tbuckley/cabot-search huggingface dataset:
Lymphopenia is an important prognostic factor in peripheral T-cell lymphoma (NOS) treated with anthracycline-containing chemotherapy
Authors: Yu Ri Kim, Jin Seok Kim, Soo Jeong Kim, Hyun Ae Jung, Seok Jin Kim, Won Seog Kim, Hye Won Lee, Hyeon Seok Eom, Seong Hyun Jeong, Joon Seong Park, June-Won Cheong, Yoo Hong Min
Journal: Journal of Hematology & Oncology (2011)

Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is a heterogeneous group of aggressive T-cell lymphomas with poor treatment outcomes. The aim of this study was to evaluate whether lymphopenia at diagnosis would have an adverse effect on survival in patients with PTCL-NOS treated with anthracycline-containing chemotherapy.A total of 118 patients with PTCL-NOS treated with anthracycline-containing chemotherapy from 4 Korean institutions were included.Thirty-six patients (30.5%) had a low absolute lymphocyte count (ALC, < 1.0 × 109/L) at diagnosis. Patients with lymphopenia had shorter overall survival (OS) and progression-free survival (PFS) rates compared with patients with high ALCs (P = 0.003, P = 0.012, respectively). In multivariate analysis, high-intermediate/high-risk International Prognostic Index (IPI) scores and lymphopenia were both associated with shorter OS and PFS. Treatment-related mortality was 25.0% in the low ALC group and 4.8% in the high ALC group (P = 0.003). In patients considered high-intermediate/high-risk based on IPI scores, lymphopenia was also associated with shorter OS and PFS (P = 0.002, P = 0.001, respectively).This study suggests that lymphopenia could be an independent prognostic marker to predict unfavorable OS and PFS in patients with PTCL-NOS treated with anthracycline-containing chemotherapy and can be used to further stratify high-risk patients using IPI scores.
Hematogenous Friedländer's Bacillus Osteomyelitis
Authors: Alan G. Smith
Journal: JAMA (1966)

ACUTE hematogenous osteomyelitis in the long bones of adults is a rare disease. In 1938 Zadek<sup>1</sup>described the condition and reported nine cases which illustrated typical findings. He emphasized that hematogenous osteomyelitis in adults has a slow and insidious onset. The temperature and white blood cell count (WBC) are often only slightly elevated. The process begins in the diaphysis rather than metaphysis. There may be spread along the whole length of bone and extension into the joints. X rays reveal spotty atrophy of the cortex over an area of several inches. There is local erosion of bone, no sequestrum formation occurs, and new bone formation has a laminated appearance. Trueta<sup>2</sup>in 1959 divided acute hematogenous osteomyelitis into three types: infant, childhood, and adult. The findings in each type were distinct and the diverse clinical picture of each age group was logically explained. In adults, he described findings similar
Practice changing mature results of RTOG study 9802: another positive PCV trial makes adjuvant chemotherapy part of standard of care in low-grade glioma
Authors: M. J. van den Bent
Journal: Neuro-Oncology (2014)

The long-term follow-up of the RTOG 9802 trial that compared 54 Gy of radiotherapy (RT) with the same RT followed by adjuvant procarbazine, CCNU, and vincristine (PCV) chemotherapy in high-risk low-grade glioma shows a major increase in survival after adjuvant PCV chemotherapy. Median overall survival increased from 7.8 years to 13.3 years, with a hazard ratio of death of 0.59 (log rank: P = .002). This increase in survival was observed despite the fact that 77% of patients who progressed after RT alone received salvage chemotherapy. With this outcome, RT + PCV is now to be considered standard of care for low-grade glioma requiring postsurgical adjuvant treatment. Unfortunately, studies on molecular correlates associated with response are still lacking. This is now the third trial showing benefit from the addition of PCV to RT in grade II or III diffuse glioma. The optimal parameter for selecting patients for adjuvant PCV has not yet been fully elucidated, but several candidate markers have so far emerged. It is still unclear whether temozolomide can replace PCV and whether initial management with chemotherapy only is a safe initial treatment. Potentially, that may adversely affect overall survival, but concerns for delayed RT-induced neurotoxicity may limit acceptance of early RT in patients with expected long term survival. The current evidence supports that in future trials, grades II and III tumors with similar molecular backgrounds should be combined, and trials should focus on molecular glial subtype regardless of grade.
Predicting decline and survival in severe acute brain injury: the fourth trajectory
Authors: Claire J Creutzfeldt, W T Longstreth, Robert G Holloway
Journal: BMJ (2015)

