tbuckley/cabot-search huggingface dataset:
Differential effects of isoproterenol on sustained ventricular tachycardia before and during procainamide and quinidine antiarrhythmic drug therapy.
Authors: M L Markel, W M Miles, J C Luck, L S Klein, E N Prystowsky
Journal: Circulation (1993)

Autonomic modulation, especially increased sympathetic activity may play a role in the genesis of ventricular arrhythmias. The purpose of this study was to determine whether beta-sympathetic stimulation with isoproterenol would alter sustained ventricular tachycardia (VT) circuits similarly during the drug-free and antiarrhythmic drug-treated states.Twenty-five patients with repeatedly inducible, hemodynamically stable, sustained VT were evaluated by programmed ventricular stimulation. In the antiarrhythmic drug-free state, isoproterenol (0.03 microgram/kg per minute) shortened the following intervals (in milliseconds; mean +/- SEM; 25 patients; paired t test): sinus cycle length (792 +/- 37 to 568 +/- 18; (p < 0.001), ventricular paced QT interval (386 +/- 8 to 348 +/- 6; p < 0.001), ventricular paced QRS duration (185 +/- 4 to 182 +/- 4; p = 0.014), ventricular effective (238 +/- 5 to 208 +/- 4; p < 0.001) and functional (261 +/- 6 to 227 +/- 5; p < 0.001) refractory periods, and the VT cycle length (VTCL) (311 +/- 9 to 291 +/- 9; p < 0.001). Isoproterenol (0.03 microgram/kg per minute) was administered during 31 antiarrhythmic drug trials (procainamide, n = 18; quinidine, n = 13) in 22 patients. Isoproterenol shortened the sinus cycle length, QT interval during ventricular pacing, and ventricular effective and functional refractory periods before and during procainamide and quinidine therapy (ANOVA; isoproterenol effect, p < or = 0.0002 for all). The amount of decrease in these intervals with isoproterenol was the same before and during procainamide and quinidine therapy (ANOVA interaction, p = NS for all). The QRS duration during ventricular pacing and VTCL were also shortened by isoproterenol before and during procainamide (baseline, n = 17; QRS, 182 +/- 4 to 178 +/- 4 msec; VTCL, n = 18, 314 +/- 11 to 291 +/- 11 msec; during procainamide, QRS, 218 +/- 7 to 197 +/- 6 msec; VTCL, 422 +/- 15 to 359 +/- 11 msec) and quinidine (baseline, n = 13; QRS, 190 +/- 6 to 185 +/- 5 msec; VTCL, n = 12, 298 +/- 10 to 280 +/- 9 msec; during quinidine, QRS, 223 +/- 9 to 208 +/- 8 msec; VTCL, 415 +/- 14 to 355 +/- 10 msec) (isoproterenol effect p < or = 0.0003 for all). However, the amount of decrease in QRS duration and VTCL with isoproterenol was greater during procainamide and quinidine than in the drug-free state (ANOVA interaction, p < or = 0.02 for all). These changes continued to be significant when normalized for the initial QRS duration and VTCL (p < or = 0.03 for all).Isoproterenol affects presumed reentrant sustained VT circuits less in the absence of antiarrhythmic drugs but markedly attenuates the antiarrhythmic drug-induced slowing of sustained VT. To the extent that the change in QRS duration reflects a change in conduction within the VT circuit, these data imply that the attenuation of drug-induced slowing of VT by isoproterenol is due to a greater change in conduction rather than refractoriness.
Cyclin D1 is up-regulated in hepatocytes in vivo following cell-cycle block induced by retrorsine
Authors: Sabrina Pitzalis, Silvia Doratiotto, Marianna Greco, Stefania Montisci, Daniela Pasciu, Giovanna Porcu, Paolo Pani, Sergio Laconi, Ezio Laconi
Journal: Journal of Hepatology (2005)
The Role of &lt;EMPH TYPE="ITAL"&gt;APOE&lt;/EMPH&gt; ∊4 in Modulating Effects of Other Risk Factors for Cognitive Decline in Elderly Persons
Authors: Mary N. Haan
Journal: JAMA (1999)

