tbuckley/cabot-search huggingface dataset:
Bichat guidelines for the clinical management of viral encephalitis and bioterrorism-related viral encephalitis
Authors: P Bossi, A Tegnell, A Baka, F van Loock, A Werner, J Hendriks, H Maidhof, G Gouvras
Journal: Eurosurveillance (2004)

Most of the viruses involved in causing encephalitis are arthropod-borne viruses, with the exception of arenaviruses that are rodent-borne. Even if little information is available, there are indications that, most of these encephalitis-associated viruses could be used by aerosolisation during a bioterrorist attack. Viral transfer from blood to the CNS through the olfactory tract has been suggested. Another possible route of contamination is by vector-borne transmission such as infected mosquitoes or ticks. Alphaviruses are the most likely candidates for weaponisation. The clinical course of the diseases caused by these viruses is usually not specific, but differentiation is possible by using an adequate diagnostic tool. There is no effective drug therapy for the treatment of these diseases and treatment is mainly supportive, but vaccines protecting against some of these viruses do exist.
Biochemical failure after radiation therapy for prostate cancer: Racial differences
Authors: D. Chi, A. E. Hirsch, G. A. Gignac
Journal: Journal of Clinical Oncology (2009)

e16071 Background: Many guidelines for prostate cancer treatment are based on clinical trials with predominantly white patient (pt) populations. The generalizability of these results assumes similar tumor biology among all races. We set out to examine biochemical failure (PSA failure) rates in a cohort of pts after definitive external beam radiation (EBRT) in the racially diverse population at our institution. Methods: We conducted an IRB-approved retrospective review of pts treated with definitive EBRT from January 2000 to April 2008. We excluded from analysis pts who received brachytherapy, salvage, adjuvant or palliative radiation. Race, country of origin, diagnostic data, pre- and post-treatment PSA, Gleason score (GS), clinical stage (CS), and treatment history were reviewed. CS was based on the original clinician's assessment at time of diagnosis. PSA failures were defined using 1996 ASTRO criteria. Two cohorts were grouped by race: white and nonwhite. Statistical analysis was performed using Fisher's Exact test. Results: One hundred seventy-four pts were treated with definitive EBRT. Forty-four pts were white and 130 were nonwhite. Both cohorts demonstrated similar distributions in GS and CS (see Table ). The white cohort had a high proportion of pts with a pretreatment PSA &lt;10 ng/ml (66%) as compared to the nonwhite cohort (46%). Distribution of race/region of origin is: White 44 (25%), Black-American 78 (45%), Black-Caribbean 28 (16%), Black-African 2 (1%), Hispanic 21 (12%), Asian 1 (1%). Just under 50% of each group received neoadjuvant androgen deprivation therapy. PSA failure rate was 7% for the white cohort and 13% for nonwhite (p = 0.41). Conclusions: In this retrospective analysis, there was no statistical difference among races with regard to PSA failure rates. The PSA and Gleason trends in each cohort were consistent with published data on this topic. Dedicated evaluation of the prognostic value of traditional risk stratification in nonwhite pt populations in a prospective trial is warranted. [Table: see text] No significant financial relationships to disclose.
Abstract 18634: Serial Changes in Right Ventricular Geometry and Function in Patients After Left Ventricular Assist Device Implantation
Authors: Ana Garcia-Alvarez, Leticia Fernandez-Friera, Joe F Lau, Simonette T Sawit, Jesus G Mirelis, Javier G Castillo, Sean Pinney, Anelechi C Anyanwu, Valentin Fuster, Javier Sanz, Mario J Garcia
Journal: Circulation (2010)

Background: Left ventricular assist device (LVAD) support causes left ventricular (LV) unloading with decrease in volumes and leftward shifting on the interventricular septum. However, the contribu...
Abstract 4349: Usefulness of Echocardiographic Measures of Dyssynchrony in Patients with Borderline QRS Duration for Selection for Resynchronization Therapy
Authors: Olusegun Oyenuga, Hideyuki Hara, Hidekazu Tanaka, Han-Na Kim, Samir Saba, John Gorcsan
Journal: Circulation (2008)

