tbuckley/cabot-search huggingface dataset:
Refusal to treat AIDS and HIV positive patients.
Authors: R Gillon
Journal: BMJ (1987)

Gillon, a physician and editor of the Journal of Medical Ethics, refutes the justifications expressed by some physicians for their refusal to care for AIDS or HIV positive patients. He argues that an important element of being a health care professional is the assumption of a special and supererogatory obligation to benefit one's patients, even when this entails real risks. The author also rejects, as outside the norms of professional conduct, withholding treatment because of moral disapproval by the physician of patients' life styles. He cites the principles of professional conduct enunciated by Britain's General Medical Council, which hold that, "in pursuance of its primary duty to protect the public the Council may institute disciplinary proceedings when a doctor appears seriously to have disregarded or neglected his professional duties, for example by failing to visit or to provide or arrange treatment for a patient when necessary."This report discusses the ethical considerations of refusal to treat AIDS patients. Empirical evidence indicates that risk to doctors and other health care workers of occupational acquisition of AIDS virus infection is of very low probability. However the perception of risk on the part of the health care worker is an important factor which must be considered. An important component of being a health care professional is the obligation to benefit one's patients. The report considers the possibility that doctors may withdraw from their normal obligation to treat their patients if the patient's illness has resulted from some voluntary action of which the doctor disapproves, such as homosexuality or drug abuse.
Epigenetic Silencing of the <i>PTEN</i> Gene in Melanoma
Authors: Alireza Mirmohammadsadegh, Alessandra Marini, Sandeep Nambiar, Mohamed Hassan, Andrea Tannapfel, Thomas Ruzicka, Ulrich R. Hengge
Journal: Cancer Research (2006)

Abstract Phosphatase and tensin homologue deleted from chromosome 10 (PTEN) seems to be an important tumor suppressor gene in melanoma. Because the PTEN gene is only infrequently deleted or mutated, and because the PTEN protein is low to absent in a significant number of melanomas, we investigated alternative methods of epigenetic silencing. We did quantitative positional methylation analysis (pyrosequencing) on 37 sera from melanoma patients and on 21 pairs of corresponding sera and melanoma specimens in addition to Taqman reverse transcription-PCR. We report significant positional PTEN promoter methylation in 62% of circulating DNA isolated from sera of patients with metastatic melanoma. The percentage of methylation of a selected CpG island in blood showed a correlation with methylation levels in the corresponding melanoma tissue. Moreover, high percentages of PTEN methylation were associated with low PTEN transcription levels. Using the demethylation agent 5-aza-2′-deoxycytidine, reduced methylation and a corresponding increase in PTEN protein were observed in BLM melanoma cells, leading to reduced AKT activity in an in vitro kinase assay. In summary, epigenetic PTEN silencing seems to be a relevant mechanism of inactivating this tumor suppressor gene in melanoma that may promote melanoma development by derepression of the AKT pathway. (Cancer Res 2006; 66(13); 6546-52)
Primary Melanoma of the Spinal Cord: A Case Report, Molecular Footprint, and Review of the Literature
Authors: Alexander D. Fuld, Maren E. Speck, Brent T. Harris, Nathan E. Simmons, Christopher L. Corless, Gregory J. Tsongalis, David A. Pastel, Alan C. Hartford, Marc S. Ernstoff
Journal: Journal of Clinical Oncology (2011)
Nonblack Patients With Sickle Cell Disease Have African βs Gene Cluster Haplotypes
Authors: Zora R. Rogers
Journal: JAMA (1989)

Of 18 nonblack patients with sickle cell disease, 14 had sickle cell anemia, 2 had hemoglobin SC disease, and 2 had hemoglobin S-beta o-thalassemia. The beta s gene cluster haplotypes that were determined in 7 patients were of African origin and were identified as Central African Republic, Central African Republic minor II, Benin, and Senegal. The haplotype Central African Republic minor II was present on the beta o-thalassemia chromosome in 2 patients. None of 10 patients whose alpha-gene status was determined had alpha-thalassemia-2. These data strongly support the concept that the beta s gene on chromosome 11 of these individuals is of African origin and that the alpha-gene locus on chromosome 16 is of white or native American origin. The clinical severity of the disease in these nonblack patients is appropriate to their haplotype without alpha-thalassemia-2 and is comparable with that of black patients. All persons with congenital hemolytic anemia should be examined for the presence of sickle cell disease regardless of physical appearance or ethnic background.
THE OUTLOOK IN SERUM THERAPY.
Authors: CHARLES T. McCLINTOCK
Journal: JAMA (1896)

