tbuckley/cabot-search huggingface dataset:
Medical Ethics — Malpractice and the Conscience of the Practitioner
Authors: William J. Curran
Journal: New England Journal of Medicine (1971)

AN aftermath of the recent changes in abortion laws in various states has been the fear of some medical practitioners that any refusal on their part to perform an abortion or to take part in an abortion procedure might subject them to legal action, or to harassment, or to discharge from the staff of a hospital. The serious discussion of a constitutional, legal right to an abortion on the part of a woman has provoked the argument that the pregnant patient can require her physician to perform an abortion at her request.In New York, after the decision of Stewart . . .
Roles of AKT and sphingosine kinase in the antiapoptotic effects of bile duct ligation in mouse liver
Authors: Yosuke Osawa, Yusuf A. Hannun, Richard L. Proia, David A. Brenner
Journal: Hepatology (2005)

Tumor necrosis factor (TNF) receptor- and Fas-mediated apoptosis are major death processes of hepatocytes in liver disease. Although antiapoptotic effects in the injured liver promote chronic hepatitis and carcinogenesis, scant information is known about these mechanisms. To explore this issue, we compared acute liver injury after TNF-alpha or anti-Fas antibody (Jo2) between livers from sham-operated mice and chronic injured liver via bile duct ligation (BDL). BDL inhibited hepatocyte apoptosis induced by TNF-alpha but not by Jo2. On the other hand, BDL inhibited the massive hemorrhage seen in livers treated with either TNF-alpha or Jo2. Inactivation of AKT blocked the antiapoptotic effect of BDL. Sphingosine kinase knockout mice also lost the antihemorrhagic effect of BDL and attenuated the antiapoptotic effects of BDL. In bile duct-ligated livers, hepatic stellate cells (HSCs) were activated and produced tissue inhibitor of metalloproteinase 1 in a sphingosine kinase (SphK)-1-dependent mechanism. In conclusion, BDL exerts antiapoptotic effects that appear to require activation of AKT in hepatocytes and SphK in HSCs.
King Death: The Black Death and Its Aftermath in Late-Medieval England
Authors: John Muendel
Journal: JAMA (1997)

The Black Death of 1348-1350 is without a doubt the most celebrated case of bubonic plague. By the 14th century, Christian ships, designed to withstand the choppy waters of the Atlantic year-round, passed through the Strait of Gibraltar, carrying the disease into northern realms via the fleas of the black rats that had climbed aboard. Although areas with different ecologies responded to the plague with varying degrees of contagion, the pestilence, originating in China, wiped out at least one third of the population of Europe. In recent years, however, scholars have tended to downplay the demographic losses of the Black Death because, beginning almost a century before, the effects of an over-crowded Europe were already taking place as the failure of agricultural resources to meet the demands of a bloated population caused famine and scarcity, and consequently a decided plunge in the number of European inhabitants. In his
Savings From Outpatient Antibiotic Therapy for Osteomyelitis
Authors: John M. Eisenberg
Journal: JAMA (1986)

Clinical, economic, and epidemiologic data were used to compare the costs of conventional inpatient care of osteomyelitis with the costs of early-discharge treatment using a once-daily parenteral antibiotic at home. Estimated expenses included inpatient medical care, outpatient visits, supplies, child care, home care, transportation, and lost productivity. Early-discharge treatment was associated with lower medical direct, nonmedical direct, and indirect expenses than conventional inpatient treatment. Estimated savings per patient ranged from $510 to $22,232 (demonstrating the wide differences in estimated savings when different sources of data on hospital costs are used). These savings are due to large decreases in inpatient costs, which are partially offset by increased outpatient costs. However, because outpatient costs are more often borne by patients than are inpatient costs, early-discharge treatment could be more expensive from the patient's perspective, despite its savings for the hospital and for society as a whole. (<i>JAMA</i>1986;255:1584-1588)
Cause of AIDS
Authors: G C Cook
Journal: BMJ (1996)

