tbuckley/cabot-search huggingface dataset:
High-dose megestrol acetate in advanced or recurrent endometrial carcinoma: a Gynecologic Oncology Group Study.
Authors: S S Lentz, M F Brady, F J Major, G C Reid, J T Soper
Journal: Journal of Clinical Oncology (1996)

PURPOSE Progestins represent the most widely used form of endocrine therapy in advanced or recurrent endometrial carcinoma. Based on encouraging response rates in breast cancer with high-dose megestrol acetate (MA) 800 mg/d, this phase II trial assessed response rates in patients with endometrial carcinoma treated with high-dose MA. PATIENTS AND METHODS Sixty-three patients with recurrent or advanced endometrial carcinoma were entered into this Gynecologic Oncology Group (GOG) study. Patients had either failed to respond to or were considered incurable with local therapy and had not received prior cytotoxic or hormonal therapy. MA 800 mg/d was administered orally in divided doses. Standard GOG toxicity criteria were used. RESULTS Of 63 patients entered, 58 were assessable for toxicity and 54 for response. Of 13 responders (24%), six (11%) had a complete and seven (13%) a partial response. Four of the responses lasted greater than 18 months. Twelve patients (22%) had stable disease. The response rate of patients with grade 1 or 2 lesions (11 of 30, 37%) was significantly higher (P = .02) than that of patients with more poorly differentiated tumors (two of 24, 8%). There was no difference in response rates comparing advanced versus recurrent disease, cell type, including papillary serous lesions, site of disease, prior radiation, age, or weight. The median progression-free survival (PFS) and overall survival intervals were 2.5 and 7.6 months, respectively. Grade 3 weight gain (&gt; 20%) was seen in three patients and grade 3/4 hyperglycemia in three. Three deaths secondary to cardiovascular events were possibly related to therapy; diabetes was also a contributing factor in all three cases. CONCLUSION High-dose MA is active in endometrial carcinoma, but appears to have no advantage over lower-dose progestins.
Long-Term Multivitamin Supplementation and Cognitive Function in Men
Authors: Francine Grodstein, Jacqueline O’Brien, Jae Hee Kang, Rimma Dushkes, Nancy R. Cook, Olivia Okereke, JoAnn E. Manson, Robert J. Glynn, Julie E. Buring, J. Michael Gaziano, Howard D. Sesso
Journal: Annals of Internal Medicine (2013)

Multivitamins are commonly used to prevent various chronic conditions, but whether they prevent age-related cognitive decline is unclear. In a substudy of a large randomized trial of male physician...
Tumour Biomarker and Plasma Time Course Data from Abigail, A Phase II Study of 1st-Line Bevacizumab + Chemotherapy in Advanced Non-Squamous Non-Small-Cell Lung Cancer (NS-NSCLC)
Authors: M. Reck, V.A. Gorbunova, E. Juhasz, B. Szima, S. Orlov, C. Yu, C. Pallaud, S.J. Scherer, V. Archer, T.S.K. Mok
Journal: Annals of Oncology (2012)
Noninvasive Helicobacter pylori testing was as effective as endoscopy for managing dyspepsia
Authors: McColl Ke
Journal: BMJ (2003)

patients with positive results were prescribed a 7-day course of H. pylori eradication treatment with omeprazole, 20 mg twice daily; clarithromycin, 250 mg 3 times daily; and amoxicillin, 500 mg (or metronidazole, 400 mg) 3 times daily. Main outcome measures Change from baseline on the Glasgow Dyspepsia Severity Score (GDSS). Secondary outcomes were use of medical resources, patient assessment of the procedures, and safety.
Prostaglandin F2 alpha inhibits the ammoniagenic response to acute acidosis in LLC-PK1 cells.
Authors: A Sahai, M Goyal, R L Tannen
Journal: Journal of the American Society of Nephrology (1990)

