tbuckley/cabot-search huggingface dataset:
A Phase II Study of Gefitinib for Aggressive Cutaneous Squamous Cell Carcinoma of the Head and Neck
Authors: Carol M. Lewis, Bonnie S. Glisson, Lei Feng, Fiona Wan, Ximing Tang, Ignacio I. Wistuba, Adel K. El-Naggar, David I. Rosenthal, Mark S. Chambers, Robert A. Lustig, Randal S. Weber
Journal: Clinical Cancer Research (2012)

Abstract Purpose: To determine the disease control rate and toxicity of treating patients with aggressive cutaneous squamous cell carcinoma (CSCC) with neoadjuvant gefitinib. Experimental Design: A prospective phase II clinical trial evaluating neoadjuvant gefitinib given prior to standard treatment with surgery and/or radiotherapy. Patients with stable disease after one cycle received escalated doses. Patients who responded were given gefitinib during radiation therapy, as well as maintenance therapy after definitive treatment. We analyzed the correlation between epidermal growth factor receptor (EGFR) expression, mutation status, and gene copy number on available tissue samples and clinical response. Results: Twenty-three patients were accrued and 22 patients were evaluable for response prior to definitive local treatment; complete responses were attained by 18.2% of patients and partial responses by 27.3%. Grades 2 to 3 toxicities were observed in 59.1% of patients experiencing class-specific effects during induction therapy. After induction, 11.8% underwent surgery alone, 17.6% had definitive radiation, 11.8% were treated with radiation and concurrent gefitinib, and 47% had surgery with postoperative radiation and concurrent gefitinib. Median follow-up for the censored observations was 32 months. Two-year overall, disease-specific, and progression-free survival rates were 72.1%, 72.1%, and 63.6%, respectively. No EGFR-activating mutations were identified in tumor samples available from 10 patients. No associations between EGFR correlative studies and patient outcomes were identified. Conclusions: Gefitinib, in the neoadjuvant setting, was active and well tolerated in patients with aggressive CSCC and did not interfere with definitive treatment. In view of the 18% complete response rate we observed, EGFR tyrosine kinase inhibitors should be further explored in the treatment of aggressive CSCC. Clin Cancer Res; 18(5); 1435–46. ©2012 AACR.
Effect of Cytomegalovirus Infection Status on First-Year Mortality Rates among Orthotopic Liver Transplant Recipients
Authors: Matthew E. Falagas
Journal: Annals of Internal Medicine (1997)

Background: To reduce the mortality rate associated with liver transplantation, it is important to identify the risk factors for increased mortality among liver transplant recipients. It has been suggested that cytomegalovirus (CMV) infection is one such risk factor, but no studies have examined mortality rates associated with the CMV serologic status of the donor and recipient by using multivariate techniques. Objective: To study the effect of CMV on 1-year mortality rates in orthotopic liver transplant recipients. Design: Intention-to-treat analysis of a cohort. Patients: 146 liver transplant recipients who were enrolled in a multicenter, randomized, placebo-controlled, intervention trial. Setting: Four university-affiliated transplantation centers. Results: 1-year mortality rates for the four strata of donor and recipient CMV serologic status before transplantation were as follows: seronegative donor and recipient, 11%; seronegative donor and seropositive recipient, 22%; seropositive donor and recipient, 30%; and seropositive donor and seronegative recipient, 44% (P = 0.0091). Multivariate analysis using a time-dependent Cox proportional-hazards model showed that retransplantation (relative risk, 4.6 [95% CI, 1.9 to 10.7]; P < 0.001); total number of units of blood products administered during transplantation (relative risk, 1.006 per unit [CI, 1.003 to 1.010]; P < 0.001); and presence of CMV disease (relative risk, 3.9 [CI, 1.8 to 8.5]; P < 0.001), invasive fungal disease (relative risk, 3.3 [CI, 1.5 to 7.1]; P = 0.0020), and bacteremia (relative risk, 2.5 [CI, 1.2 to 5.2]; P = 0.0136) were independently associated with higher mortality rates. If post-transplantation variables that were highly correlated with donor and recipient CMV serologic status were restricted from the model, donor and recipient CMV serologic status was the only pretransplantation variable independently associated with higher mortality rates (P = 0.002). Conclusion: Donor and recipient CMV serologic status is a significant pretransplantation determinant for death in liver transplant recipients.
Cradle-to-cradle stewardship of drugs for minimizing their environmental disposition while promoting human health. II. Drug disposal, waste reduction, and future directions.
Authors: Christian G Daughton
Journal: Environmental Health Perspectives (2003)

