tbuckley/cabot-search huggingface dataset:
Continuous non-invasive blood pressure monitoring: reliability of Finapres device during the Valsalva manoeuvre
Authors: B. P M IMHOLZ, G. A V. MONTFRANS, J. J SETTELS, G. M A V. D. HOEVEN, J. M KAREMAKER, W. WIELING
Journal: Cardiovascular Research (1988)

Because of the inherent risks of intra-arterial blood pressure monitoring a new non-invasive device, Finapres, which measures blood pressure continuously in the finger, was evaluated in 14 hypertensive and one normotensive subject. Brachial intra-arterial and finger pressures were compared during a control period and a subsequent Valsalva manoeuvre. Visually, blood pressures measured by Finapres faithfully reproduced the intra-arterial recordings in all subjects. From each pressure signal beat to beat systolic, diastolic, and mean blood pressure values and their differences were obtained and the time course of the response and its characteristic features were analysed. During the control period the Finapres measurements were lower than intra-arterial systolic, mean, and diastolic pressures (mean(SD) 1(9.6), 9(6.8), and 4(6.1) mmHg respectively). During the response to the Valsalva manoeuvre the brachial-finger pressure differences showed limited deviation from those during the control period; median differences were at most 6 mmHg occurring late during the intrathoracic strain period and 7 mmHg during the post-release blood pressure overshoot. In general, the Finapres device reproduced intra-arterial patterns faithfully. This device appears to offer a reliable alternative to intra-arterial blood pressure monitoring.
Lower Purkinje cell counts in the cerebella of four autistic subjects: initial findings of the UCLA-NSAC Autopsy Research Report
Authors: E R Ritvo, B J Freeman, A B Scheibel, T Duong, H Robinson, D Guthrie, A Ritvo
Journal: American Journal of Psychiatry (1986)

As part of an autopsy research project, the brains of four autistic subjects were examined and compared with those of three comparison subjects without CNS pathology and one with phenytoin toxicity. The cerebellum was selected for initial investigation because pathognomonic symptoms and neurophysiological measures suggest that pathology may exist in the cerebellar-vestibular axis in certain patients. Total Purkinje cell counts were significantly lower in the cerebellar hemisphere and vermis of each autistic subject than in the comparison subjects.
Graded Effects of Proteinuria on HDL Structure in Nephrotic Rats
Authors: Gregory C. Shearer, John W. Newman, Bruce D. Hammock, George A. Kaysen
Journal: Journal of the American Society of Nephrology (2005)

Nephrotic syndrome is characterized by increased triglycerides resulting from decreased clearance of VLDL and chylomicrons. These triglyceride-rich lipoproteins are structurally altered by interaction with HDL derived from animals with proteinuria and not as a consequence of hypoalbuminemia. HDL isolated from rats with massive proteinuria is depleted in apolipoprotein E (apoE). It is unknown at what threshold of urinary albumin loss HDL structure is altered, and it is unknown what effects proteinuria has on apolipoproteins other than apoE. Two models of albuminuria were used in Sprague-Dawley rats: Adriamycin and passive Heymann nephritis (HN). The adriamycin group was divided into minimal albumin excretion (MAE) and intermediate albumin excretion (MAE, 1 to 40; intermediate albumin excretion, 60 to 210 mg/d per 100 g body wt). Urinary albumin excretion exceeded 300 mg/d per 100 g body wt in the HN rats. HDL apolipoprotein composition was analyzed with SDS-PAGE densitometry and liquid chromatography-time of flight mass spectrometer mass spectrometry. HDL apoA-IV content relative to apoA-I was reduced at all levels of albuminuria (P < 0.0001). ApoE was not reduced in MAE but was significantly reduced in IAE (72%; P < 0.001). By contrast, apoA-II and apoC-III were each significantly increased with increasing UAE. ApoA-IV and apoE were decreased to approximately 10% of control in HDL isolated from rats with HN, whereas apoA-II, apoC-II, and apoC-III were each significantly increased relative to apoA-I. HDL is structurally altered by levels of albuminuria that are insufficient to change serum albumin levels and is progressively altered as albuminuria increases.
Chemical Coding of Neurons and Plurichemical Transmission
Authors: J B Furness, J L Morris, I L Gibbins, M Costa
Journal: The Annual Review of Pharmacology and Toxicology (1989)