A kidney epithelial cell line, LLC-PK1, which does not synthesize prostaglandins, provides an ideal in vitro model system to investigate the effect of prostaglandins in the regulation of renal ammoniagenesis. Previous studies from our laboratory have demonstrated significant increases in glutamine-dependent ammonia and alanine production by rocked cultures of LLC-PK1 cells subjected to either acute metabolic or respiratory acidosis. In the study presented here, experiments were conducted to investigate the role of prostaglandin F2 alpha (PGF2 alpha) and prostaglandin E2 (PGE2) in the response of ammonia metabolism to acute metabolic acidosis by LLC-PK1 cells. A low dose of PGF2 alpha (0.1 ng/mL) dramatically inhibited the stimulatory effect of a low pH (pH 6.8) on ammonia production. In contrast, the inhibition of cytosolically generated alanine was less dramatic and averaged only 20% of the effect on ammonia production. Furthermore, PGF2 alpha increased cellular alpha-ketoglutarate concentration, suggesting an increase in intramitochondrial pH. Thus, the cellular mechanism of PGF2 alpha action appears to involve either interference with the cytosolic pH signal or its translation to the intramitochondrial compartment. The inhibitory response of PGF2 alpha on pH-stimulated ammoniagenesis was progressively lost at higher concentrations. Both low-dose (0.1 ng/mL) and high-dose (10 ng/mL) PGF2 alpha had no significant effect on the basal rates of ammonia and alanine production at pH 7.4. PGE2, on the other hand, did not exhibit any significant response on ammonia or alanine production at either pH 6.8 or 7.4 when given in a wide range of doses.(ABSTRACT TRUNCATED AT 250 WORDS)
Profiling tissue-resident T cell repertoires by RNA sequencing
Authors: Scott D. Brown, Lisa A. Raeburn, Robert A. Holt
Journal: Genome Medicine (2015)

Deep sequencing of recombined T cell receptor (TCR) genes and transcripts has provided a view of T cell repertoire diversity at an unprecedented resolution.Beyond profiling peripheral blood, analysis of tissueresident T cells provides further insight into immunerelated diseases.We describe the extraction of TCR sequence information directly from RNA-sequencing data from 6738 tumor and 604 control tissues, with a typical yield of 1 TCR per 10 million reads.This method circumvents the need for PCR amplification of the TCR template and provides TCR information in the context of global gene expression, allowing integrated analysis of extensive RNA-sequencing data resources.
Downside of becoming a richer country
Authors: Esha Chhabra
Journal: BMJ (2015)

Since Vietnam graduated from low income to middle income status, donors have stopped supporting HIV/AIDS programmes and the government is struggling to fill the gap. Esha Chhabra reports

Getting richer has been a double edged sword for Vietnam. The country moved from low income to middle income status in 2010. Since then, aid it receives from the international community for programmes such as HIV/AIDS treatment has been dropping. That’s troublesome given that Vietnam relies on donor support for about 75% of the budget for HIV services1 and the disease is spreading in its mountainous regions.

The World Bank and UK Department for International Development (DFID) were the first major donors to end existing HIV programmes in the country without making any plans for further support; others are following suit. In 2013, DFID finished a six year project that had provided a total of $36.5m (£24m; €33m), and in 2012 the World Bank wrapped up a $38.5m project that had spanned eight years.2

Now the, US President’s Emergency Plan for AIDS Relief (PEPFAR) and the Global Fund are reportedly winding down their contributions as well. Launched in 2004, PEPFAR has given $634m to Vietnam’s HIV response programme. But funding has dropped from $87m in 2010 to $69m in 2013 and $65m in 2014.3 Global Fund’s total budget for HIV programmes in Vietnam is $77m for 2014-17.4 The fund hasn’t announced the budget for after 2017, but local officials say they are not hopeful.