A year ago, in a paper read before this Section, I stated that an average of the reports from serum treatment in diphtheria showed a reduction of 50 per cent. in mortality. I repeat this statement to-day with all confidence. Then we had reports from a few thousand cases, to-day from hundreds of thousands. With the profession at large there is no longer any question as to the value of this treatment. Here and there some belated traveler may be heard crying that we are on the wrong road, that trouble and disappointment alone await us. The observer whose opposition has attracted the widest attention in the past year is possibly Dr. Lenox Brown of London. Dr. Brown is a very able man, an authority on many subjects. He attacks the statistics, makes much of the harmful effects of the serum, and enters a general denial against all the claims
What about the politics of the reforms?
Authors: C. Peedell
Journal: BMJ (2011)

Walshe and Ham have taken the government’s stated objectives at face value, with no attempt to acknowledge and put into context the political ideology underpinning these reforms.1 The coalition government has a clear agenda to replace a large chunk of the public sector with the private and third sectors. “Rolling back the state” through privatisation, a reduction in the public sector workforce, and national pay bargaining and pension rights is one of the key supply side economic policies that this government thinks are necessary to tackle our dire economic situation. A low tax, low inflation, …
Post-traumatic nightmares as a dysfunctional state
Authors: Tore A. Nielsen, Anne Germain
Journal: Behavioral and Brain Sciences (2000)

That PTSD nightmares are highly realistic threat simulations triggered by trauma is difficult to reconcile with the disturbed, sometimes debilitating sleep and waking functioning of PTSD sufferers. A theory that accounts for fundamental forms of imagery other than threat scenarios could explain the selection of many more adaptive human functions – some still pertinent to survival today. For example, interactive characters, a virtually ubiquitous form of dream imagery, could be simulations of attachment relationships that aid species survival in many different ways. [Revonsuo]
Taking babies' rectal temperature.
Authors: J Kai
Journal: BMJ (1993)

kinase advocated by Eamshaw and Beard.23 Their conclusion that "intraoperative thrombolysis . .has considerable advantages" is surprising given the paucity of experience with the technique.We suggest that surgeons interested in the technique should first discuss it with a vascular radiologist and perhaps carry out thrombolysis in the angiographic suite before surgery if required.
Gravlee Jet Irrigator
Authors: Leo B. Twiggs, Philip J. DiSaia, C. Paul Morrow, Duane E. Townsend, Charles E. Schwinn
Journal: JAMA (1976)

The Gravlee jet irrigator was used in 556 women with abnormal uterine bleeding. The irrigator failed to demonstrate endometrial adenocarcinoma in 14 of 25 patients. In ten of these 14, the specimens were found to be unsatisfactory. Twenty-six percent (16 of 61) of those patients with unsatisfactory specimens had a proliferative endometrial lesion. The false-negative rate in diagnosing endometrial cancer with an adequate specimen was 27% (4 of 15). Forty-eight of 61 cases of hyperplastic endometrial lesions were not diagnosed by means of jet irrigation. The irrigation failed to detect premalignant endometrial lesions and was not sufficiently reliable to exclude endometrial carcinoma when a satisfactory negative specimen was obtained. (<i>JAMA</i>235:2748-2750, 1976)
Social Psychotherapy and Course of the Disease
Authors: Ronald Grossarth-Maticek
Journal: Psychotherapy and Psychosomatics (1980)

This paper is designed to introduce anew therapeutic approach into the treatment of cancer patients and to give some first results of our work. The basic idea is that the development of cancer depends to a great extent on a patient's social environment and the interrelation between environment and patient. A disturbed attitude on the part of the patient towards it and towards himself can influence adversely the development of cancer. The aim of social psychotherapy is to modify such attitudes, i.e. to influence the disease by psychological means.
Fluid shear stress inhibits vascular inflammation by decreasing thioredoxin-interacting protein in endothelial cells
Authors: Hideyuki Yamawaki, Shi Pan, Richard T. Lee, Bradford C. Berk
Journal: Journal of Clinical Investigation (2005)

