tbuckley/cabot-search huggingface dataset:
Tragic choices in health care: lessons from the Child B case
Authors: C. Ham
Journal: BMJ (1999)

Four years ago the case of Jaymee Bowen, more commonly known as Child B, captured the newspaper headlines. The coming together of a father who was determined to seek the treatment he believed was best for his daughter, doctors who disagreed about what treatment was appropriate, health service managers who were prepared to take a stand on the use of resources on services of questionable effectiveness, lawyers willing to test the decision of the health authority in the courts, and journalists who saw the case as exemplifying the dilemmas of health service decision making meant that Jaymee's story caught the public imagination and highlighted the challenge of rationing.1 The way in which the case was handled contains important lessons for decision makers in health authorities and primary care groups charged with making difficult choices in health care.

#### Summary points

The Child B case showed that decisions on funding experimental and costly treatments raise ethical and practical dilemmas

Concern to use resources for the benefit of the whole population has to be weighed against the urge to respond to the needs of individuals

The decision making process must be rigorous and fair

Decision makers should explain the reasons behind decisions, show that these are relevant, give the opportunity for appeal, and ensure the process is regulated

Not all these conditions were fulfilled in the Child B case—health authorities and primary care groups should learn from this experience

To understand the significance of the case it is important to recount some of the detail of what happened at the time. Jaymee Bowen was an articulate and lively 6 year old when, in 1990, she was diagnosed as having non-Hodgkin's lymphoma. She was treated at Addenbrooke's Hospital in Cambridge, but in 1993 was diagnosed as having a second cancer, acute myeloid leukaemia. Jaymee underwent …
Immortalization of osteoclast precursors by targeting Bcl -XL and Simian virus 40 large T antigen to the osteoclast lineage in transgenic mice.
Authors: T A Hentunen, S V Reddy, B F Boyce, R Devlin, H R Park, H Chung, K S Selander, M Dallas, N Kurihara, D L Galson, S R Goldring, B A Koop, J J Windle, G D Roodman
Journal: Journal of Clinical Investigation (1998)

Cellular and molecular characterization of osteoclasts (OCL) has been extremely difficult since OCL are rare cells, and are difficult to isolate in large numbers. We used the tartrate-resistant acid phosphatase promoter to target the bcl-XL and/or Simian Virus 40 large T antigen (Tag) genes to cells in the OCL lineage in transgenic mice as a means of immortalizing OCL precursors. Immunocytochemical studies confirmed that we had targeted Bcl-XL and/or Tag to OCL, and transformed and mitotic OCL were readily apparent in bones from both Tag and bcl-XL/Tag mice. OCL formation in primary bone marrow cultures from bcl-XL, Tag, or bcl-XL/Tag mice was twofold greater compared with that of nontransgenic littermates. Bone marrow cells from bcl-XL/Tag mice, but not from singly transgenic bcl-XL or Tag mice, have survived in continuous culture for more than a year. These cells form high numbers of bone-resorbing OCL when cultured using standard conditions for inducing OCL formation, with approximately 50% of the mononuclear cells incorporated into OCL. The OCL that form express calcitonin receptors and contract in response to calcitonin. Studies examining the proliferative capacity and the resistance of OCL precursors from these transgenic mice to apoptosis demonstrated that the increased numbers of OCL precursors in marrow from bcl-XL/Tag mice was due to their increased survival rather than an increased proliferative capacity compared with Tag, bcl-XL, or normal mice. Histomorphometric studies of bones from bcl-XL/Tag mice also confirmed that there were increased numbers of OCL precursors (TRAP + mononuclear cells) present in vivo. These data demonstrate that by targeting both bcl-XL and Tag to cells in the OCL lineage, we have immortalized OCL precursors that form bone-resorbing OCL with an efficiency that is 300-500 times greater than that of normal marrow.
Detection of recipient's cells in liver graft using antibodies to mismatched class I MHC antigens
Authors: A. Grassi, M. Susca, M. Guidi, M. Ravaioli, E. De Raffele, G. Grazi, A. Cavallari, A. D'Errico, A. Bontadini, M. Strazzabosco, D. Zauli, F.B. Bianchi, G. Ballardini
Journal: Journal of Hepatology (2003)
Fibrates and medroxyprogesterone acetate induce apoptosis of primary Burkitt's lymphoma cells and cell lines: potential for applying old drugs to a new disease
Authors: S L Fenton, Q T Luong, A Sarafeim, K J W Mustard, J Pound, J C Desmond, J Gordon, M T Drayson, C M Bunce
Journal: Leukemia (2003)
Giant atypical lymphoid hyperplasia of the colon
Authors: W.-C. Huang, T.-Y. Hsieh, H.-C. Chu, T.-K. Chao, T.-Y. Huang
Journal: Endoscopy (2010)

