tbuckley/cabot-search huggingface dataset:
Contrasting effects of calcium channel blockade versus converting enzyme inhibition on proteinuria in African Americans with non-insulin-dependent diabetes mellitus and nephropathy.
Authors: A Guasch, M Parham, C F Zayas, O Campbell, C Nzerue, E Macon
Journal: Journal of the American Society of Nephrology (1997)

Hypertension is a common finding in non-insulin-dependent diabetes mellitus (NIDDM) nephropathy. African Americans have a high prevalence of NIDDM and hypertension, and are relatively resistant to the antihypertensive effects of converting enzyme inhibitors (CEI) but respond well to calcium channel blockers (CCB). In the long-term study presented here, the effects of isradipine, a dihydropyridine calcium antagonist, on the course of the nephropathy were investigated and compared with the effects of captopril in 31 African Americans with NIDDM and proteinuria (> or = 500 mg/day). The patients were stratified by levels of GFR and proteinuria, and they were randomized to receive isradipine (N = 16) or captopril (N = 15); doses were adjusted to maintain similar BP levels (< 140/90). At 6 months, mean arterial pressure was similar (102 +/- 3 and 104 +/- 3 mm Hg in the isradipine and captopril groups, respectively) and GFR was unchanged (delta = -4 +/- 3 and +1 +/- 3 ml/min/1.73 in the isradipine and captopril groups, respectively; P = NS). However, proteinuria in the isradipine group increased by approximately 50% (2.01 +/- 0.40 versus 3.04 +/- 0.70 mg/mg creatinine at baseline versus 6 months, respectively, P < 0.05), whereas captopril reduced proteinuria by 30% after 6 months (2.85 +/- 0.70 at baseline versus 2.30 +/- 0.70 mg/mg creatinine, P < 0.05). Dietary protein, sodium intake, and HbA1C levels were similar in both groups and did not differ from baseline. It was concluded that over 6 months, captopril reduces and isradipine increases proteinuria in African Americans with NIDDM and nephropathy. Whether this contrasting effect on proteinuria will result in different rates of progression is not known, but dihydropyridine CCB should be used cautiously in African Americans with diabetic nephropathy.
T1 Mapping by CMR Imaging
Authors: Andreas A. Kammerlander, Beatrice A. Marzluf, Caroline Zotter-Tufaro, Stefan Aschauer, Franz Duca, Alina Bachmann, Klaus Knechtelsdorfer, Matthias Wiesinger, Stefan Pfaffenberger, Andreas Greiser, Irene M. Lang, Diana Bonderman, Julia Mascherbauer
Journal: JACC. Cardiovascular imaging (2015)
Abstract 15308: Reduction of LV Diastolic Wall Tension by Ranolazine Led to Improved Diastolic Coronary Blood Flow During Demand-Induced Acute Myocardial Ischemia in Anesthetized Canine
Authors: Liguo Chi, Haiyun Ling, Dillon Phan, Wei Wang, Arvinder K Dhalla, Luiz Belardinelli
Journal: Circulation (2013)

Ranolazine (RAN) is a first in class late Na current inhibitor approved for the treatment of angina. It has been postulated that the anti-ischemic effect of RAN is due to a decrease in Na+-dependent Ca2+ overload that leads to an improvement in diastolic function and blood flow to the ischemic area. The purpose of present study was to determine whether acute treatment with RAN reduces LV diastolic tension during demand-induced ischemia. Anesthetized beagles (n=11) were subjected to demand-induced ischemia by causing stenosis (~50% blood flow reduction) in both LCX and LAD coronary arteries and followed by a period of 5 min of pacing at 2X basal heart rate. After 30 min i.v. infusion of vehicle (Veh, n=5) or RAN (n=6, 0.1 mg/kg + 0.03 mg/kg/min), the fast pacing period was repeated. RAN significantly decreased ischemia-induced elevation of S-T segment in an epicardial ECG lead (1.2±0.4 vs. pre-treat 4.6±1.0 p<0.05 and Veh 3.5±1.3 fold of baseline), and reduced the increase in LVEDP (7.1±1.6 vs. pre-treat 1...
Abstract 059: N-acylhydrazone Derivative Improves Cardiac Hypertrophy and Dysfunction in Spontaneously Hypertensive Rats Submitted to Myocardial Infarction
Authors: Gisele Zapata-Sudo, Jaqueline S Silva, Sharlene L Pereira, Rodolfo C Maia, Carlos A Fraga, Eliezer J Barreiro, Roberto T Sudo
Journal: Circulation Research (2013)