Although echo dyssynchrony has not replaced routine selection criteria for cardiac resynchronization therapy (CRT) in patients with wide QRS, our objective was to test the hypothesis that dyssynchrony may assist in selection of patients for CRT with borderline QRS duration. We studied 119 heart failure patients referred for CRT; all were Class III-IV with ejection fraction (EF) ≤35%: 79 had Wide-QRS ≥130ms (169 ±28ms), and 40 had Borderline-QRS 100 –130ms (116 ±7ms). Dyssynchrony was assessed using tissue Doppler (TDI) longitudinal velocities from apical views (≥65ms opposing wall delay) and speckle tracking radial strain (≥130 ms septal to post. wall delay). Pulsed Doppler assessed interventricular mechanical delay (IVMD) (≥40ms), and filling time/RR interval (FT/RR ≤40%). Patients were followed for 8±5 months. Response to CRT was defined as ≥15% increase in EF. Overall, 77% of the Wide-QRS group were EF responders in contrast to 65% of the Borderline-QRS group. TDI was 87% sensitive and 67% specific for predicting response in the Wide-QRS group, but only 46% specific in the Borderline-QRS group. Radial dyssynchrony was the best predictor of response in the Borderline-QRS group with 80% sensitivity and 92% specificity. Although IVMD and FT/RR had low sensitivities, they were 100% specific. EF response to CRT is less frequent in patients with Borderline-QRS than in those with Wide-QRS. Radial dyssynchrony appears to be the best predictor of EF response in Borderline-QRS patients; IVMD and FT/RR were highly specific. A combined echo assessment of dyssynchrony has potential to assist in selection of patients for CRT with borderline QRS.
870. Gene Transfer in the Sandhoff Murine Model Using Lentiviral Vectors
Authors: Elena L. Aronovich, Jason B. Bell, Lalitha R. Belur, Joel L. Fransden, Roland Gunther, Brenda Koniar, David C. C. Erickson, R. Scott McIvor, Perry B. Hackett, Chester B. Whitley
Journal: Molecular Therapy (2004)

The Sleeping Beauty (SB) transposon system created at the University of Minnesota is one of the few non-viral gene therapy systems that are able to integrate genes into human chromosomes. This is especially relevant for treating genetic disorders that require sustained expression of the therapeutic transgene. The purpose of this study is to evaluate SB-mediated transposition as a tool for safe, efficient, stable, non-viral gene therapy in a model lysosomal disorder, mucopolysaccharidosis (MPS) type VII. Cis SB transposon plasmids were constructed to deliver both the T2 transposon and SB11 transposase on the same plasmid (Geurts et al., Mol. Ther. v. 8, p. 108-17, 2003). For MPS VII, we constructed a transposon carrying the human -glucuronidase (GUSB) cDNA driven by a strong ubiquitous CAGGS promoter, and with SB11 transcribed from the intermediate-strength ubiquitin C promoter. Expression levels of SB11 in murine liver were confirmed by Western analysis. MPS VII mice completely deficient in GUSB activity were hydrodynamically injected with 25 g of plasmids that either did, or did not, express SB11. Blood samples for plasma isolation were collected 24 h after treatment and biweekly thereafter. An injection was deemed technically successful by the observation of plasma GUSB levels >100-fold of wild type levels 24 h following treatment. Four weeks after treatment, all plasma GUSB activities were below the lowest level of detection (probably not due to immune response because Bethesda Assays did not indicate the presence of GUSB inhibitors). Mice were euthanized 3 months after treatment. At that time GUSB activity in liver homogenates from mice that received transposase was 10-fold higher compared to that in the no-transposase control group, which was equal to approximately 1% of the value for normal untreated mice. Transgene frequency (as estimated by GUSB histochemical staining of frozen liver sections) was below 0.1% in the former group, but virtually undetectable in mice receiving transposon without transposase. Toluidine blue staining of liver sections was used to evaluate whether the amount of enzyme expressed from the transposons was sufficient to reduce the number and size of pathologic lysosomal inclusion in livers. GUSB activity levels in the spleen, lung, and kidney were  1% wild type levels and also produced transient expression of exceedingly high levels of circulating GUSB enzyme. These studies define a pattern of biodistribution and transgene expression that may be therapeutic for other MPS diseases in addition to MPS VII.
Hormonal manipulation of prostate cancer with sequential androgen blockade.
Authors: K. B. Olson, S. Daignault, D. A. Hamstra, K. J. Pienta
Journal: Journal of Clinical Oncology (2010)

