tbuckley/cabot-search huggingface dataset:
Metabolism of very low density lipoproteins after cessation of cholesterol feeding in rabbits. A factor potentially contributing to the slow regression of atheromatous plaques.
Authors: A Daugherty, G Schonfeld, B E Sobel, L G Lange
Journal: Journal of Clinical Investigation (1986)

Aortic atheromatous plaques regress slowly in cholesterol-fed rabbits that have been returned to normal laboratory diet. To delineate metabolic factors potentially responsible for persistence of atherosclerosis under these conditions, the physical, chemical, and metabolic characteristics were determined for lipoproteins of d less than 1.006 g/ml; such lipoproteins are thought to be the major determinant of progression of atherosclerotic lesions in cholesterol-fed rabbits. At the time of return to a normal laboratory diet regimen after 3 mo of feeding with cholesterol-enriched laboratory diet, plasma cholesterol concentrations were 2,275 +/- 252 mg/dl, mostly attributable to cholesteryl ester-rich very low density lipoproteins (VLDL). On the hypercholesterolemic diet, fractional catabolic rates of plasma clearance of 125I-labeled VLDL were reduced (0.011 +/- 0.002 vs. 0.151 +/- 0.015 h-1), but the total VLDL catabolic rate was increased considerably (17.1 +/- 2.2 vs. less than 1.2 +/- 0.4 mg of protein/kg X d), because of the expansion of the endogenous pool of cholesteryl ester-rich VLDL. The total catabolic rate of VLDL was maintained above estimated control values (5.8 +/- 0.7 mg protein/kg X d) even 10 wk after return of the rabbits to a normal chow regimen, an effect attributable to continued high rates of cholesteryl ester-rich VLDL synthesis in liver. Accumulation of cholesteryl ester-rich VLDL into aortic tissue persisted at a high rate. Thus the persistence of aortic atheromatous lesions after cessation of cholesterol feeding was attributable in part to continued high rates of hepatic production of cholesteryl ester-rich VLDL and its persistent delivery into the aortic wall.
Liquid Paraffin in Baking
Authors: J. B. M. Coppock, R. C. A. Bradshaw
Journal: BMJ (1948)

<h3>Abstract</h3> The linkage between environment, a species’ fitness and its abundance is central to the theory of evolution. So far, all studies of this linkage have been heuristic and empirical due to an inability to determine fitness either experimentally (independent of abundance) or theoretically (from species-environment interaction). One category of such studies involves the Abundant Centre Hypothesis which posits that a species’ abundance rises to a maximum at the centre of its range. We argue that the confusing mix of results from ACH studies arises from ignoring the central premise that the abundance distribution cannot be independent of the environment. First, we employed a theoretical framework to identify an environmental context (an elevational transect; 200-2800 m in the eastern Himalayas) likely to favour ACH. We then improved upon some previously identified conceptual and methodological shortcomings of ACH studies. Using systematically collected bird data (245 species; 15867 records) from that transect we found that the community average abundance profile is symmetric, as expected by ACH. Notwithstanding which, the abundance profiles of individual species showed a small degree of asymmetry which was correlated with elevation. This elevational dependence may be due to the hard elevational limits at the lower and upper ends of the mountain, as expected from theoretical considerations. We also showed that the average abundance profile shape is close to gaussian, while ruling out uniform and inverted-quadratic shapes. This work demonstrates that selecting a particular category of environmental contexts can help in integrating theoretical tools into a field dominated by empirical studies. Such a union should spur the development of more detailed and testable theoretical models for better insights in an important field.
Gender, Histology, and Time of Diagnosis Are Important Factors for Prognosis: Analysis of 1499 Never-Smokers with Advanced Non-small Cell Lung Cancer in Japan
Authors: Tomoya Kawaguchi, Minoru Takada, Akihito Kubo, Akihide Matsumura, Shimao Fukai, Atsuhisa Tamura, Ryusei Saito, Masaaki Kawahara, Yosihito Maruyama
Journal: Journal of Thoracic Oncology (2010)
Recovery After Violence and Human Rights Abuses
Authors: Thomas B. Cole, Annette Flanagin
Journal: JAMA (2013)