Due to the massive data sets available for drug candidates, modern drug discovery has advanced to the big data era. Central to this shift is the development of artificial intelligence approaches to implementing innovative modeling based on the dynamic, ...Read More
Phase II Trial of Cetuximab With or Without Paclitaxel in Patients With Advanced Urothelial Tract Carcinoma
Authors: Yu-Ning Wong, Samuel Litwin, David Vaughn, Seth Cohen, Elizabeth R. Plimack, James Lee, Wei Song, Michael Dabrow, Marion Brody, Holly Tuttle, Gary Hudes
Journal: Journal of Clinical Oncology (2012)

The benefit of salvage chemotherapy is modest in metastatic urothelial cancer. We conducted a randomized, noncomparative phase II study to measure the efficacy of cetuximab with or without paclitaxel in patients with previously treated urothelial cancer.Patients with metastatic urothelial cancer who received one line of chemotherapy in the perioperative or metastatic setting were randomly assigned to 4-week cycles of cetuximab 250 mg/m(2) with or without paclitaxel 80 mg/m(2) per week. We used early progression as an indicator of futility. Either arm would close if seven of the initial 15 patients in that arm progressed at the first disease evaluation at 8 weeks.We enrolled 39 evaluable patients. The single-agent cetuximab arm closed after nine of the first 11 patients progressed by 8 weeks. The combination arm completed the full accrual of 28 patients, of whom 22 patients (78.5%) had visceral disease. Twelve of 28 patients had progression-free survival greater than 16 weeks. The overall response rate was 25% (95% CI, 11% to 45%; three complete responses and four partial responses). The median progression-free survival was 16.4 weeks (95% CI, 12 to 25.1 weeks), and the median overall survival was 42 weeks (95% CI, 30.4 to 78 weeks). Treatment-related grade 3 and 4 adverse events that occurred in at least two patients were rash (six cases), fatigue (five cases), and low magnesium (three cases).Although it had limited activity as a single agent, cetuximab appears to augment the antitumor activity of paclitaxel in previously treated urothelial cancers. The cetuximab and paclitaxel combination merits additional study to establish its role in the treatment of urothelial cancers.
A Prospective Study of Spontaneous Fetal Losses after Induced Abortions
Authors: Susan Harlap, Patricia H. Shiono, Savitri Ramcharan, Heinz Berendes, Frederick Pellegrin
Journal: New England Journal of Medicine (1979)

The incidence of spontaneous abortions was observed among 31,917 women followed from their first prenatal visit. Life-table analysis showed that losses in the first trimester were not significantly affected by previous induced abortions, nor was any change in the risk of second-trimester losses detected among the 1493 parous women who reported having had induced abortions after childbirth. There was, however, an increase in the incidence of midtrimester losses among the 2019 nulliparous women with previous induced abortions; the age-adjusted rate of loss was 59.9 per 100,000 women at risk per day, as compared with 24.2 among the 12,042 control nulliparous women (P less than 0.001). The relative risk increased with the number of previous induced abortions and was not explained by the distribution of demographic and social variables. The risk decreased from 3.27 (95 per cent confidence limits, 1.72 to 6.23) after abortions induced before 1973, mainly by dilation and curettage, to 1.42 (0.76 to 2.65) after those done since 1973, when the more gentle technic of cervical dilation by use of laminaria was introduced. These findings indicate that there is little or no risk of spontaneous abortions after induced abortions when performed by current technics.
Intraoperative endocardial mapping during sinus rhythm: relationship to site of origin of ventricular tachycardia.
Authors: M G Kienzle, J Miller, R A Falcone, A Harken, M E Josephson
Journal: Circulation (1984)

