tbuckley/cabot-search huggingface dataset:
Unexpectedly severe toxicity from intensive early treatment of childhood lymphoblastic leukemia.
Authors: G K Rivera, W E Evans, D K Kalwinsky, J Mirro, J Ochs, L W Dow, M Abromowitch, C H Pui, G V Dahl, A T Look
Journal: Journal of Clinical Oncology (1985)

In early 1984, we treated 13 consecutive patients with acute lymphoblastic leukemia (ALL) using an induction regimen of rapidly rotated combinations of prednisone, vincristine, asparaginase, teniposide (VM-26), cytosine arabinoside, and high-dose methotrexate (MTX) followed by leucovorin rescue. The intent of this clinical trial, designated Total Therapy Study XI, is to test the hypothesis that greater initial leukemia cell kill will decrease opportunities for the development of drug-resistant mutants, with resultant improvement in the length of disease-free survival. Five patients experienced life-threatening gastrointestinal toxicity within three weeks of the start of treatment. One died. Three other patients had severe abdominal pain, abdominal distention, diarrhea, and weight loss, but not gastrointestinal bleeding. In the remaining five patients, toxicity was rapidly reversible, and each child was able to complete the planned course of chemotherapy. The study was then amended to switch high-dose MTX from the induction phase to the consolidation phase, allowing at least one week for mucosal recovery. Among the next 28 patients who were treated, none showed evidence of severe gastrointestinal toxicity. Patients now receive high-dose MTX alone as consolidation therapy and are tolerating it adequately. Drug timing should be examined critically when intensified multiple-agent regimens are being devised for initial treatment of ALL.
Low-Frequency Brain Oscillations in Schizophrenia
Authors: John Lisman
Journal: JAMA Psychiatry (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 Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Psychiatry journal
Differences in characteristics of United States hematopoietic stem cell transplant (HSCT) centers by proportion of ethnic minorities
Authors: C. J. Schwake, M. Eapen, M. M. Horowitz, F. R. Loberiza
Journal: Journal of Clinical Oncology (2004)

6028 Background: The International Bone Marrow Transplant Registry has reported higher mortality in Hispanics with leukemia and received HLA-identical sibling transplantation when compared to whites. It is unknown if transplant center characteristics can partially explain this disparity. We hypothesize that transplant centers do not systematically differ according to the proportion of minorities transplanted. We compared the characteristics of transplant centers that perform a higher proportion of minorities to centers performing transplants to a predominantly white population. Methods: We obtained center characteristics on 116 U.S. transplant centers performing HLA-identical sibling transplantation and compared the following: physician and other health care provider; transplant unit procedure and resources; and, medical center organization according to the volume percentage of minorities transplanted (high ≥ 20% vs. low< 20 %) and percentage of Hispanics transplanted (high ≥10% vs. low <10 %). Results: Centers transplanting a higher proportion of minorities were more likely to perform fewer transplants/year (40 v 66, p<.01), have fewer devoted transplant beds (10 v 13, p<.05), more likely to be in an urban setting (93% v 73%, p<.01), have lower physician to patient ratio (1:13 v 1:16, p<.03), and were more likely to follow survivors after a year after transplantation (83% v 66%, p<.03). Centers transplanting a higher proportion of Hispanics were also more likely to perform fewer transplants/year (36 v 62, p<.02), have fewer devoted transplant beds (7 v 12, p<.001), less likely to be transplanted in centers performing outpatient transplants (25% vs 56%, p<.005), more likely to be in urban setting (96% v 77%, p<.02), and less likely to have a post-transplant immunization protocol (61% v 83%, p<.01). Conclusions: Center characteristics appear to differ according to the proportion of minorities transplanted; further studies should address the association of these characteristics and it's impact on mortality No significant financial relationships to disclose.
Behavioral precipitants to civil commitment
Authors: L C Rubin, M J Mills
Journal: American Journal of Psychiatry (1983)

The authors examined retrospectively the prehospitalization behavior of 66 voluntary and involuntary psychiatric patients to determine precipitating factors in each person's hospitalization. Involuntary patients had engaged in dangerous acts directed against others more frequently than had voluntary patients. However, very little significant harm was caused by members of either group.
Multicenter phase II study of pre-administrated uracil/tegafur (UFT) plus gemcitabine for unresectable/recurrent pancreatic cancer
Authors: S. Nakamori, W. Endo, Y. Hasuike, S. Masutani, T. Morimoto, H. Ozato, T. Shibata, Y. Takeda, K. Tohno, M. Monden
Journal: Journal of Clinical Oncology (2005)