Cognitive decline in elderly persons is often an early predictor of dementia. Subclinical cardiovascular disease (CVD) and diabetes mellitus may contribute to substantial decline in cognitive function in the elderly. These risks may be modified by gene-environment interactions between apolipoprotein E (APOE) genotype and CVD risk factors or subclinical CVD.To examine the association between subclinical CVD and decline in cognitive functioning in the elderly and to examine effect modification by the APOE genotype of the association between subclinical disease and cognitive decline.The Cardiovascular Health Study, a population-based, prospective cohort study.A total of 5888 randomly selected Medicare-eligible participants from Sacramento County, California; Forsyth County, North Carolina; Washington County, Maryland; and Pittsburgh, Pa, aged 65 years or older, who were recruited in 1989-1990 (n = 5201) and in 1992-1993 (n = 687) and who were followed up for 7 and 5 years, respectively.Change over time in scores on the Modified Mini-Mental State Examination and the Digit Symbol Substitution Test as a function of APOE genotype, subclinical CVD, and diabetes mellitus.Seventy percent of participants had no significant decline on the Modified Mini-Mental State Examination. Systolic blood pressure, the ankle-arm brachial index, atherosclerosis of the internal carotid artery, diabetes mellitus, and several diagnoses of prevalent CVD were significantly associated with declines in scores on the Modified Mini-Mental State Examination and the Digit Symbol Substitution Test. The rate of cognitive decline associated with peripheral vascular disease, atherosclerosis of the common and internal carotid arteries, or diabetes mellitus was increased by the presence of any APOE epsilon4 allele.Most healthy elderly people did not experience cognitive decline. Measures of subclinical CVD were modest predictors of cognitive decline. Those with any APOE epsilon4 allele in combination with atherosclerosis, peripheral vascular disease, or diabetes mellitus were at substantially higher risk of cognitive decline than those without the APOE epsilon4 allele or subclinical CVD. High levels of atherosclerosis increased cognitive decline independently of APOE genotype.
Double-wave reentry as a mechanism of acceleration of ventricular tachycardia.
Authors: J Brugada, L Boersma, C Kirchhof, P Brugada, M Havenith, H J Wellens, M Allessie
Journal: Circulation (1990)

By using a Langendorff-perfused ring of anisotropic rabbit epicardium, sustained reentrant ventricular tachycardia with a cycle length of 168 +/- 13 msec (n = 26) was induced by programmed electrical stimulation. Continuous left ventricular epicardial mapping with 256 simultaneously recorded unipolar electrograms demonstrated that the tachycardia was based on circuital movement of the impulse around a fixed obstacle. Because of the anisotropic properties of the myocardium, the circuit consisted of a ring with segments in which the circulating wave propagated slowly (20 +/- 2 cm/sec) or faster (62 +/- 4 cm/sec). This was related to transverse or longitudinal propagation in relation to fiber direction. In six of 26 experiments, sudden acceleration in rate of the tachycardia was observed during programmed electrical stimulation. This acceleration was caused by the occurrence of double-wave reentry (two successive waves traveling in the same direction and using the same circuit). In one of the experiments, induction of double-wave reentry was only possible at basal conditions but not after the administration of a class III antiarrhythmic drug. In a seventh experiment, induction of double-wave reentry became possible after the administration of a class IC antiarrhythmic drug. Because conduction velocity around the ring was depressed during acceleration, the total revolution time of the circuit during double-wave reentry was about 120% of that during single-wave reentry. Ventricular tachycardias in which double-wave reentry could be elicited had longer cycle lengths (197 +/- 11 vs. 156 +/- 8 msec, p less than 0.001) and larger excitable gaps (71 +/- 16 vs. 28 +/- 5 msec, p less than 0.001) than those not showing this phenomenon. Double-wave reentry might have important clinical implications in understanding ventricular tachycardia acceleration during programmed electrical stimulation, proarrhythmic effects of drugs, and pathophysiology of rapid ventricular tachycardias.
Respiratory and Auditory Cortical Processing in Children with Obstructive Sleep Apnea Syndrome
Authors: Jingtao Huang, Carole L. Marcus, Paul W. Davenport, Ian M. Colrain, Paul R. Gallagher, Ignacio E. Tapia
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Rationale: Children with obstructive sleep apnea syndrome (OSAS) have impaired cortical processing of respiratory afferent stimuli, manifested by blunted sleep respiratory-related evoked potentials (RREP). However, whether this impairment is limited to respiratory stimuli, or reversible after successful treatment, is unknown. We hypothesized that, during sleep, children with OSAS have (1) abnormal RREP, (2) normal cortical processing of nonrespiratory stimuli, and (3) persistence of abnormal RREP after treatment.Objectives: To measure sleep RREP and auditory evoked potentials in normal control subjects and children with OSAS before and after treatment.Methods: Twenty-four children with OSAS and 24 control subjects were tested during N3 sleep. Thirteen children with OSAS repeated testing 4–6 months after adenotonsillectomy.Measurements and Main Results: RREP were blunted in OSAS compared with control subjects (N350 at Cz −27 ± 15.5 vs. −47.4 ± 28.5 μV; P = 0.019), and did not improve after OSAS treatment (N350 at Cz pretreatment −25.1 ± 7.4 vs. −29.8 ± 8.1 post-treatment). Auditory evoked potentials were similar in OSAS and control subjects at baseline (N350 at Cz −58 ± 33.1 vs. −66 ± 31.1 μV), and did not change after treatment (N350 at Cz −67.5 ± 36.8 vs. −65.5 ± 20.3).Conclusions: Children with OSAS have persistent primary or irreversible respiratory afferent cortical processing deficits during sleep that could put them at risk of OSAS recurrence. OSAS does not seem to affect the cortical processing of nonrespiratory (auditory) afferent stimuli during sleep.
Disappearance half-time of endogenous and exogenous secretin in dogs.
Authors: P J Curtis, H R Fender, P L Rayford, J C Thompson
Journal: Gut (1976)