Regions in the vasculature that are exposed to steady laminar blood flow are protected from atherosclerosis as compared with regions where flow is disturbed. We found that flow decreased TNF-mediated VCAM1 expression by inhibiting JNK and p38. JNK inhibition correlated with inhibition of apoptosis signal–regulating kinase 1 (ASK1), a JNK and p38 activator. Thioredoxin-interacting protein (TXNIP) is a stress-responsive protein that inhibits thioredoxin (TRX) activity. Since thioredoxin inhibits ASK1, we hypothesized that changes in TXNIP-TRX-ASK1 interactions mediate the antiinflammatory effects of flow. To explore this, we used perfused vessels and cultured ECs. Exposure of rabbit aortae or ECs to normal flow (12 dyn/cm2, 24 hours) was associated with decreased TXNIP expression and increased TRX activity compared with exposure to low flow (0.4 dyn/cm2). Normal flow inhibited TNF activation of JNK/p38 and VCAM1 expression. In cultured ECs, reduction of TXNIP expression by small interfering RNA increased TRX binding to ASK1 and inhibited TNF activation of JNK/p38 and VCAM1 expression. Conversely, overexpression of TXNIP stimulated JNK and p38. In aortae from TXNIP-deficient mice, TNF-induced VCAM1 expression was inhibited. The data suggest that TXNIP and TRX are key components of biomechanical signal transduction and establish them as potentially novel regulators of TNF signaling and inflammation in ECs.
A 47-Year-Old Man With Asymptomatic Hepatitis C Infection
Authors: Michael F. Sorrell
Journal: JAMA (1996)

<b>Dr Delbanco:</b>Mr E is a 47-year-old married man. In 1992, while in prison, he was found to have asymptomatic hepatitis C infection. Currently he works part-time through a temporary agency. He does not have health insurance, but receives care at an inner-city neighborhood health center. Mr E has been in good medical health except for a long history of substance abuse. At 19 years of age he began to experiment with marijuana, followed thereafter by the use of heroin intravenously, "uppers and downers," and cocaine. He denies using drugs in the past 3 months since leaving prison. He has used little alcohol over the years, drinking one or two beers about twice a month. He has smoked for many years and currently smokes 1½ packs per day. In 1991 he tested positive for syphilis and received a series of six injections of a penicillin preparation. In 1992 he took
Environmental Determinants of Infectious Disease: A Framework for Tracking Causal Links and Guiding Public Health Research
Authors: Joseph N.S. Eisenberg, Manish A. Desai, Karen Levy, Sarah J. Bates, Song Liang, Kyra Naumoff, James C. Scott
Journal: Environmental Health Perspectives (2007)

BackgroundDiscoveries that emerging and re-emerging pathogens have their origin in environmental change has created an urgent need to understand how these environmental changes impact disease burden. In this article we present a framework that provides a context from which to examine the relationship between environmental changes and disease transmission and a structure from which to unite disparate pieces of information from a variety of disciplines.MethodsThe framework integrates three interrelated characteristics of environment–disease relationships: a) Environmental change manifests in a complex web of ecologic and social factors that may ultimately impact disease; these factors are represented as those more distally related and those more proximally related to disease. b) Transmission dynamics of infectious pathogens mediate the effects that environmental changes have on disease. c) Disease burden is the outcome of the interplay between environmental change and the transmission cycle of a pathogen.ResultsTo put this framework into operation, we present a matrix formulation as a means to define important elements of this system and to summarize what is known and unknown about the these elements and their relationships. The framework explicitly expresses the problem at a systems level that goes beyond the traditional risk factor analysis used in public health, and the matrix provides a means to explicitly express the coupling of different system components.ConclusionThis coupling of environmental and disease transmission processes provides a much-needed construct for furthering our understanding of both specific and general relationships between environmental change and infectious disease.
Studies of Cardiopulmonary Blood Volume
Authors: GILBERT E. LEVINSON, ALBERT D. PACIFICO, MARTIN J. FRANK
Journal: Circulation (1966)