4152 Background: Gemcitabine (GEM) remains the standard of care for advanced pancreatic cancer. The rationale to develop the pretreatment of 5-fluorouracil (5-FU) and GEM combination in pancreatic cancer is based on that 5-FU is a major mediator of GEM uptake. Our objective was to evaluate the efficacy and toxicity of pre-administration of UFT (uracil/tegafur: prodrug of 5-FU) and GEM combination therapy for unresectable/recurrent pancreatic cancer in outpatient setting. Methods: Major eligibility criteria: histologically or cytologically proven pancreatic adenocarcinoma, measurable disease, age 20–80 yrs, good performance status (50 -100 in KPS), normal renal, liver, and bone marrow function, capable oral intake, and written informed consent. UFT (250 mg/ m2/day) was orally administrated from day 1 through day 6 and from day 8 through 13, and GEM (800 mg/m2, div/30min) was administrated on day 7 and 14, and one week rest every 3 weeks based on the result of the previous phase I study. Results: 36 pts (24 male, 12 female) were enrolled (median age, 63.8 yrs). 24 pts were considered to be unresectable (15: liver metastasis, 2: lymph node, 7: locally advanced). 12 pts were recurrent pancreatic cancer after curative surgery (7: liver metastasis, 3: lung metastasis, 2: local reccuremce). 32 pts were evaluable for efficacy and were treated at outpatient clinic. Median KPS was 90 (range 100 - 50). Median number of courses administrated was 4 (range 1–20). There were 8 partial responses (25%), 18 pts (56%) had stable disease, and 6 pts (19%) had a progression. Reduced CA19–9 level less than a half of that at starting time was observed in 11 pts (34%). Median progression-free survival time was 6.7 months (range 1–21). Median survival time was 8.3 months (range 1.5–26). Grade 3 toxicities were leucopenia (19%), neutropenia (12%), thoronbocytopenia (3%), nausea (3%), and liver dysfunctions (3%). There was no Grade 4 toxiciety. Conclusion: Pre-administrated UFT plus GM is a promising treatment for unresectable/recurrent pancreatic cancer due to a favorable prognosis and less toxicity in outpatient setting. No significant financial relationships to disclose.
The ratio of HBsAg, anti-HCV and anti-HIV positivity in patients indicated for fiberoptic bronchoscopy before the procedure
Authors: Seyfettin Gumus, Mehmet Aydogan, Omer Deniz, Alper Gundogan, Gurkan Mert, Ergun Tozkoparan, Hayati Bilgic
Journal: European Respiratory Journal (2012)

INTRODUCTION:  Performing fiberoptic bronchoscopy has many risks for the bronchoscopy personnel. May be the most important risk is the transmission of tuberculosis bacilli from the patient to the bronchoscopy personnel. In addition, transmission of blood-borne viruses such as hepatitis B, HCV and HIV might be the other important risk for the bronchoscopy personnel particularly for the bronchoscopist. Splash of bronchial secretions to conjunctiva might be considered as the main route of transmission. Non-intact skin exposure might be the second route.   AIM:  The aim this study was to investigate the ratio of the patients having positive results for blood-borne viruses undergoing bronchoscopy before the procedure.   METHOD:  We retrospectively screened the medical files/records of the patients undergoing bronchoscopy procedure between May 2011 and January 2012.   RESULTS:  There were 183 patients with a bronchoscopy indication. Mean age was 35±17. 123 patients had HBsAg, anti-HCV and anti-HIV test results. HBsAg was positive in five patients (4%). Anti-HCV and anti-HIV test results of all the patients were negative.   DISCUSSION:  In our country, different results for HBsAg positivity, between 2%-10%, were reported in different studies. Our results are similar the results of these studies. A ratio of 4% HBsAg positivity should not be seen as a small ratio. Absence of anti-HCV and anti-HIV positivity might be attributed to the small number of study group.   CONCLUSION:  This study suggests that bronchoscopy personnel are under the risk of hepatitis B transmission. Large studies are needed to indicate the transmission risk of blood-born viruses for the bronchoscopy personnel.
Dasatinib suppresses TGFβ-induced epithelial mesenchymal transition and inhibits pulmonary fibrosis
Authors: Motoyasu Kato, Fumiyuki Takahashi, Shigehiro Yagishita, Tetsuhiko Asao, Ryota Kanemaru, Kentaro Suina, Hario Bascoro, Fariz Nurwidya, Isao Kobayashi, Keiko Muraki, Tadashi Sato, Naoko Shimada, Motomi Takahashi, Kazuhisa Takahashi
Journal: European Respiratory Journal (2014)

