tbuckley/cabot-search huggingface dataset:
Homozygosity of Chromosome 13 in Retinoblastoma
Authors: Thaddeus P. Dryja, Webster Cavenee, Raymond White, Joyce M. Rapaport, Robert Petersen, Daniel M. Albert, Gail A. P. Bruns
Journal: New England Journal of Medicine (1984)

We studied the frequency of chromosome 13 homozygosity in tumor tissue obtained directly from eyes harboring retinoblastomas. The data indicate that approximately half of all retinoblastomas are homozygous for large portions of 13q, that the homozygosity occurs in vivo and not as an event secondary to culture of the tumor cells, that chromosome 13 homozygosity is not correlated with the degree of histopathologic differentiation of the tumor, and that the homozygosity occurs in both sporadic and hereditary retinoblastomas. The development of chromosome 13 homozygosity may represent a fundamental event in the oncogenesis of a considerable number of retinoblastomas. This finding may have implications for the genetic counseling of patients with hereditary retinoblastoma. It may also be important in understanding the mechanism of oncogenesis of other tumors, especially hereditary tumors.
Rationing is needed in the US
Authors: A. M Ali
Journal: BMJ (2009)

A public plan by President Obama’s team may reduce the number of uninsured people in the United States but seems unlikely to curb rising healthcare costs.1 Indeed, Medicare is a federal programme whose escalating costs are as unsustainable as the private sector’s. The problem lies deeper: an unwillingness to accept the need for rationing.

When …
Operational Research — Dangers of Potholing
Authors: John Lister
Journal: New England Journal of Medicine (1959)

ABRANCH of medicine that is normally little publicized received well deserved recognition in a recent television program in which Surgeon Lieutenant Commander Rawlins, R.N., introduced a film showing the kind of research that has led to the latest developments in the technic of escaping from submerged military aircraft.In the past, "ditched" aircraft have tended to float long enough to give the crew a fair chance of effecting an escape, but the advent of the jet plane has greatly altered the position. In these planes the engines not only are exceedingly heavy but also, being basically little more than highly . . .
358. Lentiviral Vector Integration in Mouse Bone Marrow Stem Cells Undergoing Gene Therapy
Authors: Xiaolin Wu, Weijing He, Shawn M. Burgess, Robert A. Clark, Senlin Li
Journal: Molecular Therapy (2006)

Although patients with X-linked severe combined immunodeficiency (X-SCID) were cured with hematopoietic stem cell (HSC) gene therapy, three of the treated X-SCID patients developed leukemia. In these clinic trials, moloney murine leukemia virus (MLV) was used as the vector. Since recent studies suggest lentiviral vector may be the better choice, it was used in our research projects of HSC gene therapy in mice. These mice served as a model to investigate whether lentivectors are associated with cancer development as MLV. We examined (1) the distribution of lentiviral vector insertions in the mouse genome and (2) tumor development. Genomic DNA was isolated from peripheral blood of three recipient mice two months after transplantation of bone marrow stem cells transduced ex vivo with lentiviral vectors. The DNA was pooled and subjected to a high-throughput method to rapidly clone the genomic regions adjacent to proviral integrations. A total of 1152 clones were sequenced. 1038 sequences had high quality insert, many of which were duplicates. Among the 246 unique integration sites, 115 integration sites (47%) were located in genes identified in RefSeq, while only 9 (3.0%) lentiviral integrations were located ± 1kb relative to the transcription start sites. These results indicate that compared with MLV, lentivectors do not preferentially integrate around transcription start sites and the reduced propensity of lentiviral vectors to incorporate into promoter-proximal regions may contribute to their safety in gene therapy. This claim is supported by our observation that there was no rapid weight loss, no enlarged thymus, lymph nodes, liver, or spleen, and no other tumor appearance among these bone marrow reconstituted mice even 18 months post transplant.
Chronic phenacetin nephropathy.
Authors: N G Sanerkin
Journal: BMJ (1971)

SUMMARY

Five cases of papillary necrosis are presented, four giving a history of prolonged excessive consumption of phenacetin—containing analgesic mixtures (chronic phenacetin nephropathy), the fifth in association with gout.



