tbuckley/cabot-search huggingface dataset:
Independent effects of obesity and insulin resistance on postprandial thermogenesis in men.
Authors: K R Segal, J Albu, A Chun, A Edano, B Legaspi, F X Pi-Sunyer
Journal: Journal of Clinical Investigation (1992)

The putative blunted thermogenesis in obesity may be related to insulin resistance, but insulin sensitivity and obesity are potentially confounding factors. To determine the independent effects of obesity and insulin resistance on the thermic effect of food, at rest and after exercise, lean and obese men were matched at two levels of insulin sensitivity determined by insulin-stimulated glucose disposal (milligrams per kilogram fat-free mass [FFM] per minute) during the euglycemic, hyperinsulinemic (40 mU/m2.min) clamp: 5.4 mg/kg FFM for the lean and obese groups with low insulin sensitivity, and 8.1 mg/kg FFM for the groups with high insulin sensitivity. The two lean groups were matched for percent fat (approximately 15 +/- 1% fat), as were the two obese groups (approximately 33 +/- 2% fat). Energy expenditure was measured for 3 h in the fasting state and for 3 h after a 720-kcal mixed meal, each at rest and immediately after 1 h of cycling at 100 W. The thermic effect of food (TEF) was calculated as the postprandial minus fasting energy expenditure (kcal/3 h) during rest and after exercise. During rest, TEF was blunted by both obesity (24 +/- 5 and 34 +/- 6 kcal/3 h for obese groups with low and high insulin sensitivity vs. 56 +/- 6 and 74 +/- 6 kcal/3 h for the lean groups with low and high insulin sensitivity; P less than 0.01 lean vs. obese) and insulin resistance (insulin-resistant less than insulin-sensitive, at both levels of obesity; P less than 0.01). After exercise, TEF was also impaired in the obese (47 +/- 6 and 44 +/- 5 kcal/3 h for the insulin-resistant and -sensitive groups) and in the lean insulin-resistant (55 +/- 5 kcal/3 h), compared with the lean insulin-sensitive men (71 +/- 3 kcal/3 h), P less than 0.01. Compared with rest, TEF after exercise was improved, but not normalized, in both obese groups (P less than 0.05), but unchanged in the lean groups. These results suggest that both insulin resistance and obesity are independently associated with impaired TEF at rest, but the responsiveness of thermogenesis to exercise before a meal is related to the obese state and not independently to insulin resistance per se.
Human Breast Cancer Cells Selected for Resistance to Trastuzumab <i>In vivo</i> Overexpress Epidermal Growth Factor Receptor and ErbB Ligands and Remain Dependent on the ErbB Receptor Network
Authors: Christoph A. Ritter, Marianela Perez-Torres, Cammie Rinehart, Marta Guix, Teresa Dugger, Jeffrey A. Engelman, Carlos L. Arteaga
Journal: Clinical Cancer Research (2007)

We have investigated mechanisms of acquired resistance to the HER2 antibody trastuzumab in BT-474 human breast cancer cells.BT-474 xenografts established in athymic nude mice were eliminated by trastuzumab. Continuous cell lines (HR for Herceptin resistant) were generated from tumors that recurred in the presence of continuous antibody therapy.The isolated cells behaved resistant to trastuzumab in culture as well as when reinjected into nude mice. They retained HER2 gene amplification and trastuzumab binding and were exquisitely sensitive to peripheral blood mononuclear cells ex vivo in the presence of the antibody. The HR cells exhibited higher levels of phosphorylated epidermal growth factor receptor (EGFR) and EGFR/HER2 heterodimers. Phosphorylation of HER2 in HR cells was inhibited by the EGFR tyrosine kinase inhibitors erlotinib and gefitinib. Gefitinib also inhibited the basal association of p85 with phosphorylated HER3 in HR cells. Both inhibitors as well as the dual EGFR/HER2 inhibitor, lapatinib, induced apoptosis of the HR cells in culture. Growth of established HR5 xenografts was inhibited by erlotinib in vivo. In addition, the HR cells overexpressed EGFR, transforming growth factor alpha, heparin-binding EGF, and heregulin RNAs compared with the parental trastuzumab-sensitive cells.These results are consistent with the inability of trastuzumab to block the heterodimerization of HER2 and suggest that amplification of ligand-induced activation of ErbB receptors is a plausible mechanism of acquired resistance to trastuzumab that should be investigated in primary mammary cancers.
Mechanical Ventilation for the Elderly
Authors: James Maurer, James Turner, Fred Weinbaum
Journal: JAMA (1993)

