tbuckley/cabot-search huggingface dataset:
Phase I trial of micronized formulation carboxyamidotriazole in patients with refractory solid tumors: pharmacokinetics, clinical outcome, and comparison of formulations.
Authors: E C Kohn, W D Figg, G A Sarosy, K S Bauer, P A Davis, M J Soltis, A Thompkins, L A Liotta, E Reed
Journal: Journal of Clinical Oncology (1997)

PURPOSE Cytostatic agents targeted against angiogenesis and tumor cell invasive potential form a new class of investigational drugs. Orally administered carboxyamidotriazole (CAI) (NSC609974) is both antiangiogenic and antimetastatic. An encapsulated micronized powder formulation has been developed to optimize CAI administration. A phase I dose escalation trial with pharmacokinetic analysis has been performed. PATIENTS AND METHODS Twenty-one patients with refractory solid tumors and good end organ function and performance status were enrolled onto the study. Patients received a test dose followed 1 week later by daily administration of CAI in the encapsulated micronized formulation at doses of 100 to 350 mg/m2. Patients remained on CAI until disease progression or dose-limiting toxicity. Plasma samples were taken to characterize the pharmacokinetic parameters of this formulation of CAI. RESULTS All patients were assessable for toxicity and 18 were assessable for pharmacokinetics and response analysis. Grade 1 and 2 gastrointestinal side effects were observed in up to 50% of patients. Dose-limiting toxicity was observed in both patients treated at 350 mg/m2/d, consisting of reversible grade 2 to 3 cerebellar ataxia (n = 1) and confusion (n = 1). One minor response (MR) was observed in a patient with renal cell carcinoma and another nine patients had disease stabilization (MR + SD = 47%). Pharmacokinetic analysis demonstrated reduced bioavailability (58% reduction) compared with the PEG-400 liquid formulation previously reported. CONCLUSION The better toxicity profile of encapsulated micronized CAI with similar frequency of disease stabilization and ease of administration compared with the liquid or gelatin capsule, suggests that the micronized formulation is a preferable formulation for subsequent studies. A dose of 300 mg/m2/d is proposed for phase II investigations.
Postdisaster psychosocial intervention: a field study of the impact of debriefing on psychological distress
Authors: C M Chemtob, S Tomas, W Law, D Cremniter
Journal: American Journal of Psychiatry (1997)

Following a catastrophic natural disaster, the authors evaluated whether brief psychological intervention (debriefing 6 months later) reduced disaster-related psychological distress as measured by the Impact of Event Scale.Two groups of subjects who had been exposed to Hurricane Iniki in Hawaii were assessed before and after participating in a multihour debriefing group. The intervention aimed to provide ventilation of feelings, normalization of responses, and education about normal psychological reactions to the disaster in a context of group support. To provide a partial control for the passage of time, the pretreatment assessment of the second group was concurrent with the posttreatment assessment of the first group.A repeated measures analysis of variance indicated that Impact of Event Scale scores were reduced in both groups after the treatment.There is preliminary empirical support for the effectiveness of postdisaster psychological intervention and for the feasibility of treatment research in postdisaster environments.
Successful treatment of stage III neuroblastoma based on prospective biologic staging: a Children's Cancer Group study.
Authors: K K Matthay, C Perez, R C Seeger, G M Brodeur, H Shimada, J B Atkinson, C T Black, R Gerbing, G M Haase, D O Stram, P Swift, J N Lukens
Journal: Journal of Clinical Oncology (1998)