Chlamydial infection is asymptomatic in England as well as Tanzania EDITOR,-H Grosskurth and colleagues con- clude that infection with Chlamydia trachomatis is commonly asymptomatic among rural Tanza- nian men.'In our experience, it is commonly asymptomatic among urban men in Lancashire, England.During April 1994 to April 1995, 84 male patients were seen in whom C trachomatis infection was diagnosed on culture.Of these, only 43 complained of urethral discharge or dysuria, or both.Forty one had no symptoms of urethritis.It is our policy to trace all sexual con- tacts of patients infected with C trachomatis.Eighteen of the 84 patients were contacts, but only one was symptomatic.The remaining 66, who were not known contacts, were diagnosed by routine screening.C trachomatis is a common cause of sexually transmfiitted diseases world wide and if not treated can lead to severe complications, especially in women.2Since 1988 it has been our policy to screen all men and women attending our department for C trachomatis infection.Some authors have argued against universal screening of men attending sexually transmitted diseases clinics,3 but, given our experience and that the true cost of any undiagnosed genital chlamydial infection to the community will be high, we will continue our current policy.We believe that the "syndromic approach" to the management of sexually transmitted diseases will not adequately address the impact of asymptomatic diseases and may lead to major gaps in programmes to control sexually transmitted diseases.
Physical activity to prevent obesity in young children
Authors: S Kapoor
Journal: BMJ (2006)

Physical activity to prevent obesity in young children Negative outcome or protocol problem?Editor-Although the article by Reilly et al on physical activity to prevent obesity in young children emphasises that adherence to protocol was good, 1 an interview with Reilly on the Today programme (7.20 am, 6 October 2006) cited the difficulty in getting children to increase their activity as much as required-that is, not a negative outcome, but a problem in achieving sufficient increase to make the intervention effective.Which was the case?
Abstract 2547: NCI-60 combination screening matrix of approved anticancer drugs
Authors: Susan L. Holbeck, Jerry M. Collins, James H. Doroshow
Journal: Cancer Research (2011)

Abstract Anticancer drugs are rarely curative as single agents, thus most treatment regimens utilize a combination of agents. Selection of rational combinations based upon presumed mechanisms of action is an active area of research. Nonetheless, treatment regimens may have built up over time by addition of new agents to existing standards of care. In order to establish a framework for extending our understanding combination therapy, we have initiated an additional approach: the systematic testing of all pairwise combinations of FDA-approved anticancer drugs in the NCI-60 panel of human tumor cell lines. About 100 small molecule drugs are approved for cancer treatment worldwide – testing all 5000 pairwise combinations in each of 60 cell lines will require 300,000 experiments. Combinations are tested at 3 or more concentrations of each agent, and single agents are tested on the same plates, requiring ∼ 5 million wells. To date, about 100 pairs of drugs have been tested in the NCI-60 in a pilot phase – the high-throughput phase has just begun. Some combinations of drugs, such as bortezomib combined with cladribine, show better than single agent activity in nearly all cell lines tested. Other combinations, such as doxorubicin plus lapatinib, show more restricted benefit, with some cell lines showing enhanced growth inhibition or cell kill, while in other cell lines the combination is antagonistic or identical to the more active single agent. The NCI-60 panel of cell lines has been extensively molecularly characterized, with publicly available data including gene mutation, DNA copy number, DNA methylation, and expression of mRNA, protein and microRNA. The patterns of cell line sensitivity for a particular drug combination can be used to probe these molecular characterization data, generating hypotheses about potential predictive markers and/or mechanisms of action. Probing the doxorubicin plus lapatinib patterns reveals a strong correlation with MDR activity, with high MDR expressing lines showing enhanced combination activity. The most promising combinations identified from NCI-60 testing are being tested in vivo to determine the therapeutic index. Already 2 combinations have demonstrated promising xenograft activity. The combination screening data, along with tools to analyze the data, will be made available to the public through the NCI web site. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2547. doi:10.1158/1538-7445.AM2011-2547
Effect of hydrogen peroxide on prostaglandin production and cellular integrity in cultured porcine aortic endothelial cells.
Authors: A R Whorton, M E Montgomery, R S Kent
Journal: Journal of Clinical Investigation (1985)

