tbuckley/cabot-search huggingface dataset:
Abstract 6094: Alterations in Blood Flow Reserve Secondary to Decompensated Diabetes Mellitus - Preliminary Results Obtained by Myocardial Contrast Echocardiography
Authors: Natanael V Moraes, Carolina P Oliveira, Jeane Tsutsui, Antônio C Lerário, Wilson Mathias
Journal: Circulation (2008)

Diabetes mellitus (DM) is one of the most important health problems in developed countries. Poor blood glucose control is known to be associated with clinical symptoms and increased risk for cardiovascular complications. Myocardial contrast echocardiography (MCE) has been demonstrated to be valuable for assessing myocardial blood flow reserve (MBFR) in patients with obstructive coronary artery disease and in those with microcirculatory alterations. We hypothesized that DM would result in impairment of MBFR, as measured by MCE, even in patients without obstructive coronary artery disease. Methods: We studied 30 patients with DM (mean age 55 years, 13 men) and 10 control subjects (mean age 53 years, 5 men) with normal global and regional systolic function. MBFR was determined by quantitative contrast echocardiography during dipyridamol (0.84 mg/Kg) stress using intravenous commercialy available microbubbles contrast (Definity, Bristol-Myers Squibb). Diabetic patients were studied in a decompensated state, with mean glycosylated hemoglobin of 9.0% (ranging from 8.5% to 13.0%). Quantification of peak myocardial intensity (A), microbubble velocity (Beta) and MBFR (peak dipyridamol/baseline AxBeta) were measured off line using Q-Lab software (Philips Medical Imaging). All patients underwent computed tomography coronary angiography (64 slices) which demonstrated no obstructive coronary artery disease. Results: Values of A (dB), Beta (1/s), and AxBeta (dB/s) both at baseline and during dipyridamol stress are described in Table . MBFR was significantly lower in patients with decompensated DM than in control subjects (1.58 versus 2.87; p&lt;0.001). Conclusion: These preliminary results suggest that diabetic patients with poor blood glucose control and no obstructive coronary artery disease have impaired MBFR. MCE may be a useful noninvasive technique for evaluating changes in MBFR in this group of patients.
Abstract 14024: Tbx18-Reprogrammed Cardiomyocytes Exhibit Pacemaker Phenotype with Upregulated Calcium and Voltage-Sependent Clock Mechanisms
Authors: Nidhi Kapoor, Eduardo Marban, Hee Cheol Cho
Journal: Circulation (2011)

The heartbeat originates within the sinoatrial node (SAN), a diminutive, highly specialized structure containing a small number ( 2+ -dependent “clock” pathways. The maximum diastolic potential was depolarized in Tbx18-NRCMs in comparison to GFP-transduced controls (-47±10 vs. -73±6 mV) with accompanying reductions in I K1  (p f  (-5.2±1.3 pA/pF at -140 mV, n=3). An index of automaticity (the % of autonomously-beating cells multiplied by the frequency of AP oscillations in those cells) was much greater in Tbx18-NRCMs compared to controls (70±16 vs. 13±4 % bpm, p 2+  release events (LCRs) that preceded each whole-cell Ca 2+  transient, mimicking LCRs observed in native SAN cells. LCRs were not detected in control NRCMs. Ryanodine (10 μM) suppressed the spontaneous beating rate by 47±6% in Tbx18-NRCMs but only by 12±2% in controls (p 2+ ] i  stores was observed in Tbx18-NRCMs which can be attributed to increased SERCA2a activity due to downregulation and phosphorylation of phospholamban (PLN), an inhibitor of SERCA. Tbx18 expression led to a relative increase in the protein level of phosphorylated PLN (Ser16) similar to the relative p-PLN increase in adult SAN. In addition, Tbx18-NRCMs shrank in size, exhibited sparse myofibrils, ceased to express connexin 43 and atrial natriuretic peptide and exhibited increased levels of cAMP and HCN4, reproducing key features of SAN cells. The data indicate that expression of a single transcription factor suffices to create induced pacemaker cells from working cardiomyocytes.
Lipid and inflammatory risk worsens over 3 years in youth with type 2 diabetes: The TODAY clinical trial
Authors: R. S. Weinstock, S. Caprio, Kenneth Copeland, S. S. Gidding, Kathryn Hirst, Elyse B. Katz, L. L. Katz, S. Marcovina, K. J. Nadeau, D. M. Nathan
Journal: Diabetes Care (2013)
Superkids: competent children of psychotic mothers
Authors: Carol Kauffman, Henry Grunebaum, Bertram Cohler, Enid Gamer
Journal: American Journal of Psychiatry (1979)