We have used a sensitive and specific radioimmunoassay to measurespectively. the disappearance half-times of exogenous porcine secretin and endogenous canine secretin in the dog and found them to be 2-45 and 2-85 minutes, respectively.
RADIUM (MESOTHORIUM) NECROSIS
Authors: FREDERICK L. HOFFMAN
Journal: JAMA (1925)

An investigation into the subject of radium necrosis was suggested to me by a number of unusual cases of necrosis among young women living in the Oranges and Newark, N. J., all of whom had at one time or another been employed at a radium plant engaged in the manufacture of luminous watch dials. The facts of the situation were first brought to my attention by the executive secretary of the New Jersey Consumers' League with the request that I investigate the circumstances and contribute the results of my research toward a possible solution of a serious industrial disease problem. What follows represents rather the results of a fact finding process than of a technical investigation into matters of detail for which I would not be qualified. Interviews were had as nearly as possible with all the interested parties as well as with attending physicians, dentists or others in position
300. Gene Therapy for Gastric Cancer Cells Via CEA-Targeted Adv-FZ33
Authors: Toshihiro Tanaka, Jianhua Huang, Sachie Hirai, Motomu Kuroki, Masahide Kuroki, Naoki Watanabe, Kazunori Kato, Hirofumi Hamada
Journal: Molecular Therapy (2006)

Introduction At present, adenoviral vectors have been widely used for gene transfer into tumor cells primarily because they can be produced in high titers and can infect many different cell types. However, a major problem when utilizing the adenoviral vectors for gene therapy applications is thought to be related to low transduction efficiency due to weak expression of the adenovirus receptor, coxsackie– adenovirus receptor (CAR) in cancer cells, or side effects due to expression of CAR in normal cells. There is an urgent requirement to improve the specificity of gene delivery via adenoviral vectors in the context of cancer gene therapy. Experimental design We constructed a fiber modified Ad5 vector (Adv-FZ33) in which a IgG-binding domain (Z33) derived from staphylococcal protein A was inserted into the HI loop of knob protein. We then evaluated on both in vitro and in vivo levels the extent of retargeting towards and therapeutic effectiveness against CEA-positive gastric cancers when using the fully human CEA antibody (C2-45) complex with this modified vector. Results In vitro LacZ or EGFP reporter gene expression after infection with Adv-FZ33 vectors conjugated to anti-CEA mAb was approximately 20 times higher than that obtained with vector conjugated to the control mAb (human IgG4). We generated Ax3CAUP-FZ33, which is an Adv-FZ33 derivative vector expressing a therapeutic gene, namely E. coli uracil phosphoribosyltransferase (UPRT) which converts 5FU directly to 5-fluorouridine monophosphate. When conjugated with the anti-CEA mAb, C2-45, Ax3CAUP-FZ33 enhanced the cytotoxicity of 5FU (19.7-fold in terms of IC50 values) against gastric cancer cells. In a nude mouse peritoneal dissemination model, use of Ax3CAUP- FZ33 conjugated with anti-CEA mAb C2-45, in combination with 5FU administration, resulted in greatly enhanced anti-tumor effects against CEA-positive cancer cells. Tumor growth in mice treated with Ax3UP-FZ33/C2-45/5FU was significantly suppressed, and tumor volumes were less than a quarter of those of the control IgG4 group (total weight, 0.12 ± 0.11 g; P < 0.05). Furthermore, we examined the survival effects of Ax3UP-FZ33 conjugated with anti- CEA mAb plus 5FU in mice with peritoneal disseminated gastric cancer. The median survival time of the Ax3CAUP-FZ33/C2-45/5FU group was significantly longer than those of the PBS and 5FU only treatment groups (p<0.01, versus PBS and 5FU only groups). On the other hand, no significant difference was present between the Ax3CAUP-FZ33/5FU or Ax3CAUP-FZ33/IgG4/5FU groups and the PBS or 5FU only groups. Conclusions These data suggest that CEA-targeted FZ33-mutant adenovirus- mediated gene delivery offers a strong and selective therapeutic modality against CEA-producing cancers. This novel strategy may be a promising tool for cancer gene therapy.
On advising politicians
Authors: M McKee
Journal: BMJ (1994)