Oxidative damage to the vascular endothelium may play an important role in the pathogenesis of atherosclerosis and aging, and may account in part for reduced vascular prostacyclin (PGI2) synthesis associated with both conditions. Using H2O2 to induce injury, we investigated the effects of oxidative damage on PGI2 synthesis in cultured endothelial cells (EC). Preincubation of EC with H2O2 produced a dose-dependent inhibition (inhibitory concentration [IC50] = 35 microM) of PGI2 formation from arachidonate. The maximum dose-related effect occurred within 1 min after exposure although appreciable H2O2 remained after 30 min (30% of original). In addition, H2O2 produced both a time- and dose-dependent injury leading to cell disruption, lactate dehydrogenase release, and 51Cr release from prelabeled cells. However, in dramatic contrast to H2O2 effects on PGI2 synthesis, loss of cellular integrity required doses in excess of 0.5 mM and incubation times in excess of 1 h. The superoxide-generating system, xanthine plus xanthine oxidase, produced a similar inhibition of PGI2 formation. Such inhibition was dependent on the generation of H2O2 but not superoxide in that catalase was completely protective whereas superoxide dismutase was not. H2O2 (50 microM) also effectively inhibited basal and ionophore A23187 (0.5 microM)-stimulated PGI2 formation. However, H2O2 had no effect on phospholipase A2 activity, because ionophore A23187-induced arachidonate release was unimpaired. To determine the effects on cyclooxygenase and PGI2 synthase, prostaglandin products from cells prelabeled with [3H]arachidonate and stimulated with ionophore A23187, or products formed from exogenous arachidonate were examined. Inhibition of cyclooxygenase but not PGI2 synthase was observed. Incubation of H2O2-treated cells with prostaglandin cyclic endoperoxide indicated no inhibition of PGI2 synthase. Thus, in EC low doses of H2O2 potently inhibit cyclooxygenase after brief exposure whereas larger doses and prolonged exposure are required for classical cytolytic effects. Surprisingly, PGI2 synthase, which is known to be extremely sensitive to a variety of lipid peroxides, is not inhibited by H2O2. Lipid solubility, enzyme location within the EC membrane, or the local availability of reducing factors may explain these results, and may be important determinants of the response of EC to oxidative stress.
Chlormethiazole addiction: unusual presentation.
Authors: J M Cushnie, D I Ben-Tovim, P Kopelman
Journal: BMJ (1978)

1 in 10 (or greater) chance of diagnosing a brain tumour is not to be missed, then referral of all stroke patients with the appropriate evolution would completely swamp the available CAT scanning resources.Stroke evolution is only one factor determining the attitude of a general physician towards the management of a stroke patient.Considering the scarcity and the costliness of the new diagnostic machinery, information is required concerning the incidence of tumour or subdural haematoma in stroke patients as they present on the general medical ward.
Comparison between leukocyte interferon alpha plus ribavirin and R-alpha2B interferon plus ribavirin for treatment of CHC in naive patients: a multicenter randomized Italian study
Authors: Giorgio Barbarini, Giuseppe Barbaro, Adriano Pellicelli, Luigi Fruttaldo, Donato Bacca, Sergio Babudieri, Donato Torre, Giovanni Rizzo, Ruggiero Francavilla, Mauro Annese
Journal: Journal of Hepatology (2002)
On the Failure to Eradicate Measles
Authors: Herbert A. Schreier
Journal: New England Journal of Medicine (1974)

IN 1967, at the American Public Health Association meeting in San Francisco,1 a paper was presented that announced the possibility of complete eradication of measles by the end of that year. Six years later, and some 10 years after the highly effective live measles-virus vaccines were licensed in the United States, we are still faced with a measles problem of epidemic proportions. There is almost uniform agreement that measles is still a problem because of a failure to vaccinate children against the disease.2 , 3 A brief look at the measles vaccination program over the last 10 years will prove useful in . . .
Brain cells can regenerate
Authors: A. Berger
Journal: BMJ (1998)

Scientists have proved that human neurons are able to regenerate. Dr Fred Gage and colleagues at the Salk Institute for Biological Studies in California, together with doctors at the Sahlgrenska University Hospital in Sweden, have shown that new neurons do develop after birth.

This flies in the face of conventional wisdom, which suggests that brain cells, unlike all other cell types, do not reproduce.