PURPOSE To identify a biologically favorable and unfavorable subset of patients with Evans stage III neuroblastoma and to determine whether treatment stratification would improve the event-free survival (EFS) for high-risk patients and maintain excellent EFS for the lower-risk patients. PATIENTS AND METHODS Risk stratification was performed by age, MYCN gene copy number, Shimada histopathologic classification, and serum ferritin level. Lower-risk patients were treated on the less intensive Children's Cancer Group (CCG)-3881, whereas high-risk patients were treated on CCG-3891, which included more intensive multimodality therapy and, in some cases, autologous bone marrow transplantation (ABMT). RESULTS Of 228 Evans stage III patients entered onto the study, 92% also met the definition of International Neuroblastoma Staging System (INSS) stage 3. One hundred forty-three patients met the lower-risk criteria, which included 89 patients less than 1 year of age and 54 patients 1 year of age or greater, and favorable biology, whereas 85 patients were 1 year of age or greater and biologically unfavorable. Biologically unfavorable patients 1 year of age or greater who underwent gross surgical resection had improved survival, whereas the outcome of infants or biologically favorable older patients did not change according to resection. The EFS rate at 4 years was 100% for the patients with favorable biology of any age, 90% for those less than 1 year of age but with at least one unfavorable characteristic, and 54% for Evans stage III patients 1 year of age or greater with unfavorable biology. Age, ferritin level, MYCN copy number, Shimada histopathology, primary site, and intraspinal extension were significant univariate prognostic factors for all patients, but only MYCN copy number and age were independent factors in multivariate analyses. CONCLUSION The excellent survival of the biologically favorable group and the historically improved EFS of the biologically unfavorable group suggest that biologic staging should be used to define the prognosis and treatment of stage III neuroblastoma.
Abstract 17485: Novel Role of NADPH Oxidase Subunit p67phox C-terminus Region in Mediation of {alpha}1-Adrenergic Receptor-Induced Cardiac Hypertrophy
Authors: Guiqing Zhao, Chongxu Zhang, Xianyao Xu, Qiong Zhao, J. D Lambeth, Lei Xiao
Journal: Circulation (2011)

We previously reported that α1-adrenergic receptor (α1AR)-induced hypertrophy in adult rat ventricular myocytes (ARVM) was mediated via activation of MEK1/2-ERK1/2 cascade. The hypertrophy was atte...
Pulmonary mycobacterial infection in allogeneic hematopoietic stem cell transplanted (HSCT) patients: A study of 7 cases
Authors: Emilie Catherinot, Elisabeth Rivaud, Patrick Honderlick, Nathalie Dhedin, Felipe Suarez, Colas Tcherakian, Olivier Lortholary, Pierre Cahen, Louis-Jean Couderc
Journal: European Respiratory Journal (2011)

Rationale: Allogeneic HSC transplantation is being used to treat a wide spectrum of diseases. Opportunistic infection remains an important factor determining outcome. However, information about frequency and presentation of mycobacterial infections is limited.

Methods: Records from all allogeneic HSCT patients admitted in our institution for mycobacterial infection from January 1, 2003 to December 31, 2010 were reviewed.

Results: During the eight years of study, 178 HSCT patients have been admitted for pulmonary complications. 7 patients have had a diagnosis of mycobacterial infection.

View this table:

Table 1





Conclusion: Mycobacterial infection is rare (4%) in French HSCT patients with pulmonary complication. The infection is lung limited. It usually occurs in the first post-transplantation year. The clinical course under treatment is favorable in most cases.
Accurate, reproducible, and quantitative measurement of protein analyte concentration(s) in tissue slides
Authors: David Rimm, Robert Camp, Allison Welsh, Christopher Moeder, Jennifer Giltnane, Sharon Pozner-Moulis, Marisa Dolled-Filhart, Harriet Kluger, Gina Chung, Mark Gustavson, Jason Christiansen
Journal: Clinical Cancer Research (2008)

ED01-02  Immunohistochemistry (IHC) has been used as a tool for over a quarter of a century to assess protein concentration within the context of the spatial information that is the keystone of anatomic pathology. During that time period the chromogenic method itself has changed very little and as a result the output is still largely subjective and fraught with error as a function of uncontrolled variables. This has led to recent attempts at standardization (the 2007 ASCO/CAP guidelines for HER2 assessment) which are likely to be just the beginning of the changes that will be necessitated by the push toward evidence-based medicine and personalized medicine requiring companion diagnostics. Unfortunately, those guidelines resort to “proficiency testing” as a standard, rather than a National Institute of Standards (NIST) approved, absolute physical standard that could be based on molecular parameters and reproduced at all users’ sites. Toward the goal of generating such a standard that could be used as a future method for absolute standardization of IHC, we have invented the fluorescence-based AQUA method. This technology uses molecular co-localization to derive exact protein concentrations within subcellular compartments. It allows assessment of accuracy and reproducibility in a manner similar to an ELISA or RIA assay and has been shown to have CVs less than 5%. However, its use has revealed significant, inherent variability associated with the process of measuring protein concentrations using antibody-based methods on formalin fixed, paraffin embedded tissue. Key examples include pre-analytic variables (like time to fixation), section oxidation, lot-to-lot antibody inconsistency and other variables. These variables can be detected and standardized with a series of extrinsic and intrinsic controls. Extrinsic controls are used to show the exact concentration of both HER2 and ER using standards that can be reproduced and tested, independent of site or personnel. Intrinsic controls are more challenging, and definitive methods are still in development. Ultimately, we believe that the measurement of a protein analyte in tissue on a slide will be as accurate, objective and reproducible as measurement of a serum sodium or a blood glucose.
Use of tamoxifen for breast cancer: twenty-eight years later.
Authors: I A Jaiyesimi, A U Buzdar, D A Decker, G N Hortobagyi
Journal: Journal of Clinical Oncology (1995)

