tbuckley/cabot-search huggingface dataset:
Phase I Trial of Intravesical Gemcitabine in Bacillus Calmette-Guérin–Refractory Transitional-Cell Carcinoma of the Bladder
Authors: Guido Dalbagni, Paul Russo, Joel Sheinfeld, Madhu Mazumdar, William Tong, Farhang Rabbani, Machelle S. Donat, Harry W. Herr, Pramod Sogani, Dominique dePalma, Dean Bajorin
Journal: Journal of Clinical Oncology (2002)

PURPOSE: The aim of this phase I study was to determine the safety and toxicity profile of gemcitabine administered as an intravesical agent in patients with transitional-cell carcinoma (TCC) of the bladder. PATIENTS AND METHODS: Patients with superficial bladder cancer refractory to intravesical bacillus Calmette-Guérin (BCG) therapy and refusing a cystectomy were considered eligible for the trial. Gemcitabine was given in the bladder for 1 hour twice weekly in 100 mL sodium chloride for a total of six treatments. After a 1-week break, a second course of six treatments over 3 weeks was given, followed by response assessment. Four dose levels were explored: 500 mg, 1,000 mg, 1,500 mg, and 2,000 mg. RESULTS: Eighteen patients completed therapy: three at 500 mg, six at 1,000 mg, three at 1,500 mg, and six at 2,000 mg. No grade 3 or 4 toxicity was observed at 500 mg. At 1,000 mg, three patients developed hematuria and one had a skin reaction resembling grade 3 hand-foot syndrome. Three patients at 1,500 mg had no grade 3 or 4 toxicity. Of six patients at 2,000 mg, one had grade 3 thrombocytopenia and neutropenia without infection. Seven patients had a complete response (negative cytology and posttreatment biopsy), and four patients had a mixed response (negative bladder biopsy but positive cytology). CONCLUSION: Gemcitabine has substantial activity as an intravesical agent in BCG-refractory TCC and warrants further investigation. Therapy given twice weekly was associated with minimal bladder irritation and tolerable myelosuppression. The recommended phase II dose for twice-weekly therapy is 2,000 mg.
Verapamil ameliorates the clinical and pathological course of murine myocarditis.
Authors: R Dong, P Liu, L Wee, J Butany, M J Sole
Journal: Journal of Clinical Investigation (1992)

The effects of the calcium channel blocking agent, verapamil, were studied in a murine model of viral myocarditis. Three groups of 8-wk-old DBA/2 mice (n = 25 each) were inoculated with 10 plaque-forming units of encephalomyocarditis virus and randomized to three treatment regimens. Group 1 mice received verapamil intraperitoneally (5 mg/kg per d) for 7 d before infection, followed by verapamil orally (mean dose of 3.5 mg/mouse per d) in drinking water during infection. Group 2 mice received only verapamil orally starting on day 4 after infection, coincident with peak viremia. Group 3 (infected control) received no verapamil in regular drinking water after viral inoculation. Additional control animals were studied in group 4 (n = 21), consisting of uninfected control animals receiving intraperitoneal and oral verapamil at doses identical to group 1, and in group 5 (n = 21), consisting of uninfected and untreated controls. Animals were randomly killed from each group (n = 7) at 7, 14, and 28 d after infection. Routine histology was performed blindly on an apical slice of each heart and semi-quantitatively graded for inflammation, necrosis, calcification, and fibrosis on a scale of 0-4. Digital planimetry was performed to measure the absolute and relative areas of inflammation and necrosis. The pretreated animals in group 1 showed marked reduction in inflammation and necrosis (score of 3.7 +/- 1.4 vs. 8.7 +/- 2.0 in group 3 on day 14, P < 0.05) and were indistinguishable from the posttreated group 2 mice (score of 4.0 +/- 1.5 vs. 8.7 +/- 2.0 in group 3 on day 14, P < 0.05). All the uninfected control animals (groups 4 and 5) showed no myocardial lesions whether treated with verapamil or not. Quantitative planimetry confirmed decreased inflammation and necrosis (2.0 +/- 3.3% in group 1 and 3.5 +/- 3.1% in group 2 vs. 21.9 +/- 22.6% in group 3 on day 14). Untreated infected hearts injected with liquid silicone rubber exhibited extensive areas of focal microvascular constriction and microaneurysm formation; verapamil treatment in either group 1 or 2 completely abolished these abnormalities, resembling uninfected controls in groups 4 or 5. We conclude that verapamil, whether given before infection or after peak viremia in an encephalomyocarditis model of murine myocarditis, significantly reduces the microvascular changes and myocardial necrosis, fibrosis, and calcification leading to cardiomyopathy. This suggests the potentially important role of calcium and microvascular spasm in the pathogenesis of viral myocarditis leading to dilated cardiomyopathy, and may have future therapeutic implications.
Impact of Chronic Kidney Disease on Platelet Function Profiles in Diabetes Mellitus Patients With Coronary Artery Disease Taking Dual Antiplatelet Therapy
Authors: Dominick J. Angiolillo, Esther Bernardo, Davide Capodanno, David Vivas, Manel Sabaté, José Luis Ferreiro, Masafumi Ueno, Pilar Jimenez-Quevedo, Fernando Alfonso, Theodore A. Bass, Carlos Macaya, Antonio Fernandez-Ortiz
Journal: Journal of the American College of Cardiology (2010)
Metabolism of apolipoproteins B-48 and B-100 of triglyceride-rich lipoproteins in patients with familial dysbetalipoproteinemia.
Authors: A F Stalenhoef, M J Malloy, J P Kane, R J Havel
Journal: Journal of Clinical Investigation (1986)