The distribution and significance of the renal parenchymal contraction in chronic phenacetin nephropathy is discussed in relation to the medullary necrosis. It is suggested that such contraction is not due to a ”primary chronic interstitial nephritis”, but to parenchymal atrophy and fibrosis consequent upon the medullary necrosis, particularly when the latter predisposes to superimposed renal infection.



In the absence of diabetes mellitus or obstructive uropathy, phenacetin abuse would appear to be the commonest cause of renal papillary necrosis and parenchymal contraction, but other conditions, including gout, may sometime produce an identical picture.
"PULMONARY TUBERCULOSIS ASSOCIATED WITH BRONCHIAL OBSTRUCTION"
Authors: John Ritter
Journal: JAMA (1928)

<h3>To the Editor:</h3> —A clinical note on this subject inThe Journal, April 21, concerns a 3 year old child, who became suddenly ill and after ten months developed meningitis and died. A diagnosis of miliary tuberculosis was made. The most striking feature is the frequent negative Pirquet tests. These tests were from the beginning positive signs of a disseminated tuberculosis. Even a tuberculin test made some months before the sudden onset would in all probability have been negative. The infant from the onset was tuberculotoxic and in that state it is impossible for the body, with added tuberculin, to produce an allergic reaction, and the negative reaction pointed definitely to an active tuberculous condition. In the tuberculously infected, in the patient suffering from localized disease and in pulmonary tuberculosis, not too progressive or too far advanced, the tuberculin test is always positive and the test remains positive only as
ALTERNATIVELY SPLICED TISSUE FACTOR IS HIGHLY EXPRESSED IN COMPLEX HEMORRHAGIC CAROTID AND CLINICALLY UNSTABLE CORONARY PLAQUES
Authors: Chiara Giannarelli, David T. Rodriguez, Claudia Calcagno, Randolph Hutter, Antoine Millon, Peter Faries, Zahi Fayad, Roger Hajjar, Valentin Fuster, Juan Badimon
Journal: Journal of the American College of Cardiology (2013)
Trends in the management and burden of alcoholic liver disease
Authors: Philippe Mathurin, Ramon Bataller
Journal: Journal of Hepatology (2015)

Alcoholic liver disease (ALD) is the most prevalent cause of advanced liver disease in Europe and is the leading cause of death among adults with excessive alcohol consumption. There is a dose-response relationship between the amount of alcohol consumed and the risk of ALD. The relative risk of cirrhosis increases in subjects who consume more than 25 g/day. The burden of alcohol-attributable liver cirrhosis and liver cancer is high and is entirely preventable. Health agencies should develop population-based policies to reduce the prevalence of harmful and/or hazardous alcohol consumption and foster research in this field to provide new diagnostic and therapeutic tools. Disease progression of patients with ALD is heavily influenced by both genetic and environmental factors. Non-invasive methods for the diagnosis of fibrosis have opened new perspectives in the early detection of advanced ALD in asymptomatic patients. Alcoholic hepatitis, the most severe form of ALD, carries a high short-term mortality (around 30-50% at 3 months). Corticosteroids improve short-term survival in patients with severe alcoholic hepatitis but duration of therapy should be adapted to early response. Liver transplantation is the best option for patients with severe liver dysfunction. However, alcohol relapse after transplantation remains a critical issue and drinking habits of transplanted patients need to be routinely screened.
A Cost-Benefit Analysis of Immunization for Pneumococcal Pneumonia
Authors: Kevin M. Patrick
Journal: JAMA (1981)

To determine whether immunization against pneumococcal pneumonia could be justified on the basis of a favorable benefit to cost ratio, we evaluated the projected impact of a program of pneumococcal vaccination on the population of a health maintenance organization. Retrospective data on average provider and patient costs associated with episodes of pneumococcal pneumonia were coupled with forecasts of the likely effectiveness of currently available vaccine and its impact on anticipated incidence of pneumonia. We found that when provider-centered and patient-centered costs and benefits were added, a program of immunizing those traditionally considered to be at high risk of contracting pneumococcal pneumonia (50 years of age and older; patients with chronic diseases of the heart, liver, lungs, or kidneys; and those with diabetes mellitus) was justified on a cost-benefit basis. (<i>JAMA</i>1981;245:473-477)
Myocardial metabolic studies in prolapsing mitral leaflet syndrome.
Authors: G Natarajan, F K Nakhjavan, D Kahn, S Yazdanfar, W Sahibzada, F Khawaja, H Goldberg
Journal: Circulation (1975)