Since the 1980s, the occurrence of pharmaceuticals and personal care products (PPCPs) as trace environmental pollutants, originating primarily from consumer use and actions rather than manufacturer effluents, continues to become more firmly established. The growing, worldwide importance of freshwater resources underscores the need for ensuring that any aggregate or cumulative impacts on (or from) water supplies are minimized. Despite a paucity of effects data from long-term, simultaneous exposure at low doses to multiple xenobiotics (particularly non-target-organism exposure to PPCPs), a wide range of proactive actions could be implemented for reducing or minimizing the introduction of PPCPs to the environment. Most of these actions fall under what could be envisioned as a holistic stewardship program--overseen by the health care industry and consumers alike. Significantly, such a stewardship program would benefit not just the environment--additional, collateral benefits could automatically accrue, including the lessening of medication expense for the consumer and improving patient health and consumer safety. In this article (the second of two parts describing the "green pharmacy") I focus on those actions and activities tied more closely to the end user (e.g., the patient) and issues associated with drug disposal/recycling that could prove useful in minimizing the environmental disposition of PPCPs. I also outline some recommendations and suggestions for further research and pose some considerations regarding the future. In this mini-monograph I attempt to capture cohesively for the first time the wide spectrum of actions available for minimizing the release of PPCPs to the environment. A major objective is to generate an active dialog or debate across the many disciplines that must become actively involved to design and implement a successful approach to life-cycle stewardship of PPCPs.
Miss, Mister, Doctor: Distinguishing titles
Authors: R. MacPherson
Journal: Journal of the Royal Society of Medicine (2006)

How we are titled is of little consequence I found the editorial (April 2006 JRSM 1 ) on how we are titled most interesting.This is a continuation of the debate that the dental profession has been having for many years, fuelled by both an influx of overseas graduates styling themselves as 'Doctor', and by the development of the role of dentists from 'toothwrights' to practitioners with a more holistic approach encompassing the oral health and wellbeing of those in their care.However all of us, physicians, surgeons, general practitioners and dentists have one thing in commonpatients.But that may be about to change.The same week as the editorial appeared, the chief executive of the Sussex Partnership NHS Trust ordered staff not to refer to people receiving medical care as patients but as clients.This not only demonstrates a misunderstanding of our roles but also devalues both practitioners and those that we care for.Patients are not simply clients or users of health services.Patients are those receiving care, who are given time, are listened to and treated with sympathy, understanding and expertise.There is something special about the term patient, and although to give a precise dictionary definition is difficult, it is well understood by those who deliver the care.How we are titled may well, as the editorial states, be of little consequence; far more important is how we refer to, and perceive, those in our care.
Platelet Size and Number in Alcoholic Thrombocytopenia
Authors: Mervyn A. Sahud
Journal: New England Journal of Medicine (1972)

STUDIES of platelet volume, size, and function have demonstrated that large, heavy platelets represent younger, more physiologically active forms and that small platelets represent older, senescent forms.1 2 3 4 5 6 7 Garg, Amorosi and Karpatkin8 showed that determination of the megathrombocyte number on a peripheral blood smear is useful in estimation of megakaryocytopoiesis and platelet turnover. We studied the platelet-size distribution in patients with acute alcoholism and thrombocytopenia to determine if the percentage of megathrombocytes is related to platelet number and recovery from thrombocytopenia. Such a relation would suggest that alcohol affects megakaryocyte activity.9 10 11 12 13 Materials and MethodsDaily platelet counts14 and estimation of platelet-size . . .
Video-endoscopes in Comparison with Fiberscopes: Quantitative Measurement of Optical Resolution
Authors: K. Knyrim, H.K. Seidlitz, F. Hagenmüller, M. Classen
Journal: Endoscopy (1987)