In a case-based review in this issue, Crosby discusses the clinical management of a patient with chronic weakness, pain, and posttraumatic stress disorder (PTSD) as a consequence of the trauma she experienced as a refugee from the civil war in Somalia. This management includes a multidisciplinary approach designed to be culturally acceptable to the patient. Also in this issue, 2 related Viewpoints summarize new evidence-based guidelines from the World Health Organization (WHO) to help with clinical management of patients exposed to trauma and violence. Van Ommeren and colleagues discuss new WHO recommendations, many based on substantial evidence, for management of acute stress symptoms after trauma exposure, especially in low- and middle-income countries with limited resources. For example, these guidelines recommend cognitive behavioral therapy with a trauma focus for trauma-exposed adults with acute stress symptoms and PTSD and recommend against the use of benzodiazepines for acute stress and against the use of antidepressants as first-line treatment for PTSD unless there is concurrent moderate to severe depression. Feder and coauthors3 summarize other WHO recommendations, primarily based on low to moderate levels of evidence, to assist clinicians with decisions about and management of women exposed to intimate partner violence. The guidelines recommend cognitive behavioral therapy or eye movement desensitization and reprocessing interventions, delivered by health care professionals with a good understanding of violence against women, for those with PTSD who are no longer experiencing violence.
THE CLIMATES OF THE WORLD, IN REFERENCE TO THEIR EFFECTS ON MAN'S GENERAL WELFARE AND DESTINY
Authors: T. G. Hake
Journal: BMJ (1853)

At the present hour, when millions of human beings are leaving their homes in Europe, or contemplate doing so, for countries which may or may not possess a climate similar to that which gave them birth, it cannot fail to be perceived that many interesting inquiries are thereby laid open to science, on which none but the physiologist can enter with advantage.

It the race of man, then, in all its varieties, affords general expression of the existing climates of the world, in reference to the circumstances which contribute to healthy organization; if one climate maintains, while another modifies more or less the characteristics of human beings, as is undoubtedly the case, it cannot be out of season to make this investigation: With what result to his own physical conformation and moral character, and more especially to that of his descendants does man, born in a congenial climate, emigrate at random into different zones?

Having examined this subject in its many bearings, both by collating the written observations of travellers made cursorily without any immediate scientific object, and by questioning intelligent persons from our colonies, and other newly formed states, I premise with confidence that it is one which is most important and curious. To take a common example; - What a diversity of effects must obviously arise from one member of a family taking up his permanent abode in a portion of the American, and another in a part of the Australasian continent. Both regions afford climates which are called delightful and healthy; but their separate influence on the organization of the European is already perceptible. Indeed, it has been forcibly argued that man cannot travel out of his own zone without entailing extinction on his race. Be this as it may, an inquiry into the subject of isogenetic  or congenial zones is of sufficient moment, under the existing conditions and inevitable redistribution of nations, to give basis to a branch of science; nor will it be passed over without due consideration in this series of papers.
Potential Usefulness of Single Nucleotide Polymorphisms to Identify Persons at High Cancer Risk: An Evaluation of Seven Common Cancers
Authors: Ju-Hyun Park, Mitchell H. Gail, Mark H. Greene, Nilanjan Chatterjee
Journal: Journal of Clinical Oncology (2012)

To estimate the likely number and predictive strength of cancer-associated single nucleotide polymorphisms (SNPs) that are yet to be discovered for seven common cancers.From the statistical power of published genome-wide association studies, we estimated the number of undetected susceptibility loci and the distribution of effect sizes for all cancers. Assuming a log-normal model for risks and multiplicative relative risks for SNPs, family history (FH), and known risk factors, we estimated the area under the receiver operating characteristic curve (AUC) and the proportion of patients with risks above risk thresholds for screening. From additional prevalence data, we estimated the positive predictive value and the ratio of non-patient cases to patient cases (false-positive ratio) for various risk thresholds.Age-specific discriminatory accuracy (AUC) for models including FH and foreseeable SNPs ranged from 0.575 for ovarian cancer to 0.694 for prostate cancer. The proportions of patients in the highest decile of population risk ranged from 16.2% for ovarian cancer to 29.4% for prostate cancer. The corresponding false-positive ratios were 241 for colorectal cancer, 610 for ovarian cancer, and 138 or 280 for breast cancer in women age 50 to 54 or 40 to 44 years, respectively.Foreseeable common SNP discoveries may not permit identification of small subsets of patients that contain most cancers. Usefulness of screening could be diminished by many false positives. Additional strong risk factors are needed to improve risk discrimination.
Ankylosing spondylitis patients with and without psoriasis do not differ in disease phenotype
Authors: Pedro Machado, Robert Landewé, Jürgen Braun, Xenofon Baraliakos, Kay-Geert A Hermann, Benjamin Hsu, Daniel Baker, Désirée van der Heijde
Journal: Annals of the Rheumatic Diseases (2013)

