tbuckley/cabot-search huggingface dataset:
Establishing a Nicotine Threshold for Addiction -- The Implications for Tobacco Regulation
Authors: Neal L. Benowitz, Jack E. Henningfield
Journal: New England Journal of Medicine (1994)

On February 25, 1994, the Food and Drug Administration (FDA) released a letter to the Coalition on Smoking or Health announcing its intention to consider regulating cigarettes. The agency's premises were that the vast majority of tobacco users self-administer the product for the drug effects of nicotine and to sustain addiction and that cigarette manufacturers control the levels of nicotine in cigarettes to maintain this addiction. The FDA further raised the possibility of regulating cigarettes on the basis of their nicotine content to prevent addiction.On February 28, 1994, the ABC news program Day One presented evidence that tobacco manufacturers . . .
Epidemiologic evidence for the development of serovar-specific immunity after gonococcal infection.
Authors: F A Plummer, J N Simonsen, H Chubb, L Slaney, J Kimata, M Bosire, J O Ndinya-Achola, E N Ngugi
Journal: Journal of Clinical Investigation (1989)

We tested the hypothesis that strain-specific immunity occurs after gonococcal infection in a longitudinal study of 227 prostitutes resident in one small community who experienced frequent gonococcal infections. Women were examined and cultured for Neisseria gonorrhoeae at 2-wk intervals. Gonococcal isolates were typed according to protein 1 serovar, auxotype, and beta-lactamase plasmid type, and classified as to serovar and strain. The hypothesis was tested by comparing the predictions of the hypothesis with the observations of the study. Over the 14-mo period of the study, major changes in the prevalence of specific serovars were observed in the gonococcal population infecting these women. Women with HIV infection experienced a higher rate of gonococcal infection (0.56 +/- 0.03 vs. 0.46 +/- 0.04, P less than 0.05, t test) compared with HIV-negative women and were more likely to experience multiple infections with the same strain. The duration of prostitution was inversely related to the frequency of gonococcal infection. Women experiencing an infection with a specific gonococcal serovar were at a 2- to 10-fold reduced risk of reinfection with the same serovar, except for the 1B-1 serovar. The results of the study were consistent with all four predictions of the hypothesis. Infection with a specific gonococcal serovar results in specific but incomplete protection against subsequent infection with the homologous serovar. The mechanism of this protection remains to be determined.
New and not so new vaccines
Authors: T. Jefferson
Journal: BMJ (1996)

severe hypoglycaemia over a period of between five and 15 years is either mild or negligible.For a few individuals, with vulnerability factors which as yet remain obscure, brain function may be permanently and importantly affected.Strict gly- caemic control has the great benefit of reducing target organ damage-delaying the onset and slowing the progress of retin- opathy, nephropathy, and neuropathy-but brings with it a threefold increase in severe hypoglycaemia."2No one doubts that severe hypoglycaemia should be avoided, but patients and their carers are right in demanding more research to help them make intelligent decisions about the long term trade off between the Scylla of hyperglycaemia and the possible Charybdis of hypoglycaemia.
Effect of the Oral Administration of Branched Chain Amino Acids on Hepatic Encephalopathy in the Rat
Authors: Christian Beaubernard, Marie-Louise Delorme, Pierre Opolon, Mlchele Boschat, Joelle Morin, Marie-Plerre Oryszcyn, Dominique Franco
Journal: Hepatology (1984)