The metabolism of apolipoproteins B-48 and B-100 (apo B-48 and B-100) in large triglyceride-rich lipoproteins was studied in three adults with familial dysbetalipoproteinemia (F. dys.) and compared to that of normolipidemic subjects. One Caucasian F. dys. subject was apparently homozygous for the common form of apo E-2, (Arg158----Cys), whereas the two Black subjects were homozygous for a different apo E-2 mutant (Arg145----Cys), which displays much less defective binding to cells than apo E-2 (Arg158----Cys). The lipoproteins were labeled with 125I and injected intravenously into fasted recipients. The results indicate that the terminal catabolism of triglyceride-rich lipoproteins of intestinal and hepatic origin is markedly impaired in apo E2/2 homozygotes with alleles Arg158----Cys and Arg145----Cys; despite long residence times, apo B-48 of chylomicrons and apo B-100 of large very low density lipoproteins are not converted appreciably to intermediate or low density lipoproteins in apo E2/2 homozygotes.
Renewing licence in person cuts deaths among elderly drivers
Authors: Janice Hopkins Tann
Journal: BMJ (2004)

The government's Social Exclusion Unit (SEU) has announced far-reaching proposals which it hopes will end the stigma and discrimination attached to mental illness and encourage people back into meaningful lives.This week the unit launched its report, Mental Health and Social Exclusion, which calls for health services to focus on the social as well as medical needs of hundreds of thousands of people excluded from wider society by mental illness.The report sets out a five year plan with an ambitious antistigma and discrimination campaign aimed at employers, schools, and the media, which it hopes will dispel cultural myths that people with mental illness are dangerous, unstable, and unemployable.All psychiatric patients in hospital are to be given vocational advice and support, and trusts will be told to strengthen links with job centres.NHS day centres must be redesigned with a focus on re-integrating patients into the community via job training, advice about employment, education, or voluntary work.
Objective quantitative analysis of eosinophils and bronchial epithelial cells in induced sputum by laser scanning cytometry
Authors: G Woltmann, R J Ward, F A Symon, D A Rew, I D Pavord, A J Wardlaw
Journal: Thorax (1999)

<h3>BACKGROUND</h3> Sputum induction is an important non-invasive technique for measuring airway inflammation in asthma. Cell numbers are often too low for flow cytometric analysis. Laser scanning cytometry (LSC) is a novel technique that allows objective multicolour fluorescence analysis of cells on a microscope slide. <h3>METHODS</h3> LSC was used to determine sputum eosinophil and bronchial epithelial cell counts. We first confirmed that we could measure eosinophil counts accurately in peripheral blood using α-major basic protein (MBP) immunofluorescent staining. Sputum induction was performed according to standard protocols. Sputum samples from eight normal controls and 12 asthmatic patients were analysed by LSC and manual counting by two independent observers. Octospot cytospins were fixed and stained with mouse-α-human-MBP monoclonal antibody or mouse-α-human-cytokeratin antibody and goat-α-mouse Oregon Green conjugated second antibody. <h3>RESULTS</h3> Sputum induction provided a mean (SE) of 0.99 (0.2) × 10<sup>6</sup> cells per donor. More than 3000 cells on three cytospins per slide were analysed per cell type. The intraclass correlation coefficient (R) and standard deviation (SD) of differences in eosinophils determined by manual counting and LSC were 0.9 and 2.1, respectively, and for bronchial epithelial cell counts they were 0.7 and 2.0. Selective detection of labelled cells was confirmed visually after relocation. <h3>CONCLUSION</h3> Eosinophils and bronchial epithelial cells can be accurately and reproducibly counted in an objective manner. LSC is therefore a potentially powerful new method for immunophenotyping leucocytes and epithelial cells objectively in induced sputum in patients with asthma.
Avian-Battey mycobacteria infection.
Authors: S H Ferguson
Journal: BMJ (1969)