Patients with prolapsing mitral leaflet syndrome (PML) frequently have chest pain of undetermined etiology. Twenty-three patients with PML underwent cardiac hemodynamic, angiographic, and metabolic studies. The latter were performed during control spontaneous heart rate and tachycardia by right atrial pacing. Myocardial supply-demand ratio (DPTI:SPTI) was estimated from the planimetric integration of the diastolic area (diastolic pressure time index = DPTI) and systolic area (systolic pressure time index = SPTI) of the central aortic pressure. Chest pain during pacing occurred in five patients. In two patients, it was associated with ST depression typical of ischemia on the electrocardiogram. Myocardial lactate abnormalities (lactate production or less than 10% extraction) occurred in seven patients during pacing tachycardia and was present in two patients during control state. DPTI:SPTI ratio during control state was 1.22 (+/- 0.07 SE) and decreased to 0.85 (+/- 0.05 SE) during pacing tachycardia. It is concluded that the myocardial lactate abnormalities in PML, which were present in approximately 30% of the patients in the present series, are most likely due to myocardial hypoxia. Whether or not the hypoxia is secondary to "small vessel disease" is not elucidated by this study.
Study of a Preceptor Program
Authors: John Z. Bowers
Journal: JAMA (1960)

During the past four years we have evaluated a preceptor program which has been required for all medical students at the University of Wisconsin since 1925. Opinions of alumni and students on a variety of items, a historical note, and restatement of the objectives and methods of the program based, in part, on our studies are included in this report.  History  A preceptor is traditionally envisaged as a physician who gives a highly personal training to an undergraduate medical student. The usual picture of a preceptor is that of a general practitioner in a rural setting with a student accompanying him in his manifold medical activities. In earlier days the terms preceptorship and apprenticeship were used interchangeably to describe the predominant system of medical education in the United States. From the founding of the colonies until the establishment of the first department of medicine at Philadelphia in 1765, medical schools
Ethical Review of Health Systems Research in Low- and Middle-Income Countries: A Conceptual Exploration
Authors: Adnan A. Hyder, Abbas Rattani, Carleigh Krubiner, Abdulgafoor M. Bachani, Nhan T. Tran
Journal: The American Journal of Bioethics (2014)

Given that health systems research (HSR) involves different aims, approaches, and methodologies as compared to more traditional clinical trials, the ethical issues present in HSR may be unique or particularly nuanced. This article outlines eight pertinent ethical issues that are particularly salient in HSR and argues that the ethical review process should be better tailored to ensure more efficient and appropriate oversight of HSR with adequate human protections, especially in low- and middle-income countries. The eight ethical areas we discuss include the nature of intervention, types of research subjects, units of intervention and observation, informed consent, controls and comparisons, risk assessment, inclusion of vulnerable groups, and benefits of research. HSR involving human participants is necessary to ensure health systems strengthening and quality of care and to guide public policy intelligently. Health systems researchers must carefully define their intent and goals and openly clarify the values that may influence the premises and design of protocols. As new types of population-level research activities become more commonplace, it is critical that institutional review board (IRB) and research ethics committee (REC) review processes evolve to evaluate these research protocols in ways that address the nuanced features of these studies.
N-acetylcysteine prevents development of the hyperdynamic circulation in the portal hypertensive rat
Authors: Bimbi Fernando, Richard Marley, Steve Holt, Radhi Anand, David Harry, Peter Sanderson, Roy Smith, George Hamilton, Kevin Moore
Journal: Hepatology (1998)