e15033 Background: The treatment of biochemically recurrent prostate cancer continues to be controversial. While androgen deprivation therapy with an LHRH agonist is the current standard of care, it is associated with a growing list of potential toxicities. Sequential androgen blockade (SAB), with a 5-alpha reductase inhibitor and a nonsteroidal antiandrogen, has been shown to decrease PSA and delay disease progression in patients with biochemical recurrence. Methods: We performed a retrospective review of 61 prostate cancer patients treated at a single institution with a combination of oral finasteride 5mg and bicalutamide 50 mg. 22 patients were treated with continuous SAB and 39 were treated intermittently based on PSA. 55 patients had a rising PSA after definitive treatment; 6 patients had no local definitive treatment. In addition to local treatments, over 50% had received other treatments for their prostate cancer: 24 had received LHRH agonists prior to SAB (duration 4-54 months), 13 had prior chemotherapy and 4 had been on vaccine trials. 14 patients had evidence of metastatic disease prior to initiation of SAB (4 with lympadenopathy, 7 with bone metastases; 2 with nodal and bone disease; 1 with lung metastases). Kaplan-Meier methods were used to determine duration of response. Results: Excluding 5 patients with undetectable PSAs at the time of SAB initiation, median PSA decline at 3 months was 90%. With a median follow up of 44 months (range 3-149 months), median duration of response to SAB was 72.5 months (95% CI 38, 87). Response was noted across all Gleason scores with median duration in Gleason 7, 8 and 9 disease of 72.5, 72.5 and 82.3 months respectively. Currently 35 patients remain on SAB with median follow up of 29 months. 21 patients treated with SAB were later treated with LHRH analogs; median response duration to subsequent LHRH in this group was 24 months (95% CI 6, 47). Treatment was well tolerated. Conclusions: In this heterogeneous group of prostate cancer patients, SAB was well tolerated with a median duration of biochemical control of just over 6 years. Our observations suggest that further study of this combination in randomized trials may be warranted. No significant financial relationships to disclose.
Identification and characterization of novel AML1-ETO fusion transcripts in pediatric t(8;21) acute myeloid leukemia
Authors: Yubin Ge, Katherine M. Lafiura, Larry H. Matherly, Jeffrey W. Taub, Yaddanapudi Ravindranath
Journal: Cancer Research (2006)

