tbuckley/cabot-search huggingface dataset:
Proliferating cell nuclear antigen and mitotic activity in rectal cancer: predictor of response to preoperative irradiation.
Authors: C G Willett, G Warland, R Cheek, J Coen, J Efird, P C Shellito, C C Compton
Journal: Journal of Clinical Oncology (1994)

This study examines the association between the pathologic response of rectal cancer after irradiation and its pretreatment proliferative state as assayed by proliferating cell nuclear antigen (PCNA) and mitotic activity.Ninety patients with clinical stage T3 and T4 rectal cancer received preoperative irradiation followed by surgery. Pretreatment tumor biopsies were scored for PCNA activity (number of tumor cells staining immunohistochemically with an anti-PCNA monoclonal antibody) and the number of mitoses per 10 high-powered fields (hpf). Postirradiation surgical specimens were examined for extent of residual disease.The tumors of 33 of 90 patients (37%) exhibited marked pathologic downstaging (no residual tumor or cancer confined to the rectal wall) after preoperative irradiation. Two features were independently associated with the likelihood of marked pathologic regression after preoperative irradiation: lesion size and PCNA/mitotic activity. When stratified by tumor size, marked tumor regression occurred most frequently in smaller tumors with high PCNA/mitotic activity compared with larger tumors with lower PCNA/mitotic activity. Intermediate downstaging rates were seen for small or large tumors with moderate PCNA/mitotic activity.Tumor PCNA/mitotic activity predicts the likelihood of response to irradiation, which may aid in formulating treatment policies for patients with rectal cancer.
Endothelial-to-mesenchymal transition contributes to fibro-proliferative vascular disease and is modulated by fluid shear stress
Authors: Jan-Renier A J Moonen, Ee Soo Lee, Marc Schmidt, Monika Maleszewska, Jasper A Koerts, Linda A Brouwer, Theo G van Kooten, Marja J A van Luyn, Clark J Zeebregts, Guido Krenning, Martin C Harmsen
Journal: Cardiovascular Research (2015)

AimsNeointimal hyperplasia is a common feature of fibro-proliferative vascular disease and characterizes initial stages of atherosclerosis. Neointimal lesions mainly comprise smooth muscle-like cells. The presence of these lesions is related to local differences in shear stress. Neointimal cells may arise through migration and proliferation of smooth muscle cells from the media. However, a role for the endothelium as a source of smooth muscle-like cells has largely been disregarded. Here, we investigated the role of endothelial-to-mesenchymal transition (EndMT) in neointimal hyperplasia and atherogenesis, and studied its modulation by shear stress.
Euglycemic Diabetic Ketoacidosis in a Patient With Type 2 Diabetes After Treatment With Empagliflozin
Authors: Paris Roach, Paul Skierczynski
Journal: Diabetes Care (2015)

Sodium–glucose cotransporter 2 (SGLT2) inhibitors have been associated with euglycemic diabetic ketoacidosis (eDKA). All reports to date have involved canagliflozin (Invokana; Janssen Pharmaceuticals), with the exception of one case associated with ipragliflozin (1). It has been anticipated that eDKA is a class effect, but no case reports of eDKA with other SGLT2s have been reported. Here, we report a case of eDKA in a patient with type 2 diabetes treated with empagliflozin.

A 64-year-old woman with a 15-year history of type 2 diabetes and a 5-day history of treatment with empagliflozin (Jardiance; Boehringer Ingelheim) presented to the emergency room (ER) for evaluation of shortness of breath. She had been treated with insulin for 10 years. At the time she started empagliflozin, she was taking liraglutide 1.8 mg per day. She had …
Male subfertility: is pregnancy the only issue?
Authors: L Glover, P D Abel, K Gannon
Journal: BMJ (1998)

The management of male subfertility is changing radically. The advent of intracytoplasmic sperm injection in particular has given some men the chance to father children even when they have no sperm in their ejaculate. However, the focus on pregnancy as the most important outcome of subfertility treatment appears to have taken place to the exclusion of other outcomes, such as the psychological well being of the couple and, in particular, of the man. Traditionally the little research there has been into psychological responses has focused on women. Recently a start has been made in redressing this imbalance, and it appears that men's experiences of, and responses to, subfertility are fundamentally different from that of their partners.