A 57-year-old woman with a history of acute myelogenous leukemia had received chemotherapy. Thereafter, she was relatively stable with complete remission.
Clinical Investigation and JAMA
Authors: Thomas P. Stossel
Journal: JAMA (1987)

Modern medicine is an increasingly complex and troubled profession, but most will agree that science is at its heart. People know this and demand technical and scientific excellence as well as caring from their physicians. Consumers' wishes aside, the constant evaluation and reevaluation of the knowledge base in medicine—pathogenesis, diagnosis, and therapy—is a medical categorical imperative. Physical, biologic, and behavioral sciences underpin medicine, but the science that is unique to medicine is clinical investigation. All kinds of research are needed. The fund of medical knowledge seems vast indeed, but the reservoir of ignorance is even greater. The revolutions of the past decade in molecular genetics, cell biology, neurobiology, and artificial intelligence are dazzling, and the opportunities to diminish this reservoir have never been better. The exploding possibilities, however, are constrained by limited resources, a limitation that is all the more frustrating because of the opportunities. Here, the practicing physician can
Voluntary National Examining Board.
Authors: Emil Amberg
Journal: JAMA (1902)

Detroit, Mich., May 12, 1902. <h3>To the Editor:</h3> —I again endorse the idea of a voluntary national examining board. The establishment of such a board and the movement toward interstate reciprocity can go very well in hand, and will probably do so for some time to come. It is to be hoped that all those who will participate in the meeting of the American Medical Association at Saratoga-especially those who will attend in an official capacity—will study the subjects and become familiar with the various sides of the questions. Some information may be furnished by the confederation of members of Reciprocating State Medical Examining and Licensing Boards, a meeting of which, as I understand, will take place in Chicago, May 20. Very truly yours,
Roles of Angiotensin II Type 2 Receptor Stimulation Associated With Selective Angiotensin II Type 1 Receptor Blockade With Valsartan in the Improvement of Inflammation-Induced Vascular Injury
Authors: Lan Wu, Masaru Iwai, Hironori Nakagami, Zhen Li, Rui Chen, Jun Suzuki, Masahiro Akishita, Marc de Gasparo, Masatsugu Horiuchi
Journal: Circulation (2001)

Background To investigate the effect of angiotensin (Ang) II type 1 receptor (AT 1 ) blocker on vascular remodeling and explore the possibility of the involvement of Ang II type 2 receptor (AT 2 ) stimulation in this process, we examined the effects of the selective AT 1 blocker valsartan on the vascular injury in wild-type (Agtr2+) and AT 2 -null (Agtr2−) mice. Methods and Results Neointima formation and the proliferation of vascular smooth muscle cells (VSMCs) induced by cuff placement on the femoral artery were greater in Agtr2− mice than those in Agtr2+ mice. Treatment of mice with valsartan at a dose of 1 mg · kg −1 · d −1 , which did not influence systolic blood pressure, significantly decreased neointima formation and the proliferation of VSMCs, whereas the valsartan was less effective in Agtr2− mice. Moreover, cuff placement increased the expression of monocyte chemoattractant protein-1 (MCP-1); inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β; and infiltration of CD45-positive leukocytes and macrophages in the injured arteries and further enhanced them in Agtr2− mice, suggesting the antagonistic effects of AT 1 and AT 2 for vascular inflammation. Valsartan attenuated the expression of MCP-1, TNF-α, IL-6, IL-1β, and infiltration of leukocytes and macrophages in the injured arteries; however, these effects of valsartan were less prominent in Agtr2− mice. Conclusions These results suggest that the stimulation of the AT 2 receptor after AT 1 blockade is important in the improvement of the inflammatory vascular injury.
Prototype matching together with operational criteria would make a better approach to psychiatric classification
Authors: PICHET UDOMRATN
Journal: World Psychiatry (2012)

In 1980, the American Psychiatric Association introduced panic disorder in the DSM-III and provided diagnostic criteria for that new disorder 1. At that time, several Asian psychiatrists manifested a resistance to use the new diagnosis, due to the lack of a corresponding terminology in their native languages 2. This would have not happened if in DSM-III a prototype had been provided as an example or illustrative case. 