4326  t(8;21)(q22;q22) is a balanced translocation between chromosomes 8 and 21, resulting in the fusion of the 5’ end of the AML1 gene normally located on chromosome 21q22 with the 3’ end of the ETO on chromosome 8q22. t(8;21) is one of the most common cytogenetic abnormalities in childhood acute myeloid leukemia (AML), present in ∼12% of cases and has been considered a favorable prognostic factor in several studies. Transcription of the AML1 gene is regulated by two independent promoters (P1 and P2) and alternative splicing. Thus, three transcript isoforms of AML1, designated AML1a, AML1b (both transcribed from promoter P2), and AML1c (transcribed from promoter P1) have been identified. It is conceivable that the AML1-ETO gene is also regulated by these two promoters. By amplification and sequencing of cDNAs derived from RNAs prepared from 8 primary AML specimens with t(8;21), we found that: (i) both AML1b-ETO (A1bE) and AML1c-ETO (A1cE) fusion transcript forms were detected; (ii) both AML1b and AML1c sequences were in-frame with ETO (Table 1); and (iii) out-of-frame A1bE and A1cE transcripts were also identified in these specimens at high frequencies. The out of frame fusion transcripts were likely due to alternative splicing and/or internal deletions in either the AML1 or ETO portions of the fusion transcripts, and encoded truncated or forms otherwise unrecognizable as AML1-ETO protein. While out-of-frame forms of AML1-ETO have been described, our results are the first to suggest that these may represent the major forms of fusion transcript in t(8;21) myeloblasts. In contrast, no such gene alterations were found in the native AML1 gene, suggesting that the heterogeneity of the AML1-ETO fusion transcripts is AML1-ETO fusion gene specific. Cotransfection of the AML1-ETO fusion transcript constructs with a CD36 promoter (a known AML1 targeted promoter) reporter gene construct, demonstrated AML1b repressor function of the fusion proteins. Further experiments are needed to determine the functional roles of these fusion proteins in relation to chemotherapy sensitivity in t(8;21) AMLs and the possible heterogeneity in treatment response of t(8;21) AML. Table 1. Summary of in-frame forms of A1bE and A1cE
Toward Predictable Repair of Regurgitant Aortic Valves
Authors: Gösta B. Pettersson, Adrian C. Crucean, Robert Savage, Carmel M. Halley, Richard A. Grimm, Lars G. Svensson, Sepehre Naficy, A. Marc Gillinov, Jingyuan Feng, Eugene H. Blackstone
Journal: Journal of the American College of Cardiology (2008)
Modulation of inflammation and angiogenesis and changes in ECM GAG-activity via dual delivery of nucleic acids
Authors: Shane Browne, Michael G. Monaghan, Eva Brauchle, Daniel Carvajal Berrio, Sandrine Chantepie, Dulce Papy-Garcia, Katja Schenke-Layland, Abhay Pandit
Journal: Biomaterials (2015)
A relationship between anatomical and physiological brain pathology in schizophrenia: lateral cerebral ventricular size predicts cortical blood flow
Authors: K F Berman, D R Weinberger, R C Shelton, R F Zec
Journal: American Journal of Psychiatry (1987)

The authors studied the relationship between lateral cerebral ventricular size and regional cerebral blood flow during mental activation in 30 patients with schizophrenia. Patients with large ventricles had diffusely lower cortical gray matter blood flow than patients with small ventricles. In addition, an inverse correlation between ventricular size and prefrontal blood flow was observed while patients were attempting to solve a neuropsychological test specifically related to the prefrontal cortex. These data suggest that structural brain pathology impairs prefrontal physiology in schizophrenia, implicating a neural mechanism for the intellectual deficits characteristic of this disorder.
Drug points: Lichenoid drug eruption with proton pump inhibitors
Authors: J L Bong
Journal: BMJ (2000)

We report a patient who developed a recurrent lichenoid eruption after treatment with omeprazole, lansoprazole, and pantoprazole.

An 81 year old man presented with a three month history of a widespread pruritic rash. He suffered from oesophagitis and had been taking omeprazole 20 mg/day for nine months. Examination …
Abstract 3487: Enoxaparin Reduces Recurrent MI and Death in Patients with STEMI Undergoing Fibrinolysis who Achieve Early ST Resolution: The ExTRACT-TIMI 25 ECG Study
Authors: Benjamin M Scirica, David A Morrow, Robert P Giugliano, Stephen D Wiviott, Marc S Sabatine, Amy Shui, Carolyn H McCabe, Elliott M Antman, Eugene Braunwald
Journal: Circulation (2006)

Background: Early and sustained reperfusion are major goals in the treatment of STEMI. ST segment resolution (STRes) is an early non-invasive marker of epicardial reperfusion. In the ExTRACT-TIMI 2...
Abstract 2244: A Novel Micropace-Ablate Protocol Eliminates Coagulum Formation in Radiofrequency Ablation
Authors: Bernard Lim, K.l. Venkatachalam, Susan Johnson, Arshad Jahangir, Samuel Asirvatham
Journal: Circulation (2007)

