tbuckley/cabot-search huggingface dataset:
Endurance Exercise Improves Molecular Pathways of Aerobic Metabolism in Patients With Myositis
Authors: Li Alemo Munters, Ingela Loell, Elena Ossipova, Joan Raouf, Maryam Dastmalchi, Eva Lindroos, Yi‐Wen Chen, Mona Esbjörnsson, Marina Korotkova, Helene Alexanderson, Kanneboyina Nagaraju, Leslie J. Crofford, Per‐Johan Jakobsson, Ingrid E. Lundberg
Journal: Arthritis & Rheumatology (2016)

Objective Endurance exercise demonstrates beneficial effects in polymyositis/dermatomyositis (PM/DM); however, the molecular effects of exercise on skeletal muscle are incompletely understood. We undertook this controlled pilot study to investigate the effects of a 12‐week endurance exercise training program on the molecular profile of skeletal muscle in patients with established PM/DM compared to a nonexercised control group of patients with established PM/DM. Methods Fifteen patients (7 in the exercise group and 8 in the control group) with paired baseline and 12‐week follow‐up muscle biopsy samples were included. Messenger RNA expression profiling, mass spectrometry–based quantitative proteomics, and immunohistochemical analyses were performed on muscle biopsy samples to determine molecular adaptations associated with changes in clinical measurements induced by endurance exercise. Results Compared to the control group, the exercise group improved in minutes of cycling time ( P &lt; 0.01) and V o 2 max ( P &lt; 0.05). The exercise group also had reduced disease activity ( P &lt; 0.05) and reduced lactate levels at exhaustion ( P &lt; 0.05). Genes related to capillary growth, mitochondrial biogenesis, protein synthesis, cytoskeletal remodeling, and muscle hypertrophy were up‐regulated in the exercise group, while genes related to inflammation/immune response and endoplasmic reticulum stress were down‐regulated. Mitochondrial pathways including the oxidative phosphorylation metabolic pathway were most affected by the endurance exercise, as demonstrated by proteomics analysis. The exercise group also showed a higher number of capillaries per mm 2 in follow‐up biopsy samples ( P &lt; 0.05). Conclusion Our data indicate that endurance exercise in patients with established PM and DM may activate an aerobic phenotype and promote muscle growth and simultaneously suppress the inflammatory response in these patients’ muscles, as supported by a combination of data on gene expression, proteomics, and capillary density in repeated muscle biopsies.
Comparison of mania and depression after brain injury: causal factors
Authors: R G Robinson, J D Boston, S E Starkstein, T R Price
Journal: American Journal of Psychiatry (1988)

Patients who developed secondary mania after brain injury (N = 17) had a significantly greater frequency of injury to right hemisphere areas connected with the limbic system than poststroke patients with major depression (N = 31), who had injury primarily in the left frontal cortex and basal ganglia. For patients without mood disturbance after brain injury (N = 28), the location of the lesion was not significant. Secondary mania patients also had a significantly greater frequency of family history of affective disorder than did the other two groups. These results suggest that an interaction between injury to certain areas of the right hemisphere and genetic factors or other neuropathological conditions produces secondary mania.
&lt;italic&gt;In Vitro&lt;/italic&gt; Transformation of Normal Cells to Tumor Cells by Carcinogenic Hydrocarbons&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Yoheved Berwald, Leo Sachs
Journal: JNCI Journal of the National Cancer Institute (1965)

The application of benzo[a]pyrene (BP) to normal hamsterembryo cells in culture produced transformed cells. These cells showed: 1) a hereditary random pattern of growth; 2) the ability to grow continuously in culture; 3) progressive growth as tumors after subcutaneous inoculation into adult hamsters; 4) a resistance to the toxic action of BP when tested at a later stage of growth in culture. Transformed cells in culture were obtained with the in vivo carcinogenic hydrocarbons BP, 3-methylcholanthrene (MCA), 7,12-dimethylbenz[a]anthracene, and 10-methylbenz [a]anthracene, but not in untreated hamster-embryo cultures or with the in vivo noncarcinogenic hydrocarbons 8-methylbenz[a]anthracene, chrysene, and pyrene. It was shown that carcinogenic hydrocarbons can directly induce in vitro the transformation of normal cells to tumor cells. Fibroblastic and epithelial-type cells were found in transformed cells in culture and in tumors produced by cell inoculation into animals. There was a high frequency of cell transformation, and with BP the maximum value obtained was 25.6 percent transformed clones. Application of BP at various times before clones were stained and examined indicated that between 1 and 2 days after addition of carcinogen are required for expression of the transformed state. This result suggests that the expression of transformation requires a process associated with cell division. Addition of BP to clones indicated that not all clones are equally transformable. Treatment of normal SWR mouse-embryo cultures with BP and MCA produced transformed cells, which were not found in short-term cultures of untreated controls. After longer periods in culture, clones with a random pattern of growth were also found in untreated controls, and both the treated and untreated mouse cells grew progressively as tumors after inoculation into adult SWR mice. For experiments without any appreciable spontaneous background of transformation, hamster cells are therefore preferable to mouse cells.
Caesarean section rate hits 20% in 1999-2000
Authors: Annabel Ferriman
Journal: BMJ (2001)