PURPOSE The mechanisms of antitumor activity, clinical pharmacology, toxicity, and efficacy of tamoxifen in women with early and advanced breast cancer and the drug's potential role in prevention of breast cancer were reviewed. DESIGN A comprehensive review of the literature from 1966 to 1994 was conducted; reports were identified using the Cancerline and Medline data bases. RESULTS The cellular actions of tamoxifen are not completely understood, but it appears that the drug's antiproliferative effects are mediated primarily by inhibition of the activities of estrogen through binding to estrogen receptors (ERs). Disease-free and overall survival rates have been increased in postmenopausal women with ER-positive tumors when tamoxifen has been used as adjuvant therapy (irrespective of nodal status). In premenopausal women, adjuvant therapy with tamoxifen has been associated with prolongation of disease-free survival, but its impact on survival remains to be defined. Tamoxifen is the initial hormonal treatment of choice in both premenopausal and postmenopausal women with ER-positive metastatic disease. Retrospective review of adjuvant therapy studies showed an approximately 39% reduction in the incidence of contralateral primary breast carcinoma in tamoxifen-treated women, which indicates that tamoxifen could have a role in breast cancer prevention. CONCLUSION The use of tamoxifen has resulted in a substantial modification of breast cancer's natural history, particularly in postmenopausal women. Ongoing clinical trials will examine the effects of tamoxifen therapy on lipids, coagulation proteins, bone, and endometrium, and its effectiveness as an agent in the prevention of breast cancer.
Combination procarbazine and temozolomide for temozolomide-resistant adult gliomas
Authors: P. Kavan, F. Huang, D. Roberge
Journal: Journal of Clinical Oncology (2006)

11503 Background: As Temozolomide has become incorporated in the first line treatment of glioblastoma multiforme as well as the salvage therapy of many low-grade gliomas, we are increasingly faced with Temozolomide failures. There is currently no standard second-line chemotherapy for Temozolomide-resistant tumors. In what is usually a palliative setting, toxicity and convenience are important considerations in the choice of a second-line regimen. Methods: We reviewed our experience with a combination oral regimen for Temozolomide failure. The regimen consisted of a 28-day cycle with Procarbazine given at 100–150mg/m 2 /d on days 1–5, and Temozolomide at 150mg/m 2 /d on days 1–5. This was initiated at the time of radiological and/or clinical progression while on Temozolomide, and continued until further progression or toxicity was documented. Results: 12 patients, median age 52 (range 38–68), were treated with concomitant Procarbazine and Temozolomide at our institution since November 2004. All patients had histologically confirmed gliomas (glioblastoma multiforme (10), grade II oligodendroglioma (1), grade II oligoastrocytoma (1)), and all had undergone prior maximal safe resection and external beam radiotherapy. All patients were receiving Temozolomide, either in the adjuvant setting (after concurrent chemo-radiotherapy in 6 of 12), or as salvage monotherapy for recurrence. No patient met the RECIST criteria for PR. Patients progressed after a median of 2 cycles (range: 1–10) but the 6-month actuarial progression-free survival was 40% (80% of patients with SD had glioblastoma multiforme). No Grade 3 or 4 toxicity was seen. No patient discontinued treatment because of toxicity. The Procarbazine dose was prophylactically reduced (75mg/m 2 /d) in one patient with poor hematological tolerance to prior chemotherapy. Conclusions: The combination of Procarbazine and Temozolomide given in a 28-day cycle is a well-tolerated oral second-line regimen for glioma patients failing Temozolomide. The activity of this regimen is modest but prolonged progression-free survival can be seen. [Table: see text]
Screening for hydroxychloroquine retinopathy
Authors: K. May, T. Metcalf, A. Gough, C. Blyth, C. Lane
Journal: BMJ (1998)