Radiofrequency (RF) ablation for cardiac arrythmias is an established curative therapy. However, catheter-tip coagulum formation leading to thromboembolic stroke is a persistent problem despite heparinization. Recent studies demonstrated an up to 70% incidence of thrombus formation on the catheter tip during ablation and a 10 % incidence of thromboembolic events. Catheter tip thrombus can impede the delivery of RF energy to the tissue, resulting in reduced efficacy and longer procedure times. Here we report on a novel method to prevent coagulum formation on ablation catheters by delivering a negative charge to the catheter tip to repel negatively charged fibrinogen molecules during RF ablation. A novel circuit was built with a charge delivery unit using a 9 voltage battery to deliver a fixed offset direct current charge, placed in parallel to the RF delivery unit for negative charge placement during RF delivery. In in-vivo canine experiments (n=50) standard 6/4, 8/5 ablation catheters and catheters with abraded tips were advanced from right femoral veins into atria and ventricles under intra-cardiac echo (ICE) and biplane fluoroscopic guidance. The dogs received 1 of 2 therapies: no RF energy delivered with and without negative charge delivery, RF energy delivery with and without negative charge delivery. The presence of thrombus was identified with ICE. The catheter tips were examined also macroscopically with visual inspection and also with field emission scanning electron microscopy (FESEM). FESEM of the catheter tips showed surface coverage of fibrin clot of the catheter tip to be 90 % for non-charged catheters compared to 0 % (p&lt; 0.01) in negatively-charged catheters. There was no significant difference in surface coverage of fibrin clot between negatively-charged catheters with the abraded tips (98.8%) and non-charged catheters with smooth tips (90.7 %, p=ns). Clot volume formed on the catheter tip decreased with increased amount of charge. Application of a negative charge did not affect the quality of the intracardiac electrograms or induce malignant ventricular arrhythmias. Negative charge delivery during RF ablation is feasible and safe and can eliminate coagulum formation, potentially reducing thromboembolic complications.
Serum anti-Müllerian hormone concentration in women with polycystic ovary syndrome and type 1 diabetes mellitus
Authors: Agnieszka Łebkowska, Agnieszka Adamska, Monika Karczewska-Kupczewska, Agnieszka Nikołajuk, Elżbieta Otziomek, Robert Milewski, Maria Górska, Sławomir Wołczyński, Irina Kowalska
Journal: Metabolism (2016)
US Congress considers medical privacy bill
Authors: James Ciment
Journal: BMJ (1999)

The US Congress is considering passing the nation's first comprehensive medical privacy bill. The multipart legislation–termed the Medical Information Privacy and Security Act (MIPSA)—would require a patient's consent before the transfer of medical records. Congress has set a deadline of August 1999 for debate about the bill.

A statement issued by the bill's sponsor, Democratic senator Patrick Leahy of Vermont, said MIPSA would create “a set of rules and norms to govern the disclosure of personal health …
Modulated release of cyclosporine from soluble vinyl pyrrolidone–hydroxyethyl methacrylate copolymer hydrogels
Authors: Alberto Gallardo, Fernando Fernández, Alejandro Cifuentes, José-Carlos Dı́ez-Masa, Paloma Bermejo, Mercedes Rebuelta, Antonio López-Bravo, Julio San Román
Journal: Journal of Controlled Release (2001)
Effect of Intensive Statin Therapy on Regression of Coronary Atherosclerosis in Patients With Acute Coronary Syndrome
Authors: Takafumi Hiro, Takeshi Kimura, Takeshi Morimoto, Katsumi Miyauchi, Yoshihisa Nakagawa, Masakazu Yamagishi, Yukio Ozaki, Kazuo Kimura, Satoshi Saito, Tetsu Yamaguchi, Hiroyuki Daida, Masunori Matsuzaki
Journal: Journal of the American College of Cardiology (2009)
Abstract 13165: The Evolving Economic Burden of Heart Failure In Alberta
Authors: Padma Kaul, Finlay A McAlister, Justin A Ezekowitz, Jeffrey A Bakal, Hude Quan, Konrad Fassbender, Merrill L Knudtson, Paul W Armstrong
Journal: Circulation (2010)