[Background] Epithelial-mesenchymal transition (EMT) of alveolar epithelial cells may contribute to the pathogenesis of idiopathic pulmonary fibrosis (IPF). It has been reported that imatinib attenuated bleomycin (BLM)-induced fibrosis in mice. Dasatinib (DAS) is tyrosine kinase inhibitor against platelet derived growth factor receptor as well as imatinib. However, there have been no studies on the effects of DAS on pulmonary fibrosis. [Aim] Our aim is to investigate the effect of DAS on TGFβ-induced EMT in human alveolar epithelial cells in vitro and to evaluate the efficacy of DAS on lung fibrosis in vivo. [Materials and Methods] A549 cells were stimulated with TGFβ and treated with or without DAS. We analyzed epithelial and mesenchymal markers by quantitative real time PCR and western blot and cell motility by wound healing assay. We developed a mouse model for pulmonary fibrosis by intravenous injection of BLM. Either DAS or vehicle was administered by oral gavage, and mice were sacrificed on day 22. We evaluated pathological findings and measured the collagen contents in the lungs of the mice. [Results] In vitro , TGFβ-induced expression of mesenchymal proteins and transcriptional factors were significantly suppressed by the treatment with DAS. Furthermore, DAS markedly inhibited TGFβ-induced cell motility. In vivo, treatment with DAS significantly attenuated BLM-induced lung fibrosis and collagen contents in the lungs. [Conclusion] These findings suggest that DAS inhibits pulmonary fibrosis by suppressing TGFβ-induced EMT. DAS may be a promising and novel anti-fibrotic agent for the prevention of IPF.
Thymidylate synthase expression and response to irinotecan/5-fluorouracil therapy in advanced colorectal cancer (CRC).
Authors: S. Jhatakia, H. J. Miller, D. Sigal
Journal: Journal of Clinical Oncology (2010)

e14123 Background: Molecular diagnostics are at the forefront of cancer therapy. Defining cellular profiles of malignancies facilitates selecting the most efficacious chemotherapy regimen. Thymidylate synthase (TS) is a critical enzyme in DNA synthesis and the target of 5-fluorouracil (5FU). Previous studies have identified an inverse relationship between tumoral TS expression and 5FU efficacy in colorectal cancer. Saltz et al described irinotecan (CPT-11) as an effective agent even in patients with high TS levels when combined with 5FU. Noda et al confirmed the relationship in 27 Japanese patients treated with IFL (5FU, CPT-11 and leucovorin). This association highlights the ability to treat patients with high TS expression using 5FU and CPT-11 combinations. Our study was designed to confirm these findings. Methods: TS gene expression was measured from metastatic tumors (primary tumor tissue was used if metastatic was not available) via RT-PCR extraction of formalin-fixed, paraffin-embedded samples. No clear cutoff exists for high and low TS expression; therefore, 3 separate cutoffs were assessed as previously published in the literature. A total of 36 patients treated with an CPT-11/5FU based regimen for advanced colorectal cancer were evaluated. Fifteen tissue blocks had limited tissue and analysis was not done. Seventeen patients had full follow-up data and are included in this interim analysis. The TS gene expression was then correlated to the response of the CPT-11- 5FU based regimen. Primary endpoints included clinical benefit (CR+PR+SD) and time to treatment failure (TTF). Results: Clinical benefit and TTF were found to be comparable in patients treated with an CPT-11-5FU combination regardless of TS expression (Table). Conclusions: This study provides additional data confirming that CPT-11-5FU combination therapies for advanced CRC can be effective even in patients with elevated TS mRNA values across all three reported TS cutoff values. TS ≥ 1.6 TS < 1.6 P value TS ≥ 2.76 TS < 2.76 P value TS ≥ 4 TS < 4 P value CB (%) 50 100 0.10 50 77.8 0.34 50 63.6 0.60 PD (%) 50 0 50 22.2 50 36.4 TTF (weeks) 44.3 16.8 0.93 40.9 34.8 0.72 32.0 39.9 0.66 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Response Genetics
Combination chemotherapy with irinotecan and cisplatin in elderly patients (≥65 years) with extensive-disease small-cell lung cancer
Authors: G. Lee, K. Kim, Y. Cho, H. Kim, I. Hwang, H. Kim, J. Kang, J. Jang, J. Lee
Journal: Journal of Clinical Oncology (2007)