<h3>To the Editor.</h3> —In response to the review by Cohen et al<sup>1</sup>in the February 24 issue of<i>JAMA</i>, we retrospectively studied patients treated in our 12-bed surgical intensive care unit (SICU). Our hospital is a 487-bed community hospital with a level I trauma center. It has separate surgical, medical, respiratory, and coronary care units. The SICU is staffed by full-time surgical intensivists who supervise the care of critically ill patients on all the surgical subspecialties. We analyzed the care of octogenarians and nonagenarians who were admitted to the SICU and mechanically ventilated for at least 3 days to determine SICU mortality rates and hospital mortality rates. We determined long-term survival and quality of life. From January 1 until December 31, 1990, there were 356 patient admissions to the SICU. Eighty-five percent of these patients survived their ICU stay. Ninety-seven (27%) of the admissions were for octogenarians or nonagenarians
Acidic fibroblast growth factor and heart development. Role in myocyte proliferation and capillary angiogenesis.
Authors: G L Engelmann, C A Dionne, M C Jaye
Journal: Circulation Research (1993)

Proliferative growth of the ventricular myocyte (cardiomyocyte) is primarily limited to fetal and early neonatal periods of development. In concert with the neonatal "transition" from proliferative to hypertrophic growth, ventricular remodeling of the nonmyocyte compartment is characterized by increased extracellular matrix synthesis/deposition and capillary angiogenesis. A role for locally generated and bioactive ventricular acidic fibroblast growth factor (aFGF) in these processes is proposed and substantiated by the following: 1) colocalization of aFGF peptide and fibroblast growth factor receptor (flg) transcripts to the developing fetal cardiomyocyte by immunohistochemistry, immunoelectron microscopy, and in situ hybridization, 2) continued localization of aFGF peptide and transcripts to the neonatal/mature cardiomyocyte, and 3) localization of flg immunoreactivity and transcripts to specific neonatal ventricular nonmuscle cell types. Specific ventricular cell types at distinct developmental stages appear to be responsive to ventricular myocyte-derived aFGF (myocytes in the fetal heart and nonmyocytes/endothelial cells in the neonatal heart). These data indicate that expression of aFGF and one of its receptors (flg) are most pronounced in the fetal to early neonatal ventricle, the presence of both suggesting an autocrine/paracrine growth regulatory function. As the animal matures, ventricular capillary angiogenesis may be facilitated by "release" of cardiomyocyte-derived fibroblast growth factors into the surrounding extracellular space/matrix functioning as a "paracrine" angiogenic stimuli. Therefore, the results of our study suggest that myocyte-derived aFGF may function to increase the fetal ventricular cardiomyocyte population in absolute number as well as to facilitate the subsequent increase in capillary angiogenesis that occurs during cardiomyocyte maturation and ventricular remodeling.
Glutethimide Poisoning
Authors: Alfred R. Hansen, Katherine A. Kennedy, John J. Ambre, Lawrence J. Fischer
Journal: New England Journal of Medicine (1975)

THE coma induced by large overdoses of glutethimide (Doriden) is similar to that produced by the barbiturates. The clinical course of the glutethimide-intoxicated patient, however, is often complex. The coma may be of unusually long duration, with unexplained variations in depth.1 2 3 Management of glutethimide intoxication is further complicated by a poor correlation between the concentration of glutethimide in plasma and the clinical course of the patient.4 5 6 7 Although other explanations can be offered, the peculiarities associated with glutethimide intoxication could involve the formation and accumulation of an active metabolite. Ambre and Fischer8 have advanced this hypothesis by showing that 4-HG (4-hydroxy-2-ethyl-2-phenylglutarimide), . . .
Effect of ultrasmall superparamagnetic iron oxide nanoparticles (Ferumoxtran-10) on human monocyte-macrophages in vitro
Authors: Karin Müller, Jeremy N. Skepper, Mihaly Posfai, Rikin Trivedi, Simon Howarth, Claire Corot, Eric Lancelot, Paul W. Thompson, Andrew P. Brown, Jonathan H. Gillard
Journal: Biomaterials (2006)
Paralysis of Serratus Anterior after Glandular Fever
Authors: H. C. Saksena
Journal: BMJ (1943)

