tbuckley/cabot-search huggingface dataset:
Combination therapy with interferon alfa-2a and interleukin-2 for the treatment of metastatic cancer.
Authors: F M Marincola, D E White, A P Wise, S A Rosenberg
Journal: Journal of Clinical Oncology (1995)

Here we report the long-term follow-up evaluation of a phase I/II study of toxicity and response of combination interferon alfa-2a (IFN alpha) and interleukin-2 (IL-2) in patients with metastatic cancer.From November 1987 through October 1990, 189 patients were treated with 379 courses. IFN alpha (3 x 10(6) U/m2) was administered three times per day as an intravenous (IV) bolus with IV IL-2 2.6 x 10(6) IU/m2 (six patients, group 1), 7.8 x 10(6) IU/m2 (32 patients, group 2), or 11.7 x 10(6) IU/m2 (26 patients, group 3). Subsequently, IFN alpha dose was escalated to 6 x 10(6) U/m2 plus IL-2 11.7 x 10(6) IU/m2 (22 patients, group 4). Two further dosage schedules of IL-2 were tested at 7.8 x 10(6) IU/m2 (29 patients, group 5) and 15.6 x 10(6) IU/m2 (74 patients, group 6); however, because of IFN alpha-related toxicity, these two groups received IFN alpha once per day (6 x 10(6) U/m2). A treatment course consisted of two cycles (maximum, 15 doses per cycle) separated by a 10-day interval.All patients were assessable for response: 82 patients had melanoma, 75 renal cell carcinoma (RCC), and 16 colorectal cancer. There were two treatment-related deaths. The objective response rate was 23% (43 patients). Response rates were 17%, 19%, 19%, 32%, 41%, and 16%, respectively, for groups 1 through 6. Ten responses are still ongoing (nine in RCC patients) at 57 to 74 months, and 21 patients are alive, for an overall 5-year survival rate of 11%. The median potential follow-up period was 65 months. Although a significantly higher response rate was noted for group 4 (highest dose of IFN alpha three times per day), no benefit for survival and increased toxicity were noted in this group.Based on these findings, we conclude that further studies of this combination treatment are not warranted.
Hemolytic anemia after fludarabine therapy for chronic lymphocytic leukemia.
Authors: R B Weiss, J Freiman, S L Kweder, L F Diehl, J C Byrd
Journal: Journal of Clinical Oncology (1998)

A report of the clinical features, treatment, and outcome of patients who developed hemolytic anemia (HA) temporally associated with fludarabine (Fludara; Berlex Laboratories, Richmond, CA) therapy for chronic lymphocytic leukemia (CLL).Data on 24 patients who developed HA related to fludarabine therapy were collected from the Spontaneous Reporting System of the Food and Drug Administration (FDA) and the Walter Reed Army Medical Center (Washington, DC).Seventeen (71%) patients developed HA after either the first, second, or third cycle of this drug. The longest duration of fludarabine therapy before HA occurred was six cycles. The median decline in hematocrit from baseline during the hemolytic episode was 14.1 (range, 8.0 to 28.9) for the 18 patients for whom this information was available. For the 11 patients for whom transfusion requirements were known, the number of transfusions administered ranged between three and 36. Seven (29%) patients died of medical complications associated with the HA. Seven of eight patients who were re-challenged with fludarabine after an episode of HA developed recurrent HA, and three of these patients died.HA associated with fludarabine therapy appears to be uncommon, but it can be severe and fatal, especially if a patient is re-treated with this drug after a previous episode of HA. The mechanism of this toxicity is unknown, but it may be caused by the release of a suppressed auto-antibody to a native red cell antigen.
COPD prevalence in Yigilca, a town in rural area of Duzce, Turkey: Insight from the Melen study
Authors: Leyla Yilmaz Aydin, Talha Dumlu, Yusuf Aydin, Serkan Bulur, Melih Engin Erkan, Hulya Coskun, Kezban Suner, Hakan Ozhan
Journal: European Respiratory Journal (2011)

Introduction: COPD prevalence varies across countries and different groups within countries. There are only three local epidemiological studies on COPD prevalence among Turkish population. COPD diagnosed by spirometry in two of them.

Aim: To determine COPD prevelance using spirometry and symptom based criteria in Yigilca, a town in rural area of Duzce.

Methods: The Melen Study was a cross-sectional study conducted in May and June, 2010. Study population was inhabitants of 21000 people in Yigilca. Health service of the region was supplied by six family physicians. 400 subjects from each family physician were randomly selected from electronical data base. Interviews were made by researchers face to face. The questionnaire consist of demographic and socioeconomical variables, the history items of dyspnea, cough, sputum and smoking habits.