18135 Background: Combination chemotherapy with irinotecan and cisplatin is one of the standard treatments for patients with small-cell lung cancer (SCLC). In elderly patients, however, its efficacy and toxicity has not been well documented. In this Phase II study, we assessed the efficacy and toxicity of combination chemotherapy with irinotecan and cisplatin and examined whether advanced age compromises it in elderly patients with previously untreated extensive-disease small-cell lung cancer (ED-SCLC). Methods: In this study, 43 previously untreated elderly patients (65 years or older) with ED-SCLC were given combination chemotherapy consisting of irinotecan 60mg/m 2 on days 1, 8 and 15 and cisplatin 60mg/m 2 on days 1. The treatment was repeated every four weeks until patients completed the maximum six cycles. Results: Patients consisted of 34 men and 9 women, whose median age was 70 years (range 65 - 81 years). A complete response and a partial response were observed in 23.3% (10/43) and 58.1% (25/43), respectively. The overall response rate was 81.4% (95% C.I; 69.7 - 93.0%). The overall median survival was 10.3 months (range 7.8 - 12.7 months). The 1-year and 2- year survival rates were 31.8% and 3.4%, respectively. The median progression-free survival was 8.32 months (range 6.8 - 9.8 months). Major toxicities included neutropenia (grade 3 to 4, 55.9%), leukopenia (grade 3 to 4, 46.5%), infection (grade 3 to 4, 37.3%) and diarrhea (grade 3 to 4, 30.3%). Incidence of febrile neutropenia was significantly higher in patients with ECOG performance status 2 compared with ECOG performance 1 (70.7% vs. 5.2%; p &lt; 0.001). There were two treatment related deaths in patients ECOG performance status 2. Conclusions: Our results indicate that combination chemotherapy with irinotecan and cisplatin is an effective treatment for elderly patients with ED-SCLC. However, physicians should be aware of the mortality and morbidity due to myelosuppression following this treatment in elderly ED-SCLC patients with ECOG performance status 2. No significant financial relationships to disclose.
Expression and Role of the ErbB3-Binding Protein 1 in Acute Myelogenous Leukemic Cells
Authors: Le Xuan Truong Nguyen, Li Zhu, Yunqin Lee, Lynn Ta, Beverly S. Mitchell
Journal: Clinical Cancer Research (2016)

The ErbB3-binding protein 1 (Ebp1) has been implicated in diverse cancers as having either oncogenic or tumor suppressor activities. The present study was undertaken to determine the effects of Ebp1 expression in AML cells and to determine the mechanisms by which Ebp1 promotes cell proliferation in these cells.The expression of Ebp1 was studied in mononuclear cells obtained from the peripheral blood of 54 patients with AML by Western blot analysis. The effects of Ebp1 expression on proliferating cell nuclear antigen (PCNA) expression and cell proliferation was measured using Western blot analysis, immunoprecipitation, in vitro ubiquitination, and colony-forming assays. The role of Ebp1 in promoting rRNA synthesis and cell proliferation was evaluated by measuring the level of pre-rRNA and the recruitment of Pol I to rDNA.Ebp1 is highly expressed in acute myelogenous leukemia (AML) cells and regulates the level of ribosomal RNA (rRNA) synthesis by binding to RNA Polymerase I (Pol I) and enhancing the formation of the Pol I initiation complex. Ebp1 also increases the stability of PCNA protein by preventing its interaction with Mdm2, for which it is a substrate.These results demonstrate an important role of Ebp1 in promoting cell proliferation in AML cells through the regulation of both rRNA synthesis and PCNA expression. Clin Cancer Res; 22(13); 3320-7. ©2016 AACR.
A phase Ib study to evaluate the safety and efficacy of AMG 655 in combination with gemcitabine (G) in patients (pts) with metastatic pancreatic cancer (PC)
Authors: H. L. Kindler, L. Garbo, J. Stephenson, J. Wiezorek, T. Sabin, M. Hsu, F. Civoli, D. Richards
Journal: Journal of Clinical Oncology (2009)