BlumsHepisodes, dyskinetic movement disorder, and adoption as a drug of abuse, may all be added to the record of a drug which has already been associated with a small number of fatalities.As with other drugs introduced as substitutes for the amphetamines, claims have been made that fenfluramine is a drug of low toxicity which does not stimulate the central nervous system.These assertions can no longer be sustained, and it is imperative that the same caution be exercised in the use of this drug as would be appropriate to other central nervous stimulants.-Iam, etc.,
Determinants of Aggressive End-of-Life Care for Taiwanese Cancer Decedents, 2001 to 2006
Authors: Siew Tzuh Tang, Shiao-Chi Wu, Yen-Ni Hung, Jen-Shi Chen, Ean-Wen Huang, Tsang-Wu Liu
Journal: Journal of Clinical Oncology (2009)

To assess the association between aggressiveness of end-of-life (EOL) care and patient demographics, disease characteristics, primary physician's specialty, hospital characteristics, and availability of health care resources at the hospital and regional levels in Taiwan for a cohort of 210,976 cancer decedents in 2001 to 2006.This retrospective cohort study examined administrative data. Aggressiveness of EOL care was examined by a composite measure adapted from Earle et al. Scores range from 0 to 6, with higher scores indicating more aggressive EOL care.The mean composite score for aggressiveness of EOL care was 2.04 (mean) +/- 1.26 (standard deviation), increasing from 1.96 +/- 1.26 in 2001 to 2.10 +/- 1.26 in 2006. Each successive year of death significantly increased the composite score. Cancer decedents received more aggressive EOL care if they were male, younger, single, had a higher level of comorbidity, had more malignant and extensive diseases or hematologic malignancies, were cared for by oncologists, and received care in a hospital with a greater density of beds.Controlling for patient demographics and cormorbidity burden, EOL care in Taiwan was more aggressive for patients with cancer with highly malignant and extensive diseases, for patients with oncologists as primary care providers, or in hospitals with abundant health care resources. Health policies should aim to ensure that all patients receive treatments that best meet their individual needs and interests and that resources are devoted to care that produces the greatest health benefits.
Photodynamic therapy for cancer of the pancreas
Authors: S G Bown
Journal: Gut (2002)

Background: Few pancreatic cancers are suitable for surgery and few respond to chemoradiation. Photodynamic therapy produces local necrosis of tissue with light after prior administration of a photosensitising agent, and in experimental studies can be tolerated by the pancreas and surrounding normal tissue. Aims: To undertake a phase I study of photodynamic therapy for cancer of the pancreas. Patients: Sixteen patients with inoperable adenocarcinomas (2.5–6 cm in diameter) localised to the region of the head of the pancreas were studied. All presented with obstructive jaundice which was relieved by biliary stenting prior to further treatment. Methods: Patients were photosensitised with 0.15 mg/kg meso-tetrahydroxyphenyl chlorin intravenously. Three days later, light was delivered to the cancer percutaneously using fibres positioned under computerised tomographic guidance. Three had subsequent chemotherapy. Results: All patients had substantial tumour necrosis on scans after treatment. Fourteen of 16 left hospital within 10 days. Eleven had a Karnofsky performance status of 100 prior to treatment. In 10 it returned to 100 at one month. Two patients with tumour involving the gastroduodenal artery had significant gastrointestinal bleeds (controlled without surgery). Three patients developed duodenal obstruction during follow up that may have been related to treatment. There was no treatment related mortality. The median survival time after photodynamic therapy was 9.5 months (range 4–30). Seven of 16 patients (44%) were alive one year after photodynamic therapy. Conclusions: Photodynamic therapy can produce necrosis in pancreatic cancers with an acceptable morbidity although care is required for tumours invading the duodenal wall or involving the gastroduodenal artery. Further studies are indicated to assess its influence on the course of the disease, alone or in combination with chemoradiation.
Alexander Gordon Bearn
Authors: D G. James
Journal: BMJ (2009)