In a follow-up study of children of psychotic mothers, the authors examined a subgroup of outstandingly talented, colorful, and competent "high-risk" children. These children and their mothers were given a variety of psychological tests and were interviewed individually. They were then compared with a control group of children whose mothers had no psychiatric illness. The 6 most socially and intellectually competent high-risk children were strikingly more competent, colorful, creative, and talented than the 6 highest functioning control children. They more often reported having a best friend and had extensive and positive contact with an extrafamilial adult. Another important variable in the prediction of high social competence among children at high risk is a warm relationship with the mother.
Abstract 3114: Progression of Aortic Stenosis is slowed by Angiotensin-Converting Enzyme Inhibition but not by Angiotensin II Type 1 Receptor Blockade
Authors: Kana Wakabayashi, Akiko Goda, Shinji Nakao, Misato Otsuka, Mika Matsumoto, Chikako Tsutsumi, Masaaki Lee, Takeshi Tsujino, Tohru Masuyama
Journal: Circulation (2006)
Hormone replacement therapy and hip fracture risk : population based case-control study
Authors: Karl Michaëlsson, John A. Baron, Bahman Y. Farahmand, Olof Johnell, Cecilia Magnusson, Per-Gunnar Persson, Ingemar Persson, Sverker Ljunghall
Journal: BMJ (1998)

OBJECTIVE: To determine the relative risk of hip fracture associated with postmenopausal hormone replacement therapy including the effect of duration and recency of treatment, the addition of progestins, route of administration, and dose. DESIGN: Population based case-control study. Setting: Six counties in Sweden. SUBJECTS: 1327 women aged 50-81 years with hip fracture and 3262 randomly selected controls. MAIN OUTCOME MEASURE: Use of hormone replacement therapy. RESULTS: Compared with women who had never used hormone replacement therapy, current users had an odds ratio of 0.35 (95 % confidence interval 0.24 to 0.53) for hip fracture and former users had an odds ratio of 0.76 (0.57 to 1.01). For every year of therapy, the overall risk decreased by 6% (3% to 9%): 4% (1% to 8%) for regimens without progestin and 11% (6% to 16%) for those with progestin. Last use between one and five years previously, with a duration of use more than five years, was associated with an odds ratio of 0.27 (0.08 to 0.94). After five years without hormone replacement therapy the protective effect was substantially diminished (-7% to 48%). With current use, an initiation of therapy nine or more years after the menopause gave equally strong reduction in risk for hip fracture as an earlier start. Oestrogen treatment with skin patches gave similar risk estimates as oral regimens. CONCLUSIONS: Recent use of hormone replacement therapy is required for optimum fracture protection, but therapy can be started several years after the menopause. The protective effect increases with duration of use, and an oestrogen-sparing effect is achieved when progestins are included in the regimen.
545. Lentiviral Vector Mediated Gene Transfer of the Anti HIV Gene revM10 into Primitive Hematopoietic Cells for Gene Therapy of HIV Infection
Authors: Ingrid Bahner, Gerald Cho, Barbara Engels, Denise Peterson, Karen Pepper, Donald B. Kohn
Journal: Molecular Therapy (2004)

Lentiviral vectors are well suited for the transduction of resting hematopoietic progenitor cells. Yet, delivery of an anti-HIV gene using such a vector poses a challenge because the anti-HIV gene might reduce the otherwise high titer of the lentiviral vector preparation needed for efficient transduction of resting hematopoietic progenitor cells. The revM10 anti-HIV gene might reduce the titer by preventing export of unspliced packaging or vector message. Therefore, we investigated packaging and vector constructs that either contained or lacked the 5' splice donor site, reasoning that the deletion of this splice site might reduce the dependence of the resulting transcripts on the rev protein. The presence of the RRE in such 5' splice site deleted vectors was also evaluated. Theoretically, the presence of the RRE could lead to competition with the packaging construct for rev binding during packaging, leading to a diminished titer. Alternatively, the presence of the RRE could lead to an increased amount of vector transcripts being exported into the cytoplasm, leading to an increased titer. Furthermore, the combination of the revM10 and the RRE in one vector construct might be additive, synergistic or even antagonistic during both the packaging process and in their anti-HIV activity in the transduced target cell. Therefore, the presence of the RRE was evaluated in two different locations in the lentiviral vector: located outside the internal transcript and thus active only during packaging or located inside the internal transcript and thus active during both packaging and in the transduced target cells. Analysis of the different combinations of modified vector and packaging constructs revealed that the combination of revM10 with RRE in a vector containing the 5' splice site resulted in high titer vector preparations independent of whether the packaging construct contained a 5' splice site or not. Analysis of the location of the RRE in the lentiviral vector containing the revM10 gene revealed that the presence of the RRE in the internal transcript increased the anti-HIV activity, indicating that the combination of revM10 and RRE is either additive or synergistic but not antagonistic.
Handbook of Vertigo
Authors: Michael E. Glasscock, Roberto A. Cueva, Britt A. Thedinger
Journal: Annals of Internal Medicine (1991)