The alpha adrenoceptor subtypes mediating vasoconstriction to exogenous agonists and to spinal sympathetic nerve stimulation have been characterized in the autoperfused (constant flow) femoral (predominantly skeletal musculature) and saphenous (predominantly cutaneous) vascular beds of the pithed rat. Intra-arterial infusion of the alpha-1 adrenoceptor agonist, methoxamine, increased perfusion pressure in both vascular beds over the same range of infusion rates, and the maximum responses were similar. The selective alpha-2 adrenoceptor agonist, B-HT 933, also increased perfusion pressure in both beds, although the maximum response to B-HT 933 in the saphenous bed was approximately twice that observed in the femoral bed. Responses to methoxamine were blocked by the alpha-1 adrenoceptor antagonist, prazosin (0.1 mg/kg), but not the alpha-2 adrenoceptor antagonist, rauwolscine (1 mg/kg), or by the selective postjunctional alpha-2 adrenoceptor antagonist, SK&amp;F 104078 (1 mg/kg). Conversely, responses to B-HT 933 were blocked by rauwolscine and by SK&amp;F 104078, but not by prazosin. Vasopressor responses to B-HT 933 in both vascular beds of the rat hindlimb also were reduced markedly by the calcium channel blocker, nifedipine (1 mg/kg), whereas responses to methoxamine were relatively resistant to inhibition by nifedipine. In the femoral bed, as in the systemic arterial circulation, responses to sympathetic nerve stimulation were strongly inhibited by prazosin, were potentiated by rauwolscine and were unaffected by SK&amp;F 104078. In contrast, in the saphenous arterial bed, the responses to sympathetic nerve stimulation were inhibited by all three antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)
Omeprazole and aryl hydrocarbon hydroxylases: Should we be worried? Diaz D, Fabre I, Daujat M, Saint Aubert B, Bories P, Michel H, Maurel P. Omeprazole is an aryl hydrocarbon-like inducer of human hepatic cytochrome P450. Gastroenterology 1990;99:737–747
Authors: J Kolars
Journal: Hepatology (1991)
Treatment of Chronic Hepatitis D with Interferon Alfa-2a
Authors: Patrizia Farci, Antonella Mandas, Alessandra Coiana, Maria Eliana Lai, Valeer Desmet, Peter Van Eyken, Yukio Gibo, Luciano Caruso, Sergio Scaccabarozzi, Domenico Criscuolo, Jean-Charles Ryff, Angelo Balestrieri
Journal: New England Journal of Medicine (1994)

Chronic hepatitis D is a severe and rapidly progressive liver disease for which no therapy has been proved effective. To evaluate the efficacy of treatment with interferon, we studied 42 patients with chronic hepatitis D who were randomly assigned to receive either 9 million or 3 million units of recombinant interferon alfa-2a (three times a week for 48 weeks) or no treatment.
Distribution of chromosome length variation in natural isolates of Escherichia coli
Authors: U. Bergthorsson, H. Ochman
Journal: Molecular Biology and Evolution (1998)

Large-scale variation in chromosome size was analyzed in 35 natural isolates of Escherichia coli by physical mapping with a restriction enzyme whose sites are restricted to rDNA operons. Although the genetic maps and chromosome lengths of the laboratory strains E. coli K12 and Salmonella enterica sv. Typhimurium LT2 are highly congruent, chromosome lengths among natural strains of E. coli can differ by as much as 1 Mb, ranging from 4.5 to 5.5 Mb in length. This variation has been generated by multiple changes dispersed throughout the genome, and these alterations are correlated; i.e., additions to one portion of the chromosome are often accompanied by additions to other chromosomal regions. This pattern of variation is most probably the result of selection acting to maintain equal distances between the replication origin and terminus on each side of the circular chromosome. There is a large phylogenetic component to the observed size variation: natural isolates from certain subgroups of E. coli have consistently larger chromosome, suggesting that much of the additional DNA in larger chromosomes is shared through common ancestry. There is no significant correlation between genome sizes and growth rates, which counters the view that the streamlining of bacterial genomes is a response to selection for faster growth rates in natural populations.
Thymosin Beta 4 Is Dispensable for Murine Cardiac Development and Function
Authors: Indroneal Banerjee, Jianlin Zhang, Thomas Moore-Morris, Stephan Lange, Tao Shen, Nancy D. Dalton, Yusu Gu, Kirk L. Peterson, Sylvia M. Evans, Ju Chen
Journal: Circulation Research (2011)