Dr Gage's team took postmortem brain tissue from five patients who had received an intravenous injection of …
Collecting patient data will help UK become world leader in research, says Cameron
Authors: A. Gulland
Journal: BMJ (2012)

Relaxing regulations on the collection and use of patient data will help the UK to become the “best place in the world to conduct cutting edge research,” prime minister David Cameron said in a speech at the launch of the Global Health Policy Summit in London.

He told a meeting of around 500 policy makers, politicians, scientists, and business leaders from around the world on 1 August that he had come to “sell what was great about Great Britain.”

He said that changes would be made to the NHS Constitution so that patients would have to opt out if they did not want their data to be collected and used for research …
Angioscopic evaluation of atherosclerotic plaques: Validation by histomorphologic analysis and association with stable and unstable coronary syndromes
Authors: Torsten Thieme, Klaus D. Wernecke, Rudolph Meyer, Elke Brandenstein, Dirk Habedank, Antje Hinz, Stephan B. Felix, Gert Baumann, Franz X. Kleber
Journal: Journal of the American College of Cardiology (1996)
Synthetic isoquinoline in acute respiratory disease.
Authors: J. A. Smith, M. B. Eadie, N. R. Grist, J. H. Lawson, K. W. Martin, I. W. Pinkerton
Journal: BMJ (1968)

progesterone combinations.But so far as the combined preparations are concerned, my find- ings fail to confirm her hypothesis that depression and loss of libido is dose-specific.With the seven different products in use in. the Croydon clinic from J]962 to 1967, the incidence varied from 12.4 to 23.8 % over an average of 21.9 cycles, compared with Dr. Grant's range of from 10 to 34% over an average of 14.9 cycles with the same preparations.For the strongly progestogenic tablets with ethinyl- oestradiol the incidence was 17.2% compared with Dr. Grant's 28%, and with mestranol 16.7% (Dr.Grant 17%), and for the inter- mediate combined tablets with ethinyloestradiol 23.8% (Dr.Grant 20%) and with mestranol 18.8% (Dr.Grant 16%).As in the case of headache, a change from one preparation to another with a different oestrogen/progesterone combination only occasionally resulted in sustained relief, and I had one patient who developed a psychotic depression on Volidan (megestrol acetate, ethinyloestradiol), who later found that her identical twin sister had had a similar reaction on a different compound.That the response is specific there seems little doubt, but, as with the development of migraine, is the specificity as much in the patient as in the pill ?-I am, etc.,
The E280A presenilin 1 Alzheimer mutation produces increased Aβ42 deposition and severe cerebellar pathology
Authors: Cynthia A. Lemere, Francisco Lopera, Kenneth S. Kosik, Corrine L. Lendon, Jorge Ossa, Takaomi C. Saido, Haruyasu Yamaguchi, Andres Ruiz, Alonso Martinez, Lucia Madrigal, Liliana Hincapie, Juan Carlos Arango L., Douglas C. Anthony, Edward H. Koo, Alison M. Goate, Dennis J. Selkoe, Juan Carlos Arango V.
Journal: Nature Medicine (1996)
Primary cutaneous CD30+ T-cell lymphoma responsive to topical imiquimod (AldaraR)
Authors: B. Didona, R. Benucci, P. Amerio, F. Canzona, O. Rienzo, R. Cavalieri
Journal: British Journal of Dermatology (2004)

CD30+ anaplastic large cell lymphoma is a primary cutaneous lymphoproliferative disorder with a high rate of spontaneous regression (almost 25%). The suggested therapies are radiation, surgery and methotrexate. We describe two patients with nonregressing primary cutaneous CD30+ T‐cell lymphoma that was successfully treated with topical imiquimod 5% cream (Aldara®, 3M) three times weekly for 6 weeks. In both cases we obtained complete clinical remission, confirmed by histology. No recurrences were observed during the following 8 months. We consider that topical application of an immune response modifier, such as imiquimod, could be a good alternative to other potentially more dangerous or aggressive treatments.
Life threatening lactic acidosis
Authors: M Lemyze, J F Baudry, F Collet, N Guinard
Journal: BMJ (2010)

An 83 year old woman with diabetes presented to the emergency department with progressive shortness of breath and a two week history of diarrhoea. Her drugs included aspirin, 75 mg four times a day; a combination of irbesartan with hydrochlorothiazide, 300/25 mg four times a day; and metformin, 1000 mg three times a day. She had no previously known renal insufficiency, but on arrival she was oliguric, disoriented, and confused. 