Actually, one prototype may not be sufficient to make a diagnostician fully understand a particular disorder, especially if it has a variety of clinical presentations, as is the case for panic disorder (the so-called “many faces of panic disorder“ 3). Moreover, prototypes from one country might not fit well in another country where culture and beliefs are different. For example, southern Thai women with gastrointestinal symptoms, who would be labeled as having panic disorder by Western psychiatrists, may present themselves as having “rook lom” (“wind illness”) 4. This comes from the traditional belief that humans are composed of four elements: earth, water, wind (lom), and fire.

In this particular context, the panic disorder prototype for Thai clinicians could be adapted as follows: “Patients who match this prototype have many clinical presentations. In southern Thailand, they may have initial symptoms of feeling the “lom” moving upward in the abdomen and the patient may try to push down on the abdomen in an attempt to force the “lom” out. Then the “lom” may still continue to move upward and compress the heart, causing their hearts pounding fast and hard, which may be followed by rapid and deep breathing, and later developing dizziness or headache. Most of them have a fear of “lom” moving into the head, which would cause unconsciousness, or death…”. So, when applying the prototype approach for psychiatric diagnosis, the content needs to be adapted to suit specific cultures and contexts.

Regarding the clinical utility of prototype matching, I agree with Westen’s view that it is clinically helpful and easy to use in everyday practice. Clinicians in both low and middle income countries, who see 50-100 or more cases per day in their outpatient settings, may find the prototype approach to be more practical than extensive interviews to explore fulfillment of the diagnostic criteria of conventional classifications. However, research psychiatrists may not prefer this alternative approach to recruit their patients, due to the necessity to collect homogeneous samples for research purposes and reduce research risk 5.

To sum up, using both the operational and prototype matching approaches for diagnosing psychiatric patients should be recommended. Prototype matching together with operational approaches such as the DSM-like format (diagnostic criteria with arbitrary cutoff points) would aid trainees in clearly understanding mental disorders and would help clinicians to develop mental representations of different kinds of disorders.
Discussing Hidden Bias in Observational Studies
Authors: Paul R. Rosenbaum
Journal: Annals of Internal Medicine (1991)

▪ In observational studies or nonrandomized experiments, treated and control groups may differ in their outcomes even if the treatment has no effect; this may happen if the groups were not comparable before the start of treatment. The groups may fail to be comparable in either of two ways: They may differ with respect to characteristics that have been measured, in which case there is an overt bias, or they may differ in ways that have not been measured, in which case there is a hidden bias. Overt biases are controlled through adjustments, such as matching. Hidden bias is more difficult to address because the relevant measurements are not available. A sensitivity analysis asks how much hidden bias would need to be present if hidden bias were to explain the differing outcomes in the treated and control groups. A sensitivity analysis provides a tangible and specific framework for discussing hidden biases.
The NHS reforms in England: four challenges to evaluating success and failure
Authors: Srinivasa Vittal Katikireddi, Martin McKee, Peter Craig, David Stuckler
Journal: Journal of the Royal Society of Medicine (2014)

Since 1948, the National Health Service (NHS) has undergone repeated organisational changes,1 but none so large or complex as the 2012 Health and Social Care Act (HSCA). Its stated purpose was to liberate the NHS from direct ministerial control, transferring responsibility to the independent body, NHS England, to deliver on an annual mandate from ministers. NHS England oversees local Clinical Commissioning Groups (CCGs), which were intended to allow general practitioners to decide on the commissioning of certain services from ‘any qualified provider’. An extensive network of new entities was created to facilitate this, such as Clinical Senates and Health and Wellbeing Boards, while some existing bodies had their powers enhanced, such as the economic regulator Monitor.

The resulting NHS system is extremely complex, with many uncertainties about how it should work and examples of a reality which differs from stated intentions. For example, the newly ‘liberated’ head of NHS England must now meet with the Secretary of State weekly, so that direct ministerial control continues.

Whenever large-scale reforms take place, they should be accompanied by robust evaluation to inform future policy. The latest change to the English NHS has been described as ‘so large you could probably see it from space’,2 but despite this we may never know its true impact on population health.