Editor—The editorial on screening for hydroxychloroquine retinopathy covered none of the recent publications on the subject and failed to distinguish those cases in which screening is necessary.1

Levy et al’s review of 1505 patients found no cases of proved retinopathy in patients taking <6.5 mg/kg/day of hydroxychloroquine but one case in a patient taking a higher dose.2 Silman and Shipley point out that “bull’s eye retinopathy” can occur in patients not taking hydroxychloroquine.3 Indeed, Scherbel et al reported that the incidence of maculopathy in patients with rheumatoid arthritis was greater in untreated patients than in those receiving hydroxychloroquine or chloroquine.4 Mavrikakis and colleagues’ study of 360 patients identified two cases of retinopathy with daily doses <6.5 mg/kg.5 In both of these cases the cumulative dose exceeded 700 g.

Research confirms that hydroxychloroquine is safer than chloroquine and that at a daily dose of hydroxychloroquine <6.5mg/kg the risk of retinopathy is negligible if patients are younger than 60 years with normal renal and liver function.2 In these circumstances regular screening is unnecessary, although we suggest recording visual acuity before starting treatment.

We recommend ophthalmic screening in the following patients, for whom evidence suggests an increased risk of hydroxychloroquine retinopathy: patients with known retinal disease or visual impairment; with renal or liver impairment; over 60 years old; receiving a daily dose greater than 6.5mg/kg; or who have received an accumulated dose above 500 g.

Screening should take the form of an initial ophthalmic assessment and annual ophthalmic review for the duration of treatment. The best form of ophthalmic assessment is unclear and currently depends on the preferences of the screening ophthalmologist. We recommend visual acuity, automated perimetry, and funduscopy, ideally with initial fundal photographs. Fluorescein angiography should be used in elderly people to differentiate between age related macula degeneration and hydroxychloroquine toxicity when continuing treatment with hydroxychloroquine is deemed essential.

The decision to stop treatment will depend on the opinion of both the ophthalmologist and the treating physician, taking into account the likelihood that retinal and visual changes are due to hydroxychloroquine, the extent of retinal damage, and the risk of increased disease activity after stopping treatment. It should be noted that effects of stopping treatment are uncertain as both progression and reversibility have been reported.
Tuberculosis in patients with different lung neoplasm: The analysis of 17126 patients. MDCT with perfusion, virtual bronchoscopy and pulmonary angiography
Authors: Tamara Milosavljevic, Aleksandar Ivkovic, Zoran Radovanovic
Journal: European Respiratory Journal (2013)

Purpose: The aim of the study was to correlate the frequency of different malignancies in patients with tuberculosis  Material and Methods: The group of analyzed patients consisted of 14762 patients who underwent MDCT examination of lung under suspicion of lung malignancies. There were 9011 males (59.32%) and 5751 females (40.68%). Also we examined 2422 with laryngeal cancer, and 483 with thoracic trauma. MRI with DWI was performed in 451 patients.  Results: Out of 14762 examined patients there were 14221 (96.33%) with detected lung cancer. Among them different stages of TB were identified and confirmed with additional diagnostic investigations in 5841 (39.57%) patients. It was confirmed that in 84% of patients with TB there were tumors with slow progression, opposite to lower frequency of TB in patients with metastatic disease and sarcomas. In the group of patients with laryngeal cancer, lung TB was diagnosed in 121 (4.99%) patients. Out of 483 patients with thoracic trauma tuberculosis was identified in 18 patients, and confirmed in other 36. Additional in patients with trauma 4 lung cancer were diagnosed. In all patients diagnosis of tuberculosis was confirmed with standard methods, in the group of surgically treated through pathological examination.  Conclusion: CT scan is powerful diagnostic tool in accidentally diagnosis of different stages of tuberculosis in patients examined under suspicions of lung neoplasm. Patients with cavernous TB were more prone to lung neoplasm. In patients with laryngeal cancer it was observed fibrous-caseous forms of TB. MRI with DWI is great tool for determining of lymph nodes and mediastinum.
CHOP is the standard regimen in patients &gt; or = 70 years of age with intermediate-grade and high-grade non-Hodgkin's lymphoma: results of a randomized study of the European Organization for Research and Treatment of Cancer Lymphoma Cooperative Study Group.
Authors: U Tirelli, D Errante, M Van Glabbeke, I Teodorovic, J C Kluin-Nelemans, J Thomas, D Bron, G Rosti, R Somers, V Zagonel, E M Noordijk
Journal: Journal of Clinical Oncology (1998)