Designed for easy reference, this handbook seeks to simplify the diagnosis and treatment of vertigo. By defining the clinical features of the most common disorders, it provides information that should enable the reader to order proper diagnostic tests, identify the cause of the vertigo, and develop both simple and more elaborate treatment plans as necessary. The coverage includes discussions of physiology and anatomy, and a series of case studies.
Assessment of PSA and digital rectal examination (DRE) for the detection of Gleason ≥ 7 prostate cancer in a referral population
Authors: C. A. O’Brien, S. Mongoue-Tchokote, L. Collins, S. Spurgeon, L. Peters, T. M. Beer, M. Mori, M. Garzotto
Journal: Journal of Clinical Oncology (2006)

4633 Background: The value of both PSA and DRE for prostate cancer detection have recently been called into question when examined in screening and prostatectomy series (NEJM 350:2239, J Urol 172:1297). The effectiveness of these parameters for detection of clinically significant cancer is not fully characterized. We studied their utility for the detection of aggressive prostate cancer (Gleason Score ≥ 7) in a referral population of men. Methods: Data were collected on 1,699 referred men with a serum PSA of ≤ 10 ng/ml who underwent a prostate biopsy (minimum 6 cores) between 1993 and 2004. Variables analyzed included: age, race, family history, DRE (normal vs. suspicious vs. cancer-likely) and PSA. Thirty percent of the data were randomly reserved for study validation. Logistic regression analysis was performed to estimate the odds ratio and the 95% confidence intervals. Results: Gleason grade ≥ 7 prostate cancer was detected in 157 subjects (9.2%). Using the model building data set (n = 1,184), independent predictors of Gleason ≥ 7 cancer were an elevated PSA and an abnormal DRE only (see table ). Based on these results, a clinically-applicable nomogram was constructed and using the independent validation set (n = 515). The area under the ROC was 0.70 for the model. Conclusions: Although the use of PSA and DRE have recently come under intense scrutiny, they independently predict the presence of aggressive prostate cancer in a contemporary referral population. Improvement in prostate-cancer survival associated with successful treatment of localized disease requires the successful early detection of aggressive prostate cancer. Our results demonstrate that PSA and DRE, currently recommended screening interventions by the ACS and AUA, remain useful for the detection of aggressive prostate cancer in the PSA era. [Table: see text] No significant financial relationships to disclose.
TCR Gene Rearrangements and Expression of the Pre-T Cell Receptor Complex During Human T-Cell Differentiation
Authors: Bianca Blom, Martie C.M. Verschuren, Mirjam H.M. Heemskerk, Arjen Q. Bakker, Ellen J. van Gastel-Mol, Ingrid L.M. Wolvers-Tettero, Jacques J.M. van Dongen, Hergen Spits
Journal: Blood (1999)
Abstract 4950: Infection with Enterovirus Produces Myocarditis in a Non-Human Primate Model
Authors: Nancy Halnon, Cheryl Cammock, Morgan Singletary, James Blanchard, Jill Skoczylas, Paul Krogstad
Journal: Circulation (2008)