Aims: Ventricular dysfunction is observed in arterial hypertension and myocardial infarction (MI). The N -acylhydrazone derivative, 3,4-methylenedioxybenzoyl-2-thienylhydrazone (LASSBio-294), which has been described as a potent cardiac inotropic agent with vasodilator properties, was orally administrated in spontaneously hypertensive rats (SHR) submitted to experimental MI. Methods and Results: Protocols were approved by Animal Care and Use Committee at Universidade Federal do Rio de Janeiro. Male SHR (12 - 14 week-old) were randomly divided in sham-operated (SHAM) and infarcted groups (MI) and were treated or not with LASSBio-294 (20 mg/kg p.o.) during 8 weeks. Under sevoflurane anesthesia, the animals were submitted to a ligature of the anterior descending coronary artery to produce the MI. After 8 weeks, rats were submitted to treadmill test and also, the following hemodynamic parameters were analyzed: left ventricular end diastolic pressure (LVEDP), left ventricular end-systolic pressure (LVESP) and LV contractility (dp/dt max ). Hypertrophy was measured using the relation between heart weight to body weight (heart/BW). The volume fraction of collagen (%) was determined by measuring the area of stained tissue within a given field by picrosirius red staining. The results are presented in the following table. Conclusions: Treatment of infarcted SHR with LASSBio-294 reduced intolerance to exercise, ventricular dysfunction, cardiac hypertrophy and fibrosis.
Mutator Phenotype in Human Hematopoietic Neoplasms and Its Association With Deletions Disabling DNA Repair Genes and bcl-2 Rearrangements
Authors: Stefano Indraccolo, Sonia Minuzzo, Laura Nicoletti, Elisabetta Cretella, Martin Simon, Georg Papakonstantinou, Rüdiger Hehlmann, Marta Mion, Roberta Bertorelle, Jelena Roganovic, Luigi Chieco-Bianchi
Journal: Blood (1999)
Diagnosis and management of diabetes in children and young people: summary of updated NICE guidance
Authors: Zosia L Beckles, Julie A Edge, Moira A Mugglestone, M Stephen Murphy, Jerry K H Wales
Journal: BMJ (2016)

#### What you need to know Type 1 diabetes affects more than 25 000 children and young people in the United Kingdom and type 2 affects about 500, with both types becoming more common.1 Life threatening complications, including diabetic ketoacidosis (DKA), can occur with both type 1 and type 2 diabetes. Prompt recognition and effective management of diabetes and associated complications are essential. This article summarises new recommendations from the National Institute for Health and Care Excellence (NICE), which for the first time cover type 2 diabetes and the recognition and management of DKA in children and young people.2 #### What's new in this guidance? NICE recommendations are based on systematic reviews of best available evidence and explicit consideration of cost effectiveness. When minimal evidence is available, recommendations are based on the Guideline Development Group's experience and opinion of what constitutes good practice. Evidence levels for the recommendations are given in italic in square brackets. ### General principles #### Type 1 and type 2 diabetes: recognition, diagnosis, and referral
津巴布韦呼吁：本国霍乱疫情进入紧急状况，亟需医疗援助
Authors: Ryan, Truscott, 刘定华, 崔巍
Journal: BMJ (2009)

津巴布韦最终宣布：由于霍乱疫情席卷全国而医疗资源紧缺，造成了国内形势紧张，呼吁国际社会为其提供援助。 卫生部长David Parirenyatwa详细列举了抵抗疫情所需的短缺物品和资金，包括药品、实验试剂、肾科设备、洗衣设备、X线胶片、高压锅、食物以及约1100万美元（700万英镑，900万欧元）薪酬支付给正在罢工的医生护士。
Abstract 11199: Impact of Rosuvastatin Treatment on Reduction of Thrombus Burden in Rat Acute Inferior Vena Cava Constriction
Authors: Sarah Chua, Jiunn-Jye Sheu, Steve Leu, Tzu Hsien Tsai, Hon-Kan Yip
Journal: Circulation (2014)