The subject of this study was the optical performance of video-endoscopic systems (VE) in terms of maximal resolving power and resolvable picture elements. Olympus, Toshiba/Machida, Fujinon, and Welch Allyn video gastroscopes were tested. A GIF Q 10 fiberscope from Olympus was also included for comparison. The resolution measurements were made at various distances using two independent methods - electronic analysis of the TV signal, and visual evaluation of the resolution, of a standardized test target. The results obtained with the two methods were in perfect agreement.
Abstract S4-02: Integrated genomic analyses of members of protein kinase C family identifies subtype specific alterations as novel therapeutic targets
Authors: RC Natrajan, A Leonidou, R Brough, J Frankum, PT Wai, CK Ng, JS Reis-Filho, CJ Lord, A Ashworth
Journal: Cancer Research (2013)

Abstract Introduction Members of the protein kinase C family are serine/threonine kinases that are involved in proliferation, apoptosis, cell survival and migration, and have been implicated in tumorigenesis. Recently PRKCE has been found to be up-regulated in triple-negative (TN) breast cancers and has been proposed as a target for therapeutic intervention. The aims of this study were to determine i) whether different members of the PKC family are dysregulated and/ or mutated in specific subtypes of breast cancer, ii) to investigate the impact of silencing or overexpression of members of the PKC family in cell line models representative of the different breast cancer subtypes. Material and methods: We obtained expression and mutational data from the cancer genome atlas (TCGA) project from 567 and 640 samples subjected to microarray-based gene expression profiling and whole exome sequencing, respectively. Pair-wise SAM analysis of TCGA gene expression data was performed to identify differential expression between subgroups (ER+, HER2+ and TN). Potential driver mutations were identified through the algorithm CHASM. Subtype specific dependencies were identified from the re-analysis of publicly available siRNA kinome-wide screens in a panel of 20 breast cancer cell lines. In vitro assessment of gene overexpression was assessed in MCF10A cells by wound healing scratch assays and 3D growth in Matrigel. Results PRKCA, B, I and Q were expressed at significantly higher levels in TN breast cancers. Higher expression of PRKCE was significantly associated with ER-negativity, whereas high PRKCD expression was associated with ER-positivity. Analysis of siRNA kinome-wide screen data resulted in a significant reduction in survival associated with PRKCI and PRKCE in ER-negative cells, PRKCQ in triple-negative cells, and PRKCD in ER-positive cells. Furthermore meta-analysis of published exome and whole genome sequencing data identified potentially activating recurrent kinase domain mutations in PRKCB (0.93%), Q (1.25%) and Z (0.93%), with mutations in PRKCZ being associated with higher gene expression. Forced expression of wild-type PRKCQ and PRKCZ in MCF10A cells resulted in the formation of irregular acini in 3D cell culture and expression of wild-type PRKCZ resulted in increased migration. Conclusions Differential expression of members of the protein kinase C family, are associated with different molecular subtypes of breast cancer. Furthermore, we have shown that breast cancer cells are dependent upon expression of these family members in vitro, which are associated with different cellular phenotypes. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr S4-02.
S135 A retrospective multi-centre study of the effects of allogeneic haematopoietic stem cell transplantation on pulmonary function
Authors: R. T. Dharmagunawardena, R. M. Pearce, J. Lee, J. F. Apperley, T. Littlewood, K. M. Wilson, K. Orchard, G. Jackson, J. A. Snowden, K. Kirkland, G. Cook, R. Hubbard, J. Brown
Journal: Thorax (2011)