MEDITCLSHJ6NAL 7It is probable that this condition is more common than supposed.Prof. F. J. Browne has found that the lungs of stillborn foetuses often float in water, which shows that some aeration has taken place.This post-mortem test of stillbirth is thus of little significance.DeLee said that he has heard babies sneeze and cough in utero, and even hiccup.We have seen that at an early date in development the movements of respiration have been tried out.For a cry to be heard, however, there must be air in the uterus, with a variable degree of foetal anoxaemia, rise in CO2 pressure, and peripheral stimulation.The cry will be quiet and whimpering if the asphyxia and peripheral stimulation are slight, but loud and gasping if these are severe.It is in the last group that the foetus is distressed and requires immediate delivery.In our case there is little doubt that air was drawn into the uterus along the examining hand between pains, and the long second stage and prolonged manipulation caused partial asphyxia and stimulation of the foetus.Rapid delivery possibly saved the child's life.
Activation of endogenous deltaF508 cystic fibrosis transmembrane conductance regulator by phosphodiesterase inhibition.
Authors: T J Kelley, L Al-Nakkash, C U Cotton, M L Drumm
Journal: Journal of Clinical Investigation (1996)

Many heterologously expressed mutants of the cystic fibrosis transmembrane conductance regulator (CFTR) exhibit residual chloride channel activity that can be stimulated by agonists of the adenylate cyclase/protein kinase A pathway. Because of clinical implications for cystic fibrosis of activating mutants in vivo, we are investigating whether deltaF508, the most common disease-associated CFTR mutation, can be activated in airway epithelial cells. We have found that, 36Cl- efflux can be stimulated 19-61% above baseline by beta-adrenoreceptor agonists and cGI-phosphodiesterase inhibitors in transformed nasal polyp (CF-T43) cells homozygous for the deltaF508 mutation. The increase in 36Cl- permeability is diminished by protein kinase A inhibitors and is not mediated by an increase in intracellular calcium concentrations. Preincubation of CF-T43 cells with CFTR anti-sense oligonucleotides prevented an increase in 36Cl- efflux in response to beta-agonist and phosphodiesterase inhibitor. Primary cells isolated from CF nasal polyps gave similar results. These data indicate that endogenous levels of deltaF508 protein can be stimulated to increase 36Cl- permeability in airway epithelial cells.
Clinical and Laboratory Features of Epidemic St. Louis Encephalitis
Authors: Paul M. Southern, James W. Smith, James P. Luby, Jack A. Barnett, Jay P. Sanford
Journal: Annals of Internal Medicine (1969)

An epidemic of St. Louis encephalitis in Dallas, Tex., in 1966 again showed the characteristic clinical and epidemiological features of this disease: the occurrence of encephalitis in elderly persons in urban areas during summer and early autumn. Headache, fever, nuchal rigidity, confusion, and tremor were outstanding clinical features. Prospective sequential clinical studies commonly showed isolated cranial-nerve dysfunction, pathological reflexes, and nystagmus. Cerebrospinal fluid pleocytosis with a predominance of mononuclear cells and a normal cerebrospinal fluid glucose also were characteristic. Even though symptoms and signs suggestive of urinary tract infection were common, urine cultures for bacteria were usually negative. Electromyographic abnormalities and elevations in serum aldolase values were frequent and suggested diffuse, lower, motor-neuron dysfunction.
A CASE OF ACUTE ASCENDING PARALYSIS
Authors: H. J. Dean
Journal: BMJ (1909)

ACUTE ASCENDING PARALYSIS. [MErICALJOBUNAL 529 seizures, and I have found, post mortem, that they were suffering from one of these morbid infections.It is a common thing to find on the post-mortem table patches of bronchopneumonia, the appearances of which would accord with clinical notes in the case- book reporting the occurrence of seizures; and, if the brain be examined microscopically, it is easy to prove that these fits may correspond with acute degenerative changes, doubtless caused partially by congestive stasis and partially by a toxic condition of the blood exciting and accelerating the process of neural decay.Bacterial invasion, secondary or terminal, of the organs of the body of a non-specific nature, therefore, may accelerate the morbid process of decay or bring about a fatal termination.In conclusion, I thank the Fellows for their kind atten- tion, for I am not unmindful of the fact that many distinguished men have preceded me in the delivery of the Morison lectures.I feel that I have dealt imperfectly with a very difficult albeit important subject still in its infancy; and I can only hope that the words of the old philosopher, Lucretius, may come true, "that one thing after another will grow clear, and dark night will not rob you of the road, to keep you from surveying the utmost things of Natare; in such wise things will light the torch for other things."
Effect of intravenous nitroglycerin on collateral blood flow and infarct size in the conscious dog.
Authors: B I Jugdutt, L C Becker, G M Hutchins, B H Bulkley, P R Reid, C H Kallman
Journal: Circulation (1981)