Mapping-guided endocardial resection has proved to be an effective therapy for recurrent sustained ventricular tachycardia. However, some patients cannot be mapped during ventricular tachycardia, so that guidance from findings during normal sinus rhythm would be highly desirable. We examined the frequency, timing, and duration of several abnormal types of electrograms recorded endocardially during sinus rhythm and related these findings to activation mapping during sustained ventricular tachycardia. Thirteen patients with extensive myocardial infarction complicated by recurrent sustained ventricular tachycardia were studied intraoperatively during sinus rhythm and induced ventricular tachycardia with a standardized mapping scheme involving the entire endocardial surface. Fractionated electrograms (multicomponent with amplitude less than 1 mV and duration greater than 50 msec) were recorded in all patients. This type of electrogram could be recorded at up to 36% of mapped sites. Split electrograms (two components separated by isoelectric period) were also frequently seen but involved only a mean of 5.8% of mapped sites. Late electrograms (inscribed entirely after the QRS complex) were only recorded in four of 13 patients at a mean of 5% of mapped sites. The location of these electrograms was related to an arbitrary 8 cm2 zone around the earliest site of endocardial activation recorded during ventricular tachycardia. The longest fractionated electrogram was closely related to nine of 22 morphologies of induced ventricular tachycardia, split electrograms were related to seven of 16 morphologies, and late electrograms to two of four morphologies. We have concluded that extremely abnormal electrograms recorded endocardially during sinus rhythm are widespread in patients with extensive myocardial infarction complicated by ventricular tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS)
Aerobic interval training attenuates remodelling and mitochondrial dysfunction in the post-infarction failing rat heart
Authors: Jasenka Kraljevic, Jasna Marinovic, Danijel Pravdic, Petra Zubin, Zeljko Dujic, Ulrik Wisloff, Marko Ljubkovic
Journal: Cardiovascular Research (2013)

Following a large myocardial infarction (MI), remaining viable muscle often undergoes pathological remodelling and progresses towards chronic heart failure. Mitochondria may also be affected by this process and, due to their functional importance, likely contribute to the progression of the disease. Aerobic interval training (AIT) has been shown effective in diminishing pathological myocardial transformation, but the effects of AIT on mitochondrial function in hearts undergoing remodelling are not known. Adult female Sprague–Dawley rats were randomized to either 8 weeks of aerobic interval treadmill running (5 days/week), which started 4 weeks after left coronary artery ligation (MI-Trained), or a sedentary group (MI-Sedentary). Echocardiography was performed before and after the 8-week period, at which point the left ventricles (LVs) were also harvested. Twelve weeks after surgery, MI-Sedentary rats had significantly lower LV fractional shortening compared with MI-Trained rats. Complex I-dependent respiration assessed in isolated LV mitochondria was decreased by ∼37% in MI-Sedentary and 17% in MI-Trained animals (group differences P < 0.05), compared with sham-operated animals. This was paralleled with diminished ATP production and increased degree of protein oxidation in MI-Sedentary rats. The enzymatic activity of complex I was also decreased to a greater extent in MI-Sedentary than in MI-Trained animals, with no evidence of its reduced expression. When complex II substrate was used, no differences among the three groups were observed. Exercise reduces LV contractile deterioration in post-infarction heart failure and alleviates the extent of mitochondrial dysfunction, which is paralleled with preserved complex I activity.
Motilin induces gall bladder emptying and antral contractions in the fasted state in humans
Authors: Y C Luiking, T L Peeters, M F J Stolk, V B Nieuwenhuijs, P Portincasa, I Depoortere, G P van Berge Henegouwen, L M A Akkermans
Journal: Gut (1998)

Background —Animal studies have shown that motilin affects gall bladder motility. In humans, no effect has been shown, but erythromycin, a motilin receptor agonist, induces gall bladder emptying. Aims —To explore the effect of increasing doses of exogenous motilin on gall bladder volume and antral contractility in the fasted state in humans. Methods —After an overnight fast, eight healthy men received increasing intravenous doses of Leu 13 -motilin (KW-5139) or 0.9% NaCl in a double blind, randomised fashion. Gall bladder volume and antral contraction frequency were determined by ultrasonography. Results —Infusion of motilin increased plasma motilin levels. Motilin induced a reduction in gall bladder volume of 8.0 (5.0)%, 17.1 (5.0)%, 18.5 (4.7)%, and 16.1 (4.9)% of baseline volume at the end of infusion of 2, 4, ,8 and 16 pmol/kg/min respectively, compared with mean stable gall bladder volumes during placebo infusion (p&lt;0.05). Antral contraction frequency increased during motilin infusion, but not during placebo infusion (p&lt;0.05). Conclusions —Exogenous motilin reducted fasting gall bladder volume and increased antral contractions. After reaching maximal reduction, the gall bladder volume did not decrease further during continuous motilin infusion at higher doses and stayed at the same reduced volume. The degree of gall bladder volume reduction during motilin infusion mimicked gall bladder emptying preceding antral phase III activity of the migrating motor complex in humans. This study indicates that motilin may play a physiological role in the regulation of gall bladder emptying in the fasted state.
Staged coil treatment in patients with very severe emphysema
Authors: Harald Trautmann, Frauke Paulus, Hans Jörg Baumann, Ulrich Sander
Journal: European Respiratory Journal (2014)