Illness trajectories depicting how function declines to death with certain diseases, such as cancer, can help with palliative care. <b>Creutzfeldt and colleagues</b> propose a fourth trajectory is needed for patients with severe acute brain injury to improve decision making and standards of care
Filamin A regulates focal adhesion disassembly and suppresses breast cancer cell migration and invasion
Authors: Yingjie Xu, Tarek A. Bismar, Jie Su, Bin Xu, Glen Kristiansen, Zsuzsanna Varga, Lianghong Teng, Donald E. Ingber, Akiko Mammoto, Rakesh Kumar, Moulay A. Alaoui-Jamali
Journal: The Journal of Experimental Medicine (2010)

The actin cross-linking protein filamin A (FLNa) functions as a scaffolding protein and couples cell cytoskeleton to extracellular matrix and integrin receptor signaling. In this study, we report that FLNa suppresses invasion of breast cancer cells and regulates focal adhesion (FA) turnover. Two large progression tissue microarrays from breast cancer patients revealed a significant decrease of FLNa levels in tissues from invasive breast cancer compared with benign disease and in lymph node-positive compared with lymph node-negative breast cancer. In breast cancer cells and orthotopic mouse breast cancer models, down-regulation of FLNa stimulated cancer cell migration, invasion, and metastasis formation. Time-lapse microscopy and biochemical assays after FLNa silencing and rescue with wild-type or mutant protein resistant to calpain cleavage revealed that FLNa regulates FA disassembly at the leading edge of motile cells. Moreover, FLNa down-regulation enhanced calpain activity through the mitogen-activated protein kinase-extracellular signal-regulated kinase cascade and stimulated the cleavage of FA proteins. These results document a regulation of FA dynamics by FLNa in breast cancer cells.
Genetic Ablation of PKC Epsilon Inhibits Prostate Cancer Development and Metastasis in Transgenic Mouse Model of Prostate Adenocarcinoma
Authors: Bilal Bin Hafeez, Weixiong Zhong, Jamey Weichert, Nancy E. Dreckschmidt, Mohammad Sarwar Jamal, Ajit K. Verma
Journal: Cancer Research (2011)

Abstract Protein kinase C epsilon (PKCϵ), a novel PKC isoform, is overexpressed in prostate cancer (PCa) and correlates with disease aggressiveness. However, the functional contribution of PKCϵ to development or progression of PCa remained to be determined. Here we present the first in vivo genetic evidence that PKCϵ is essential for both the development and metastasis of PCa in the transgenic mouse model of prostate adenocarcinoma (TRAMP). Heterozygous or homozygous genetic deletions of PKCϵ in FVB/N TRAMP inhibited PCa development and metastasis as analyzed by positron emission tomography/computed tomography, tumor weight determinations, and histopathology. We also examined biomarkers associated with tumor progression in this model, including markers of survival, proliferation, angiogenesis, inflammation, and metastatic progression. To find clues about the genes regulated by PKCϵ and linked to the Stat3 signaling pathway, we carried out focused PCR arrays of JAK/STAT signaling in excised PCa tissues from PKCϵ wild-type and nullizygous TRAMP mice. Notably, PKCϵ loss was associated with significant downregulation of proliferative and metastatic genes C/EBPβ (CCAAT/enhancer binding protein β), CRP (C-reactive protein), CMK, EGFR (epidermal growth factor receptor), CD64, Jun B, and gp130. Taken together, our findings offer the first genetic evidence of the role of PKCϵ in PCa development and metastasis. PKCϵ may be potential target for prevention and/or treatment of PCa. Cancer Res; 71(6); 2318–27. ©2011 AACR.
Calcium-activated chloride current in rabbit ventricular myocytes.
Authors: A C Zygmunt, W R Gibbons
Journal: Circulation Research (1991)