Spirometry was performed with Vitalograph ALPHA. COPD defined as a history of dyspnea, cough or sputum production, and post-bronchodilator FEV1/FVC<70.

Results: A total of 2298 subjects (1471 female, 827 male with a mean age of 50) were interviewed. Spirometry was performed in 1468 of 2298 participants. COPD prevalence for adults and adults aged ≥40 years old were 4,9% and 6.7%, respectively. Post-bronchodilator FEV1/FVC<70 were detected in 7,4% of 1468 participants. Sixty five percent of the study population (1495 subjects) had never smoked. Crude smoking rate of the population was 17%.

Conclusion: Although results are consistent with the literature, our study revealed a lower prevalence than other two epidemiological studies in Turkey those used spirometry in diagnose. Low levels of smoking prevalence and rural area might be effective in low prevalence.
Nutrition of Mouse Ascites Tumor Cells in Primary Culture. II. Specific Requirement for Glucose&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: J F Morgan, C P Eng
Journal: JNCI Journal of the National Cancer Institute (1970)

Primary monolayer cultures were prepared from mouse ascites tumor cells of the Ehrlich-Lettré line and cultivated in chemically defined media containing various carbohydrates as the sole energy source. An absolute glucose requirement for culture survival was found, which could be satisfied by either the alpha or beta forms. The cultures died within 2-3 days when D-mannose, D-fructose, or D-galactose was substituted for D-glucose. Of over 50 other carbohydrates and related compounds tested, none could replace glucose. Cells of the Ehrlich and Ehrlich-Lettré lines suspended in balanced salt solutions containing various carbohydrates removed D-glucose, D-mannose, D-fructose, D-glucosamine, and 2-deoxy-D-glucose from the suspending fluid. In the presence of D-glucose, culture survival was inhibited by D-mannose, D-fructose, L-glucose, and D-galactose. D-Glucosamine and 2-deoxy-D-glucose strongly inhibited culture survival with the 50% inhibition points at 375 mg/liter and 62.5 mg/liter, respectively. The inhibition by D-glucosamine could be reversed by alpha- and beta-glucose, but not by D-mannose or D-fructose. The inhibition by 2-deoxy-D-glucose could be reversed completely by alpha- and beta-glucose, to a slight degree by D-mannose, and not at all by D-fructose.
The Flowering of London Pride: Finding a Name for It
Authors: Arthur Crisp, David Innes Williams, Robin Price
Journal: Journal of the Royal Society of Medicine (2001)

In the 1970s, university funding, which had risen progressively over the preceding years, began to plateau. The University of London was especially afflicted. There was a need to rationalize resources and the vice-chancellor of the day, Lord Annan (previously provost of University College London), saw opportunity and advantage in tackling medicine first. At the time the Faculty of Medicine comprised 12 so-called undergraduate medical schools, 13 exclusively postgraduate medical institutes, 5 dental schools, 2 schools of pharmacy and the school of veterinary medicine. Its excellence was not much in dispute. In the main, these schools were academically, geographically and financially separate from the University multifaculty institutions. London academic medicine attracted postgraduate students from around the world much in the way that Vienna had a century before. But its academic foundations were becoming less secure in that the schools were often divorced from mainstream sciences within the University at large. With financial imperatives in mind it was also apparent that maintenance of a large number of adjacent but administratively separate and small medical schools was especially expensive. Hidden agendas may have included ideas surfacing in two of the major multifaculty institutes, ultimately to break away from the federal University and take segments of academic medicine with them. It was also felt that, if London academic medicine could be rationalized, the process might serve as a model for dealing with other Faculties. At this time the Faculty of Medicine within the University was an active body, largely in the hands of clinical academics, determining academic standards and coming to involve individual medical schools somewhat more robustly. A working party was set up with Sir Brian Flowers (rector of Imperial College and subsequently Lord Flowers) as its chairman.
Pulmonary noxious exposure (PNE) and tobacco smoking (TS) in home oxygen therapy (HOT) patients
Authors: Fabrizio Facchini, Laura De Lozzo, Samantha Angioletti, Luigi Marino, Stefano Nardini
Journal: European Respiratory Journal (2013)