A 2014 report written by the Vietnamese Ministry of Health with UNAIDS and its development partners estimated that the resource gap caused …
Continuous Dialysis with Bicarbonate/Lactate-Buffered Peritoneal Dialysis Fluids Results in a Long-Term Improvement in Ex Vivo Peritoneal Macrophage Function
Authors: Suzanne Jones, Clifford J. Holmes, Ruth K. Mackenzie, Rachel Stead, Gerald A. Coles, John D. Williams, Dirk Faict, Nicholas Topley
Journal: Journal of the American Society of Nephrology (2002)

To circumvent the potentially negative consequences of long-term exposure to unphysiologic acidic lactate-buffered peritoneal dialysis fluids (PDF), neutral pH solutions buffered with bicarbonate/lactate have recently been introduced in phase 2 and 3 clinical trials. This study examines the longitudinal changes in peritoneal macrophage (PMØ) function in patients dialyzed continuously with either lactate (LPD; 40 mM lactate, pH 5.2)-buffered or bicarbonate/lactate (TBL; 25 mM/15 mM bicarbonate/lactate, pH 7.3)-buffered PDF. Before the study, during the run in period of a phase 3 clinical trial, all patients had been taking LPD for at least the previous 18 wk. At the beginning of the study (day 0), both constitutive and serum-treated zymosan (STZ) stimulated tumor necrosis factor alpha (TNF-alpha) synthesis were assessed in PMØ isolated from 12-h dwell effluent (with 1.36% glucose) in all patients. The patients were subsequently randomized to either continuous TBL or LPD therapy and PMØ function was assessed after further 3- and 6-mo periods in all patients. At all time points measured STZ induced a dose-dependent increase in PMØ TNF-alpha secretion (P = 0.043 versus control for doses greater than 100 microg/ml). In patients continuously dialyzed with LPD, constitutive PMØ TNF-alpha synthesis levels (mean +/- SEM, pg/10(6) PMØ per18 h, n = 5 patients) were 154 +/- 65, 261 +/- 60, and 101 +/- 99 at 0, 3, and 6 mo, respectively. Stimulated STZ (1000 microg/ml) levels were 1340 +/- 519, 1046 +/- 586, and 758 +/- 250 at 0, 3, and 6 mo, respectively. In patients dialyzed with TBL, constitutive PMØ TNF-alpha synthesis levels (pg/10(6) PMØ per 18 h, n = 5 patients) were 300 +/- 136, 106 +/- 35, and 213 +/- 62 at 0, 3, and 6 mo, respectively. Stimulated STZ (1000 microg/ml) levels were 1969 +/- 751, 1541 +/- 330, and 2670 +/- 671 at 0, 3, and 6 mo, respectively. At 6 mo, STZ-stimulated PMØ TNF-alpha synthesis was significantly higher in patients treated with TBL compared with those treated with LPD (P = 0.0035). These data suggest that in patients continuously dialyzed with a neutral pH solution, there is a long-term improvement in PMØ function compared with patients on conventional therapy. Better PMØ function suggests improved host defense status and may affect the peritoneum's susceptibility to infection and potentially reduce the negative consequences of repeated intraperitoneal inflammation on long-term membrane function.
Waldenstrom's Macroglobulinemia Associated Bone Disease the UAMS Experience
Authors: Xenofon Papanikolaou, Sarah Waheed, Bart Barlogie, Daisy V. Alapat, Donghoon Yoon, Manoj Kumar, Aasiya Matin, Hongyun Zhu, Cerisse Harcourt, Maurizio Zangari
Journal: Blood (2014)
Enalapril attenuates increased gene expression of extracellular matrix components in diabetic rats.
Authors: T Nakamura, T Takahashi, M Fukui, I Ebihara, S Osada, Y Tomino, H Koide
Journal: Journal of the American Society of Nephrology (1995)