Recognition of the need to take into account psychological outcomes of subfertility and its management is not new but it seems to have slipped …
BRAF and NRAS mutational status in clear cell sarcoma
Authors: C. Robert, S. Berissi, C. Kannengiesser, J. M. Coindre, B. Bui, P. Peyrot, L. Lacroix, P. Terrier, A. Le Cesne
Journal: Journal of Clinical Oncology (2005)

9000 Background: Clear-cell-sarcoma (CCS) also known as melanoma of the soft parts (MSP) is a rare cancer of adolescents and young adults arising in the deep soft tissues. Several clinical and pathological data demonstrate features typical of melanoma (the propensity for lymph node metastasis, expression of melanoma markers:HMB45, S100. Conversely, deep location in the soft tissues and recurrent t(12;22) translocation coding for the fusion protein EWS-ATF1 are rather suggestive of soft tissue sarcoma (STM). Data comparing gene expression profiles of CCS, melanomas and STM showed that CCS clustered with melanoma rather than with STM. BRAF mutations are frequently found in cutaneous melanoma (40–60%) but are not found in distinct melanoma subtypes(mucosal or uveal). Upstream of BRAF, on the same MAP kinase pathway NRAS is also frequently mutated in melanoma, with a mutually exclusive spectrum of mutations for these two genes. Our objective was to evaluate the frequency of BRAF and NRAS mutations is CCS. Methods: DNA was prepared from paraffin-embeded tissues of 22 CCS carrying the t(12;22) translocation and six melanoma. PCR amplification of BRAF exons 11 and 15 as well as NRAS codons 12, 13 and 61 were performed and PCR products were sequenced. Phosphorylation of ERK was studied using an anti-phospho-ERK antibody SIGMA). Results: Only one of the 22 CCS harboured a BRAF mutation (V599E) (4.5%). Two mutations of NRAS (codon 61) were also found with no overlap with the BRAF mutation. Among the 6 melanomas, one had a BRAF (V599E) and three others had a NRAS mutation. Immunostaining with the anti phospho-ERK antibody showed faint positivity in 8/14 CCS. Among the 6 melanoma, 4 displayed ERK phosphorylation, which was strictly correlated to the presence of NRAS or BRAF activating mutations. Conclusions: BRAF and NRAS mutations are rarely present in CCS. Only 1/22 BRAF mutation and 2/22 NRAS mutation were found. in our serie. These results suggest that although genomic profiling showed that CCS clustered with melanoma, most of them occur independently of BRAF and NRAS mutations frequently found in cutaneous melanoma. No significant financial relationships to disclose.
High-titer HER-2/neu protein-specific antibody can be detected in patients with early-stage breast cancer.
Authors: M L Disis, S M Pupa, J R Gralow, R Dittadi, S Menard, M A Cheever
Journal: Journal of Clinical Oncology (1997)

PURPOSE To evaluate HER-2/neu-specific antibody immunity in patients with breast cancer, to determine the rate of occurrence of serum antibodies to HER-2/neu in patients with breast cancer, and to relate the presence of specific immunity to overexpression of HER-2/neu protein in primary tumor. METHODS The antibody response to HER-2/neu protein was analyzed in 107 newly diagnosed breast cancer patients. Sera was analyzed for the presence of HER-2/neu-specific antibodies with a capture enzyme-linked immunosorbent assay (ELISA) and verified by Western blot. Sera from 200 volunteer blood donors was used as a control population. RESULTS The presence of antibodies to HER-2/neu correlated with the presence of breast cancer. HER-2/neu antibodies at titers of &gt; or = 1:100 were detected in 12 of 107 (11%) breast cancer patients versus none of 200 (0%) normal controls (P &lt; .01). The presence of antibodies to HER-2/neu also correlated to overexpression of HER-2/neu protein in the patient's primary tumor. Nine of 44 (20%) patients with HER-2/neu-positive tumors had HER-2/neu-specific antibodies, whereas three of 63 (5%) patients with HER-2/neu-negative tumors had antibodies (P = .03). The antibody responses could be substantial. Titers of greater than 1:5,000 were detected in five of 107 (5%). CONCLUSION The presence of HER-2/neu antibodies in breast cancer patients and the correlation with HER-2/neu-positive cancer implies that immunity to HER-2/neu develops as a result of exposure of patients to HER-2/neu protein expressed by their own cancer. These findings should stimulate further studies to develop the detection of immunity to oncogenic proteins as tumor markers, as well as the development and testing of vaccine strategies to induce and augment immunity to HER-2/neu for the treatment of breast cancer or prevention of recurrent disease.
Abstract 9718: Rising Antibiotic Resistance: Changes in Microbial Patterns in Cardiac Implantable Electronic Device Infections
Authors: James C Hansen, Hemal M Nayak, Joshua D Moss, John F Beshai, Mark D Metzl, Sorin Lazar, Martin C Burke
Journal: Circulation (2011)