Background and aim : HOT is the treatment of choice for any hypoxemic chronic respiratory failure. There is insufficient knowledge of how many HOT patients are smokers (S), former smokers (EX) or never smokers (NS) and which characteristics they have. We surveyed for PNE and TS 136 HOT Patients.  Method : The database of HOT patients followed up by our unit was analysed for information about PNE and TS; then telephone interviews were arranged for all patients and caregivers asking history of PNE and TS.  Results : Smokers were 8,1%, P/Y=40; EX smokers 61,8% and Never Smokers 30,1%; ExCO in S was 20 ppm. S were younger (mean age 61) as compared to EX (mean age 79) or NS (mean age 73). We looked at professional exposure, home environmental pollutionand passive smoke. A negative history of PNE other than sel inflicted TS was present in only 16% of NS, 30% of EX, and 10% of S. In NS group passive smoke exposure was present in 25% of the patients, possible home environment pollution (wood fire place/burner/stoves or wood cooker) was present in about 45% of the patients, professional exposure to paint in 16% of the patients, professional exposure to polishing was present in 8% of the patients. No other causes of respiratory failure other than PNE was found in only 4% of NS.  Conclusion: In our sample PNE is frequent thus they likely give an important contribution to the condition; despite this PNE has been clinically found to be the main cause of respiratory failure in only about 4% of NS patients.  (*) Supported by an unconditioned educational grant from Medicair.
Neoadjuvant chemotherapy in operable non-small cell lung cancer
Authors: J Gittens
Journal: Thorax (2008)

Survival for patients with non-small cell lung cancer (NSCLC) has remained unchanged for over 10 years. This randomised controlled trial assessed the benefits of neoadjuvant chemotherapy in patients with operable NSCLC.

519 patients were randomised to receive surgery as soon as possible or chemotherapy as soon as possible followed by surgery 4–6 weeks from …
Association between the preoperative fasting and postprandial C-peptide AUC with resolution of type 2 diabetes 6months following bariatric surgery
Authors: Akhila Mallipedhi, Thinzar Min, Sarah L. Prior, Claire MacIver, Steve D. Luzio, Gareth Dunseath, Richard M. Bracken, Saiful Islam, Jonathan D. Barry, Scott Caplin, Jeffrey W. Stephens
Journal: Metabolism (2015)
Abstract 10137: Low-Density Lipoprotein Cholesterol is Poor Predictor of Effective Therapy as Measured by Carotid Plaque Necrotic Core Size After > 1 Year Statin Therapy
Authors: Kevin DeMarco, Hideki Ota, Alonso Collar, Chun Yuan
Journal: Circulation (2011)

Introduction: While stroke-related mortality has been decreasing, further reductions may require monitoring of individual response to therapy over and above existing risk factors such as hyperlipid...
Genetical control of B-cell responses. III. Requirement for functional mitogenicity of the antigen in thymus-independent specific responses.
Authors: A Coutinho, E Gronowicz
Journal: The Journal of Experimental Medicine (1975)

Spleen cells from C3H/HeJ mice fail to respond with polyclonal antibody synthesis to mitogenic concentrations of lipopolysaccharide (LPS) which are optimal for activating spleen cells from a high-responder strain (B10.5M). This unresponsiveness is selective for LPS, since C3H/HeJ cells respond as normals to another B-cell mitogen, purified protein derivative of tuberculin. Spleen cells from low-responder mice also fail to mount a specific anti-NNP plaque-forming cell (PFC) response, when challenged in vitro by NNP-LPS. However, C3H/HeJ cells develop normal responses to another thymus-independent hapten conjugate, DNP-AECM-Ficoll. C3H/HeJ mice fail to mount a specific anti-LPS antibody response, when challenged in vivo with doses of soluble LPS which are fully immunogenic for the high-responder strain. However, C3H/HeJ mice develop normal direct and indirect PFC responses to LPS, when challenged with a thymus-dependent form of the immunogen. These results are interpreted as indicating as absolute requirement for functional mitogenicity of the antigen, in the induction of specific thymus-independent antibody responses.
Photodynamic therapy for inoperable vulval Paget's disease using δ-aminolaevulinic acid: successful management of a large skin lesion
Authors: None Henta, None Itoh, None Kobayashi, None Ninomiya, None Ishibashi
Journal: British Journal of Dermatology (1999)

A 74‐year‐old woman with extensive inoperable vulval extramammary Paget's disease who had lymph node and pulmonary metastases, was treated with etoposide (VP16) 100 mg and 5000 cGy electron beam irradiation, which reduced the lesion by 60%. Following these interventions, the residual lesion was successfully treated with repeated photodynamic therapy using δ‐aminolaevulinic acid, which achieved a nearly complete remission.
Plasma total versus bone alkaline phosphatase as markers of bone turnover in hemodialysis patients.
Authors: P Ureña, M Hruby, A Ferreira, K S Ang, M C de Vernejoul
Journal: Journal of the American Society of Nephrology (1996)