This study was designed to assess whether the glomerular expression of mRNA for extracellular matrix (ECM) components including alpha 1 (I), alpha 1 (III), and alpha 1 (IV) collagen chains, laminin B1 and B2 chains, metalloproteinases (MMP), and tissue inhibitor of metalloproteinases (TIMP) is affected by enalapril in 12- and 24-wk-old rat after streptozotocin injection. Animals were divided into three groups; untreated diabetic rats, enalapril-treated diabetic rats, and control rats. Enalapril treatment was continued for 24 wk. Enalapril reduced both creatinine clearance (P < 0.01) and urinary protein excretion (P < 0.01) in diabetic rats. In diabetic rats, mRNA levels for alpha 1 (IV) collagen chain, laminin B1 and B2 chains, and alpha 1(I) and alpha 1(III) collagen chains increased significantly at 24 wk compared with those in controls [alpha 1(IV): 3.8-fold (P < 0.01); laminin B1: 6.2-fold (P < 0.01); laminin B2:5.4-fold (P < 0.01), alpha 1(i): 4.8-fold (P < 0.01) and alpha 1(III): 3.8-fold (P < 0.01)]. At 24 wk, mRNA levels for MMP-1 and MMP-3 fell to 40% (P < 0.01) and 20% (P < 0.01), respectively, in the glomeruli of diabetic rats compared with levels in controls. In contrast, mRNA levels for TIMP-1 and TIMP-2 increased significantly at 24 wk after streptozotocin injection (TIMP-1: 8.0-fold (P < 0.01) and TIMP-2: 6.4-fold (P < 0.01)).(ABSTRACT TRUNCATED AT 250 WORDS)
Randomized Crossover Study to Examine the Necessity of an Injection-to-Meal Interval in Patients With Type 2 Diabetes and Human Insulin
Authors: Nicolle Müller, Thomas Frank, Christof Kloos, Thomas Lehmann, Gunter Wolf, Ulrich Alfons Müller
Journal: Diabetes Care (2013)

OBJECTIVE Patients with diabetes and insulin therapy with human insulin were usually instructed to use an interval of 20–30 min between the injection and meal. We examined the necessity of the injection-to-meal interval (IMI) in patients with type 2 diabetes mellitus (T2DM) and flexible insulin therapy with human insulin. RESEARCH DESIGN AND METHODS In this randomized, open crossover trial, 100 patients with T2DM (47% men, mean age = 66.7 years) were randomized to the IMI first group (phase 1, IMI 20 min; phase 2, no IMI) or IMI last group (phase 1, no IMI; phase 2, IMI 20 min). The main outcome measures were HbA1c, blood glucose profile, incidence of hypoglycemia, quality of life, treatment satisfaction, and patient preference. RESULTS Forty-nine patients were randomized to the IMI first group and 51 patients to the IMI last group. Omitting the IMI only slightly increases HbA1c (average intraindividual difference = 0.08% [95% CI 0.01–0.15]). Since the difference is not clinically relevant, a therapy without IMI is noninferior to its application (P &amp;lt; 0.001). In the secondary outcomes, the incidence of mild hypoglycemia also did not differ between no IMI and IMI significantly (mean of differences = −0.10, P = 0.493). No difference in the blood glucose profile of both groups was found. Treatment satisfaction increased markedly, by 8.08, if IMI was omitted (P &amp;lt; 0.001). The total score of the quality of life measure did not show differences between applying an IMI or not. Insulin therapy without IMI was preferred by 86.5% of patients (P &amp;lt; 0.001). CONCLUSIONS An IMI for patients with T2DM and preprandial insulin therapy is not necessary.
Effect of Metformin Added to Insulin on Glycemic Control Among Overweight/Obese Adolescents With Type 1 Diabetes
Authors: Ingrid M. Libman, Kellee M. Miller, Linda A. DiMeglio, Kathleen E. Bethin, Michelle L. Katz, Avni Shah, Jill H. Simmons, Michael J. Haller, Sripriya Raman, William V. Tamborlane, Julie K. Coffey, Ashleigh M. Saenz, Roy W. Beck, Kristen J. Nadeau
Journal: JAMA (2015)