<h3>Introduction</h3> Allogeneic haematopoietic stem cell transplantation (HSCT) is often complicated by serious pulmonary complications including severe infections, drug toxicity and graft vs host disease. However, there is limited data on the prevalence of significant lung function defects in long-term survivors. <h3>Method</h3> We undertook a UK wide, multi-centre, retrospective study of the effects on pulmonary function in adult patients undergoing HSCT over a 4-year period. Pulmonary function tests (PFT) were evaluated at baseline (pre-transplant) and 12 months post-transplant. Impaired pulmonary function was defined as FEV<sub>1</sub> or FVC less than 80% predicted. <h3>Results</h3> 532 allogeneic HSCTs were registered in the BSBMT database, having been performed at 6 centres over the 4-year study period. 157 patients underwent PFT pre-HSCT and at least 6 months post-BMT, with 12-month data available for 90 patients (Abstract S135 table 1). The median age was 42 years (range 18–69) and 59% of patients were male. Median FEV<sub>1</sub> and FVC were 98.9% and 101% predicted respectively for patients pre-HSCT, with 25 (15.9%) patients having impaired lung function pre-HSCT. For patients with normal PFT pre-HSCT, 13 (10%) had impaired PFT at 12 months with median reduction in FEV<sub>1</sub> of 1.33 L (33.5%) (range 0.59–2.25) and FVC of 1.29 L (28.9%) (range 0.17–3.33). 38% had obstructive, 46% restrictive and 15% mixed picture spirometry pattern. 69% of patients with newly impaired PFT had acute graft vs host disease, (p=0.068). No statistically significant predictive factors were identified for newly impaired PFT: age, sex, total body irradiation, Alemtuzumab treatment, transplant intensity and type of donor. For patients with impaired PFT at baseline, 11 (44%) remained impaired at 12 months with no significant fall in spirometry values (median FEV<sub>1</sub> fell 2% and FVC rose 2%). <h3>Conclusion</h3> Although these data represent only a proportion of patients undergoing allogeneic HSCT, we found 10% of patients developed impaired PFT at 12 months with large falls in FEV<sub>1</sub> and FVC. These data suggest there may be as many as 60 to 120 HSCT recipients each year developing major impairment of lung function. Multi-centre prospective studies are required to fully characterise the frequency and risk factors for impaired PFT post-HSCT.
Long term effects of hysterectomy on mortality: nested cohort study
Authors: Lisa Iversen, Philip C Hannaford, Alison M Elliott, Amanda J Lee
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objectives</b> To investigate the long term risk (mean &gt; 20 years) of death from all causes, cardiovascular disease, and cancer in women who had or had not had a hysterectomy. <b>Design</b> Nested cohort study. <b>Setting</b> Royal College of General Practitioners9 oral contraception study. <b>Participants</b> 7410 women (3705 flagged at the NHS central registries for cancer and death who had a hysterectomy during the oral contraception study and 3705 who were flagged but did not have the operation). <b>Main outcome measures</b> Mortality from all causes, cardiovascular disease, and cancer. <b>Results</b> 623 (8.4%) women had died by the end of follow-up (308 in the hysterectomy group and 315 in the non-hysterectomy group). Older women who had had a hysterectomy had a 6% reduced risk of death compared with women of a similar age who did not have the operation (adjusted hazard ratio 0.94, 95% confidence interval 0.75 to 1.18). Compared with young women who did not have a hysterectomy those who were younger at hysterectomy had an adjusted hazard ratio for all cause mortality of 0.82 (0.65 to 1.03). Hysterectomy was not associated with a significantly altered risk of mortality from cardiovascular disease or cancer regardless of age. <b>Conclusion</b> Hysterectomy did not increase the risk of death in the medium to long term.
Safety and efficacy of purified factor IX concentrate and antifibrinolytic agents for dental extractions in hemophilia B
Authors: Benjamin Djulbegovic, Mary Marasa, Al Pesto, George M. Kushner, Terence Hadley, Geetha Joseph, George Goldsmith
Journal: American Journal of Hematology (1996)

This study evaluated the safety and efficacy of combined treatment with ϵ-aminocaproic acid or tranexamic acid and monoclonal antibody purified factor IX (MAb factor IX) for prophylaxis against bleeding in eight hemophilia B patients undergoing nine dental extraction procedures. All patients achieved excellent hemostasis without clinical evidence of thrombosis. There were no significant changes in hemoglobin or hematocrit or in markers of hemostatic system activation (prothrombin fragment F1–2, fibrinopeptide A, and fragment B β15–42) after surgery. Thus, a highly purified factor IX concentrate and antifibrinolytic therapy can be effectively and safely combined in hemophilia B patients undergoing dental extractions. © 1996 Wiley-Liss, Inc.
A single strand conformation polymorphism study of CD40 ligand. Efficient mutation analysis and carrier detection for X-linked hyper IgM syndrome.
Authors: Q Lin, J Rohrer, R C Allen, M Larché, J M Greene, A O Shigeoka, R A Gatti, D C Derauf, J W Belmont, M E Conley
Journal: Journal of Clinical Investigation (1996)