Her respiratory rate was 32 breaths/min, blood pressure was 76/46 mm Hg, heart rate was 125 beats/min, and rectal temperature reached 36.8°C. She had cool and clammy extremities and a persistent skinfold—additional evidence of severe dehydration. Arterial blood gases showed a profound lactic acidosis, with pH 6.72, partial pressure of carbon dioxide (PCO2) 14 mm Hg, partial pressure of oxygen (PO2) 106 mm Hg, bicarbonate 12 mmol/l, and a high lactate concentration of 17.4 mmol/l. Laboratory results showed a normal blood glucose concentration of 9 mmol/l, a serum urea of 22 mmol/l, a serum creatinine of 779 μmol/l, an increased serum potassium concentration of 6.8 mmol/l, and a decreased prothrombin activity of 43% (prothrombin time of 21 seconds). Chest and abdominal examination, chest radiography, urine dipstick, plasma C reactive protein (<5 mg/l), and procalcitonin (<0.5 μg/l) concentrations showed no evidence of an infection.



### 1 What are the differential diagnoses in severe lactic acidosis?

#### Short answer

In the differential diagnosis of severe lactic acidosis, poor tissue perfusion and oxygenation are the main considerations, and these occur in septic shock, acute heart failure, unrecognised bowel ischaemia, and acute liver failure. Some drugs can also cause life threatening lactic acidosis, especially metformin and nucleoside reverse transcriptase inhibitors.

#### Long answer

As originally …
Clustering of adenomas in the large intestine.
Authors: T J Eide, T Schweder
Journal: Gut (1984)

In a necropsy study of 68 men and 36 women with single or multiple adenomas of the large intestine the distribution of all adenomas within the bowel in individual patients was examined. Each adenoma was recorded both by its distance in centimetres from the caecal pole and by the intestinal segment in which it was found. Adenomas in individual patients were shown to occur significantly closer together than expected from the general distribution of adenomas within each age group. The statistically significant, but not very strong effect of clustering may be caused by the existence of one or more fields of the large intestine specific to individuals who have a higher than average propensity for neoplastic development.
Occluded Pancreatic Endoprostheses - Analysis of the Clogging Material
Authors: M. Provansal-Cheylan, J. P. Bernard, A. Mariani, N. Soehendra, M. Cremer, J. Sahel, H. Sarles
Journal: Endoscopy (1989)

One of the most common late complications of transpapillary pancreatic endoprostheses is clogging of the endoprosthesis lumen. In this study we analysed the morphology and the biochemical nature of the contents of 10 clogged pancreatic endoprostheses.
Fenofibrate Lowers Plasma Triglycerides and Increases LDL Particle Diameter in Subjects With Type 2 Diabetes
Authors: Juha Vakkilainen, George Steiner, Jean-Claude Ansquer, Hëlinä Perttunen-Nio, Marja-Riitta Taskinen
Journal: Diabetes Care (2002)

Subjects with type 2 diabetes have an increased risk of coronary artery disease (CAD). The typical dyslipidemia in type 2 diabetes consists of hypertriglyceridemia, low HDL cholesterol level, and preponderance of small, dense LDL particles. Epidemiological studies have linked all these lipid abnormalities with CAD. The Diabetes Atherosclerosis Intervention Study (DAIS) has recently reported that treatment with fenofibrate results in favorable changes in the plasma lipid profile and a significant reduction in the progression of CAD in subjects with type 2 diabetes (1). We have now determined the long-term effect of fenofibrate on LDL peak particle diameter in 46 Finnish DAIS study participants with type 2 diabetes.

The baseline characteristics in our DAIS subpopulation were similar to those in the whole cohort (2). Subjects were randomly assigned micronized 200 mg fenofibrate once daily ( n =25) or placebo ( n =21) for at least 3 years. Data obtained at randomization were used as the baseline data, and …