Previous studies assessing the effect of metformin on glycemic control in adolescents with type 1 diabetes have produced inconclusive results.To assess the efficacy and safety of metformin as an adjunct to insulin in treating overweight adolescents with type 1 diabetes.Multicenter (26 pediatric endocrinology clinics), double-blind, placebo-controlled randomized clinical trial involving 140 adolescents aged 12.1 to 19.6 years (mean [SD] 15.3 [1.7] years) with mean type 1 diabetes duration 7.0 (3.3) years, mean body mass index (BMI) 94th (4) percentile, mean total daily insulin 1.1 (0.2) U/kg, and mean HbA1c 8.8% (0.7%).Randomization to receive metformin (n = 71) (≤2000 mg/d) or placebo (n = 69).Primary outcome was change in HbA1c from baseline to 26 weeks adjusted for baseline HbA1c. Secondary outcomes included change in blinded continuous glucose monitor indices, total daily insulin, BMI, waist circumference, body composition, blood pressure, and lipids.Between October 2013 and February 2014, 140 participants were enrolled. Baseline HbA1c was 8.8% in each group. At 13-week follow-up, reduction in HbA1c was greater with metformin (-0.2%) than placebo (0.1%; mean difference, -0.3% [95% CI, -0.6% to 0.0%]; P = .02). However, this differential effect was not sustained at 26-week follow up when mean change in HbA1c from baseline was 0.2% in each group (mean difference, 0% [95% CI, -0.3% to 0.3%]; P = .92). At 26-week follow-up, total daily insulin per kg of body weight was reduced by at least 25% from baseline among 23% (16) of participants in the metformin group vs 1% (1) of participants in the placebo group (mean difference, 21% [95% CI, 11% to 32%]; P = .003), and 24% (17) of participants in the metformin group and 7% (5) of participants in the placebo group had a reduction in BMI z score of 10% or greater from baseline to 26 weeks (mean difference, 17% [95% CI, 5% to 29%]; P = .01). Gastrointestinal adverse events were reported by more participants in the metformin group than in the placebo group (mean difference, 36% [95% CI, 19% to 51%]; P < .001).Among overweight adolescents with type 1 diabetes, the addition of metformin to insulin did not improve glycemic control after 6 months. Of multiple secondary end points, findings favored metformin only for insulin dose and measures of adiposity; conversely, use of metformin resulted in an increased risk for gastrointestinal adverse events. These results do not support prescribing metformin to overweight adolescents with type 1 diabetes to improve glycemic control.clinicaltrials.org Identifier: NCT01881828.
Hic-5 deficiency attenuates the activation of hepatic stellate cells and liver fibrosis through upregulation of Smad7 in mice
Authors: Xiao-Feng Lei, Wenguang Fu, Joo-ri Kim-Kaneyama, Tomokatsu Omoto, Takuro Miyazaki, Bo Li, Akira Miyazaki
Journal: Journal of Hepatology (2015)
Doc, Shouldn't We Be Getting Some Tests?
Authors: Charles L Loprinzi, Daniel Hayes, Tom Smith
Journal: Journal of Clinical Oncology (2003)

ERE’S THE CASE: Mrs. Smith presents herself to a medical oncologist. She had been treated by oncology colleagues down the street (whose clinical abilities are respected). Having presented in the recent past with nodepositive, hormone receptor‐negative breast cancer, she subsequently completed all planned antitumor therapy, including breast-conserving surgery, adjuvant doxorubicin/ cyclophosphamide chemotherapy for four cycles, adjuvant paclitaxel chemotherapy for four cycles, and primary breast radiation therapy. She transferred her care to the present oncologist because she was concerned that her prior oncologist, although performing what she thought were detailed histories and physical examinations and recommending yearly mammograms, wasn’t recommending any other follow-up surveillance tests. She knew she still had an appreciable risk of cancer recurrence, and she knew other women from her support group who were getting regular follow-up tests, including chest x-rays and serum marker tests.
Phase II trial of two-weekly gemcitabine in patients with advanced biliary tract cancer
Authors: M. Penz, G.V. Kornek, M. Raderer, H. Ulrich-Pur, W. Fiebiger, A. Lenauer, D. Depisch, G. Krauss, B. Schneeweiss, W. Scheithauer
Journal: Annals of Oncology (2001)
High-dose chemotherapy followed by autologous stem cell transplantation for relapsed/refractory primary mediastinal large B-cell lymphoma
Authors: T Aoki, K Shimada, R Suzuki, K Izutsu, A Tomita, Y Maeda, J Takizawa, K Mitani, T Igarashi, K Sakai, K Miyazaki, K Mihara, K Ohmachi, N Nakamura, H Takasaki, H Kiyoi, S Nakamura, T Kinoshita, M Ogura
Journal: Blood Cancer Journal (2015)