To examine the role of the 5-hydroxytryptamine<sub>1B</sub>(5-HT<sub>1B</sub>) and 5-HT<sub>3</sub> receptor subtypes in the analgesia produced by 5-HT (serotonin) agonists, we assessed the effect of antisense oligodeoxynucleotides (AODNs) designed to “knock down” the number of these receptor subtypes on analgesia produced by intrathecal (i.t.) 5-HT, the 5-HT<sub>1B</sub> receptor agonist, 7-trifluoromethyl-4-(4-methyl-1-piperazinyl)-pyrrolo[1,2-a]quinoxaline maleate (CGS-12066A), and the 5-HT<sub>3</sub> receptor agonist, 2-methyl-5-HT. Groups of mice (<i>n</i> = 17–20) were injected i.t. on days 1, 3, and 5 with one of the AODNs, a mismatch oligo, or saline. On day 6, all mice were injected i.t. with 70.5 nmol of 5-HT, 44.4 nmol of CGS-12066A, or 49 nmol of 2-methyl-5-HT by lumbar puncture. Following testing, spinal cords were rapidly removed and prepared for receptor binding assays. Treatment with AODN for 5-HT<sub>1B</sub> receptors produced a 70% reduction in ligand binding to this receptor subtype. After treatment with AODN for 5-HT<sub>3</sub> receptors, ligand binding to this receptor subtype was undetectable. In mice tested with i.t. 5-HT, tail-flick analgesia was attenuated only in mice treated with the 5-HT<sub>3</sub> receptor AODN. Mice treated with the AODN designed to knock down 5-HT<sub>1B</sub> receptors or with its mismatch oligo were not significantly different from controls. In mice tested with i.t. administration of CGS-12066A, none of the oligo treatments produced a significant attenuation of analgesia. In mice tested with i.t. administration of 2-methyl-5-HT, only 5-HT<sub>3</sub> receptor AODN attenuated analgesia. Thus, 5-HT and 2-methyl-5-HT analgesia are mediated by the 5-HT<sub>3</sub> receptor subtype. However, spinal CGS-12066A analgesia appears not to be mediated by either the 5-HT<sub>1B</sub> or the 5-HT<sub>3</sub> receptor subtypes.
Exosomes mediate the cell-to-cell transmission of IFN-α-induced antiviral activity
Authors: Jianhua Li, Kuancheng Liu, Yang Liu, Yan Xu, Fei Zhang, Huijuan Yang, Jiangxia Liu, Tingting Pan, Jieliang Chen, Min Wu, Xiaohui Zhou, Zhenghong Yuan
Journal: Nature Immunology (2013)
Recent developments in endocrinology and paracrinology of blastocyst implantation in the primate
Authors: D Ghosh, J Sengupta
Journal: Human Reproduction Update (1998)

It is becoming increasingly evident that growth factors and cytokines play crucial roles in the process of blastocyst implantation. Endometrial differentiation and secretions, embryo development and secretions, and embryo-endometrium interaction leading to implantation require continuous and synchronous dialogue between these two compartments involving endocrine and paracrine regulators. In this review, a model of the endocrinology and paracrinology of blastocyst implantation in the primate is described.
Full cardiopulmonary resuscitation should not be used for ordinary dying
Authors: Gordon Caldwell
Journal: BMJ (2015)

The Analysis article on when and how to discuss “do not resuscitate” decisions with patients evades discussing the difference between ordinary dying and dying from cardiac arrest and attempted full cardiopulmonary resuscitation (CPR).1

In ordinary dying the vital organs fail and the heart is the last vital organ to stop. In cardiac arrest the heart is the first vital organ to …
Prostate Cancer Mortality following Active Surveillance versus Immediate Radical Prostatectomy
Authors: Jing Xia, Bruce J. Trock, Matthew R. Cooperberg, Roman Gulati, Steven B. Zeliadt, John L. Gore, Daniel W. Lin, Peter R. Carroll, H. Ballentine Carter, Ruth Etzioni
Journal: Clinical Cancer Research (2012)

[corrected] Active surveillance has been endorsed for low-risk prostate cancer, but information about long-term outcomes and comparative effectiveness of active surveillance is lacking. The purpose of this study is to project prostate cancer mortality under active surveillance followed by radical prostatectomy versus under immediate radical prostatectomy.A simulation model was developed to combine information on time from diagnosis to treatment under active surveillance and associated disease progression from a Johns Hopkins active surveillance cohort (n = 769), time from radical prostatectomy to recurrence from cases in the CaPSURE database with T-stage ≤ T2a (n = 3,470), and time from recurrence to prostate cancer death from a T-stage ≤ T2a Johns Hopkins cohort of patients whose disease recurred after radical prostatectomy (n = 963). Results were projected for a hypothetical cohort aged 40 to 90 years with low-risk prostate cancer (T-stage ≤ T2a, Gleason score ≤ 6, and prostate-specific antigen level ≤ 10 ng/mL).The model projected that 2.8% of men on active surveillance and 1.6% of men with immediate radical prostatectomy would die of their disease in 20 years. Corresponding lifetime estimates were 3.4% for active surveillance and 2.0% for immediate radical prostatectomy. The average projected increase in life expectancy associated with immediate radical prostatectomy was 1.8 months. On average, the model projected that men on active surveillance would remain free of treatment for an additional 6.4 years relative to men treated immediately.Active surveillance is likely to produce a very modest decline in prostate cancer-specific survival among men diagnosed with low-risk prostate cancer but could lead to significant benefits in terms of quality of life.
Mortality After Cure of Testicular Seminoma
Authors: Gunar K. Zagars, Matthew T. Ballo, Andrew K. Lee, Sara S. Strom
Journal: Journal of Clinical Oncology (2004)