This study was performed to determine whether nitroglycerin (NG) can increase collateral flow to ischemic myocardium and reduce ultimate infarct size.Permanent occlusion of the mid-circumflex coronary artery was produced in 43 previously instrumented conscious dogs and within 3 minutes, 6-hour intravenous in- fusions were begun of saline (controls, n = 18), NG in doses to reduce mean arterial pressure by 10% but not below 90 mm Hg (n = 15), or NG followed by methoxamine (MX) to correct the NG-induced fall in blood pressure (n = 10).After sacrifice 2 days later, the occluded coronary bed was defined by postmortem coronary arteriography and masses of infarct and occluded bed were measured by planimetry of weighed rings of the left ventricle (LV).Infarct size was significantly less with NG than saline, both as a percent of LV (12.1 vs 6.4%, p < 0.05) and as a percent of occluded bed (32.0 vs 15.9%,p < 0.005).NG plus MX did not reduce infarct size more than NG alone: 6.6 vs 6.4% of LV, and 16.0 vs 15.9% of occluded bed.Masses of LV and occluded bed did not differ significantly among the three groups.Coronary blood flow (CBF), measured by 7-10-,gm radioactive microspheres, increased by more than 50% throughout the occluded bed (p < 0.005) after NG, and was more than the spontaneous increase seen in controls (p < 0.05), but MX had no additional effect on CBF over NG alone.Six-hour infusions of NG therefore decreased infarct size and improved CBF, and addition of MX to reverse the systemic effects of NG did not lessen the benefit.The results suggest that under the con- ditions of this study, myocardial protection by NG did not depend on a decrease in myocardial oxygen demands, but rather on an increase in collateral flow resulting from a direct vasodilating action of NG on the coronary bed.
Mental health tsar wants staff to be more positive about the service
Authors: L. Eaton
Journal: BMJ (2008)

Professionals working in mental health services need a more positive stance when describing the services they provide, England’s national director for mental health, Louis Appleby, has said.

“In trying to bring about improvements you cannot present an image of a backwater,” he said. “You can’t talk about this pejoratively and then expect people to come forward for services.” 

Professor Appleby, speaking at a seminar in London on Thursday 17 July organised by the Westminster Health Forum, was discussing developments in mental health services since the implementation of the national service framework for mental health in 1999.

His comments were an indirect reference to press reports a few weeks earlier in which the incoming president of the Royal College of Psychiatrists, Dinesh Bhugra, told the Observer newspaper that he wouldn’t want any of …
Ulcerogenicity of piroxicam: an analysis of spontaneously reported data.
Authors: A C Rossi, J P Hsu, G A Faich
Journal: BMJ (1987)

Previous reports have suggested that piroxicam may be more ulcerogenic than other non-steroidal anti-inflammatory drugs (NSAIDs) in use. Critics have attributed this putative relation to flawed comparisons of spontaneously reported data. In this study cases of upper gastrointestinal bleeding, perforation, and ulcer reported to the Food and Drug Administration9s spontaneous reporting system over 12 years were examined. Reporting rates for eight NSAIDs were compared over identical periods of their marketing life cycles. After adjustments were made for the heterogeneity in the underlying reporting rates the difference in rates between piroxicam and the other drugs was considerably reduced but piroxicam retained its top ranking among the drugs; however, large and clinically important differences in the frequency of cases of upper gastrointestinal bleeding, perforation, and ulcer between piroxicam and the rest of the NSAIDs compared probably do not exist.
Treatment of Alcoholism and Nicotine Dependence
Authors: Robert S. Zucker
Journal: JAMA (1996)

<h3>To the Editor.</h3> —In the introduction to their study of mortality following inpatient treatment for addictions, Dr Hurt and colleagues<sup>1</sup>state that "a key outcome of alcoholism treatment is mortality." This questionable assumption, combined with the results of the study showing that the majority of alcoholics in their inpatient cohort died of tobacco-related causes, leads them to conclude that "nicotine dependence treatment is imperative in this group." While preventing premature death has been shown to be one of the benefits of a formal inpatient addictions treatment program,<sup>2</sup>as compared with detoxification only, this is not truly a major treatment goal. The goal of rehabilitation programs for alcoholics, just as the goal for any rehabilitation program, should be to improve functional outcome. Some indicators of functional outcome are social stability and psychosocial adjustment.<sup>3</sup>In fact, it has been suggested that only in publicly funded, inner-city programs, in which
Polymorphisms of Asparaginase Pathway and Asparaginase-Related Complications in Children with Acute Lymphoblastic Leukemia
Authors: Mohsen Ben Tanfous, Bahram Sharif-Askari, Francesco Ceppi, Haithem Laaribi, Vincent Gagné, Julie Rousseau, Malgorzata Labuda, Lewis B. Silverman, Stephen E. Sallan, Donna Neuberg, Jeffery L. Kutok, Daniel Sinnett, Caroline Laverdière, Maja Krajinovic
Journal: Clinical Cancer Research (2014)