Background:  This study tested the hypothesis that rosuvastatin reduces thrombus burden through inhibiting inflammation and suppressing reactive oxygen species (ROS) generation in an inferior vena cava Constriction (IVC CO )-induced deep vein thrombosis (DVT) rat model.   Methods and Results:  12-week-old male Sprague-Dawley rats (n=24) were equally divided into sham control (group 1: laparotomy only), IVC CO  (group 2: IVC constriction), and IVC CO  + rosuvastatin (20 mg/kg/day, orally after induction of IVC constriction) (group 3). IVC diameter was measured by days 0 and 14 and the right hindlimb thickness was measured by day 0, 7, and 14 prior to scarifying the animals. The results showed significantly increased IVC diameter and hindlimb thickness in group 2 than in groups 1 and 3, and significantly increased in group 3 than in group 1 by day 14 after the procedure (all p   Conclusion:  Rosuvastatin treatment significantly reduced IVC thrombus burden through inhibiting inflammatory response and oxidative stress in a rodent model of DVT.   Key words:  inferior vena cava constriction, deep vein thrombosis, rosuvastatin, inflammation, oxidative tress, reactive oxygen species
Cardiovascular Disease Among Survivors of Adult-Onset Cancer: A Community-Based Retrospective Cohort Study
Authors: Saro H. Armenian, Lanfang Xu, Bonnie Ky, Canlan Sun, Leonardo T. Farol, Sumanta Kumar Pal, Pamela S. Douglas, Smita Bhatia, Chun Chao
Journal: Journal of Clinical Oncology (2016)

Cardiovascular diseases (CVDs), including ischemic heart disease, stroke, and heart failure, are well-established late effects of therapy in survivors of childhood and young adult (< 40 years at diagnosis) cancers; less is known regarding CVD in long-term survivors of adult-onset (≥ 40 years) cancer.A retrospective cohort study design was used to describe the magnitude of CVD risk in 36,232 ≥ 2-year survivors of adult-onset cancer compared with matched (age, sex, and residential ZIP code) noncancer controls (n = 73,545) within a large integrated managed care organization. Multivariable regression was used to examine the impact of cardiovascular risk factors (CVRFs; hypertension, diabetes, dyslipidemia) on long-term CVD risk in cancer survivors.Survivors of multiple myeloma (incidence rate ratio [IRR], 1.70; P < .01), carcinoma of the lung/bronchus (IRR, 1.58; P < .01), non-Hodgkin lymphoma (IRR, 1.41; P < .01), and breast cancer (IRR, 1.13; P < .01) had significantly higher CVD risk when compared with noncancer controls. Conversely, prostate cancer survivors had a lower CVD risk (IRR, 0.89; P < .01) compared with controls. Cancer survivors with two or more CVRFs had the highest risk of CVD when compared with noncancer controls with less than two CVRFs (IRR, 1.83 to 2.59; P < .01). Eight-year overall survival was significantly worse among cancer survivors who developed CVD (60%) when compared with cancer survivors without CVD (81%; P < .01).The magnitude of subsequent CVD risk varies according to cancer subtype and by the presence of CVRFs. Overall survival in survivors who develop CVD is poor, emphasizing the need for targeted prevention strategies for individuals at highest risk of developing CVD.
Daily weanscreen in mechanically ventilated patients; effects on sedation, analgesics and duration
Authors: J. van Rosmalen, F. van Beers, A. van Hees, P. Vos, P. van Berkom, J.A.H. van Oers
Journal: European Respiratory Journal (2011)

Introduction:  The duration of mechanical ventilation (MV-duration) should be limited as much as possible to avoid complications.   Objective:  The aim of the study was to find out the impact of a daily weanscreen on MV-duration.   Setting:  A 20-bed mixed medical-(neuro-)surgical Intensive Care Unit.   Methods:  In 2009 the sedationgoal was prescribed each day by the intensivist. In 2010 we introduced a 4 interventions weanscreenprotocol, including: Daily Spontaneous Awakening Trial (SAT), Rapid Shallow Breathing Index (RSBI), Spontaneous Breathing Trial (SBT) and MD enumerates reason to continue. From Januari to December 2010 we assessed all ventilated patients every day from Monday to Friday. The subsequent 4 steps of the weanscreenprotocol were carried out by a ventilation practitioner (R.N.) to promote extubation. The amount of sedatives per year was divided by the number of ventilated patients, resulting in an average dose midazolam/propofol/morphine per patient. The MV-duration was evaluated and compared with 2009.   Results:  The 672 patients in 2010 were compared to 594 patients in 2009. SAPSII was the same in both cohorts, Median MV-duration decreased from 42 to 38 hours (n.s. Mann-Witney U test). Together with a small increase in the use of propofol we observed a substantial reduction in the use of midazolam and morphine.   Conclusions:  In our population we succeeded in reducing the use of midazolam and morphine by a daily 4 component-weanscreen, and a 10% decrease in MV-duration (statistically n.s.).
Vascular Abnormalities Induced by Benzo[&lt;italic&gt;a&lt;/italic&gt;]pyrene: An &lt;italic&gt;In Vivo&lt;/italic&gt; Study in the Hamster Cheek Pouch&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Koshilya Rijhsinghani, Ph.D., Melvin Greenblatt, M.D., Philippe Shubik, Ph.D., M.D.
Journal: JNCI Journal of the National Cancer Institute (1968)