Provisional figures from the Department of Health suggest that the rate for caesarean sections in England hit an all time high of more than 20% in 1999-2000.

Caesarean delivery rates have climbed steadily since the second world war. From a level of under 3% in the 1950s, the proportion of deliveries that were by caesarean section had risen to 9% by 1980 and to12% …
Polypharmacy and comorbidities in veteran patients with end-stage cancer
Authors: M. Choi, S. Nichols, T. Khansur
Journal: Journal of Clinical Oncology (2008)

20560 Background: Polypharmacy increases the risk of drug-drug interactions, adverse drug reactions, noncompliance and treatment costs. Age and comorbidities are correlated with a higher incidence of polypharmacy. There is very limited data on polypharmacy in end-stage cancer patients. Methods: Tumor registry data of 1570 patients diagnosed at GV Montgomery VAMC between 2005–2007 were reviewed. Computerized pharmacy and medical records of 148 patients with metastatic cancer with survival of < 1year were analyzed for polypharmacy and comorbidities. Patients with > 1year survival were excluded (these included mostly prostate cancer, lymphoma and head/neck cancer). Descriptive statistics were used to summarize the data. Results: The mean age of the study population was 66 years (range; 44–88) with 99% male. Lung (99), colorectal (14) and pancreas (14) cancer were the most common cancers diagnosed. Patients had an average of three (range 0–8) comorbid conditions; hypertension, COPD, coronary artery disease and hyperlipidemia were the most common conditions. Median number of medication at diagnosis of cancer was 6 (range; 0–15), and increased to 8 in patients receiving chemotherapy. Fifty percent of patients received chemotherapy, 34% only received supportive care and 16% palliative radiation therapy alone. Carboplatin and paclitaxel were the most common agents used in chemotherapy. Median survival of all patients was 2.8 months. Major polypharmacy(>5 drugs) occurred in 69% of patients and use of >10 drugs was observed in 18% of patients. 30% of patients were noted to be taking a lipid lowering medication (statin). Conclusions: There is a very high prevalence of polypharmacy in end-stage cancer patients, especially patients treated with chemotherapy. Some of these medications may be non-essential and avoiding there use could reduce adverse reactions and simplify treatments. No significant financial relationships to disclose.
Phase I Study of Hepatic Arterial Infusion of Floxuridine and Dexamethasone With Systemic Irinotecan for Unresectable Hepatic Metastases From Colorectal Cancer
Authors: N. Kemeny, M. Gonen, D. Sullivan, L. Schwartz, F. Benedetti, L. Saltz, J. Stockman, Y. Fong, W. Jarnagin, J. Bertino, W. Tong, P. Paty
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To determine the maximum-tolerated dose (MTD) and dose-limiting toxicities of concurrent systemic irinotecan and hepatic arterial infusion (HAI) of floxuridine (FUDR) and dexamethasone in patients with unresectable hepatic metastases from colorectal cancer, to determine the safety of this combination in patients who have undergone cryosurgery, and to evaluate the pharmacokinetic effects of HAI FUDR on the metabolism of irinotecan. PATIENTS AND METHODS: Forty-six previously treated patients with unresectable liver metastases and no known extrahepatic disease were treated concurrently with intravenous irinotecan weekly for 3 weeks and with HAI of FUDR and dexamethasone for 14 days (both were recycled in 28 days). Parallel cohorts of patients treated with or without cryosurgery were entered at escalating dose levels. RESULTS: The MTD for patients who did not undergo cryosurgery was 100 mg/m 2 of irinotecan weekly for 3 weeks every 4 weeks with concurrent HAI FUDR (0.16 mg/kg/d × pump volume/flow rate) plus dexamethasone for 14 days of a 28-day cycle. The dose-limiting toxicities were diarrhea and neutropenia. The response rate (complete and partial) among all patients who did not undergo cryosurgery was 74%. All patients in the cryosurgery group responded, and seven of the eight cryosurgery patients developed normal positron emission tomography scans after chemotherapy. HAI FUDR had no effect on the metabolism of irinotecan. CONCLUSION: Combination therapy with HAI FUDR and dexamethasone plus systemic irinotecan may be safely administered to patients with unresectable hepatic metastases from colorectal cancer. The MTD has been reached for patients with unresectable disease, and we continue to investigate the MTD for patients who have undergone cryosurgery. Although the main objective of this study was to evaluate the toxicity of the combined regimen, a high response rate (74%) was observed.
Randomized trial of oral cyclophosphamide (C) with or without veliparib (V), an oral poly (ADP-ribose) polymerase (PARP) inhibitor, in patients with recurrent BRCA-positive ovarian, or primary peritoneal or high-grade serous ovarian carcinoma.
Authors: Shivaani Kummar, Amit M. Oza, Gini F. Fleming, Daniel Sullivan, David R. Gandara, Charles Erlichman, Miguel Angel Villalona-Calero, Robert Morgan, Alice P. Chen, Jiuping Jay Ji, Deborah Allen, Chih-Jian Lih, Seth M. Steinberg, P. Mickey Williams, Barbara A. Conley, James H. Doroshow
Journal: Journal of Clinical Oncology (2012)

