate-conjugated goat antihuman IgG. Attempts to elute the tumor-bound IgG with glycine-HCI buffer (pH 2.2) were most successful with the use of unfixed tissue, although the positive staining for IgG could not be entirely eliminated. The elution effects of the low-pH buffer on tissue fixed over 2 hours in 10% Formalin were minimal.