Introduction: As the number of cardiac implantable electronic devices (CIEDs) implanted has risen, so has the number of CIED infections requiring extraction. We evaluated the type and sensitivity of microbial pathogens associated with CIED infections over a 16-year period. Hypothesis: We hypothesized that antibiotic resistance in CIED infections has increased since 1995. Methods: We reviewed 202 cases of infected CIEDs requiring extraction. The database was divided into two groups: Group I included the years 1995-2002 and Group II included 2003-2010. Each case was classified as resistant or sensitive. Resistance was present if cultures revealed a methicillin- or vancomycin-resistant organism; otherwise the organism was classified as sensitive. Groups were compared using chi-square analysis, with a p-value &lt; 0.05 considered statistically significant. Results: CIED pocket infection or erosion was present in 62.9% of cases, persistent bacteremia with or without obvious endocarditis in 28.7%, and both in 8.4%. Resistance was seen in 13.7% of cases (3/41) in Group I, increasing to 34.2% of cases (55/161) in Group II (p&lt;0.0005). Cultures of hardware (device and/or lead material) increased the yield of resistant organisms to 36.6% (p&lt;0.0001 compared to Group I). The rate of infection with methicillin-resistant Staph Aureus (MRSA) more than tripled in Group II (16.8%) as compared to Group I (4.9%). There were a total of 5 in-hospital deaths. In-hospital mortality for resistant infections was 6.4%, compared to 0.7% for sensitive organisms (p&lt;0.05). Patients with organisms identified only from hardware samples represented 15.7% of the cases of resistant infections. Conclusions: The incidence of antibiotic-resistant device infections has more than doubled over the past 16 years. Device infections with MRSA have tripled since 1995. Resistant infections are associated with a significantly higher in-hospital mortality. Over 15% of resistant infections were found based on hardware culture alone, stressing the importance of this practice for identifying resistance and tailoring antibiotic therapy for efficacy. More data is needed to aid in the selection of appropriate prophylactic antibiotics for new implants and generator changes.
Gastrointestinal Complications of the Haemolytic Uraemic Syndrome
Authors: D C G Crabbe, J T Broklebank, R D Spicer
Journal: Journal of the Royal Society of Medicine (1990)

The haemolytic uraemic syndrome (HUS) is a well recognized cause of acute renal failure in children. Gastrointestinal involvement is common, and may result in rectal bleeding which can be an important presenting symptom. Previous publications have stressed the importance of correct diagnosis to avoid unnecessary surgery. Occasionally serious gastrointestinal complications do occur. We present five children with life-threatening gastrointestinal complications of the HUS and discuss the indications for laparotomy.
Serum cytokines level can differentiate active pulmonary tuberculosis from latent TB
Authors: Arto Y. Soeroto, Zulkarnain Dahlan, Cissy B. Kartasasmita, Ida Parwati
Journal: European Respiratory Journal (2013)