We have used the whole-cell patch-clamp technique to examine the ionic basis for a transient outward current in rabbit ventricular myocytes. High concentrations of intracellular calcium buffer prevented the current, isoproterenol increased it, and cadmium, nisoldipine, ryanodine, or caffeine blocked it. These data are consistent with a current that is calcium activated, by the calcium transient that causes contraction. The current was not blocked by external 4-aminopyridine or tetraethylammonium, and it was still present if external potassium was omitted and internal potassium was replaced by cesium. The current was absent when intracellular and extracellular chloride concentrations were drastically reduced, even when intracellular and extracellular potassium concentrations were normal. The current was blocked by the anion transport blockers 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid (SITS) and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) and responded to extracellular chloride changes as expected for a chloride current. We used SITS and DIDS to define the voltage dependence of the transient outward current. The current first appeared at voltages positive to the threshold of the calcium current and declined as voltage approached the calcium reversal potential. Tail-current experiments suggested that the current rectified strongly in the outward direction. We propose that the 4-aminopyridine-resistant transient outward current of rabbit ventricular myocytes is a calcium-activated chloride current.
Assessing the risk of venous thromboembolic events in women taking progestin-only contraception: a meta-analysis
Authors: S. Mantha, R. Karp, V. Raghavan, N. Terrin, K. A. Bauer, J. I. Zwicker
Journal: BMJ (2012)

<b>Objectives</b> To evaluate the risk of venous thromboembolic events associated with the use of progestin-only contraception and whether that risk differs with the mode of drug delivery (oral, intrauterine, or depot injection). <b>Design</b> Systematic review and meta-analysis of randomised controlled trials and observational studies. <b>Data sources</b> Pubmed, Embase, Cochrane Library, and reference lists of relevant reviews. <b>Study selection</b> Randomised controlled trials and case-control, cohort, and cross sectional studies with venous thromboembolic outcome for progestin-only contraception reported relative to a non-hormone comparator group. <b>Data extraction</b> Data were extracted by two independent investigators, and consensus for inclusion was reached after assessment by additional investigators. <b>Results</b> Among the 2022 unique references identified by all searches, eight observational studies fulfilled inclusion criteria. A total of 147 women across all studies were diagnosed with a venous thromboembolic event while taking progestin-only contraception, and the summary measure for the adjusted relative risk of a venous thromboembolic episode for users versus non-users of a progestin-only contraceptive was, based on the random effects model, 1.03 (95% CI 0.76 to 1.39). Subgroup analysis confirmed there was no association between venous thromboembolic risk and progestin-only pills (relative risk 0.90 (0.57 to 1.45)) or a progestin intrauterine device (0.61 (0.24 to 1.53)). The relative risk of a venous thromboembolic event for users of an injectable progestin versus non-users was 2.67 (1.29 to 5.53). <b>Conclusions</b> Published data assessing the risk of venous thromboembolism in women prescribed progestin-only contraception are limited. In this meta-analysis of eight observational studies, the use of progestin-only contraception was not associated with an increased risk of venous thromboembolism compared with non-users of hormonal contraception. The potential association between injectable progestins and thrombosis requires further study.
Evaluating Intermittent Androgen-Deprivation Therapy Phase III Clinical Trials: The Devil Is in the Details
Authors: Maha Hussain, Catherine Tangen, Celestia Higano, Nicholas Vogelzang, Ian Thompson
Journal: Journal of Clinical Oncology (2015)

Intermittent androgen deprivation (IAD) has been widely tested in prostate cancer. However, phase III trials testing continuous androgen deprivation (CAD) versus IAD have reached inconclusive and seemingly contradictory results. Different design and conduct issues must be critically evaluated to better interpret the results.Seven published phase III trials were examined for prespecified design and outcomes. Treatment specifications; primary end point; superiority versus noninferiority design assumptions, including magnitude of assumed versus observed noninferiority margin (NIM); duration of follow-up; and quality-of-life (QOL) outcomes were considered in terms of the results and conclusions reported.Five trials had a superiority and three had a noninferiority primary hypothesis. Only three trials had a uniform population and overall survival (OS) end point. All trials observed better outcomes in terms of OS and progression-free survival (PFS) than assumed at time of study design, translating into prespecified NIMs or hazard ratios that reflected larger absolute differences in OS or PFS between arms. Lower-than-expected event rates also reduced statistical power for the trials. Other factors, including length of follow-up, cause of death, QOL, and primary end point, and their impact on trial interpretation are discussed.No trial to date has demonstrated survival superiority of IAD compared with CAD. Trials concluding IAD is noninferior to CAD were based on wide NIMs that included clinically important survival differences, not likely to be considered comparable by physicians or patients. Interim analyses relying on short follow-up and including a majority of non-prostate cancer deaths will favor a noninferiority conclusion and should be interpreted cautiously. Adequate follow-up is required to ensure capture of prostate cancer deaths in both superiority and noninferiority trials.
Endotoxins prevent murine IgE production, TH2 immune responses, and development of airway eosinophilia but not airway hyperreactivity
Authors: Kerstin Gerhold, Katharina Blümchen, Anja Bock, Christine Seib, Philippe Stock, Tilmann Kallinich, Max Löhning, Ulrich Wahn, Eckard Hamelmann
Journal: Journal of Allergy and Clinical Immunology (2002)
Denatured H-ferritin subunit is a major constituent of haemosiderin in the liver of patients with iron overload
Authors: E Miyazaki
Journal: Gut (2002)