Psoriasis is an important clinical feature in ankylosing spondylitis (AS) and spondyloarthritis (SpA) in general,1 with inflammatory spinal disease developing in 5%–25% of psoriasis cases.2 ,3 However, there have been few studies assessing the differences between AS patients with and without concomitant psoriasis.4–9 

Our aim was to compare the demographic, clinical and imaging characteristics between AS patients with and without psoriasis. Baseline data from an 80% random sample of the AS Study for the Evaluation of Recombinant Infliximab Therapy (ASSERT) database were used for this analysis. Details of the ASSERT trial and study population have been previously published.10 Briefly, patients with active AS (fulfilling modified New York criteria) for at least 3 months, a Bath AS disease activity index score of at least 4 (range 0–10) and a spinal pain assessment score of at least 4 (range 0–10) were eligible for the study.

AS patients with …
Conflicts of Interest in the Management of Silent Ischemia
Authors: Thomas B. Graboys
Journal: JAMA (1989)

ON THE urging of his attentive spouse, a 45-year-old man who was previously healthy and entirely asymptomatic reluctantly agrees to undergo a "heart screening" at the local YMCA. This program, supervised by a local cardiologist in the community, consists of risk factor screening and a treadmill exercise test. Within 6 minutes of brisk walking on the treadmill, the man is stopped when the physician overseeing the test notes "an abnormality on the electrocardiogram." He is told that there may be "several heart vessel blockages," that further testing is in order, and that he should schedule an appointment with his own physician immediately. Because the man has not seen a physician since his discharge from military service 15 years earlier, he opts to be examined by the physician supervising the treadmill study. On the following day, the man undergoes a physical examination; the findings are unremarkable, blood pressure is normal, and
How and When Does Consent Bias Research?
Authors: R. H. H. Groenwold, R. van der Graaf, J. J. M. van Delden
Journal: The American Journal of Bioethics (2013)

Rothstein and Shoben (2013) claim that the magnitude of consent bias in nonintervention research is probably small. To substantiate this claim, the authors provide numerical scenarios of a hypothet...
NICE recommends drugs for moderate Alzheimer's disease
Authors: Susan Mayor
Journal: BMJ (2006)

Cholinesterase inhibitors for Alzheimer's disease should be considered in the treatment of patients with moderately severe disease but not for those with milder symptoms, says revised draft guidance issued this week for the NHS in England. The guidance follows a review of a first draft that had advised against the use of these drugs at all in the disease.

The latest guidance recommends that donepezil, galantamine, and rivastigmine should be considered in the treatment of people with Alzheimer's disease of moderate severity, defined as those with a minimental state examination score of 10-20 points.

Memantine, an N-methyl-D-aspartic acid antagonist, was not recommended as a treatment option for people with moderately severe or severe Alzheimer's disease except as …
Rates of Cutaneous Reactions to Drugs
Authors: Kenneth A. Arndt
Journal: JAMA (1976)

Rates of allergic skin reactions to commonly used drugs were estimated from data obtained on 22,227 consecutively monitored medical inpatients. A total of 57 drugs were implicated with skin reactions. Five or more reactions were attributed to each of 22 drugs (or drug groups). Many commonly used drugs did not appear to cause any allergic reactions. The study provides the practicing physician with drug-specific quantitative data that can be used to evaluate the causes of drug-induced rash, itching, or hives.
Abstract A1: Impact of <i>CYP2D6∗10</i> and <i>CYP3A5∗3</i> polymorphisms on the pharmacokinetics of tamoxifen in Asian breast cancer patients
Authors: Joanne Siok Liu Lim, Onkar Singh, Raymond Chee Hui Ng, Nan Soon Wong, Rathi Devi Ramasamy, Anupama Mahajan, Edmund Jon Deoon Lee, Balram Chowbay
Journal: Clinical Cancer Research (2010)