Partial portal vein ligation (PPVL) leads to the development of a hyperdynamic circulation. It is associated with elevated levels of tumor necrosis factor (TNF-α) and nitric oxide (NO) production, both of which can result in oxidant injury. In this study, we have investigated whether PPVL is associated with the development of oxidative stress, by measuring urinary F 2 -isoprostanes. In addition, we have examined whether N -acetylcysteine (NAC) can ameliorate oxidant injury and prevent the development of the hyperdynamic circulation. Urinary excretion of F 2 -isoprostanes increased sixfold following PPVL together with a significant increase in plasma nitrite and nitrate. Treatment with NAC inhibited the formation of F 2 -isoprostanes as well as the increase in plasma nitrite and nitrate. Hemodynamic studies in anesthetized rats showed that following PPVL, cardiac output and portal pressure increased, and systemic vascular resistance decreased, consistent with the development of a hyperdynamic circulation. These changes were prevented by chronic administration of NAC. We conclude that NAC prevents the development of the hyperdynamic circulation and that the formation of reactive oxygen species may be important in the pathogenesis of these hemodynamic changes.
Researchers identify possible physical marker of Gulf war illness
Authors: B. Roehr
Journal: BMJ (2013)

A functional change in a region of the brain may characterize what has come to be called Gulf war illness, a new study says. It says that this is the first time that a unique physical trait has been associated with the mysterious constellation of symptoms that characterize the condition.

Nearly a third of US soldiers who served in the 1990 Gulf war have reported symptoms that include pain, fatigue, and headaches, often accompanied by cognitive and gastrointestinal dysfunction. But identifying physical markers of the disease has proved elusive.

The 31 veterans who participated in the study underwent an intense three day battery of …
THE HISTOPATHOLOGY OF THE PSYCHOSES WITH SUBACUTE BACTERIAL AND CHRONIC VERRUCOSE RHEUMATIC ENDOCARDITIS
Authors: Walter L. Bruetsch
Journal: American Journal of Psychiatry (1938)

Two types of psychoses with endocarditis have been described. 1. Psychoses with subacute bacterial endocarditis, terminating in death after a sudden onset of the mental symptoms. Histologic examination revealed numerous miliary abscesses and masses of cocci in capillaries of the brain cortex. This type is rarely seen in state hospitals. 2. Psychoses with chronic rheumatic endocarditis. The patients in this group may present any reaction type. Some of the cases were diagnosed as dementia præcox, other patients as manic-depressives or involutional psychoses. A 62-Year-old patient with a rheumatic infarction of the parietaloccipital region was classified as senile psychosis. The anatomical findings in the brain consisted of small or large areas of infarction, being usually the result of rheumatic-endarteritic changes. Or the brain was grossly normal, but microscopic examination disclosed numerous acellular areas, an occasional granuloma, and small connective tissue scars. In one instance a rheumatic encephalitis was present.
Effect of computerised evidence based guidelines on management of asthma and angina in adults in primary care: cluster randomised controlled trial
Authors: M. Eccles
Journal: BMJ (2002)

<h3>Abstract</h3> <b>Objective:</b> To evaluate the use of a computerised support system for decision making for implementing evidence based clinical guidelines for the management of asthma and angina in adults in primary care. <b>Design:</b> A before and after pragmatic cluster randomised controlled trial utilising a two by two incomplete block design. <b>Setting:</b> 60 general practices in north east England. <b>Participants:</b> General practitioners and practice nurses in the study practices and their patients aged 18 or over with angina or asthma. <b>Main outcome measures:</b> Adherence to the guidelines, based on review of case notes and patient reported generic and condition specific outcome measures. <b>Results:</b> The computerised decision support system had no significant effect on consultation rates, process of care measures (including prescribing), or any patient reported outcomes for either condition. Levels of use of the software were low. <b>Conclusions:</b> No effect was found of computerised evidence based guidelines on the management of asthma or angina in adults in primary care. This was probably due to low levels of use of the software, despite the system being optimised as far as was technically possible. Even if the technical problems of producing a system that fully supports the management of chronic disease were solved, there remains the challenge of integrating the systems into clinical encounters where busy practitioners manage patients with complex, multiple conditions.
Human Serum Activities against Hemophilus influenzae, Type b
Authors: Porter Anderson, Richard B. Johnston, David H. Smith
Journal: Journal of Clinical Investigation (1972)