The aim of this study was to investigate the effect of oral administration of branched-chain amino acid (BCAA)-enriched diets after portacaval shunt (PCS) in rats. Fifty-one Sprague-Dawley male rats (200 gm) underwent PCS and 55 a sham operation. Half of the animals received BCAA 142 mg per day through a gastric tube; the other half underwent a sham procedure. Sleep disturbances were evaluated at 7, 14, and 28 days postoperatively by measurement of the excitability of the reticular brain-stem formation during the slow-wave sleep and paradoxical sleep. Animals were killed at the same intervals and liver/body weight ratio, plasma, and brain amino acids, brain norepinephrine, brain serotonin, 5-hydroxyindolacetic acid and histamine were measured. Each group of animals was matched with a similar group of sham-operated rats, i.e., receiving or not receiving BCAA. After PCS (as compared to sham-operated animals) a significant hyper-excitability of the reticular brain-stem formation was found during the slow-wave sleep. The liver/ body weight ratio was significantly lower. Tryptophan (free tryptophan in the plasma), phenylalanine, tyrosine, and histidine increased in the plasma and the brain. Leucine and isoleucine were decreased in the plasma. After PCS, an initial decrease at 7 days postoperatively of brain norepinephrine and blockade of the intracerebral metabolism of tryptophan were observed. These changes were transient and progressively disappeared at 14 and 28 days postoperatively. Brain histamine remained at a very high level through the experiment. A good correlation was demonstrated between modification of the sleep disturbance and tryptophan (or 5-hydroxyindolacetic acid) and histamine brain levels. In the PCS animals, BCAA restored the excitability of the reticular brainstem formation toward normal. The oral administration of BCAA was followed by decreased levels and a more rapid turnover of the intracerebral tryptophan. The decrease of brain serotonin and increase of histamine in the brain were corrected only transiently.
Impact of thrombus removal on myocardial reperfusion in patients with acute myocardial infarction treated with primary stenting
Authors: Eulogio Garcia, Joseph Ludwig, Raul Moreno, Leopoldo Perez Isla, Alicia Barrio, Manuel Abeytua, Javier Soriano, Carlos Crespo, Amalia Mota, Marina Paz
Journal: Journal of the American College of Cardiology (2002)
Research on problems faced by poorest nations continues to be under-resourced
Authors: J. Zarocostas
Journal: BMJ (2009)

Although the amount spent globally on health research and development has risen significantly in recent years, the health problems of people in the poorest nations continue to be overlooked by researchers, an expert report says.

The global health research budget now exceeds $160bn (£100bn; €110bn) a year, up from $30bn in 1986, said Stephen Matlin, executive director of the Global Forum for Health Research. But investment in key areas that lead to better health for poorer populations has risen only “slightly over the past few years,” he said.

Gill Samuels, who chairs the forum’s foundation council, told ministers and health experts attending the body’s annual meeting in Cuba last week that, despite advances in …
A COMPARISON OF THE MANNER OF EXCRETION OF NEUTRAL RED AND PHENOL RED BY THE FROG'S KIDNEY
Authors: Jean Oliver, Eshref Shevky
Journal: The Journal of Experimental Medicine (1929)

1. Phenol red and neutral red are excreted by the perfused frog's kidney by different routes. 2. Phenol red is excreted chiefly through the glomerulus, neutral red through the tubules. 3. Some slight excretion of each of these dyes by the converse mechanism is possible, though there is no evidence in our experiments that necessitates such a conclusion. 4. The importance of methods leading to the production of a normal volume of urine by the perfused kidney is emphasized.
The Nature of Gastric Hypersecretion of Acid in Patients with Duodenal Ulcer
Authors: J. N. Hunt, A. W. Kay
Journal: BMJ (1954)

during apnoea, so that anoxaemia cannot by itself be held responsible.The carbon dioxide tension is, however, at its lowest during the apnoeic phase (Harrison, 1939), and, since cerebral bloodeflow is directly related to the carbon dioxide tension of the blood (Kety and Schmidt, 1946), reduction of blood flow from this cause may be responsible.We have no data on this aspect. SummaryTwo patients with chronic Cheyne-Stokes respiration are described in some detail.These with a further three patients were investigated, using an ear oximeter.It has been shown that the highest arterial oxygen saturation occurs during the period of apnoea, the lowest during the hyperpnoeic interval.This is due to a delay in circulation time and has been demonstrated by means of dye time-concentration curves.The length of the apnoeic phase seems to be related to the prolongation of the circulation time.The effects of oxygen, carbon dioxide, and amino- phylline on this condition have been studied together with their effect on arterial saturation.In our patient with chronic Cheyne-Stokes respiration a mid-brain lesion is described.The mechanism caus- ing this form of respiration is discussed.It is suggested that two of the factors are a prolonga- tion of circulation time and a change in sensitivity of the respiratory centre.The latter may arise fr6m interruption of cortical pathways to this centre.We should like to express our thanks to Dr. Jean Taylor for the pathological reports, to Dr.
Calcium-Regulating Hormones in Essential Hypertension
Authors: LAWRENCE M. RESNICK
Journal: Annals of Internal Medicine (1986)