Abstract Background: Tamoxifen (TAM) is a selective estrogen receptor modulator employed in the treatment of breast cancer. It is a prodrug with a complex metabolic pathway involving several phase I and II metabolic enzymes. TAM is metabolized by cytochrome P450 (CYP) enzymes to N-desmethyltamoxifen (NDM), 4-hydroxytamoxifen (4OHT) and endoxifen (END) with 4OHT and END being the active metabolites of TAM. CYP2D6 and CYP3A4/5 comprises the major CYP isoforms mediating the metabolism of TAM although other CYP isoforms also play a role. Polymorphisms present in genes encoding these CYP enzymes may influence the metabolism and pharmacokinetics of TAM and its metabolites. Methods: A total of 116 Asian breast cancer patients were genotyped for CYP3A5∗3 polymorphism while 104 of these patients were genotyped for CYP2D6. Plasma levels of TAM and its 3 metabolites were obtained at steady state. The occurrence of hot flashes were monitored. Results: The allelic frequencies of CYP2D6∗10 and CYP3A5∗3 in the breast cancer patients were 0.52 and 0.71, respectively. The plasma END level (median; range) of patients with CYP2D6∗10/∗10 (8.85; 6.27-34.68) was significantly lower compared to patients with CYP2D6∗1/∗1 (19.55; 4.18-42.56; pCYP2D6∗1/∗10 (16.18; 9.48-33.24; pCYP2D6∗10 was 359.02 ng/ml (124.7–590.65) and was significantly higher compared to patients with CYP2D6∗1/∗1 (239.27; 40.82-584.26; p=0.012). No associations were observed between the pharmacokinetics of TAM and CYP3A5∗3. Hot flashes, a common side-effect of TAM, occurred at an overall frequency of 0.208 in the patient population. Patients homozygous for the ∗10/∗10 genotype had the highest frequency of hot flashes compared to wild-type subjects (P&amp;gt;0.05). Conclusion: This exploratory study identified CYP2D6∗10 to be an important predictor of TAM pharmacokinetics in Asian breast cancer patients. Other polymorphisms present in CYP2D6 or genes encoding other enzymes involved in metabolism of TAM may be useful in explaining inter-individual variation in TAM pharmacokinetics. Citation Information: Clin Cancer Res 2010;16(7 Suppl):A1
Richard Henry Lavelle
Authors: P. Lavelle
Journal: BMJ (2012)

Aortic dissection and rupture is a rare occurrence in pregnant and postpartum patients. This case discusses the presentation and diagnosis of a patient with an acute contained thoracic aortic aneurysm rupture at 38 weeks of gestation, after presenting with throat pain and syncope during the COVID-19 pandemic. The patient underwent emergent caesarean delivery for non-reassuring fetal heart tracing, following which continued syncope workup revealed an aortic aneurysm and pericardial effusion. Diagnosis in this case was finalised with multimodality imaging, including transthoracic echocardiogram, and the patient underwent surgical aortic repair.
Encephaloid Cancer: Removal by Operation: Ligature of the Carotid: Recovery
Authors: J. S. Smyth
Journal: BMJ (1857)

108, small.He was orderedl to have ten grains of compound gamboge pill night an(d morning, and a senna draught every four hours.He went on in the same way for the next three days.It was still necessary to give a purge every morninm.July 1]th.It was noticed that the features were more drawn; the tongue was furred; the pulse full.The state of the back re(quired the use of a water bed.July 14th.About 7 r.3i., he became quite insensible, with profuse perspiration, and yawniing occasionally.'The left pupil was contracted to aboout the size of a pin's head; the right natural.The pulse, was not perceptible.There vere no con- vulsions or dlistortioni of the features.In this condition le remainied for about an lhour, and then died.Post niortem, examiiination, twenty hours after deatlh, slhowedl the muscles wvell developed anid firm.The substance of the
Referral of Dr Peter Mansfield to the GMC
Authors: A. Majeed
Journal: BMJ (2001)

The referral by Worcestershire Health Authority of Dr Peter Mansfield to the General Medical Council raises some important issues for doctors and patients. Dr Mansfield is a retired general practitioner who works with a charity (Desumo) that offers separate rubella, measles, and mumps vaccines to the children of parents who do not wish to have the combined MMR vaccine because of fears about its supposed side effects (principally, the alleged risk of autism).1 Dr Mansfield holds some unorthodox views about health and illness, which many doctors (including myself) will disagree with. I also disagree with his view that MMR is potentially unsafe. I believe that it is a safe and effective vaccine and that health professionals should encourage its use. Despite this, I believe that the health authority was wrong to refer Dr Mansfield to the GMC and that his referral sets a dangerous precedent.