Humoral immunity to Hemophilus influenzae, type b was studied in normal human adults by means of assays for serum bactericidal and opsonizing activities against the organism and for passive hemagglutinating activity using erythrocytes sensitized with polyribophosphate, the type-specific capsular antigen. Hemagglutinating activity was detectable in about 60% of the 114 sera tested. Serum bactericidal and opsonizing activities were found in all sera tested; the levels in some sera, however, were quite low. The antibacterial activities were due not only to antibodies directed against the polyribophosphate capsule but also to antibodies that appear to be directed against somatic antigens. Type b strains differed in their susceptibility to the antisomatic antibodies of particular sera but were uniformly sensitive to anticapsular antibody.
The Clinical Approach to the Homosexual Patient
Authors: WILLIAM F. OWEN
Journal: Annals of Internal Medicine (1980)

Since publication of the Kinsey report more than 30 years ago, which estimated that 10% of the white American male population was predominantly or exclusively homosexual, several studies have indicated that heterosexuals and homosexuals cannot be distinguished on the basis of psychological adjustment or sexual response. Recent studies have also indicated the absence of homosexual stereotypes; homosexual men and women are quite diverse in the way they organize their lives sexually as well as socially. The implication of this finding for physicians is that a complete history, including sexual history, is necessary in any patient regardless of sexual orientation to determine factors that may be placing the patient at an increased risk for disease. Additionally, the primary care physician may be called upon by the homosexual patient to provide psychosexual counselling or treatment of sexual dysfunctions. Certain verbal and nonverbal signals may facilitate or inhibit the relationship between the physician and the homosexual patient. Homosexual patients may need special reassurance about confidentiality in the doctor-patient relationship and about the physician's respect for their life-styles and significant relationships.
Campaigners draw attention to disfiguring childhood disease
Authors: Peter Moszynski
Journal: BMJ (2008)

A report from the Association of American Medical Colleges suggests that all 129 member medical schools should prohibit pharmaceutical and devices manufacturers from providing gifts, food, and travel to doctors, faculty members, and students.The report will be considered at the association's meeting in June.The association set up a task force to examine industry funding and to guide the association, medical schools, and teaching hospitals in developing policies and procedures about gifts and funding from industry.The report said that medical schools and teaching hospitals had become increasingly dependent on industry support for their core educational missions."This reliance raises concerns because such support, including gifts, can influence the objectivity and integrity of academic teaching, learning, and practice, thereby calling into question the commitment of academia and industry together to promote the public's interest by fostering the most cost-effective, evidencebased medical care possible."The report called on academic medical centers "to accelerate their adoption of policies that better manage, and when necessary, prohibit, academic-industry interactions that can inherently create conflicts of interest and undermine standards of professionalism."It concluded, "Industry should voluntarily discontinue those practices that compromise professionalism as well as public trust."The New York Times noted that medical schools, with their prominent professors and impressionable trainees, were particularly attractive targets for marketing (28 April; www.nytimes.com/
ATAC trial did not report interim results
Authors: M. Baum
Journal: BMJ (2003)

EDITOR—We agree with Goodare et al that it is inappropriate to publish interim analyses.1 However, the results of the ATAC (arimidex, tamoxifen, alone or in combination) trial published in the Lancet were the first major analysis as fully defined in the protocol, not an interim analysis.2

The statistical power of the trial, defined in the protocol, determined that this analysis would be triggered at 1056 events. Using first event as the primary end point in breast cancer trials is …
Policy holders get $1.5bn rebate from health insurance firms
Authors: E. Davies
Journal: BMJ (2012)

US consumers saw nearly $1.5bn (£0.9bn; €1.2bn) in insurance rebates and overhead cost savings in 2011 because of the medical loss ratio provision in the Affordable Care Act.

The figure comes from a new Commonwealth Fund report into the requirement, which demands that health insurers spend at least 80% of their income from health insurance premiums on treatment of patients or on quality …