Introduction: We performed a pilot study to establish a non-human primate model of enteroviral infection and myocarditis. Methods: Juvenile cynomolgus monkeys were inoculated via oral (n=1) or intravenous (n=8) routes with a cloned Coxsackievirus B3 (CVB-3) or a CVB-3 /Enterovirus 86 strain (CVB-MCH) isolated from a clinical specimen from a patient with fatal myocarditis. Clinical and echocardiographic assessment was performed at baseline and at days 3, 7, 14, and 28. CVB-3 neutralizing antibody titers were measured. Viral RNA was detected by RT-PCR and culture of plasma and cardiac tissue. Animals were sacrificed at 14 or 28 days and myocardium examined for viral pathology. Results: Infection was achieved by both routes with both CVB-3 strains. Viremia was detected in 6/9, resolving after day 3. All (9/9) generated neutralizing antibody. Two animals infected with 10 7 infectious units (IU) of CVB-3 became moribund and were sacrificed at day 11 and day 14. Subsequent animals received 10 6 IU of CVB-3 and appeared well until sacrificed at day 14 (n=3) or day 28 (n=1). Three infected with 10 6 IU CVB-MCH also appeared well until sacrificed at day 28. Normal ejection fraction was maintained, but four animals had minor wall motion abnormalities. Serum troponin remained normal. Virus was present in myocardium in 5/5 tested. Multiple areas of focal cardiac injury were present in all animals and included lymphocytic or eosinophilic myocarditis (n=6), focal inflammation (n= 3), myocytolysis (n=2), ischemic foci (n=4), contraction band necrosis (n=2), and hypertrophy (n=3). Active myocarditis was present in 4/5 animals at day 14 and 2/4 at day 28. Conclusions: We were able to consistently establish infection with CVB-3 in cynomolgus monkeys resulting in clinically apparent or sub clinical disease, including myocarditis or cardiac injury persisting at 28 days. Despite adequate immune responses to clear viremia, virus persisted in the myocardium. The presence of myocyte hypertrophy and injury at 28 days in this model may provide a basis for experiments aimed at modulating immune or virus induced cardiomyopathy.
New therapeutic options in metastatic colorectal cancer
Authors: M. Czerniawska-Meler, A. I. Jagiello-Gruszfeld, J. Zbrzezniak-Smilgiewicz, S. Szablowska-Siwik
Journal: Journal of Clinical Oncology (2008)

15107 Background: The median overall survival (OS) of metastatic colorectal cancer (mCRC) patients (pts) treated with first- and second-line combination chemotherapy now extends to more than 18 months in some countries. The aim of this study is to compare the overall survival of pts with mCRC in two different years using our database. Methods: 97 patients diagnosed of mCRC during 2002 and 2005 were included in the study. In 2002 pts received only 5-Fu or capecytabine during the palliative treatment (37% of pts). In 2005 pts (63%) oxaliplatin-based therapy in the first line and FOLFIRI in 2nd line of therapy most often received. All pts were in good condition (WHO 0 or 1). In 23% of pts metastasectomy as part of palliative treatment was performed. Patients characteristics is as follow: male/female ratio: 69/31; colon/rectum: 53/47, mean of age: 59 (range 22–77 years). Location of metastatic lesions: liver - 57%, soft tissue - 41%; lungs - 16%, bone - 4%. The 49% of pts were diagnosed as primary stage IV. Survival curves were constructed according to the Kaplan-Meier method and compared by log-rank analysis Results: The median of OS for the whole group was 14 months. The median of OS in 2002 (pts who received only 5-Fu or capecytabine during the palliative treatment) was 8 months and in 2005 -18 months (p=.00014). Similarly the median of OS this part of pts (43%), who received only 1 line of chemotherapy was significantly shorter (8.5 month) than the median of OS this group of pts (57%), who received at least 2 lines of chemotherapy (19 month) p =.00049. The relevant condition of increasing the median of OS was the possibility of metastasectomy conducting (32 vs. 11 month; p <.0001). Conclusions: A positive CRC mortality trend was observed. The influencing factors were related with the use of new antineoplastic agents and possibility to perform of metastasectomy (especially liver metastatic lesions). No significant financial relationships to disclose.
Worldwide comparison of prostate needle biopsy quality in the reduction by dutasteride of prostate cancer events (REDUCE) study: Improvement with investigator training
Authors: D. G. Bostwick, C. Teloken, O. W. Brawley, M. Marberger, J. Qian, K. Drewnowska, F. Niyuhire, R. R. Rittmaster, I. L. Fowler, M. C. Somerville
Journal: Journal of Clinical Oncology (2009)