5020 Background: V+C was well tolerated in a phase I trial and responses and prolonged disease stabilization were observed in BRCA + patients (pts).To assess the relative contribution of the PARP inhibitor to the efficacy observed for the combination, we conducted a randomized multicenter trial comparing the response rate (RR) of V and C to the RR of C alone in patients with deleterious BRCA mutations and recurrent ovarian, or primary peritoneal, fallopian tube or high-grade serous ovarian cancer. Methods: Pts were ≥ 18 yrs, KPS ≥ 70%, had adequate organ function, prior therapy with PARP inhibitors was allowed.Both drugs were administered orally qd; C 50 mg, V 60 mg; 21 day cycles. Pts were randomized to receive either C alone or V+C. At disease progression, pts on C alone were allowed to cross over to the combination. Radiologic imaging was performed at baseline and q 3 cycles for assessment of response. Dose reduction of V was allowed to 40 mg for gr 3 non-hematologic or gr 4 hematologic toxicities. The study design had an 88% power to detect the difference between a 15% RR for C alone versus 35% for V+C, early closure if fewer responses were observed on the combination arm in the first 65 pts enrolled (half of the total projected accrual). Results: Total of 74 pts were enrolled (36 pts C, 38 pts V+C), median age 58 (37-79 yrs), # of prior therapies: median 4 (1-9), 2 pts had prior PARP therapy. Treatment was well tolerated, Gr ≥ 2 toxicities per arm for initial regimen (# of pts): C alone: lymphopenia (2), mucositis (1); V+C: lymphopenia (4), anemia (2), leucopenia (2), neutropenia (2). Of the 74 pts evaluable for response at the interim analysis, 3 PRs observed in 36 pts on V+C and 5 PRs of 38 pts on C alone arm; thus accrual was stopped. PAR levels assessed by validated ELISA were inhibited (&gt;80%) in PBMCs in 9/10 pts 4 hours post V, no inhibition with C alone. Conclusions: Addition of V, a PARP inhibitor, to C did not improve RR versus C alone. Exomic sequencing, gene expression studies, and Fanconi Anemia triple stain immunofluorescence (FATSI) assay for FancD2 nuclear foci formation using archival tissue are ongoing.
Safety of Radium-223 Dichloride (Ra) with Docetaxel (D) in Patients (Pts) with Bone Metastases (Mets) from Castration-Resistant Prostate Cancer (Crpc): a Phase 1/2A Clinical Trial
Authors: M.J. Morris, C. Higano, H.I. Scher, C. Sweeney, E.S. Antonarakis, D. Shevrin, C.J. Ryan, Y. Loriot, K. Fizazi, N. Pandit-Taskar, J.E. Garcia-Vargas, K. Lyseng, M. Bloma, A. Aksnes, J.A. Carrasquillo
Journal: Annals of Oncology (2014)
Hamstring injuries and predicting return to play: ‘bye-bye MRI?’
Authors: G Reurink, R Whiteley, J L Tol
Journal: British Journal of Sports Medicine (2015)

In the elite athlete setting, MRI has gradually gained a magical reputation: it is the crystal ball that answers all the questions of the injured athlete, coaching and medical staff. Without imaging the injury, there is no peace of mind within the team. There is no doubt that the evolution of imaging techniques can support the management of the injured athlete, but we argue that the current available data suggests that it is almost useless for predicting return to play (RTP) following hamstring injury.