As a different entity of diffuse large B-cell lymphoma (DLBCL) according to the current World Health Organization classification,1 primary mediastinal large B-cell lymphoma (PMBL) is different from DLBCL in terms of clinical, immunohistochemical and genetic features.2 Despite a remarkable advance with first-line treatment of PMBL patients in the rituximab era,3, 4, 5, 6, 7 10–30% of patients still experience progression or relapse. Although patients with relapsed or refractory PMBL are often treated with high-dose therapy followed by autologous stem cell transplantation (HDT/ASCT) after salvage treatment, the progression-free survival (PFS) at 5 years of 27% is unsatisfactory compared with DLBCL in the pre-rituximab era.8, 9, 10 Moreover, information regarding outcomes after HDT/ASCT for relapsed or refractory PMBL is limited in the rituximab era. Therefore, clarifying the current role of HDT/ASCT is vital to establish the optimal treatment strategy.
New Strategies in Engineering T-cell Receptor Gene-Modified T cells to More Effectively Target Malignancies
Authors: Thomas M. Schmitt, Ingunn M. Stromnes, Aude G. Chapuis, Philip D. Greenberg
Journal: Clinical Cancer Research (2015)

The immune system, T cells in particular, have the ability to target and destroy malignant cells. However, antitumor immune responses induced from the endogenous T-cell repertoire are often insufficient for the eradication of established tumors, as illustrated by the failure of cancer vaccination strategies or checkpoint blockade for most tumors. Genetic modification of T cells to express a defined T-cell receptor (TCR) can provide the means to rapidly generate large numbers of tumor-reactive T cells capable of targeting tumor cells in vivo. However, cell-intrinsic factors as well as immunosuppressive factors in the tumor microenvironment can limit the function of such gene-modified T cells. New strategies currently being developed are refining and enhancing this approach, resulting in cellular therapies that more effectively target tumors and that are less susceptible to tumor immune evasion.
Mitochondrial DNA phylogeny of the Old-World monkey tribe Papionini.
Authors: T R Disotell, R L Honeycutt, M Ruvolo
Journal: Molecular Biology and Evolution (1992)

The evolution of the Old World monkey tribe Papionini, composed of macaques, baboons, mandrills, drills, and mangabeys, was examined using mitochondrial DNA (mtDNA) sequence data on the cytochrome oxidase subunit II gene. When analyzed cladistically, these data support a baboon clade of savannah (Papio) plus gelada (Theropithecus) baboons, as well as a clade containing drill (Mandrillus) plus mangabey (Cerocebus) genera. This result stands in opposition to most morphological phylogenies, which break up the baboon clade by placing Papio and Mandrillus as sister taxa and Theropithecus as a more distantly related lineage. Analyses of COII gene sequences also suggest that the papionin ancestral stock divided into two lineages, one leading to macaques and the other to the purely African genera. From a molecular evolutionary perspective, the papionin COII gene sequences reveal a pattern of amino acid replacements concentrated in the regions spanning the mitochondrial membrane.
Exercise-induced leg pain in sport
Authors: Nat Padhiar, Nikos Malliaropoulos, Heinz Lohrer
Journal: British Journal of Sports Medicine (2015)

There is only one good, knowledge, and one evil, ignorance. Socrates

The non-specific terms ‘shin splints’1 and ‘fresher's leg’2 are often used by athletes, trainers and doctors to describe leg pain in sport. Although the history and symptoms of the different underlying conditions have been recognised for a long time, clear definitions are still missing.

In 1966, the American Medical Association (AMA) published ‘The Standard Nomenclature of Athletic Injuries’3 which was elaborated by a subcommittee of the Committee on Medical Aspects of Sports. ‘Shin splints’ were defined as ‘Pain and discomfort in the leg from repetitive running on hard surfaces or forcible, excessive use of the foot’. However, the fact that different authors …