Rationale:  Bronchoscopic treatment of severe emphysema with PneumRx Coils has been shown to improve exercise capacity, pulmonary function, and quality of life in bilaterally-treated patients and is used in routine clinical practice in a number of centers in Germany.   Aim : To evaluate whether a staged approach to coil treatment can benefit extremely severe patients.   Methods:  We selected patients in an extremely severe condition (mean FEV1 0.69L, mean FVC 1.4L, mean RV 305% pred., median 6MWT 100m) and treated the most severely damaged lobe as evidenced by visual CT analysis. Follow-up tests were conducted approximately 3 months following unilateral treatment. Ten LVRC were placed in one lobe. Patients were generally offered the second-side treatment 6 months following the first treatment.   Results:  28 patients have been treated unilaterally, with 6-month follow-up on 10 patients (FEV1+4.76% pred., RV -67.1% pred. and -2.3 points Borg dyspnoea scale.) 6MWT improved by 108m on average; however 4 out of 10 patients showed 0m improvement in their walking-range (distance until stopping by dyspnoea) following unilateral treatment. 11 patients have completed the bilateral treatment, with 6 patients reporting 6-month post-baseline results (FEV1 +4.33% pred., RV -13.2% pred., and -3.7 points Borg dyspnoea scale.) One patient had pneumonia during the follow-up visit. For the other 5 patients walking-range was +380m (mean) and +387m (median). These improvements are highly significant for such a severe group and patients continue to report high satisfaction with the procedure and results. We believe the staged coil treatment approach may be appropriate for extremely severe patients, who may not endure more aggressive treatment methods.
Measurement of Carotid Plaque Burden
Authors: J. David Spence
Journal: JAMA Neurology (2015)

Purpose of review  To describe the uses of measurement of carotid plaque burden, as total plaque area (TPA), total plaque volume (TPV), and vessel wall volume (VWV), which includes plaque burden and wall volume.  Recent findings  Measurement of plaque burden is useful for risk stratification, research into the genetics and biology of atherosclerosis, for measuring effects of new therapies for atherosclerosis, and for treatment of high-risk patients with severe atherosclerosis.  Summary  Measurement of plaque burden is far superior to measurement of carotid intima-media thickness (IMT) in many ways, and should replace it. Vessel wall volume can be measured in persons with no plaque as an alternative to IMT.
Outcomes in Localized Prostate Cancer: National Prostate Cancer Register of Sweden Follow-up Study
Authors: P. Stattin, E. Holmberg, J.-E. Johansson, L. Holmberg, J. Adolfsson, J. Hugosson
Journal: JNCI Journal of the National Cancer Institute (2010)

ConclusionA 10-year prostate cancer-specific mortality of 2.4% among patients with low-risk prostate cancer in the surveillance group indicates that surveillance may be a suitable treatment option for many patients with low-risk disease.
Reevaluation of the cox1 Group I Intron in Araceae and Angiosperms Indicates a History Dominated by Loss rather than Horizontal Transfer
Authors: N. Cusimano, L.-B. Zhang, S. S. Renner
Journal: Molecular Biology and Evolution (2007)

The origin and modes of transmission of introns remain matters of much debate. Previous studies of the group I intron in the angiosperm cox1 gene inferred frequent angiosperm-to-angiosperm horizontal transmission of the intron from apparent incongruence between intron phylogenies and angiosperm phylogenies, patchy distribution of the intron among angiosperms, and differences between cox1 exonic coconversion tracts (the first 22 nt downstream of where the intron inserted). We analyzed the cox1 gene in 179 angiosperms, 110 of them containing the intron (intron(+)) and 69 lacking it (intron(-)). Our taxon sampling in Araceae is especially dense to test hypotheses about vertical and horizontal intron transmission put forward by Cho and Palmer (1999. Multiple acquisitions via horizontal transfer of a group I intron in the mitochondrial coxl gene during evolution of the Araceae family. Mol Biol Evol. 16:1155-1165). Maximum likelihood trees of Araceae cox1 introns, and also of all angiosperm cox1 introns, are largely congruent with known phylogenetic relationships in these taxa. The exceptions can be explained by low signal in the intron and long-branch attraction among a few taxa with high mitochondrial substitution rates. Analysis of the 179 coconversion tracts reveals 20 types of tracts (11 of them only found in single species, all involving silent substitutions). The distribution of these tracts on the angiosperm phylogeny shows a common ancestral type, characterizing most intron(+) and some intron(-) angiosperms, and several derivative tract types arising from gradual back mutation of the coconverted nucleotides. Molecular clock dating of small intron(+) and intron(-) sister clades suggests that coconversion tracts have persisted for 70 Myr in Araceae, whose cox1 sequences evolve comparatively slowly. Sequence similarity among the 110 introns ranges from 91% to identical, whereas putative homologs from fungi are highly different, but sampling in fungi is still sparse. Together, these results suggest that the cox1 intron entered angiosperms once, has largely or entirely been transmitted vertically, and has been lost numerous times, with coconversion tract footprints providing unreliable signal of former intron presence.
Ischemia-induced neurogenesis of neocortical layer 1 progenitor cells
Authors: Koji Ohira, Takahiro Furuta, Hiroyuki Hioki, Kouichi C Nakamura, Eriko Kuramoto, Yasuyo Tanaka, Nobuo Funatsu, Keiko Shimizu, Takao Oishi, Motoharu Hayashi, Tsuyoshi Miyakawa, Takeshi Kaneko, Shun Nakamura
Journal: Nature Neuroscience (2009)
Role of marrow-derived monocytes and mesangial cells in removal of immune complexes from renal glomeruli.
Authors: G E Striker, M Mannik, M Y Tung
Journal: The Journal of Experimental Medicine (1979)