Thymosin beta 4 (Tβ4) is a 43-amino acid factor encoded by an X-linked gene. Recent studies have suggested that Tβ4 is a key factor in cardiac development, growth, disease, epicardial integrity, and blood vessel formation. Cardiac-specific short hairpin (sh)RNA knockdown of tβ4 has been reported to result in embryonic lethality at E14.5-16.5, with severe cardiac and angiogenic defects. However, this shRNA tβ4-knockdown model did not completely abrogate Tβ4 expression. To completely ablate Tβ4 and to rule out the possibility of off-target effects associated with shRNA gene silencing, further studies of global or cardiac-specific knockouts are critical.We examined the role of Tβ4 in developing and adult heart through global and cardiac specific tβ4-knockout mouse models.Global tβ4-knockout mice were born at mendelian ratios and exhibited normal heart and blood vessel formation. Furthermore, in adult global tβ4-knockout mice, cardiac function, capillary density, expression of key cardiac fetal and angiogenic genes, epicardial marker expression, and extracellular matrix deposition were indistinguishable from that of controls. Tissue-specific tβ4-deficient mice, generated by crossing tβ4-floxed mice to Nkx2.5-Cre and αMHC-Cre, were also found to have no phenotype.We conclude that Tβ4 is dispensable for embryonic viability, heart development, coronary vessel development, and adult myocardial function.
An American Medical Plutarch
Authors: Whitfield J. Bell
Journal: JAMA (1968)

Dr. Abner Hersey, until his death in 1817 one of the principal medical practitioners on Cape Cod, was competent and skilful in his profession; he was also, in the words of a pupil, "a mere compound of caprice and whim." He must certainly have seemed so to his colleagues, patients, and neighbors. So absurdly attached was he to simple living that he ate no meat and drank only water or milk, and wore clothes of his own design—a long, large, flapping cloak lined with baize in summer, a greatcoat made of seven calfskins for rain and cold. His abstemiousness was parsimony, and extended to the usual obligations of hospitality: notified by a sister-in-law that she intended to pay him a visit, and knowing that she lived in a more normal way than he, Hersey dispatched a note to keep her away: Madam, I can't have you here; I am sick
Hospital-Acquired Complications in a Randomized Controlled Clinical Trial of a Geriatric Consultation Team
Authors: Peter M. Becker
Journal: JAMA (1987)

As part of a controlled clinical trial of a geriatric consultation team (GCT), we investigated whether a GCT could affect the incidence of hospital-acquired complications in elderly patients. One hundred eighty-five patients, aged 75 years and older, were randomized into an intervention (N = 92) and a control (N = 93) group. Members of the intervention group received a GCT consultation and were routinely followed up throughout their hospitalization. The incidence of hospital-acquired complications for the entire study population was 38%. The type and rate of hospital-acquired complications in the intervention and control groups were not significantly different. Functional status on admission and admission to the psychiatry service were predictive for the occurrence of a hospital-acquired complication. In a broadly selected population such as this, the intensity of care available through a GCT was unable to reduce the occurrence of hospital-acquired complications. However, since this is only one aspect of a GCT function, and others may be of great importance, such aspects, and more targeted populations, must be evaluated before final conclusions can be reached about GCT efficiency.
Anterior Cruciate Ligament Tear
Authors: Kurt P. Spindler, Rick W. Wright
Journal: New England Journal of Medicine (2008)

A female high-school soccer athlete reacts to a defender, plants her leg, cuts to the left without contact, feels her leg give out, hears a pop, and has acute pain. She is unable to walk off the field or return to play. That evening her knee progressively swells. The next day she presents for evaluation. How should her case be managed?
Acute Adrenal Insufficiency and Acute Myocardial Infarction
Authors: Robert E. Quinn
Journal: New England Journal of Medicine (1956)

ACUTE adrenal insufficiency has not been previously described in association with acute myocardial infarction. Review of the available literature shows that the most recent report is that of Appel-man,1 whose patient with Addison's disease had evidence of an old myocardial infarct at the time diagnosis was made. It is the purpose of this communication to present observations on a case of acute myocardial infarction and acute adrenal insufficiency occurring simultaneously and associated with marked eosinophilia.Case ReportA 60-year-old male schoolteacher was admitted to the Surgical Service of the Veterans Administration Hospital, White River Junction, Vermont, on November 15 1954, . . .