Circulating levels of the calcium-regulating hormones, calcitonin, calcitriol, and parathyroid hormone, were analyzed in relation to plasma renin activity in 10 persons with normal blood pressure and in 51 persons with essential hypertension. Calcitriol (p< 0.008) and parathyroid hormone (p< 0.01) levels were elevated in hypertensives with low renin activity, whereas calcitonin levels were higher in patients with high renin activity (p< 0.008), compared with normotensive controls and other hypertensive patients. Continuous relationships were observed between calcitriol levels and plasma renin activity in all patients (r= -0.65,p< 0.001) and between parathyroid hormone levels and urinary sodium excretion in hypertensive patients with low renin activity (r= -0.63,p< 0.01). Together, these results support a linkage between calcium metabolism and renin-sodium factors in essential hypertension. Calcium-regulating hormones and the renin-aldosterone system may coordinately mediate the blood pressure effects of differing dietary calcium and sodium intakes at the cellular level by altering cellular handling of monovalent and divalent ions.
Searching Question: On-line or CD-ROM?-Reply
Authors: Robert Hogan
Journal: JAMA (1991)

<h3>In Reply.</h3> —Mr Nelson points out the existence of additional avenues to MEDLINE data, and I fully agree that CD-ROM products might contribute to the new standard of information arising in medicine. It was not my intention to review all methods by which one may make use of MEDLINE and related databases while describing<i>PaperChase</i>. Specifically, I have not attempted to weigh the relative merits of on-line vs CD-ROM systems. A professional biomedical librarian certainly can be an ally in identifying useful information. However, in many settings, biomedical librarians will not be available on a 24-hour-a-day basis when clinicians and other scholars may need access to the literature around-the-clock, 7 days a week. The kind of browsing that Nelson rightfully praises in the CD-ROM environment also occurs on-line and, in fact, is often very instructive both in immediate yield of desired citations and in improving technique for future searches. Nelson
ACC/AHA guidelines for the management of patients with acute myocardial infarction
Authors: None Committee Members, Thomas J. Ryan, Jeffrey L. Anderson, Elliott M. Antman, Blaine A. Braniff, Neil H. Brooks, Robert M. Califf, L. David Hillis, Loren F. Hiratzka, Elliott Rapaport, Barbara J. Riegel, Richard O. Russell, Earl E. Smith, W. Douglas Weaver, James L. Ritchie, Melvin D. Cheitlin, Kim A. Eagle, Timothy J. Gardner, Arthur Garson, Raymond J. Gibbons, Richard P. Lewis, Robert A. O'Rourke, Thomas J. Ryan
Journal: Journal of the American College of Cardiology (1996)
Association Between Increased Estrogen Status and Increased Fibrinolytic Potential in the Framingham Offspring Study
Authors: Otavio C. E. Gebara, Murray A. Mittleman, Patrice Sutherland, Izabela Lipinska, Travis Matheney, Ping Xu, Francine K. Welty, Peter W. F. Wilson, Daniel Levy, James E. Muller, Geoffrey H. Tofler
Journal: Circulation (1995)