Previous NHS reforms illustrate the challenges involved in the HSCA’s evaluation.3,4 A first challenge is political. Politicians resisted proposals to evaluate the introduction of the ‘internal market’ in the 1990s, so its impacts remain debated today. The second challenge is operational. New Labour committed funding to policy evaluations that improved understanding of processes by which change occurred, but failed to incorporate evaluation into actual policy design and implementation, so limiting the validity of their conclusions. This was again the case with the HSCA, as piloting CCGs or other elements of the reform was excluded, so precluding randomised designs which could permit causal inferences.

In 2013, the Department of Health (DH) called for research to evaluate the HSCA’s impact, issuing a second call when DH found submitted bids left ‘significant gaps’ and would not allow ‘an assessment of impact across the whole suite of reforms’.5 Both calls asked for evidence of improved outcomes, with the first call stating: ‘All projects are expected to propose an appropriate explanatory framework or counterfactual, where this is feasible, against which the effects of the reforms can be evaluated and attributed’.6

In this paper we ask, how would we know if the NHS reforms are working or not? We evaluate characteristics of the HSCA that fulfil ‘natural policy experiment’ criteria and propose alternative feasible designs.
CLINICAL, BACTERIOLOGICAL, AND IMMUNOLOGICAL CHARACTERISATION OF AMPICILLIN-RESISTANT HÆMOPHILUS INFLUENZÆ TYPE B
Authors: M.S. Schiffer, R. Schneerson, J. Maclowry, J.B. Robbins, J.W. Mcreynolds, W.J. Thomas, D.W. Bailey, E.J. Clarke, E.J. Mueller, J. Escamilla
Journal: The Lancet (1974)
Portal Diversion
Authors: Thomas E. Starzl
Journal: JAMA (1975)

PORTAL vein diversion has been used for many years to stop or prevent hemorrhage from esophageal varices or, less commonly, to treat intractable ascites. Since both the bleeding and ascites formation are due, at least in part, to blockage of the splanchnic venous return at or near the liver, the objective has been purely hemodynamic: relieve the obstruction, and the resulting portal venous hypertension will also be relieved. Within the last few years, a new dimension has been added to the old operation of portacaval shunt by employing this procedure to favorably alter the course of patients with two inborn errors of metabolism, glycogen storage disease, and type II hyperlipoproteinemia. We will discuss the potential postoperative risks borne by patients submitted to portal diversion for these new indications and the probable mechanisms that explain the benefits of portacaval shunt—these have been clarified by some recent advances in hepatic physiology. <h3>Glycogen</h3>
Cytotoxic and proliferative T cell responses in HIV-1-infected Macaca nemestrina.
Authors: S J Kent, L Corey, M B Agy, W R Morton, M J McElrath, P D Greenberg
Journal: Journal of Clinical Investigation (1995)

Macaca nemestrina has been described as an animal model for acute HIV-1 infection. This animal, unlike most infected humans, appears to contain HIV-1 replication. Therefore analysis of HIV-1-specific proliferative and cytotoxic T lymphocyte (CTL) responses following HIV-1 challenge of M. nemestrina may provide information into the role of such responses in both the control of acute HIV infection and protective immunity. Although CD4+ T cell responses to HIV-1 are generally difficult to detect in HIV-1-infected humans, early and persistent CD4+ T cell proliferative responses to HIV-1 antigens were detected in all HIV-1-inoculated M. nemestrina. HIV-1-specific CD8+ CTL responses were evaluated in PBMC by stimulation with autologous cells expressing HIV-1 genes, limiting dilution precursor frequency analysis, and T cell cloning. CTL reactive with gag, env, and nef were present 4-8 wk after infection, and persisted to 140 wk after infection. The presence of both CD4+ and CD8+ T cell responses before and after clearance of HIV-1 viremia is consistent with a role for these responses in the successful control of HIV-1 viral replication observed in M. nemestrina. Further studies of T cell immunity in these animals that resist disease should provide insights into the immunobiology of HIV-1 infection.
Carbosilane dendrimer nanotechnology outlines of the broad HIV blocker profile
Authors: L. Chonco, M. Pion, E. Vacas, B. Rasines, M. Maly, M.J. Serramía, L. López-Fernández, J. De la Mata, S. Alvarez, R. Gómez, M.A. Muñoz-Fernández
Journal: Journal of Controlled Release (2012)
Mural Thrombus in the Left Atrium Secondary to Transseptal Catheterization of the Left Side of the Heart
Authors: Alan L. Pinkerson, George A. Kelser, Paul C. Adkins
Journal: New England Journal of Medicine (1963)