Abstract Purpose: Asparaginase (ASNase) is a standard and critical component in the therapy of childhood acute lymphoblastic leukemia (ALL), but it is also associated with several toxicities. Experimental design: We recently reported the results of an association study between ASNase pathway genes and event-free survival (EFS) in childhood patients with ALL. The same polymorphisms were interrogated here in relation to allergies, pancreatitis, and thrombotic events following treatment with E. coli ASNase. Results: Among patients of the discovery group, allergies, and pancreatitis were more frequent in individuals who are homozygous for the triple-repeat allele (3R) of the asparagine synthetase (ASNS) gene, resulting in remarkably higher risk of these toxicities associated with 3R3R genotype [OR for allergies, 14.6; 95% confidence interval (CI), 3.6–58.7; P &amp;lt; 0.0005 and OR for pancreatitis, 8.6; 95% CI, 2.0–37.3; P = 0.01]. In contrast, the ASNS haplotype *1 harboring double-repeat (2R) allele had protective effect against these adverse reactions (P ≤ 0.01). The same haplotype was previously reported to confer reduction in EFS. The risk effect of 3R3R genotype was not replicated in the validation cohort, whereas the protective effect of haplotype *1 against allergies was maintained (P ≤ 0.002). Analysis with additional polymorphisms in ASNS locus in lymphoblastoid cell lines showed that haplotype *1 is diversified in several subtypes of which one was associated with reduced in vitro sensitivity to ASNase (rs10486009, P = 0.01) possibly explaining an association seen in clinical setting. Conclusions: This finding might have implication for treatment individualization in ALL and other cancers using asparagine depletion strategies. Clin Cancer Res; 21(2); 329–34. ©2014 AACR. See related commentary by Avramis, p. 230
Regulatory Status of Pancreatic Enzyme Preparations
Authors: Peter H. Rheinstein
Journal: JAMA (1990)

Hendeles and colleagues<sup>1</sup>report on three patients, each of whom took the same defective pancreatic enzyme product and each of whom obtained an unsatisfactory result. The product consisted of capsules of pancrelipase, US Pharmacopeia (USP) formulated into enteric-coated spheres. The product was sold under various names, but all brands were manufactured by and were labeled as having been manufactured by Anabolic, Inc of Irvine, Calif. Information regarding the defective product, including reports of testing conducted by the independent laboratory (Pharmichem Testing Services) and by a competitor, had been received at the Food and Drug Administration (FDA) by May 1989. The FDA's inspection of the firm revealed that there was no validation for the enteric coating process. Testing conducted by the firm confirmed that the enteric coating was ineffective. All lots were either subpotent or superpotent for one or more active ingredients. On June 14,1989, the manufacturer voluntarily instituted a
An Epidemic of Childhood Diabetes in the United States?: Evidence from Allegheny County, Pennsylvania
Authors: Tomadher M Dokheel
Journal: Diabetes Care (1993)

OBJECTIVE To evaluate IDDM trends in Allegheny County, Pennsylvania, from 1965 to 1989. RESEARCH DESIGN AND METHODS A population-based registry established in 1976—the Allegheny County Registry—was used for this study through a retrospective chart review of all cases diagnosed in the county from 1965. Through this registry, cases of IDDM patients &amp;lt;20 yr of age were identified. In addition, pediatricians in the county were contacted about IDDM cases they diagnosed between 1965 and 1989 in individuals &amp;lt;20 yr of age. RESULTS For the first time a major increase in IDDM was seen (1985–1989). This increase in IDDM was heterogenous with the rise for males being double that for females. The increase for non-white males was considerably greater than that seen for white males, and an exceptionally large increase in the youngest age-group (0–4 yr of age) was observed. CONCLUSIONS Ecological analyses indicated an association between chicken pox infection and IDDM, and this suggested that at least part of the rise may be of an infectious origin.