Tuberculosis disease occured in only 5–10% of M tuberculosis (MTB) infected individuals, the rest became latent TB. Although both have its own definition and clinical criterias but in clinical setting it is not seldom difficult to be differentiated and resulted in under or overdiagnosed of TB activity. Underdiagnosed resulted in disease progression and spreading while overdiagnosed resulted in unnecessary expose to antituberculosis drugs. The purpose of this study is to analyze whether serum levels of IFN-γ, TNF-α, IL-10 and IL-12 could be used to differentiate active pulmonary TB with latent TB.  This case control study was held in Hasan Sadikin General Hospital Bandung Indonesia between April 2011 to May 2012. Forty Pulmonary TB patients defined with positive sputum examination and forty latent TB was chosen as control to ascertain MTB exposure to those subjects. IFN-γ, TNF-α, IL-10 and IL-12 was measured with ELISA method.  Mann-Whitney test found significant differences in IFN-γ, TNF-α, and IL-12 serum level between active TB groups and latent TB but not in IL-12 level. In receiver operating characteristic (ROC) analysis, sensitivity and specificity of IFN-γ level >1.48 pg/mL 97.5% and 87.5%, TNF-α level >2.53 pg/ml 92.5% and 90%, while IL-10 level >0.26 pg/mL 70% and 82.5% (p  In conclusions, interferon-γ and tumor necrosis factor-α serum levels could be used to differentiate active pulmonary TB from Latent TB.
Reversal of Hypocalcemia and Decreased Afterload in Sepsis
Authors: ATTILA KOVACS, MICHAEL R. COURTOIS, BENICO BARZILAI, IRENE E. KARL, PHILIP A. LUDBROOK, RICHARD S. HOTCHKISS
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Sepsis is a major cause of death in intensive care units. Clinically, sepsis induces a number of physiologic and metabolic abnormalities, including decreased myocardial contractility and decreased plasma ionized calcium. There is debate about the proper therapy of hypocalcemia in sepsis because calcium administration may worsen cell function by causing intracellular Ca2 + overload. We investigated the effect of Ca2 + administration on myocardial systolic and diastolic function in an extensively utilized rat model of sepsis, i.e., the cecal ligation and puncture model (CLP). Approximately 24 h after CLP or sham surgery, rats were anesthetized and myocardial function assessed in vivo by a left ventricular Millar catheter and simultaneous two-dimensional guided M-mode echocardiography. Septic rats had a 28% decrease in peak left ventricular developed pressure, a 30% decrease in + dP/ dt, and a 23% decrease in − dP/dt (p < 0.05). Plasma ionized Ca2 + was decreased in septic compared with that in sham rats: 4.9 ± 0.9 and 5.6 ± 0.01 mg/dl, respectively (p < 0.05). CaCl2 improved both systolic and diastolic function and there was no evidence of adverse effects of Ca2 + even at supraphysiologic levels. Surprisingly, correction of decreased afterload in septic rats, using the pure α -agonist phenylephrine, caused normalization of all indices of cardiac contractility, indicating that the presumed decrease in cardiac function was due entirely to an effect of the decreased afterload to "unload" the left ventricle. We conclude that Ca2 + administration is not detrimental to cardiac function in the rat CLP model. Although the rat CLP model is widely utilized and reproduces many of the clinical hallmarks of sepsis, it does not cause intrinsic myocardial depression and, therefore, it may not be an appropriate model to investigate the clinical cardiac dysfunction that occurs in patients with sepsis.
Eyjafjallajökull 2010: Respiratory morbidity and symptoms following exposure to a volcanic eruption
Authors: Hanne Krage Carlsen, Arna Hauksdóttir, Unnur Anna Valdimarsdóttir, Ragnhildur Gudrun Finnbjornsdottir, Guðrún Pétursdóttir, Thorarinn Gíslason
Journal: European Respiratory Journal (2012)

Background : The eruption of Eyjafjallajokull, Iceland 2010 posed an opportunity to study health effects of a volcanic eruption in a society with strong infrastructure. The aim of the study was to evaluate the health of the exposed population compared to control population.

Methods : Six months after the eruption, (fall and winter 2010-11), 1148 exposed South Icelanders and 510 unexposed North Icelanders responded to a questionnaire on recent physical symptoms and questions from the European Community Respiratory Health questionnaire. The data was analyzed using logistic regression adjusted for age, gender, education and smoking status.

Results: Demographic characteristics and underlying disease rates were similar in the two groups. The exposed group reported more symptoms during the last 12 months; morning phlegm in winter, OR 1.5 (95%CI 1.3-1.8) and runny or stuffed nose, OR 1.4 (95%CI 1.2-1.6). Recent (last month) symptoms were more increased, for example cough, OR 2.6 (95%CI 1.7-3.8) and phlegm, OR 2.1 (95%CI 1.3-3.2), eye irritation, OR 2.9 (95%CI 1.8-4.5) and runny or irritated nose, OR 2.0 (95%CI 1.4-2.9). Respiratory symptoms were more prevalent among those living closest to the volcano. Upper airway symptoms coexisted, so those who reported one symptom were likely to have others also.

Discussion : Six months after the Eyjafjallajokull eruption our results indicate that the presence of volcanic ash is associated with two to three times higher recent upper airway symptom rates among the exposed population compared to the unexposed.

Conclusion: Exposure to volcanic ash may increase respiratory morbidity symptoms six months post eruption, but long-term consequences are still unknown.
Clinical Utility of Metrics Based on Tumor Measurements in Phase II Trials to Predict Overall Survival Outcomes in Phase III Trials by Using Resampling Methods
Authors: Ming-Wen An, Yu Han, Jeffrey P. Meyers, Jan Bogaerts, Daniel J. Sargent, Sumithra J. Mandrekar
Journal: Journal of Clinical Oncology (2015)