TRANSSEPTAL catheterization of the left side of the heart, as introduced by Ross et al.,1 has many advantages over previous methods of entering the left chambers of the heart. Studies in animals did not produce permanent injury to the interatrial septum or create shunting mechanisms.2 In a modification of the original procedure, after the needle is passed through the interatrial septum, the sheath catheter is advanced over the needle through the septum and into the left atrium.3 4 5 The large-bore catheter can then be advanced to the left ventricle for pressure recording and angiographic studies, or the needle can be removed . . .
An Educational Program in Digitalis Therapy
Authors: Richard I. Ogilvie
Journal: JAMA (1972)

Of 2,334 medical patients surveyed from 1967 to 1968, 22.9% had received digitalis and 21.4% of digitalis courses resulted in intoxication. Risk factors included old age, impaired renal function, myocardial infarction, severe congestive heart failure, cor pulmonale, excessive doses based on body weight, and loading courses. An educational program in digitalis use with dosage guidelines for digoxin was established. In a repeat survey in 1969 to 1970 only 12.3% of 578 digitalis courses resulted in intoxication. The number of loading courses and the total amount of drug administered as a load were reduced. Fewer patients received a daily maintenance dose of digoxin greater than 2.5μg/lb. Deaths in intoxicated patients decreased. These results indicate that an educational program in digitalis use based on clinical pharmacological principles is a valuable addition to medical education.
Maternal Mortality in Herat Province, Afghanistan, in 2002
Authors: Lynn L. Amowitz, Chen Reis, Vincent Iacopino
Journal: JAMA (2002)

ContextMaternal mortality rates in Afghanistan are estimated to be high.ObjectiveTo assess maternal mortality and human rights issues in Herat, Afghanistan.Design and SettingCross-sectional survey of 4886 Afghan women living in 7 districts in Afghanistan's Herat Province, which included 34 urban and rural villages/towns. Using structured interviews/questionnaires, these women also provided maternal mortality information on 14 085 sisters in March 2002. A survey of health facilities in the 7 districts was also conducted.ParticipantsMean (SE) age of the respondents was 31 (0.23) years (range, 15-49 years). The majority had received 0.35 (0.11) years of formal education and 4233 (88%) were married (mean [SE] age at marriage, 15 [0.3] years; range, 5-39 years). The mean (SE) number of pregnancies was 5.0 (0.08) and live births was 4.6 (0.2).ResultsThere were 276 maternal deaths among 14 085 sisters of the survey respondents (593 maternal deaths/100 000 live births per year; 95% confidence interval [CI], 557-630). Of the 276 deaths, 254 (92%) were reported from rural areas. The respondents reported the following primary problems: lack of food (41%), shelter (18%), and clean water (14%). Of 4721 respondents, 4008 (85%) wanted to get married at the time of their wedding, but 957 (20%) felt family pressure. Of 4703 women, 4117 (87%) had to obtain permission from their husband or male relative to seek health care; only 1% (54/3946) reported not being permitted to obtain prenatal care. Of 4881 women, 597 (12%) used birth control, but 23% (1013/4294) wanted to use birth control. Of 4306 women, 3189 (74%) reported that decisions about the number and spacing of children were made by husband and wife equally. Of 4637 respondents, 519 (11%) reported receiving prenatal care. Of 4624 women, 40 (0.9%) reported a trained health care worker was present at birth; 97% (4475/4612) had untrained traditional birth attendants. Only 17 of 27 listed health facilities were functional and only 5 provided essential obstetric care. Only 35 physicians served a population of 793 214.ConclusionsWomen in most of Herat Province, Afghanistan, have a high risk of maternal mortality. Human rights factors may contribute to preventable maternal deaths in the region.
[213] LIPOPOLYSACCHARIDE EXACERBATES BRAIN EDEMA AND PRODUCES COMA IN CIRRHOTIC RATS THROUGH A CYTOTOXIC MECHANISM: AN ELECTRON-MICROSCOPIC STUDY
Authors: G. Wright, N.A. Davies, D.C. Davies, H.F. Brooks, D.L. Shawcross, S.J. Hodges, R. Jalan
Journal: Journal of Hepatology (2007)