The volume of blood in the heart and lungs can be measured, by the Stewart-Hamilton principle, as the product of cardiac output and the mean transit time from right atrium to the aortic root. Although previous investigators have estimated a variety of central blood volumes, measurements of the true cardiopulmonary blood volume in man have not previously been reported. Eighty-one measurements of the total cardiopulmonary blood volume were obtained in 15 normal human subjects. At rest, total cardiopulmonary blood volume ranged from 301 to 546 ml/m 2 , with a mean of 422 ml/m 2 , and it represented 15% of estimated total blood volume. Cardiopulmonary blood volume was significantly larger in the male subjects than in the female. Reproducibility of measurements was good: the mean discrepancy between successive replications was 25 ml/m 2 and the mean coefficient of variation 3.7%. There was no correlation between cardiac output and cardiopulmonary blood volume but a significant correlation (r=0.79, P &lt;0.0001) was evident between cardiopulmonary blood volume and stroke volume. With elevation of the legs to the pedals of a bicycle ergometer, a small but statistically significant increase occurred in cardiopulmonary blood volume, but no significant changes occurred in cardiac output, heart rate, or stroke volume. With exercise, no further significant change in cardiopulmonary blood volume occurred, despite significant increases in output, rate, and stroke volume. Analysis of cardiac output measurements, both at rest and during exercise, indicates that aortic root sampling is characterized by an appreciably higher reproducibility than that reported for peripheral arterial sampling.
Developing an HIV Vaccine: The Role of Efficacy Studies in Nonhuman Primates
Authors: Klaus Überla
Journal: PLoS Medicine (2005)

The case report by Nautiyal et al. [1] is an instructive reminder that the fi rst episode of an acute painful Horner Syndrome should prompt imaging of the ipsilateral internal carotid artery, since carotid dissection (as well as other conditions, such as high-grade stenosis) needs to be ruled out.Unfortunately, the authors perpetuate the extremely common misconception that enophthalmos accompanies ptosis and miosis in human Horner Syndrome.It is only an illusion of enophthalmos caused by the ptosis.This is evident in the left eye of their patient in Figure 1 of the case report.Actual measurement with exophthalmometry clearly demonstrates the lack of enophthalmos.As stated by Loewenfeld ([2], p. 1139), "Animals such as cats, rats, or dogs have enophthalmos on the side of the sympathetic lesion.But in man, the enophthalmos is only apparent.The small palpebral fi ssure makes the eye look sunken in on the affected side, but the position of the globe in the orbit remains virtually unchanged.This has been found by all workers who have measured the supposed enophthalmos objectively."Loewenfeld cites four supportive references.Thompson and Miller ([3], p. 964) provide four additional references that the enophthalmos "is apparent rather than real.
Assessment of left atrial appendage function by transesophageal echocardiography. Implications for the development of thrombus.
Authors: C Pollick, D Taylor
Journal: Circulation (1991)

The predilection of the left atrial appendage (LAA) for thrombus formation has long been known.We prospectively studied the two-dimensional echocardiographic and Doppler patterns of LAA function in 82 patients by transesophageal echocardiography. In the 63 patients in sinus rhythm, LAA area was measured during LAA diastole at the onset of the electrocardiographic (ECG) P wave (LAAmax) and after LAA systole at the ECG R wave (LAAmin) and LAA ejection fraction was calculated as (LAAmax-LAAmin)/LAAmax; peak Doppler velocity was recorded from the LAA outlet. The 58 patients in sinus rhythm without LAA thrombus were grouped according to left atrial size on transthoracic echocardiography; 39 patients had a left atrial size of less than 40 mm (group 1) and 19 had a left atrial size of 40 mm or greater (group 2). Five patients in sinus rhythm had LAA thrombus. In the 19 patients with atrial fibrillation or flutter LAAmax was measured independent of the ECG; three of these patients had LAA spontaneous contrast, four had thrombus, and one had both. Patients in sinus rhythm without LAA thrombus demonstrated a characteristic pattern of a contractile LAA apex and a noncontractile base with color flow and pulsed Doppler evidence of LAA emptying that coincided with the P wave. Patients in sinus rhythm with LAA thrombus had a mean +/- SD LAAmax (8.0 +/- 1.5 cm2) larger than that in group 1 (5.0 +/- 1.9 cm2) (p less than 0.01) but not group 2 (6.7 +/- 3.1 cm2), LAAmin (6.5 +/- 1.0 cm2) larger than that in both group 1 (2.3 +/- 1.5 cm2) and group 2 (4.2 +/- 2.7 cm2) (p less than 0.01), and LAA ejection fraction (17 +/- 11%) and LAA velocity (0.24 +/- 0.10 m/sec) less than those in both group 1 (55 +/- 21% and 0.48 +/- 0.24 m/sec, respectively) and group 2 (45 +/- 27% and 0.46 +/- 0.24 m/sec, respectively) (p less than 0.01). Patients with atrial fibrillation or flutter with LAA spontaneous contrast and/or thrombus had LAAmax (10.4 +/- 6.6 cm2) greater than that in patients with atrial fibrillation or flutter without LAA contrast and/or thrombus (6.8 +/- 3.0 cm2) (p less than 0.05). The LAA appeared as a static pouch in seven of eight of the former compared with in two of 11 of the latter. When attempted, Doppler demonstrated a recognizable fibrillatory LAA outflow velocity pattern in none of three in the former versus four of seven in the latter group.We conclude that the LAA has a characteristic pattern of emptying in sinus rhythm. LAA thrombus formation in sinus rhythm and atrial fibrillation is associated with both poor LAA contraction and LAA dilation.
Abstract 2249: Mutations to the GSK3β regulatory region of CTNNB1 increase TCF transcription activity and are resistant to degradation by GSK3β
Authors: Heather R. Manring, Peter A. Antinozzi
Journal: Cancer Research (2012)