Although extensive evidence indicates that estrogen is responsible for the markedly decreased cardiovascular risk of premenopausal women, the mechanism through which estrogen might exert its protective effect has not been adequately explained. Since thrombosis is now recognized to play an important role in the onset of cardiovascular disease, we investigated the relation between estrogen status and fibrinolytic potential, a determinant of thrombotic risk.We determined levels of plasminogen activator inhibitor (PAI-1) antigen and tissue plasminogen activator (TPA) antigen in 1431 subjects from the Framingham Offspring Study. Fibrinolytic potential was compared between subjects with high estrogen status (premenopausal women and postmenopausal women receiving hormone replacement therapy) and low estrogen status (men and postmenopausal women not receiving hormone replacement therapy). In all comparisons, subjects with high estrogen status had greater fibrinolytic potential (lower PAI-1 levels) than subjects with low estrogen status. First, postmenopausal women receiving estrogen replacement therapy had lower levels of PAI-1 than those not receiving therapy (13.0 +/- 0.5 versus 19.5 +/- 1.0 ng/mL, P < .001). Second, premenopausal women had lower levels of PAI-1 than men of a similar age (14.8 +/- 0.6 versus 20.3 +/- 0.8 ng/mL, P < .001); this sex difference diminished when postmenopausal women not receiving hormone replacement therapy were compared with men of a similar age (19.6 +/- 0.7 versus 21.1 +/- 0.7 ng/mL, P = .089). Third, premenopausal women had markedly lower levels of PAI-1 antigen than postmenopausal women not receiving estrogen therapy (14.8 +/- 0.6 versus 19.5 +/- 1.0 ng/mL, P < .001). The between-group differences observed for TPA antigen were similar to those for PAI-1 antigen.Each of these comparisons indicates that the cardioprotective effect of estrogen may be mediated, in part, by an increase in fibrinolytic potential. These findings might provide at least a partial explanation for the protection against cardiovascular disease experienced by premenopausal women, and the loss of that protection following menopause.
Continuous renal replacement therapy in neonates and small infants: development and first-in-human use of a miniaturised machine (CARPEDIEM)
Authors: Claudio Ronco, Francesco Garzotto, Alessandra Brendolan, Monica Zanella, Massimo Bellettato, Stefania Vedovato, Fabio Chiarenza, Zaccaria Ricci, Stuart L Goldstein
Journal: The Lancet (2014)
Effects of Home Visits by Paraprofessionals and by Nurses on Children
Authors: David L. Olds, John R. Holmberg, Nancy Donelan-McCall, Dennis W. Luckey, Michael D. Knudtson, JoAnn Robinson
Journal: JAMA Pediatrics (2013)

The Nurse-Family Partnership delivered by nurses has been found to produce long-term effects on maternal and child health in replicated randomized trials. A persistent question is whether paraprofessional home visitors might produce comparable effects.To examine the impact of prenatal and infancy/toddler home visits by paraprofessionals and by nurses on child development at child ages 6 and 9 years.Randomized trial in public and private care settings in Denver, Colorado, of 735 low-income women and their first-born children (85% of the mothers were unmarried; 47% were Hispanic, 35% were non-Hispanic white, 15% were African American, and 3% were American Indian/Asian).Home visits provided from pregnancy through child age 2 years delivered in one group by paraprofessionals and in the other by nurses.Reports of children's internalizing, externalizing, and total emotional/behavioral problems, and tests of children's language, intelligence, attention, attention dysfunction, visual attention/task switching, working memory, and academic achievement. We hypothesized that program effects on cognitive-related outcomes would be more pronounced among children born to mothers with low psychological resources. We report paraprofessional-control and nurse-control differences with P < .10 given similar effects in a previous trial, earlier effects in this trial, and limited statistical power.There were no significant paraprofessional effects on emotional/behavioral problems, but paraprofessional-visited children born to mothers with low psychological resources compared with control group counterparts exhibited fewer errors in visual attention/task switching at age 9 years (effect size = -0.30, P = .08). There were no statistically significant paraprofessional effects on other primary outcomes. Nurse-visited children were less likely to be classified as having total emotional/behavioral problems at age 6 years (relative risk [RR] = 0.45, P = .08), internalizing problems at age 9 years (RR = 0.44, P = .08), and dysfunctional attention at age 9 years (RR = 0.34, P = .07). Nurse-visited children born to low-resource mothers compared with control-group counterparts had better receptive language averaged over ages 2, 4, and 6 years (effect size = 0.30, P = .01) and sustained attention averaged over ages 4, 6, and 9 years (effect size = 0.36, P = .006). There were no significant nurse effects on externalizing problems, intellectual functioning, and academic achievement.Children born to low-resource mothers visited by paraprofessionals exhibited improvement in visual attention/task switching. Nurse-visited children showed improved behavioral functioning, and those born to low-resource mothers benefited in language and attention but did not improve in intellectual functioning and academic achievement.clinicaltrials.gov Identifier: NCT00438282 and NCT00438594.
Abnormal Neurons in Teratomas in NMDAR Encephalitis
Authors: Gregory S. Day, Simin Laiq, David F. Tang-Wai, David G. Munoz
Journal: JAMA Neurology (2014)