Mutations in the gene for CD40 ligand are responsible for the X-linked form of hyper IgM syndrome. However, no clinical or laboratory findings that reliably distinguish X-linked disease from other forms of hyper IgM syndrome have been reported, nor are there tests available that can be used to confidently provide carrier detection. To identify efficiently mutations in the gene for CD40 ligand, eight pairs of PCR primers that could be used to screen genomic DNA by single strand conformation polymorphism (SSCP) were designed. 11 different mutations were found in DNA from all 13 patients whose activated T cells failed to bind a recombinant CD40 construct. The exact nature of four of these mutations, a deletion and three splice defects, could not be determined by cDNA sequencing. In addition, SSCP analysis permitted rapid carrier detection in two families in whom the source of the mutation was most likely a male with gonadal chimerism who passed the disorder on to some but not all of his daughters. These studies document the utility of SSCP analysis for both mutation detection and carrier detection in X-linked hyper IgM syndrome.
The effect of tacrolimus compared with betamethasone valerate on the skin barrier in volunteers with quiescent atopic dermatitis
Authors: S.G. Danby, J. Chittock, K. Brown, L.H. Albenali, M.J. Cork
Journal: British Journal of Dermatology (2013)

Atopic dermatitis (AD) is an inflammatory skin disease arising as a result of immune system and skin barrier defects. Topical corticosteroids are safe and effective treatments for AD, when used in short courses. Prolonged use is associated with skin barrier damage. Topical calcineurin inhibitors are alternative immune-modulating treatments for AD purported to have no negative effects on the skin barrier.To compare the effects of betamethasone valerate 0·1% cream (BMVc) and tacrolimus 0·1% ointment (TACo) on the skin barrier.Twenty volunteers with quiescent AD (no active signs for 6 months) participated in a randomized observer-blind study, wherein BMVc was applied to one forearm and TACo to the other, twice daily for 4 weeks. The biophysical/biological properties of the stratum corneum were assessed before and after treatment. Nine volunteers with active disease and 10 with healthy skin were assessed at untreated sites.BMVc significantly reduced skin barrier function, integrity and cohesion, and the levels of pyrrolidone carboxylic acid (PCA) and urocanic acid (UCA) towards the subclinical barrier defect observed in patients with AD (nonlesional sites). TACo preserved skin barrier function, integrity, cohesion and PCA and UCA levels, while significantly increasing skin hydration to levels comparable with healthy skin. Both treatments reduced skin surface pH and trypsin-like protease activity, with TACo doing so to a significantly greater degree.In quiescent AD, 4 weeks of BMVc treatment adversely affected the biophysical properties of the skin and reduced the levels of natural moisturizing factor, whereas TACo improved the condition of the skin barrier.
Immunohistochemical analysis of late local skin reactions during rush venom immunotherapy.
Authors: C. M. Jung, A. Funk, J. Rakoski, J. Ring
Journal: Allergy (1997)

During rush venom immunotherapy (VIT), about 65% of patients develop large local reactions (LLR) at the application site that last for at least 24 h. However, LLR subside during long-term treatment. To learn more about the provenance of infiltrating cells in late, local skin reactions during VIT, we analyzed the skin infiltrates of 23 Hymenoptera venom (HV)-allergic patients. Punch biopsies were obtained 24 h after s.c. injection of HV allergens from 23 HV-allergic patients and five nonallergic controls. Seven patients did not show LLR at the beginning of VIT. Ten patients had LLR when the dose of HV allergens was increased. Six patients showed reduced LLR after long-term treatment. Immunoenzymatic labeling of the cryostal sections with a panel of monoclonal antibodies was performed by the APAAP method. S.c. application of HV allergens induced a perivascular and periadnexial cutaneous mononuclear cell infiltrate consisting mainly of CD4+, CD45RO+; and HLA-DR+ cells in patients without clinically apparent LLR. In contrast, LLR were associated with a significant increase in total cells, CD4+ cells, CD8+ cells, CD11c+ cells, EG2+ cells, NP57+ cells, HLA-DR+ cells, CD45RO+ cells, CD45RA+ cells, CD23+ cells and CD25+ cells (P < 0.001). Decreased LLR after long-term VIT was correlated with a significantly reduced recruitment of CD4+ cells, EG2+ cells, and CD23+ cells as compared to LLR in the course of dose increases (P < 0.05), whereas the number of CD8+ cells, CD11c+ cells, NP57+ cells, and CD25+ cells remained high. Our data suggest that s.c. injections of HV allergens attract CD4+ helper T cells, of both the naive (CD45RA+) and memory (CD45RO+) phenotypes, to the allergen application site. LLR represent delayed allergic rather than toxic reactions to HV components and might be relevant to the development of clinical protection during VIT.