Abstract Hepatocellular carcinoma (HCC) is currently the third most common cause of cancer related mortality worldwide. As with many cancers, aberrant activation of Wnt/β-catenin signaling plays a critical pathogenic role in the disease. Somatic mutations in genes of the Wnt pathway are widely observed in tumor tissue, where it has been estimated that 15-20% of tumors possess activating mutations in beta-catenin (CTNNB1). The turnover of CTNNB1 protein is tightly regulated in cells by the degradation complex which includes the CK1α and GSK3β kinases in a complex with Axin and APC. Mutations within the CTNNB1 gene at the CK1α phosphorylation site (Ser45) and GSK3β phosphorylation sites (Ser33, Ser37, Thr41) are observed clinically and result in CTNNB1 protein accumulation and enhanced transcription of Wnt target genes. The goal of this study is to characterize additional clinically observed CTNNB1 mutations in HCC. It is hypothesized that mutations within the phosphorylation domain in exon 3 will impact the phosphorylation of these key regulatory sites of CTNNB1. To assess the impact of three observed CTNNB1 mutations (H36P, I35S and S23R) on Wnt signaling activity, mutant CTNNB1 constructs were first created and their impact on Wnt signaling was measured using a luciferase-based Wnt reporter assay in transfected HEK293T cells. Compared to the wild type CTNNB1 control, Wnt transcription activity in the presence of H36P, I35S, and S23R mutants were increased by 6.55 ± 2.08, 6.76 ± 2.44, and 2.36 ± 1.01 fold, respectively. This compared to a 5.91 ± 1.38 fold increase observed with the phosphorylation mutant S45P. To evaluate if these mutations had a measurable impact on GSK3β regulation of CTNNB1 levels, each mutant was coexpressed with a GSK3β expression vector and evaluated using the same Wnt reporter system. As anticipated, GSK3β coexpression reduced Wnt reporter activity of the CTNNB1 control by 3.6 fold ± .33 where the S45P mutant was not affected. Coexpression of GSK3β did not attenuate increased Wnt activity observed with the mutants H36P and I35S, however it did decrease activity observed with the S23R by a similar magnitude of the wild type CTNNB1 control (2.27 fold ± .93). These results describe the activating nature of H36P, S45P, and I35S which likely mediate their effect via impaired CTNNB1 phosphorylation. To a lesser extent, S23R activated Wnt activity, however, is subject to attenuation by GSK3β phosphorylation. 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 2249. doi:1538-7445.AM2012-2249
Bioassay of cholecystokinin.
Authors: E L Giannoulis, R E Barry
Journal: Gut (1982)

An in vitro bioassay for cholecystokinin which is superior to the previously described in vivo assays has been properly validated mathematically. The specificity of the assay has been assessed by measuring the potency of other polypeptides which share the same C-terminal pentapeptide sequence with cholecystokinin (gastrin, caerulin, octapeptide of cholecystokinin, and pentagastrin). The assay is shown to be quite specific for cholecystokinin. Secretin does not interfere with the assay. Comparison of the relative potency of the two commercially available preparations of cholecystokinin indicates that the two major units of measurement are almost identical in cholecystokinetic potency. One Crick Harper Raper unit of cholecystokinin (Boots) is equivalent to 1.22 +/- 0.12 Ivy dog units of cholecystokinin (Karolinska Institute). The lower limit of sensitivity for the assay was 2.5m IDU/ml.
Most patients who stop taking a statin are not intolerant, suggests study
Authors: L. Anekwe
Journal: BMJ (2013)

Nine of 10 patients who stop taking a statin because of side effects were able to restart it or take a different drug from the group and stick with it for at least 12 months, a study has found.

Researchers from Beijing and Boston studied the medical records of 108 000 people treated at two hospitals in the United States to find out how often people stop taking statins …