Background and aims: Iron is stored in hepatocytes in the form of ferritin and haemosiderin. There is a marked increase in iron rich haemosiderin in iron overloaded livers, and ferric iron in amounts exceeding the ferritin and haemosiderin binding capacity may promote free radical generation, causing cellular damage. The aim of this study was to characterise hepatic haemosiderin using four antibodies specific for either native or denatured H/L-ferritin subunits. Methods: Ferritin and haemosiderin were prepared from the livers of three patients with post-transfusional iron overload. The assembled ferritin molecules were analysed by non-denaturing polyacrylamide gel electrophoresis (PAGE)-immunoblotting. Ferritin subunits in the haemosiderin fraction were assessed by denaturing sodium dodecyl sulphate (SDS)-PAGE-immunoblotting. Distribution of native and denatured ferritin subunits in hepatocytes was examined by immunogold electron microscopy. Results: Non-denaturing PAGE-immunoblot analyses showed that the assembled liver ferritins were recognised by the antibodies for native ferritins and not by those for the denatured subunits. Both SDS-PAGE-immunoblot and immunogold electron microscopic analyses disclosed that haemosiderin of iron overloaded liver reacted predominantly to the monoclonal antibody for the denatured H-ferritin subunit, to a lesser degree to that for denatured L-ferritin, and very weakly, if any, with antibodies for native H-ferritin or L-ferritin. Conclusions: These results suggest that in iron overloaded liver, haemosiderin consists predominantly of denatured H-ferritin subunits.
Health effects of a subway environment in healthy volunteers
Authors: A. Klepczyńska Nyström, M. Svartengren, J. Grunewald, C. Pousette, I. Rödin, A. Lundin, C.M. Sköld, A. Eklund, B-M. Larsson
Journal: European Respiratory Journal (2009)

Environmental particle exposure, often estimated as the particulate mass of particles with a diameter &lt;10 μm, &lt;2.5 μm or &lt;1 μm (PM 10 , PM 2.5 or PM 1 ), is known to have a negative impact on the health of the population. Little is known about how the size and origin of particles influence the effects. We have previously shown that exposure to a road tunnel environment causes a cellular inflammatory response in the airways of healthy individuals. In the present study, our aim was to investigate potential airway health effects from exposure to a subway environment. 20 healthy volunteers were exposed to a subway and a control environment for 2 h, followed by measurements of lung function and the inflammatory response in the lower airways (bronchoscopy) and in the peripheral blood. No cellular response was found in the airways after exposure to the subway environment. In the blood, we found a statistically significant increase in fibrinogen and regulatory T-cells expressing CD4/CD25/FOXP3. Subway and road tunnel environments have similar levels of PM 10 and PM 2.5 , whilst the concentrations of ultrafine particles, nitrogen monoxide and dioxide are lower in the subway. Although no cellular response was detected, the findings indicate a biological response to the subway environment. Our studies show that using gravimetric estimates of ambient particulate air pollution alone may have clear limitations in health-risk assessment.
Desferrioxamine in the treatment of plasmodium falciparum malaria
Authors: Simone Gangarossa, Gino Schiliro, Rosario Russo
Journal: American Journal of Hematology (1992)