The vascular changes in the pouch of the hamster during application of benzo[a]pyrene were studied in vivo. There appears to be a relationship between the development of the vascular changes and histologic progress of dysplastic epithelial lesions. Benign epithelial hyperplasia is characterized by hyperemia, massive dilatation, tortuosity of large veins, and diffuse capillary neovascularization. Striking vascular alterations, such as fusiform venous and arterial abnormalities and extensive neovascularization, were regularly associated with malignant epithelial lesions. The development of benzo[a]pyrene-induced cheek-pouch carcinoma is paralleled and preceded by significant vascular stromal changes.
Monitoring hepatitis B: Detection of drug resistance
Authors: 홍선표
Journal: Clinical and Molecular Hepatology (2011)

Chronic hepatitis B (CHB) is a leading cause of cirrhosis and hepatocellular carcinoma and the management of CHB currently rests with long-term therapy using oral nucleoside analogs for sustained suppression of hepatitis B virus (HBV) replication. Drug resistance caused by emergence and selection of mutation in HBV polymerase in the presence of antiviral agents is a major limitation to the long-term efficacy of CHB. Monitoring for continued virological response throughout treatment is essential because current treatment options have limited success in achieving durable endpoints, and antiviral resistance may favorably emerge during long-term therapy. In fact, high rates of antiviral resistance have been found with long-term use of lamivudine, in up to 76% of patients treated for 5 years and with adefovir treatment in -30% at 5 years of therapy. Methods of monitoring treatment response include tests for serum aminotransferase levels, HBV DNA level, hepatitis B e antigen (HBeAg) and antibody (anti-HBe), hepatitis B surface antigen (HBsAg) or antibody (anti-HBs), and liver histology. Serum HBV DNA quantification and detection of drug-resistant mutations are the most useful molecular markers for diagnosis and management of CHB. Recent progress on viral quantification and mutant detection using real-time polymerase chain reaction, reverse hybridization, restriction fragment mass polymorphism (RFMP), ultra-deep pyrosequencing (UDPS) assays will be discussed in this article with focus on their analytical and clinical performances.
Abstract 47: GATA Factors Caught at a Crossroad of Gene Duplication with Functional Divergence
Authors: Jop H van Berlo, Jeffery D Molkentin
Journal: Circulation Research (2012)

Background Six individual members comprise the GATA family of Zn finger-containing transcription factors that play major roles in the hematopoietic system and many mesoderm and endoderm derived tissues. The adult heart expresses both GATA4 and GATA6. Here, we examined the overlapping and diverging functional roles of GATA4 and GATA6 in the adult heart, both at baseline and under stress. Results Pressure overload by transverse aortic constriction (TAC) caused a blunted hypertrophic response when GATA4 was deleted from the adult heart, with severe heart failure ensuing after 4 weeks. Similarly, deletion of GATA6 from the mouse heart showed a blunted hypertrophic response and heart failure. Next, we deleted 1 allele of GATA4 and 1 allele of GATA6 from the adult heart, also resulting in blunted hypertrophy and cardiac dysfunction. Deletion of all four alleles of GATA4 and 6 resulted in spontaneous heart failure and death by 3 months of age. These results suggested functional overlap or synergistic activation. To address this concept more directly we deleted GATA6 from the adult heart and overexpressed either GATA4 or GATA6 in a cardiac-specific manner. As expected, we were able to completely revert the phenotype to wild type when GATA6 was overexpressed in mice that had GATA6 genetically deleted. Surprisingly, overexpression of GATA4 was unable to rescue the absence of GATA6 and actually worsened cardiac function in response to pressure overload. Possible explanations for this functional divergence were suggested by an observed rarefaction in capillaries of the heart in absence of GATA4, but enhanced angiogenesis in absence of GATA6. Moreover, when we induced cardiac hypertrophy through MAPK activation, we observed a critical necessity for GATA4, while GATA6 was dispensable. Conclusion Although GATA4 and 6 may be functionally complementary for cardiac gene expression and hypertrophy, they evolved some specific roles in the heart, such as angiogenesis and stress activation. We are currently unraveling how GATA4 and 6 may differentially regulate genes.
Fertility and pregnancy in patients under age 38 following chemotherapy for breast cancer
Authors: D. Katz, H. Mazeh, L. Divinsky, M. Temper, I. Ospovat, A. Salah, T. Hamburger, D. Galinsky, B. Uziely, T. Peretz
Journal: Journal of Clinical Oncology (2009)