4501 Background: AMG 655 is an investigational, fully human agonist monoclonal antibody (IgG1) that binds human death receptor 5 (DR5), activates caspases, and induces apoptosis in sensitive tumor cells. In preclinical PC models, cooperative activity is observed when G is added to AMG 655. We performed a multi-center phase I trial to evaluate AMG 655 + G in metastatic PC pts. The primary endpoint was dose-limiting toxicity (DLT). Secondary endpoints included toxicity, pharmacokinetics, antibody formation, objective response rate, progression-free survival (PFS), 6-month and overall survival. Methods: Eligible pts had previously untreated metastatic PC and ECOG PS 0 or 1. Pts enrolled into sequential cohorts and received AMG 655 3 or 10 mg/kg IV days (D) 1 and 15 and G 1000 mg/m 2 IV D 1, 8, and 15 every 28 D. CT scans were obtained Q8 weeks. Results: 13 pts (3 mg/kg cohort = 6; 10 mg/kg cohort = 7) enrolled from 7/07–11/07. Pt characteristics: females 61%; ECOG PS 1 69%; median age 65 (range 35–81); liver metastases 77%. Median number of cycles: 6 (range 2–12). There were no DLT. Nine (69%) pts had grade 3–4 toxicity, the most common were: thrombocytopenia (4 pts), neutropenia (2 pts), and abdominal pain (2 pts). No anti-AMG 655 antibodies were detected. After one 3 or 10 mg/kg dose of AMG 655 after G, the C max and AUC of AMG 655 were similar to those in the first- in-human single-agent study (LoRusso JCO 2007; 25: abstract 3534). Preliminary data indicate no effect of AMG 655 on PK of G. Partial response 31% (4 pts, 2 unconfirmed); stable disease 38%. Median PFS: 5.3 months (95% CI, 3.5, 6.2); 6-month survival rate: 76.2% (95% CI: 42.7%-91.7%). Conclusions: AMG 655 + G is well-tolerated and may have activity in metastatic pancreatic cancer. A randomized phase II trial of G ± AMG 655 at 10-mg/kg is currently enrolling. [Table: see text]
INhaler compliance assessment in the community (INCA GP)
Authors: Imran Sulaiman, Elaine MacHale, Shona D'Arcy, Jansen Seheult, Richard Costello
Journal: European Respiratory Journal (2014)

Adherence to medication among chronic obstructive pulmonary disease (COPD) and asthma patients is known to be poor which may negatively impact on patient's clinical outcomes. In Ireland the majority of patients with obstructive airways disease are treated in the community by general practitioners (GPs), and may never be referred to a specialist. GPs tend to be extremely busy, overbooked and lacking facilities such as Respiratory Nurses. This doesn't allow for lengthy discussions with these patients, particularly regarding their inhaler management. This study aims to monitor rates of inhaler adherence and identify technique errors using novel technology (INCA).

Six GP practices were given INCA-enabled salmeterol/fluticasone diskus inhalers. GPs enrolled any patient with a history of asthma or COPD on a salmeterol/fluticasone diskus inhaler. Patients were given an INCA-enabled diskus inhaler for a month. Once returned, we downloaded all available data.

42 INCA inhalers provided us with adherence data. Looking at adherence rates in time these ranged from as high as 109% (overdosing) and as low as 8% (under-dosing). Average adherence rate, in time for a month of data, was 70%. There were technique errors noted; most frequent being, poor inspiratory flow rate and exhaling into an inhaler prior to inhalation. Combined adherence (combining errors in time and technique) was low at a rate of 59%.

This is an initial observational study on inhaler use in the community through general practitioners using a novel device, the INCA. Our study shows that adherence remains very variable and chaotic in the community. We hope to do a follow up study, educating this group of patients on inhaled medication with the aid of the INCA device.