Ovarian teratomas are frequently described in patients with N-methyl-d-aspartate receptor (NMDAR) encephalitis, yet NMDAR encephalitis is rarely described in patients with ovarian teratomas. Understanding why a minority of patients with teratomas are seen with autoimmune encephalitis may improve the management of NMDAR encephalitis and other teratoma-associated autoimmune diseases.To characterize the unique organization of neuroglial elements within ovarian teratomas resected from patients with NMDAR encephalitis.Case-control study comparing the pathological features of ovarian teratomas resected from consecutively accrued cases with NMDAR encephalitis between January 1, 2009, and December 15, 2013, and ovarian teratomas resected from controls between June 1, 2012, and June 30, 2013.Pathology tissue database at a tertiary academic care center.Five cases with teratoma-associated NMDAR encephalitis and serum or cerebrospinal fluid autoantibodies against central nervous system (CNS) NMDAR and 38 controls (39 ovarian teratomas) without neurological symptoms or signs.Formalin-fixed, paraffin-embedded ovarian teratomas were examined for the presence of CNS tissue and inflammatory infiltrates using direct microscopy, enhanced with standard histopathological and immunological stains.Frequency of detection of atypical (dysplastic) CNS neuronal elements in ovarian teratomas resected from cases vs controls, as well as characterization of the relationship between atypical neurons and immune infiltrates.Central nervous system neuronal elements were detected in 4 of 5 teratomas resected from cases with NMDAR encephalitis and in 20 of 39 controls (P = .36). Atypical neurons were seen within teratomas resected from 4 of 5 cases but not in 39 controls, reliably distinguishing teratomas associated with NMDAR encephalitis (P < .001). If found within the CNS, these histological abnormalities would have received the diagnosis of gangliogliomas (n = 3) and ganglioneuroblastoma (n = 1). Reactive changes were present in teratomas from controls, including ferruginated neurons and Rosenthal fibers. Abnormal neuroglial elements were closely related to immune infiltrates in teratomas resected from 4 of 4 cases. Inflammatory infiltrates were not associated with neuroglial tissue in 20 controls, further differentiating these populations (P < .001).Abnormal neurons within teratomas distinguish cases with NMDAR encephalitis from controls and may promote the development of autoimmunity.
Abstract LB-128: Targeted RNAi screening of an EGFR network reveals molecular determinants of tumor cell sensitivity to antibody-dependent cellular cytotoxicity (ADCC)
Authors: Joseph C. Murray, Rochelle E. Nasto, Sandra A. Jablonski, Yong Tang, Louis M. Weiner
Journal: Cancer Research (2012)

Abstract Monoclonal antibodies can modulate signal transduction and survival of tumor cells, and can induce antibody-dependent cellular cytotoxicity (ADCC) through immune effectors, such as natural killer (NK) cells. Although clinical evidence suggests a role for ADCC in effective antibody therapy, molecular determinants of ADCC responsiveness—in oncogenic signaling networks, for example—have not been identified. Using a novel high-throughput screening platform, siRNAs targeting 60 genes of an EGFR network were reverse transfected into A431 cells, and cetuximab and an NK-like cell line (NK92-CD16V) were used to induce ADCC. Primary and validation screens identified four genes whose knockdown enhanced ADCC: GRB7, PRKCE, RET and ABL1. Pharmacological inhibition of Abl kinase activity enhanced ADCC, recapitulating the effects of ABL1 gene knockdown. Additional studies revealed distinct mechanisms associated with enhanced ADCC, including increased EGFR surface expression and enhanced susceptibility to apoptosis. This screening strategy has revealed putative molecular determinants of tumor cell sensitivity to ADCC that may translate to increased monoclonal antibody efficacy in the clinic. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-128. doi:1538-7445.AM2012-LB-128
Release of atherosclerotic debris after transluminal angioplasty.
Authors: P C Block, D Elmer, J T Fallon
Journal: Circulation (1982)

To determine if there is release of endothelial cells or plaque contents after percutaneous transluminal angioplasty, effluent from atherosclerotic segments of the aorta and iliac arteries of rabbits were collected before and after angioplasty. No endothelial cells or cholesterol plates were identified in the preangioplasty effluents. Only a few single endothelial cells and cholesterol crystals were found in effluents after angioplasty. We conclude that embolization of endothelial fragments and cholesterol plates occurs during angioplasty, but only to a minor degree, and is probably not clinically important.