e16029 Background: The accuracy of prostate cancer detection by biopsy is influenced by the number and length of needle biopsy cores. We compared these two biopsy quality factors among study sites worldwide for the pre-study entry biopsies (6–12 cores) and study-mandated biopsies (10 cores) at year 2 of the REDUCE study. Methods: Prostate biopsy quality indicators were evaluated retrospectively. Data were compared from entry and year 2 biopsies for subjects enrolled in the study in 6 geographic regions (see table ). Investigator training was provided for REDUCE study protocol-required standardization prior to year 2 biopsies. Training included emphasis on quality of the biopsies. Results: Data were collected from 4638 entry and 6275 year 2 subjects, respectively. At entry, the aggregate length of biopsies, number of cores per subject, and core length differed significantly among regions (p &lt; 0.0001). Aggregate length was longest in biopsies obtained in Australia and the highest core number was observed in South America. At year 2, each region collected a mean of 10 cores per subject (per protocol), and the aggregate length and mean core length were greater than the entry biopsies (for each analyzed parameter, p &lt; 0.0001); variance among sites was reduced for all quality measures. Conclusions: There were significant differences in biopsy quality (number of cores and length of tissue obtained) around the world at entry. Following the REDUCE study protocol-required standardization and investigator training, biopsies obtained at year 2 showed an increase in the mean aggregate length, mean core number, and mean core length compared with the entry biopsies. Our data suggests that variance in biopsy quality may be reduced by investigator training, thereby optimizing quality and cancer detection. [Table: see text] [Table: see text]
Preliminary results of a phase II neoadjuvant trial with gemcitabine/oxaliplatin and cetuximab followed by surgery or concurrent intensity modulated radiation therapy (IMRT) with capecitabine for patients with borderline resectable and unresectable nonmetastatic pancreatic cancer
Authors: U. B. Chaudhary, V. Gudena, D. L. Milling, P. O'Brien, A. J. Montero, J. Brashears, D. Marshall, B. Hoffman, E. Garrett-Mayer, N. Esnaola
Journal: Journal of Clinical Oncology (2008)

15506 Background: The treatment of patients with locally advanced pancreatic cancer remains challenging with median survival in the range of 10 months. This study seeks to establish whether neoadjuvant therapy with cetuximab in combination with oxaliplatin and gemcitabine improves the rate of progression free survival (PFS) at 6 months. Methods: Pts received preoperative gemcitabine (G) 1,000 mg/m2 iv d1, oxaliplatin (O) 100 mg/m2 iv d2 every 14d for 6 cycles with cetuximab (C) 400 mg/m2 iv d1 followed by 11 weekly infusions of 250 mg/m2. Staging by CT scan and endoscopic ultrasound occurred prior to enrolment and 4 weeks after completion. Pts who were considered surgically resectable underwent surgical exploration while patients with unresectable disease were treated with IMRT at 54 Gy with concurrent capecitabine at 800 mg/m2 by mouth twice daily. Results: 26 pts have been enrolled and 15 pts have completed chemotherapy and are evaluated for response. 3 pts were taken off from the protocol prior to completing chemotherapy: allergic reaction to cetuximab(1pt), decrease in performance status(1pt), and personal preference (1pt). The median progression-free is 9.5 months 95% CI (7.23-Inf) and median overall survival is not reached. No patients had progressed at six months. 7 pts were borderline resectable while 8 had unresectable disease. 14 pts completed neoadjuvant therapy with 5 of 14 (36%) able to undergo an R0 surgical resection. 1 pt was able to undergo R0 resection after concurrent chemoradiation, for a resectability rate of 6/14 (43%). IMRT was delivered to 8 of 9 pts unresectable after GOC. 7 of 8 pts were able to complete IMRT. During GOC, 2 of 14 pts had grade 3 hematologic toxicities and 1 pt had grade 4 allergic reaction to cetuximab. During IMRT 3 of 8 pts had a maximum RTOG grade 3 acute GI toxicity. Conclusions: Early results from this study indicate that neoadjuvant GOC followed by IMRT is well tolerated with a very promising R0 resectability rate. Trial accrual continues and updated results will be presented. No significant financial relationships to disclose.
Carcinomatous Neuromyopathy
Authors: 真一郎 岩神, 理 三上, 幸司 能登, 和久 高橋, 明彦 大和田, 一彦 佐藤, 尚亮 田村, 高 檀原, 敏博 貫和, 枝郎 吉良, 芽明 古川, 慎吾 野沢
Journal: JAMA (1963)

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