In a recently published systematic review of the literature, we concluded that there is no strong evidence for any MRI finding that can guide sports physicians and radiologists in predicting prognosis for the time to RTP after an acute hamstring injury.1 This conclusion is mainly based on two limitations in the current literature: 

1.  Multiple studies on hamstring injuries found correlations between different MRI measures and the time to RTP. Unfortunately, these are limited to univariate analyses …
Complete androgen blockade as second-line hormone manipulation and delay of chemotherapy in metastatic prostate cancer
Authors: R. Kaliks-Guendelmann, P. Santi, A. Cardoso, A. Del Giglio
Journal: Journal of Clinical Oncology (2009)

e16141 Background: Complete androgen blockade (CAB) after failure of castration or androgen receptor blocker (ARB) has not shown to prolong survival in patients with metastatic prostate cancer, unlike docetaxel-based chemotherapy. The widely variable clinical benefit seen with CAB as second-line hormone manipulation still justifies the identification of the patients to whom it should be offered. Objective: to evaluate progression-free survival (PFS) and overall survival (OS) in patients treated with CAB after failure of castration or ARB and to identify clinical predictors of benefit. Methods: We performed a retrospective analysis of all patients with metastatic prostate cancer treated with CAB as second-line hormone manipulation in a single institution after September 2005. OS and PFS were estimated using Kaplan-Meyer plots. We identified 78 patients and evaluated correlations of prostate specific antigen (PSA), Gleason scores, age, type and length of first-line hormone manipulation with OS and PFS during CAB. Fifty-four patients had failed castration and 24 had failed ARB. Forty-four patients received chemotherapy after failing CAB. Results: With a median follow-up of 21 months, median PFS with CAB was 12 months (CI 6.8–17.2). We did not find any correlation of PFS with type of first-line hormone manipulation (castration vs ARB, p = 0.10), age group (≤70 or &gt;70 years old, p = 0.10), level of PSA at diagnosis (≤50 or &gt;50 ng/mL, p = 0.17) or length of first-line hormone manipulation (≤14m vs &gt;14 m, p = 0.78). There was no significant correlation between PFS and Gleason score at diagnosis (score ≤7 or &gt;7, p = 0.25), nor between the level of testosterone at the beginning of CAB and PFS. Median OS for patients on CAB after failing castration was 36 months (CI 24–48), and median OS of patients on chemotherapy was not reached at 9.5 months follow-up. Conclusions: Based on a PFS of 12 months, OS of 36 months and good patient tolerance, we believe CAB should still be used in CRPC, prior to initiation of chemotherapy. Predictors of clinical benefit are still to be identified. No significant financial relationships to disclose.
Randomized, Dose-Escalation Study of SD/01 Compared With Daily Filgrastim in Patients Receiving Chemotherapy
Authors: Eileen Johnston, Jeffrey Crawford, Susan Blackwell, Toni Bjurstrom, Pamela Lockbaum, Lorin Roskos, Bing-Bing Yang, Sheila Gardner, Mary Ann Miller-Messana, Debra Shoemaker, Jennifer Garst, Gisela Schwab
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To explore the use of SD/01 (a polyethylene glycol–conjugated filgrastim shown in preclinical studies to have a prolonged half-life) in patients with chemotherapy-induced neutropenia. PATIENTS AND METHODS: Thirteen patients with non–small-cell lung cancer were randomized to receive daily filgrastim (5 μg/kg/d) or a single injection of SD/01 (30, 100, or 300 μg/kg) 2 weeks before chemotherapy and again 24 hours after administration of carboplatin and paclitaxel. Pharmacodynamic, pharmacokinetic, and safety analyses were performed. RESULTS: Peak serum concentrations of SD/01 and the duration of increased serum concentrations were dependent on the SD/01 dose. SD/01 concentrations remained increased longer in patients with chemotherapy-induced neutropenia. Prechemotherapy median absolute neutrophil counts (ANCs) in patients receiving SD/01 were increased in a dose-dependent fashion, with the duration of this effect also being dose dependent. After chemotherapy, median ANC nadirs were similar in the filgrastim cohort and the cohort receiving SD/01 30 μg/kg, with higher nadirs seen in the cohorts receiving SD/01 100 or 300 μg/kg. Dose-limiting toxicities were not noted. CD34 + cells were mobilized in all cohorts. CONCLUSION: A single dose of SD/01 increases the serum concentration of SD/01 for several days in a dose-dependent fashion and is not associated with significant toxicity. The effects of SD/01 on ANC and CD34 + cell mobilization are comparable or greater than those achieved with daily filgrastim. The self-regulation of this molecule provides a potential therapeutic advantage in a variety of clinical settings associated with neutropenia.
Exacerbated Inflammatory Response Induced by Insulin-Like Growth Factor I Treatment in Rats with Ischemic Acute Renal Failure
Authors: MARTA FERNÁNDEZ, ALBERTO MEDINA, FERNANDO SANTOS, EDUARDO CARBAJO, JULIÁN RODRÍGUEZ, JESÚS ÁLVAREZ, ANGELES COBO
Journal: Journal of the American Society of Nephrology (2001)