Plasma total versus bone alkaline phosphatase as markers of bone turnover in hemodialysis patients. Plasma bone-specific alkaline phosphatase (bAP) has been demonstrated to be more reliable than total alkaline phosphatases (tAP) in providing information about bone turnover in patients with metabolic bone diseases. This study surveyed 42 hemodialysis patients who underwent a systematic transiliac bone biopsy for histomorphometry study. Plasma bAP was determined by using a new immunoassay (Tandem-R Ostase, Hybritech, Liège, Belgium). Plasma bAP values were compared with those of two other plasma markers of bone metabolism, namely tAP and intact parathyroid hormone (iPTH), for the correlations with bone histomorphometric parameters. Patients with high-turnover bone disease (HTBD) (N = 32) had significantly higher plasma bAP levels than patients with normal or low bone turnover (N/LTBD) (N = 10) (66.9 +/- 63.5 ng/mL versus 10.8 +/- 4.2 ng/mL, respectively). Bone formation and resorption were highly correlated in these patients, and plasma bAP levels were positively correlated with bone resorption parameters, including osteoclast surface (r = 0.39, P < 0.0001) and osteoclast number/mm2 (r = 0.36, P < 0.001), and with bone formation parameters, osteoblast surface (r = 0.50, P < 0.005), and bone formation rate (r = 0.91, P < 0.0001). The bone formation rate was better correlated with plasma bAP levels than with either plasma tAP or iPTH concentrations. Plasma bAP level equal or higher than 20 ng/mL, either alone or combined with plasma iPTH of 200 pg/mL, had the highest sensitivity, specificity, and predictability values for the diagnosis of high-turnover bone disease, and formally excluded patients with normal or LTBD. In conclusion, plasma bAP can be measured with a reliable immunoassay in hemodialysis patients. It represents a highly sensitive and specific biochemical marker of skeletal remodeling in these patients. Therefore, both serum iPTH and bAP are complementary in diagnoses of the type of renal osteodystrophy.
Hormone replacement therapy in women with breast cancer. Do the risks outweigh the benefits?
Authors: J A Roy, C A Sawka, K I Pritchard
Journal: Journal of Clinical Oncology (1996)

PURPOSE To review critically the literature regarding effects of estrogen replacement therapy (ERT)/combined estrogen and progesterone replacement therapy (HRT) on the risk of breast cancer and on other health risks and benefits in postmenopausal women, with a focus on risks and benefits in women with a previous diagnosis of breast cancer. METHOD A literature search was conducted using Medline, Cancerline, and the bibliographies of reports published as of March 1995. All five published meta-analyses that examined the risk of breast cancer in relation to ERT/HRT in otherwise healthy women were critically reviewed. All known reports of women with a history of breast cancer given ERT/HRT subsequent to diagnosis and additional reports regarding the benefits of ERT/HRT were also reviewed. RESULTS None of the five meta-analyses demonstrated a significantly increased risk of developing breast cancer in ever users compared with never users of ERT/HRT. Current use may be associated with a small increased risk. This increased risk should be balanced by the expected benefits of ERT/HRT on quality of life, bone metabolism, and cardiovascular function. Preliminary information does not suggest a major detrimental effect of ERT/HRT in women with a previous diagnosis of breast cancer, but these reports include few women with limited follow-up data. There are no randomized trials in women with a previous diagnosis of breast cancer. CONCLUSION In healthy postmenopausal women, the benefits associated with ERT/HRT outweigh the risks. In women with a previous diagnosis of breast cancer, the balance of risks and benefits should be explored in randomized controlled trials.
Phase II study of docetaxel and cisplatin in advanced non-small-cell lung cancer.
Authors: J Zalcberg, M Millward, J Bishop, M McKeage, A Zimet, G Toner, M Friedlander, C Barter, D Rischin, C Loret, R James, N Bougan, J Berille
Journal: Journal of Clinical Oncology (1998)