Background: Heart failure (HF) is a debilitating and chronic condition associated with significant morbidity and mortality. A comprehensive assessment of the economic burden of HF on the Canadian h...
HIV and infertility: time to treat
Authors: C. Gilling-Smith
Journal: BMJ (2001)

No established guidelines exist for defining access to fertility care for individuals infected with HIV. Although many in vitro fertilisation units in the United Kingdom screen patients for HIV, only a handful are prepared to treat couples if one or other partner tests positive. A premise of offering assisted conception treatment is a consideration for the welfare of any child born or affected as a result of treatment. In the case of HIV the primary concern is over the life expectancy of the infected parent and the risk of viral transmission to either the uninfected partner or offspring. 1 2 The ethical dilemmas these issues raise have, until now, provided sufficient grounds for most units offering assisted conception to close their doors to patients infected with HIV who ask for help or who test positive in their preliminary investigation.3

Combination antiretroviral therapy has produced radical improvements in life expectancy and quality of life for both children and adults infected with HIV in developed countries. Current estimates suggest that …
Abstract 198: Endothelin-1 and Phenylephrine Activate Global Protein Kinase D Similarly in Adult Cardiac Myocytes, but Differ Greatly in Nuclear versus Sarcolemmal Targeting
Authors: Julie Bossuyt, Jody L Martin, Karl Hench, Maya T Kunkel, Alexandra C Newton, Seth L Robia, Donald M Bers
Journal: Circulation (2007)

Endothelin-1(ET-1) and phenylephrine (PE) both activate hypertrophic signaling in cardiac myocytes via nuclear export of class II histone deacetylase (HDAC), and protein kinase D (PKD) is critical in mediating this for HDAC5. However, we now find that in adult ventricular myocytes PE-induced HDAC5 nuclear export is more critically PKD-dependent than for ET-1. Here, we use novel FRET-based PKD activity reporter (DKAR) and GFP-tagged PKD (both in adenoviral vectors) expressed in adult rabbit cardiac myocytes, along with confocal and TIRF microcsopy to localize ET-1 vs . PE-induced PKD activation and translocation. On-line PKD activity (sensed by DKAR FRET) was similarly activated by 100 nM ET-1, 10 μM PE or 300 nM PDBu (4.6 ± 0.4, 5.9 ± 0.7 or 5.6 ± 0.6 units) in adult myocytes overexpressing PKD. PKD-GFP expressed in myocytes is relatively uniform and cytosolic at rest (slightly higher at Z-lines), and largely non-nuclear (F nuc /F cyto 0.5 ± 0.03). ET-1 caused rapid sustained PKD recruitment to the plasma membrane (46 ± 3% increase) and also at Z-lines, but only slow and modest PKD nuclear import (12 ± 8% rise in F nuc /F cyto ). In contrast, PE more modestly increased membrane and Z-line recruitment (12 ± 0.9%), but caused more dramatic nuclear translocation (47 ± 4% rise in F nuc /F cyto ). PDBu caused both membrane (120 ± 15% increase) and nuclear localization of PKD (44 ± 4% increase in F nuc /F cyto ). Interestingly, SR Ca depletion by thapsigargin caused an ET-1-like effect, whereas strophantidin did not elicit PKD mobilization. We conclude that ET-1 and PE differ in adult myocyte PKD activation, not in extent, but in cellular localization or translocation. These results are consistent with a more prominent nuclear action of PKD in response to PE vs. ET-1, and with the more critical role of PKD in PE-induced HDAC5 nuclear export.