Phagocytosis of intravenously administered immune complexes by cells in the mesangium was investigated. The model used was that of exchange marrow transplantation between Chediak-Higashi (CH) mice and syngeneic partners after X-irradiation. This model was chosen since marrow-derived macrophages could be differentiated from resident mesangial cells by the presence of the characteristic giant lysosomes in phagocytic cells of the CH mice. Injected immune complexes were cleared normally and localized in the glomerular mesangium in CH or C57BL/6J mice receiving either C57BL/6J or CH marrow. C57BL/6J mice with CH marrow injected with immune complexes prepared with reduced and alkylated antibodies accumulated many cells within the mesangium that contained both giant lysosomes and electron dense deposits. Deposits were not found in cells with subplasmalemmal microfilaments and perpheral dense bodies. Conversely, the cells in the mesangium of CH mice with C57BL/6J marrow that contained electron dense deposits were devoid of giant lysosomes. Based on these observations, we concluded that (a) marrow-derived monocytes contribute to mesangial hypercellularity after deposition of immune complexes and (b) phagocytosis of immune complexes localized in the glomerular mesangium was by marrow-derived monocytes rather than by mesangial cells.
Impact of Human Neutralizing Antibodies on Antitumor Efficacy of an Oncolytic Adenovirus in a Murine Model
Authors: Van Tsai, Duane E. Johnson, Amena Rahman, Shu Fen Wen, Drake LaFace, Jennifer Philopena, Jonathan Nery, Monica Zepeda, Daniel C. Maneval, G. William Demers, Robert Ralston
Journal: Clinical Cancer Research (2004)

The purpose of this study was to assess the impact of anti-adenovirus neutralizing antibodies (AdNAbs) on the distribution, tolerability, and efficacy of intravenously administered oncolytic adenovirus. A translational model was developed to evaluate the impact of humoral immunity on intravenous administration of oncolytic adenovirus in humans.Initially, severe combined immunodeficient (SCID)/beige mice were passively immunized with various amounts of human sera to establish a condition of preexisting humoral immunity similar to humans. A replication-deficient adenovirus encoding beta-galactosidase (rAd-betagal) was injected intravenously into these mice. An AdNAb titer that mitigated galactosidase transgene expression was determined. A xenograft tumor-bearing nude mouse model was developed to assess how a similar in vivo titer would impact the activity of 01/PEME, an oncolytic adenovirus, after intravenous administration.In SCID/beige mice, there was a dose dependence between AdNAbs and galactosidase transgene expression; 90% of transgene expression was inhibited when the titer was 80. A similar titer reconstituted in the nude mice with human serum, as was done in the SCID/beige mice, did not abrogate the antitumor efficacy of the replicating adenovirus after intravenous administration. Viral DNA increased in tumors over time.In intravenous administration, preexisting AdNAb titer of 80 significantly attenuated the activity of a 2.5 x 10(12) particles per kilogram dose of nonreplicating adenovirus; the same titer had no affect on the activity of an equivalent dose of replicating adenovirus. Our results suggest that a majority of patients with preexisting adenovirus immunity would be candidates for intravenous administration of oncolytic adenovirus.