had been diagnosed.Desferrioxamine chelation treatment had not been suspended during this fever state.At admission the patient appeared well but had a temperature of 39°C.Desferrioxamine treatment was suspended.On the day of admission plasmodium fakiparum-ring forms and gametocytes were identified in thin blood film.Parasitemia was 20,000immc.Chloroquine resistance became manifest but quinine sulphate treatment achieved negative parasitemia 7, 14, and 28 days after beginning the treatment.One of the patient's blood donors was identified as the infection source.In our case the mild course of the disease for a non-immune subject, despite the delay in diagnosis, was surprising.The mildness of the patient's clinical picture was not related to her genetic red cell defect because she survived on blood donors' erythrocytes.The desferrioxamine treatment alone, at 50 mgikglday ( 1 gi24 hr) for 6 daysiweek (not suspended during febrile state until malaria was diagnosed) may have been responsible for an anti-plasmodium falciparum effect in our patient.As soon as the diagnosis was made the patient was started on a sodium bicarbonate infusion.Due to a previous hypersensitivity reaction to allopurinol, this drug was not used.Instead, ibuprofen was employed to reduce uric acid induced renal damage.Prednisone 35 mg twice daily was started the day prior to planned chemotherapy with daunomycin, L-asparaginase, vincristine, and prednisone (LAVP).Twelve hours after prednisone was initiated, the patient became oliguric with evidence of renal failure and serum chemistry as follows: phosphorous 5.92 mmolil, potassium 4.1 mEqil, urea 25.2 mmolil, creatinine 244 pmolil, and uric acid 1,464 p,mol/l.Hemodialysis was initiated the same day and continued for 3 consecutive days after which a rapid recovery of renal function and electrolyte balance occurred.Chemotherapy with the LAVP protocol continued after completion of dialysis along with CNS treatment using cytosine arabinoside and methotrexate via an Ommaya reservoir.A bone marrow aspirate and biopsy, thoracentesis, and CSF analysis done 2 months post-initiation of induction treatment showed no evidence of residual disease.The acute tumor lysis syndrome is a well-recognized complication of cytoreductive therapy for rapidly proliferating neoplasms.This clinical picture is usually seen after chemotherapy is employed in the treatment of non-Hodgkin's lymphomas and leukemias [ 141.Although corticosteroid-induced acute tumor lysis has previously been identified in the non-Hodgkin's lymphomas, the occurrence of massive tumor lysis in T-cell ALL after corticosteroid administration is not a well-recognized clinical entity.This case, therefore, illustrates the complications that may arise in administering corticosteroids to these patients.The early use of alkaline diuresis and, if necessary, hemodialysis, can however produce excellent clinical results without delaying the initiation of chemotherapy.
Phase II Study of Amrubicin As Second-Line Therapy in Patients With Platinum-Refractory Small-Cell Lung Cancer
Authors: David S. Ettinger, Robert Jotte, Paul Lorigan, Vicram Gupta, Lawrence Garbo, Carlos Alemany, Paul Conkling, David R. Spigel, Arkadiusz Z. Dudek, Chirag Shah, Ravi Salgia, Richard McNally, Markus F. Renschler, Jennifer W. Oliver
Journal: Journal of Clinical Oncology (2010)

Amrubicin is a synthetic anthracycline with potent topoisomerase II inhibition. This phase II study was conducted to confirm safety and activity of amrubicin in the treatment of refractory small-cell lung cancer (SCLC).Patients with refractory SCLC (either with progressive disease as best response or progression within 90 days of first-line therapy) received amrubicin (40 mg/m(2)/d for 3 every 21 days). The primary end point was overall response rate (ORR); secondary end points included progression-free survival (PFS), overall survival (OS), and change in left ventricular ejection fraction (LVEF).Seventy-five patients with a median progression-free interval after first-line therapy of 38 days were enrolled; 69 patients received a median of four amrubicin cycles (range, one to 12 cycles). The ORR was 21.3% (95% CI, 12.7% to 32.3%), with one complete response (1.3%) and 15 partial responses (20%). Median PFS and OS were 3.2 months (95% CI, 2.4 to 4.0 months) and 6.0 months (95% CI, 4.8 to 7.1 months), respectively. The ORR in 43 patients who never responded to first-line therapy was 16.3% (95% CI, 6.8% to 30.7%). Most commonly reported grade 3 or 4 adverse events included neutropenia (67%), thrombocytopenia (41%), and anemia (30%), with febrile neutropenia in 12%. There was no decrease in mean LVEF with cumulative amrubicin doses exceeding 750 mg/m(2).Single-agent amrubicin showed promising activity with a 21.3% ORR and an acceptable safety profile when used as second-line therapy patients with platinum-refractory SCLC. Amrubicin did not induce early cardiotoxicity, but its long-term effects are unknown.