PURPOSE Docetaxel (Taxotere, Rhone-Poulenc Rorer, Antony, France) and cisplatin are two of the most active single agents used in the treatment of non-small-cell lung cancer (NSCLC). A recently reported phase I study of the combination of docetaxel and cisplatin recommended a dose of 75 mg/m2 of both drugs every 3 weeks for subsequent phase II study. PATIENTS AND METHODS Eligible patients were aged 18 to 75 years with a World Health Organization (WHO) performance status &lt; or = 2 and life expectancy &gt; or = 12 weeks, with metastatic and/or locally advanced NSCLC proven histologically or cytologically. Patients were not permitted to have received prior chemotherapy, extensive radiotherapy, or any radiotherapy to the target lesion and must have had measurable disease. Concurrent treatment with colony-stimulating factors (CSFs) or prophylactic antibiotics was not permitted. Docetaxel (75 mg/m2) in 250 mL 5% dextrose was given intravenously (i.v.) over 1 hour immediately before cisplatin (75 mg/m2) in 500 mL normal saline given i.v. over 1 hour in 3-week cycles. Premedication included ondansetron, dexamethasone, promethazine, and standard hyperhydration with magnesium supplementation. RESULTS A total of 47 patients, two thirds of whom had metastatic disease, were entered onto this phase II study. The majority of patients were male (72%) and of good (WHO 0 to 1) performance status (85%). All 47 patients were assessable for toxicity and 36 were for response. Three patients were ineligible and eight (17%) discontinued treatment because of significant toxicity. In assessable patients, the overall objective response rate was 38.9% (95% confidence limits [CL], 23.1% to 56.5%), 36.1% had stable disease, and 25% progressive disease. On an intention-to-treat analysis, the objective response rate was 29.8%. Median survival was 9.6 months and estimated 1-year survival was 33%. Significant (grade 3/4) toxicities included nausea (26%), hypotension (15%), diarrhea (13%), and dyspnea mainly related to chest infection (13%). One patient experienced National Cancer Institute (NCI) grade 3 neurosensory toxicity after eight cycles. Grade 3/4 neutropenia was common and occurred in 87% of patients, but thrombocytopenia &gt; or = grade 3 was rare (one patient). Significant (grade 3/4) abnormalities of magnesium levels were common (24%). Febrile neutropenia occurred in 13% of patients and neutropenic infection in 11%, contributing to two treatment-related deaths. No neutropenic enterocolitis or severe fluid retention was reported. CONCLUSION Compared with other active regimens used in this setting, the combination of docetaxel and cisplatin in advanced NSCLC is an active regimen with a similar toxicity profile to other combination regimens.
Abstract 33: Contractile Dysfunction In The Mouse Heart Caused By Phospholipase C beta1b Mediated Activation Of Protein Kinase Calpha
Authors: David R Grubb, Yi Ma, Jieting Luo, Bryony Crook, Nicola Cooley, Helen Kiriazis, Hong Wei Qian, Paul Gregorevic, Xiao-Ming Gao, Xiao-Jun Du, Elizabeth A Woodcock
Journal: Circulation Research (2014)

The activity of the early signaling enzyme, phospholipase Cβ1b (PLCβ1b), is elevated in diseased myocardium and activity increases with disease progression. PLCβ1b and the alternative splice variant, PLCβ1a, were expressed in mouse hearts using adeno-associated viral constructs (rAAV6-FLAG-PLCβ1b, rAAV6-FLAG- PLCβ1a) delivered intravenously. Functional responses were assessed in vivo and confirmatory mechanistic studies were conducted in neonatal rat ventricular myocytes (NRVM). FLAG-PLCβ1b was expressed in all of the chambers of the mouse heart, but was highest in left ventricle, where expression was observed in &gt;90% of the cells and was localized to the sarcolemma and T-tubules. Heightened PLCβ1b expression caused a rapid loss of contractility and down-regulation of Phospholamban expression. The loss of contractility induced by PLCβ1b was reversed by inhibition of protein kinase Cα (PKCα). PLCβ1a did not affect contractile function or phospholamban expression. Mechanistic analysis performed in neonatal rat cardiomyocytes confirmed PLCβ1b increased the membrane association of PKCα as well as downstream dephosphorylation of phospholamban and depletion of the Ca2+ stores of the sarcoplasmic reticulum, both of which were mediated by PKCα. Trans-aortic constriction (TAC) resulted in progressive hypertrophy together with reduced contractility in PLCβ1a expressing mice. In PLCβ1b-expressing mice, TAC induced a similar hypertrophic response, but did not cause further contractile depression above that due to PLCβ1b expression alone, suggesting that PLCβ1b is responsible for lowering contractility in response to pressure overload. We conclude that heightened PLCβ1b activity observed in diseased myocardium contributes to pathology by PKCα-mediated contractile dysfunction. PLCβ1b is a cardiac-specific signaling system, and thus provides an ideal therapeutic target for the development of well-tolerated inotropic agents for use in failing myocardium.