PURPOSE We report the results of a randomized study of the European Organization for Research and Treatment of Cancer (EORTC) Lymphoma Group, which compared a chemotherapy regimen specifically devised for elderly patients, ie, etoposide, mitoxantrone, and prednimustine (VMP), versus the standard regimen of cyclophosphamide, doxorobucin, vincristine, and prednisone (CHOP) in patients older than 70 years of age with intermediate- and high-grade non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS Patients older than 70 years of age with stage II, III, or IV intermediate- and high-grade NHL, with an Eastern Cooperative Oncology Group (ECOG) performance status less than 4 and acceptable cardiac, renal, and liver function were randomized to receive six courses of VMP or six courses of CHOP. Between February 1989 and June 1994, 130 patients aged 70 to 93 years (median, 75) were enrolled and 120 were assessable for response, 60 patients in each arm. RESULTS Overall objective response rates were 50% and 77% in VMP- and CHOP-treated patients, respectively (P = .01), while complete response (CR) rates were borderline significant (27% v 45%; P = .06). At 2 years, the progression-free survival (PFS) rate was 25% with VMP versus 55% with CHOP (P = .002) and the overall survival (OS) rate was 30% with VMP versus 65% with CHOP (P = .004). Statistically significant more alopecia and neurologic and gastrointestinal toxicities were reported with CHOP. CONCLUSION CHOP is the standard regimen for patients &gt; or = 70 years of age with stage II to IV intermediate- and high-grade NHL.
Incidence of Fractures in Patients With Type 2 Diabetes in the SAVOR-TIMI 53 Trial
Authors: Ofri Mosenzon, Cheryl Wei, Jaime Davidson, Benjamin M. Scirica, Ilan Yanuv, Aliza Rozenberg, Boaz Hirshberg, Avivit Cahn, Christina Stahre, Krzysztof Strojek, Deepak L. Bhatt, Itamar Raz
Journal: Diabetes Care (2015)

OBJECTIVE Patients with type 2 diabetes have an increased risk of bone fractures, the predisposing factors for which are unknown. Treatment with thiazolidinediones (TZDs) further increases the incidence of osteoporotic fractures. In the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus–Thrombolysis in Myocardial Infarction 53 (SAVOR-TIMI 53) trial, fractures were considered an adverse event of special interest, and information regarding fractures was collected. RESEARCH DESIGN AND METHODS We compared the incidence of fractures among the 8,280 patients who were assigned to treatment with saxagliptin with that in the 8,212 patients who were assigned to placebo. We further analyzed the participants’ baseline characteristics and fracture risk. RESULTS During a median follow-up of 2.1 years, 241 patients (2.9%) in the saxagliptin group and 240 (2.9%) in the placebo group experienced a fracture (hazard ratio [HR] 1.00 [95% CI 0.83–1.19]). Event rates for fractures were the same in both treatment arms: 14.7 per 1,000 patient-years in the entire population and 14.0 in the on-treatment population (first event only). Fracture risk was similar in patients treated with saxagliptin or placebo across different subgroups defined by race, cardiovascular risk, and renal function. A multivariable Cox regression analysis showed that risk of fracture was associated with female sex (P &amp;lt; 0.0001), longer diabetes duration (P &amp;lt; 0.0001), older age (P = 0.002), major hypoglycemic events (P = 0.01), noncompliance with study drug (P = 0.01), and treatment with TZDs (P = 0.03). CONCLUSIONS In a large population of older patients with type 2 diabetes, treatment with saxagliptin was not associated with an increased risk of fractures. The association between longer diabetes duration and increased risk of bone fracture is an intriguing finding.
Severe depersonalization treated by behavior therapy
Authors: D Sookman, L Solyom
Journal: American Journal of Psychiatry (1978)

The author reports the use of behavior therapy in the treatment of two cases of severe intractable depersonalization. Outcome criteria included full psychiatric assessment, patients' self-ratings, and psychometric test scores. Treatment by flooding was highly effective in one case, and associated obsessive symptoms and anticipatory anxiety were substantially decreased in the other. Behavioral techniques may prove especially helpful in cases in which anticipatory anxiety, phobic avoidance, and obsessive perseveration are exacerbating features.