In agreement with recent studies showing a deleterious effect of growth hormone treatment in critically ill patients, preliminary data showed that insulin-like growth factor I (IGF-I) administration increased the mortality rate of rats with ischemic acute renal failure (ARF). The present study was designed to investigate the mechanism responsible for this unexpected effect. Male rats with ischemic ARF were given subcutaneous IGF-I, 50 microg/100 g at 0, 8, and 16 h after reperfusion (ARF+IGF-I, n = 5) or were untreated (ARF, n = 5). A group of 5 sham-operated rats were used as controls. Rats were killed 48 h after declamping, and the following studies were performed: in serum, creatinine and urea nitrogen; and in kidneys, histologic damage score, cellular proliferation by bromodeoxyuridine labeling, apoptosis by morphologic criteria, macrophage infiltration by immunohistochemistry using a specific antibody against ED-1, neutrophil infiltration by naphthol AS-D chloroacetate esterase staining, and levels of IGF-I and IGF-I receptor mRNA by RNase protection assay. ARF and ARF+IGF-I groups had a severe and similar degree of renal failure. Kidney damage was histologically more evident in ARF+IGF-I (1.9 +/- 0.1) than in ARF (1.3 +/- 0.2) rats, and the number of neutrophils/mm(2) of tissue was significantly greater in ARF+IGF-I than in ARF rats at the corticomedullary junction (52.3 +/- 5.2 versus 37.2 +/- 4.1) as well as at the renal medulla (172.5 +/- 30.0 versus 42.1 +/- 9.6). No other differences between the groups were found. It is concluded that IGF-I treatment enhanced the inflammatory response in rats with ischemic ARF. Cell toxicity derived from increased neutrophil accumulation might play a key role in the greater mortality risk of critically ill patients that are treated with growth hormone.
National HER2 testing program for breast cancer patients in Argentina
Authors: I. Frahm
Journal: Journal of Clinical Oncology (2006)

10566 Background: In Argentina, before 2003 few pathologists performed HER2 testing, using different non-standardized Inmuno-Histo-Chemical (IHC) methods with dubious and non-reproducible results and also leaving some parts of the country without HER2 diagnosis Objective: HER2 has a key role in breast cancer management, so the aim of the study was to settle a National HER2 testing Program to permit access to standardized HER2 detection all over the country, and whenever possible, to determine hormonal receptors. Methods: In August 2003, 13 pathologists formed a cooperative group and created a national framework to train and set HER2 diagnostic centres in each country region. A coordinator responsible for coaching and evaluating centres and two technical consultants in charge of quality control and technique standardization were designated. In February 2004, the program was launched. Tumors were received from 82 oncologists and breast surgeons, using a private courier created “ad hoc”. HER2 was analyzed by IHC test between February 2004 and November 2005 and performed using policlonal antibody anti Her 2 (DAKO), microwave antigenic recovery, detection system EnVision (Dako) and developed with diaminobenzidine. Results were interpreted as HercepTest guidelines. ER/PR were screened by IHC analyses. Results: 2285 HER2 tests were performed: HER2 was over-expressed (score 3+) in 18% of tumors (408). 136 (6%) samples were score 2+, 407 (18%) score 1+ and 1334 (58%) score 0. In 1532/2285 (67%) of tumor specimens ER and PR status could be determined. Conclusions: Founding HER2 National Program allowed access to HER2 testing all over the country with a standardized and reproducible technique. HER2 prevalence in our sample (18%) is similar to those previously published. Although international algorithms recommend FISH assay to HER2 2+ tumors, our Program can not afford it. ER/PR expression were decreased significantly in HER2 3+ vs. HER2 - tumors: 53% vs. 64%: p = 0.002. HER2 3+ were associated with higher levels ER/PR: 38% vs. 24% in HER2 - tumors (p &lt; 0.001). [Table: see text] No significant financial relationships to disclose.