Purpose To determine the incidence of potentially treatment-related mortality in long-term survivors of testicular seminoma treated by orchiectomy and radiation therapy (XRT). Patients and Methods From all 477 men with stage I or II testicular seminoma treated at The University of Texas M.D. Anderson Cancer Center (Houston, TX) with postorchiectomy megavoltage XRT between 1951 and 1999, 453 never sustained relapse of their disease. Long-term survival for these 453 men was evaluated with the person-years method to determine the standardized mortality ratio (SMR). SMRs were calculated for all causes of death, cardiac deaths, and cancer deaths using standard US data for males. Results After a median follow-up of 13.3 years, the 10-, 20-, 30-, and 40-year actuarial survival rates were 93%, 79%, 59%, and 26%, respectively. The all-cause SMR over the entire observation interval was 1.59 (99% CI, 1.21 to 2.04). The SMR was not excessive for the first 15 years of follow-up: SMR, 1.30 (95% CI, 0.93 to 1.77); but beyond 15 years the SMR was 1.85 (99% CI, 1.30 to 2.55). The overall cardiac-specific SMR was 1.61 (95% CI, 1.21 to 2.24). The cardiac SMR was significantly elevated only beyond 15 years (P &lt; .01). The overall cancer-specific SMR was 1.91 (99% CI, 1.14 to 2.98). The cancer SMR was also significant only after 15 years of follow-up (P &lt; .01). An increased mortality was evident in patients treated with and without mediastinal XRT. Conclusion Long-term survivors of seminoma treated with postorchiectomy XRT are at significant excess risk of death as a result of cardiac disease or second cancer. Management strategies that minimize these risks but maintain the excellent hitherto observed cure rates need to be actively pursued.
The Effect on Tumor Response of Adding Sequential Preoperative Docetaxel to Preoperative Doxorubicin and Cyclophosphamide: Preliminary Results From National Surgical Adjuvant Breast and Bowel Project Protocol B-27
Authors: Harry D. Bear, Stewart Anderson, Ann Brown, Roy Smith, Eleftherios P. Mamounas, Bernard Fisher, Richard Margolese, Heather Theoret, Atilla Soran, D. Lawrence Wickerham, Norman Wolmark
Journal: Journal of Clinical Oncology (2003)

Purpose: The National Surgical Adjuvant Breast and Bowel Project Protocol B-27 was designed to determine the effect of adding docetaxel after four cycles of preoperative doxorubicin and cyclophosphamide (AC) on clinical and pathological response rates and on disease-free and overall survival of women with operable breast cancer. Patients and Methods: Women (N = 2,411) with operable primary breast cancer were randomly assigned to receive either four cycles of preoperative AC followed by surgery (group I), or four cycles of AC followed by four cycles of docetaxel, followed by surgery (group II), or four cycles of AC followed by surgery and then four cycles of docetaxel (group III). Clinical and pathologic tumor responses to preoperative therapy were assessed. Results: Mean tumor size (4.5 cm) and other key characteristics were evenly balanced among the three treatment arms. Grade 4 toxicity was observed in 10.3% of 2,400 patients during AC treatment, and in 23.4% of 1584 patients during docetaxel treatment. Compared to preoperative AC alone, preoperative AC followed by docetaxel increased the clinical complete response rate (40.1% v 63.6%; P &lt; .001), the overall clinical response rate (85.5% v 90.7%; P &lt; .001), the pathologic complete response rate (13.7% v 26.1%; P &lt; .001), and the proportion of patients with negative nodes (50.8% v 58.2%; P &lt; .001). Pathologic primary breast tumor response was a significant predictor of pathologic nodal status (P &lt; .001). Conclusion: The addition of four cycles of preoperative docetaxel after four cycles of preoperative AC significantly increased clinical and pathologic response rates for operable breast cancer.