Purpose Phase II clinical trials inform go/no-go decisions for proceeding to phase III trials, and appropriate end points in phase II trials are critical for facilitating this decision. Phase II solid tumor trials have traditionally used end points such as tumor response defined by Response Evaluation Criteria for Solid Tumors (RECIST). We previously reported that absolute and relative changes in tumor measurements demonstrated potential, but not convincing, improvement over RECIST to predict overall survival (OS). We have evaluated the metrics by using additional measures of clinical utility and data from phase III trials. Methods Resampling methods were used to assess the clinical utility of metrics to predict phase III outcomes from simulated phase II trials. In all, 2,000 phase II trials were simulated from four actual phase III trials (two positive for OS and two negative for OS). Cox models for three metrics landmarked at 12 weeks and adjusted for baseline tumor burden were fit for each phase II trial: absolute changes, relative changes, and RECIST. Clinical utility was assessed by positive predictive value and negative predictive value, that is, the probability of a positive or negative phase II trial predicting an effective or ineffective phase III conclusion, by prediction error, and by concordance index (c-index). Results Absolute and relative change metrics had higher positive predictive value and negative predictive value than RECIST in five of six treatment comparisons and lower prediction error curves in all six. However, differences were negligible. No statistically significant difference in c-index across metrics was found. Conclusion The absolute and relative change metrics are not meaningfully better than RECIST in predicting OS.
Ifosfamide in refractory male germ cell tumors.
Authors: B M Wheeler, P J Loehrer, S D Williams, L H Einhorn
Journal: Journal of Clinical Oncology (1986)

We conducted a phase II clinical trial using ifosfamide (IFX) as a single agent in cisplatin-refractory male germ cell tumor. Thirty patients with measurable disease were treated with IFX, 2 g/m2 intravenously (IV) for 5 consecutive days every 3 weeks. N-acetylcysteine, 2 g orally every 4 hours, was given as a uroprotective agent. All patients had previously been treated with cisplatin, vinblastine, and bleomycin, and all except two also had previously received etoposide. There were six partial responses (PR) and one complete response (CR) for an overall objective response rate of 23%. The median duration of response was 3.5 months (range, 2 to 5.5 months). The median survival time was 3.5 months (range, 2 to 14+ months). The toxicity of the regimen consisted of hematuria (65% of the patients), nausea and vomiting (43%), neutropenia (WBC less than 2,000; 52%), thrombocytopenia (platelet count less than 50,000; 20%), and nephrotoxicity (12%). Hematuria was dose related, occurring in 48% of courses using 2 g/m2/d v only 5% of courses at lower doses. Serious nephrotoxicity (creatinine level greater than 6.0 mg/mL) was observed in three patients with an elevated pretreatment serum creatinine level. In conclusion, IFX is an active agent in this heavily pretreated population with advanced refractory germ cell tumor.
Diagnosis and Management of Renal Angioma
Authors: J F Abercrombie, S A V Holmes, A J Ball
Journal: Journal of the Royal Society of Medicine (1992)

Five patients with symptomatic renal angiomata are described. All presented with heavy haematuria and unilateral ureteric obstruction without evidence of a mass distorting the renal architecture. Renal angiomata are most easily diagnosed by selective renal angiography. They may be treated by intra-arterial embolization, avoiding the need for major ablative surgery.
A randomized, double-blind, double-dummy, crossover trial comparing the safety and efficacy of oral sustained-release hydromorphone with immediate-release hydromorphone in patients with cancer pain. Canadian Palliative Care Clinical Trials Group.
Authors: E Bruera, P Sloan, B Mount, J Scott, M Suarez-Almazor
Journal: Journal of Clinical Oncology (1996)

To evaluate the safety and efficacy of a new slow-release preparation of hydromorphone (SRH) in the treatment of cancer pain.Ninety-five adult patients from three Canadian Palliative Care Centers with no evidence of mental impairment received treatment for cancer pain with an oral opioid analgesic. After informed consent was obtained, patients underwent titration to a stable dose of immediate-release hydromorphone (IRH) for 48 hours, and were then randomized to receive IRH or SRH for 5 days in a double-blind basis. During day 6, a crossover took place, and patients received the alternate drug for 5 days. Pain intensity was assessed using a visual analog scale (VAS) and ordinal scale (OS). Side effects were assessed using VAS. Patients and investigators made a blinded global rating of efficacy a blinded final choice between SRH and IRH.In 75 assessable patients, pain intensity of the VAS and OS were (mean +/- SD) 27 +/- 21 and 1.3 +/- 0.6 on IRH, versus 29 +/- 21 (P = .13) and 1.3 +/- 0.6 (P = .19) on SRH, respectively. The total number of extra doses of opioids, global rating, and final blinded choice by both patients and investigators were not significantly different between IRH and SRH. Differences in side effects were not significant.Our findings suggest that SRH is as safe and effective as IRH in the treatment of cancer pain.