e11541 Background: Chemotherapy improves breast cancer outcome, but may impact fertility. Post chemotherapy fertility rates range between 10–90% among studies. Fertility post chemotherapy is most often assessed by rate of menstruation resumption- an indirect method of evaluating childbearing potential. It is noteworthy that future pregnancy is a woman's first concern not menses preservation. Variability in fertility rates along with limited data on post chemotherapy pregnancies led us to undertake this single institute retrospective study evaluating fertility and pregnancy post chemotherapy in ≤ 38 y old breast cancer patients. Methods: We reviewed medical records of 222 consecutive stage II-IIIB breast cancer patients diagnosed, treated and followed at Sharette Institute of Hadassah-Hebrew University Medical Center from 1990–2004. Inclusion criteria included age ≤ 38 years, ≥3 cycles of standard metothrexate or adriamycine based chemotherapy, metastasis-free 12 months post chemotherapy initiation or one year following GnRH analog withdrawal. Patients diagnosed with infertility prior to breast cancer diagnosis (data present for part of patients), bilateral oophorectomy or patients surviving ≤3 years from diagnosis were excluded. Patient pregnancy preference was not recorded. Fertility was defined as resumption of recurrent menses or pregnancy anytime during follow up. In case of recurrence, date of recurrence diagnosis was assigned as date of last follow up. Results: Cohort included 65 patients. Mean age 32.5±4 ys (20.3–38.5) Almost all patients (95.4%), 38 ys or younger, preserve menses following chemotherapy, and 33.9% become pregnant. Most of patients who did not conceive post chemotherapy (66.1%), were under a familial status not promoting pregnancy; 44% of all women who did not give birth post chemotherapy had at least 3 offspring at the time of diagnosis and 83% out of all women who did not have any offspring by the end of follow up were single. Conclusions: This data suggest that pregnancy potential may be even higher than our actual finding, since pregnancy is most probably not attempted by multiparous or most single patients, whom cultural constrains affect their decisions. It seems prudent to offer the subgroup of unmarried women fertility preservation. No significant financial relationships to disclose.
Gemcitabine (Gem) plus celecoxib in advanced pancreatic carcinoma: a phase II study
Authors: G. Marini, E. Simoncini, F. Valcamonico, V. Amoroso, L. Vassalli, G. Rangoni, S. Grisanti, P. Marpicati, G. A. M. Tiberio, V. D. Ferrari
Journal: Journal of Clinical Oncology (2004)

4103 Background: GEM is the most active single agent in the treatment of pancreatic carcinoma. Celecoxib is a selective cyclooxygenase-2 (COX-2) inhibitor. Recent studies in human pancreatic tumor cell lines suggest an involvement of COX-2 in the control of tumor-dependent angiogenesis and provide the rational for inhibition of the COX pathway as an effective therapeutic approach for pancreatic cancer. The aim of this study is to evaluate the toxicity, safety and efficacy of this combination regimen. Methods: From January 2001 to July 2002, 32 consecutive patients (18 male/14 female) entered the trial. Median age was 63 years (range 48–76), median PS 1 (range 0–2); 22 patients (pts) were metastatic, 10 pts had locally advanced disease. Median basal CA19.9 value was 747 U/mL (range 1–50000). A total number of 210 cycles (median 6,5 per patient; range 2–12) were administered. The schedule consisted of GEM 1000 mg/m2 (as a 30 minutes iv infusion) on days 1,8 every 3 weeks and Celecoxib 400 mg bid. Results: Grade 3 NCI-CTC haematological toxicity was neutropenia in 9% of pts. Neither grade 4 neutropenia nor grade 3–4 thrombocytopenia were observed. Grade 3 non-haematological toxicity was as follows: hepatic toxicity 9%, nausea 3%. Although the high dose of celecoxib, neither gastric toxicity nor renal failure were observed. Only 3 pts (9%) had a minimum creatinine increase. Clinical benefit was obtained in 46% of pts, 38% had no basal pain and 16% didn't achieve any symptom control. Median survival was 9,1 months; 1-year survival rate was 36%. Conclusions: The goals we achieved with celecoxib-GEM combination are very low toxicity, good quality of life and improved overall survival. Accrual is ongoing. No significant financial relationships to disclose.