What has happened in Worcestershire is that several hundred parents have decided that they do not want their children to have the combined MMR vaccine but still wish to have their children immunised and are willing for …
96 VANIN-1 ACTIVITY MODULATES THE STEATOSISSTEATOHEPATITIS TRANSITION IN PROGRESSIVE NON-ALCOHOLIC STEATOHEPATITIS
Authors: D. Concas, B. Wu, H. Kudo, A. Levene, H.C. Thomas, R.D. Goldin, M.R. Thursz, Q.M. Anstee
Journal: Journal of Hepatology (2011)
Herpes simplex virus glycoproteins gC-1 and gC-2 bind to the third component of complement and provide protection against complement-mediated neutralization of viral infectivity.
Authors: T A McNearney, C Odell, V M Holers, P G Spear, J P Atkinson
Journal: The Journal of Experimental Medicine (1987)

Cells infected with herpes simplex virus type 1 (HSV-1) form rosettes with C3b-coated erythrocytes, whereas cells infected with herpes simplex virus type 2 (HSV-2) or other herpes viruses do not. It was reported that glycoprotein C of HSV-1 (gC-1) mediates the binding of C3b-coated erythrocytes to infected cells and has regulatory (decay-accelerating) activity for the alternative pathway C3 convertase of human complement. We show here that solubilized gC-1 binds to iC3-Sepharose affinity columns. We also report that solubilized gC-2, the genetically related glycoprotein specified by HSV-2, binds to iC3-Sepharose. mAb specific for gC-1 or gC-2 and mutant viral strains were used to identify the C3-binding glycoproteins. In other experiments, HSV-1 mutant strains and recombinants, differing only in their expression of gC, were tested for sensitivity to neutralization by human complement in the presence or absence of antibodies specific for HSV gD. In either case the gC- strain was most sensitive. Expression of gC-1 or gC-2 by isogenic insertion mutants provided protection against complement-mediated neutralization. These results indicate that the genetically and structurally related gC-1 and gC-2 share the functional activity of binding to human C3 and enhance viral infectivity.
Newer drugs for focal epilepsy in adults
Authors: M. J. Brodie, P. Kwan
Journal: BMJ (2012)

A 28 year old woman sees her general practitioner after experiencing what sounds like a convulsion without any apparent provoking factor. Over the past month she has also had “blank spells” during which her husband noticed her to be unresponsive. Her general practitioner suspects she may have developed focal epilepsy and refers her to an epilepsy specialist. The specialist elicits from the patient and her husband additional features in the history that are highly compatible with seizures arising from the temporal lobe (lip smacking, ipsilateral motor automatism, and contralateral dystonia) and confirms the diagnosis by finding focal epileptiform discharges on electroencephalography and cortical dysplasia in the left temporal lobe on brain imaging. To prevent further seizures the specialist advises treatment with antiepileptic drugs (AEDs). The patient is reluctant to start treatment because she has read that AEDs have many adverse effects, could interact with her oral contraception, and are harmful for babies. She wonders if there are newer AEDs that for her might be better than the traditional ones.

Epilepsy is resistant to drug treatment in a third of patients.1 Driven by this high prevalence of drug resistance, 12 agents have been developed to treat adult epilepsy since the late 1980s. These are often referred to collectively as the “newer” antiepileptic drugs—that is, newer than the established drugs, such as phenobarbital, phenytoin, carbamazepine, sodium valproate, and several benzodiazepines, with phenobarbital having been around for 100 years.2 In this article we will review the clinical use of (in chronological order of approval in the United Kingdom) lamotrigine, gabapentin, topiramate, oxcarbazepine, levetiracetam, pregabalin, zonisamide, and lacosamide (table 1⇓). We will not discuss the other newer AEDs tiagabine and vigabatrin because they are rarely used for focal epilepsy in adults (owing to efficacy and safety concerns respectively) or eslicarbazepine acetate …