tbuckley/cabot-search huggingface dataset:
Online medical genetics resources: a US perspective
Authors: R. A Pagon
Journal: BMJ (2001)

Over the past decade daily advances in gene discovery fuelled by the human genome project have propelled molecular genetic testing into mainstream medicine. Molecular genetic testing is a sensitive, cost effective means of diagnosis, testing for carrier status, and prenatal diagnosis for many inherited disorders, and it is increasingly used for predictive and predispositional testing. Those who rely on genetic testing find it a challenge keeping up to date with information, particularly when guidelines for use lag behind the availability of tests. We looked critically at online resources relevant to geneticists, providers of primary care (who have been identified by their patients as the primary source of information on genetic testing (www.ama-assn.org/ama/pub/article/2304-2937.html)), and informed patients. 1 2

#### Summary points

For geneticists, web based resources describe mendelian disorders, genetic testing in specific inherited disorders, ethical issues and resources, and protocols for screening newborn infants

Few resources exist for providers of primary care, who need tools to identify high risk patients and guidelines on effective interventions

Websites and directories provide information for consumers on lay organisations, the management of disease, patient advocacy, and support services

We relied on our experience as medical geneticist, teachers of medical students, residents and physicians in internal medicine and family practice, and medical librarians; our participation in genetics resources on the web (GROW), which promotes the development of high quality accessible internet resources on genetics3; and the genetics in primary care project, administered by the Society for Teachers of Family Medicine and cofunded by the Health Resources and Services Administration, the National Institutes of Health, and the Agency for Health Care Policy and Research (www.mchb.hrsa.gov/html/genetics.html). We selected resources that we determined to be of high quality by using the Mitretek criteria for evaluating health information on the internet (see BMJ 's website).4

#### Uses of molecular genetic testing

Diagnosis (Friedreich's ataxia, …
Phase 1 and pharmacologic study of MS-275, a histone deacetylase inhibitor, in adults with refractory and relapsed acute leukemias
Authors: Ivana Gojo, Anchalee Jiemjit, Jane B. Trepel, Alex Sparreboom, William D. Figg, Sandra Rollins, Michael L. Tidwell, Jacqueline Greer, Eun Joo Chung, Min-Jung Lee, Steven D. Gore, Edward A. Sausville, James Zwiebel, Judith E. Karp
Journal: Blood (2006)
Response to the Letter by Pfützner and Forst
Authors: Karsten Jungheim, Theodor Koschinsky
Journal: Diabetes Care (2002)

Pfutzner and Forst (1) report that they found no significant blood glucose (BG) differences between the arm and finger during 1 ) BG decrease induced by intravenous insulin injection, and 2 ) BG increase and decrease induced by a standardized meal in combination with subcutaneous insulin injection.

As previously suggested by Pfutzner and Forst, the observed differences between our data and their observations are caused by differences in experimental design. Our study protocol aimed at rapid BG decreases and achieved a mean BG change at the finger (averaged over total decline) of 3 mg · dl−1 · min−1. Hypoglycemic values at the finger were reached faster after insulin injection. This velocity has not been repeated by Pfutzner and Forst, as their mean rate of BG decline did not exceed 2 mg · dl− · min−1 during the first hour after insulin injection and fell below 1 mg · dl−1 · min …
Statin-Induced Breast Cancer Cell Death: Role of Inducible Nitric Oxide and Arginase-Dependent Pathways
Authors: Srigiridhar Kotamraju, Carol L. Willams, Balaraman Kalyanaraman
Journal: Cancer Research (2007)

Abstract Statins are widely used cholesterol-lowering drugs that selectively inhibit the enzyme 3-hydroxy-3-methylglutaryl CoA reductase, leading to decreased cholesterol biosynthesis. Emerging data indicate that statins stimulate apoptotic cell death in several types of proliferating tumor cells, including breast cancer cells, which is independent of its cholesterol-lowering property. The objective here was to elucidate the molecular mechanism(s) by which statins induce breast cancer cell death. Fluvastatin and simvastatin (5–10 μmol/L) treatment enhanced the caspase-3–like activity and DNA fragmentation in MCF-7 cells, and significantly inhibited the proliferation of MCF-7 cells but not MCF-10 cells (noncancerous epithelial cells). Statin-induced cytotoxic effects were reversed by mevalonate, an immediate metabolic product of the acetyl CoA/3-hydroxy-3-methylglutaryl CoA reductase reaction. Both simvastatin and fluvastatin enhanced nitric oxide (·NO) levels which were inhibited by mevalonate. Statin-induced ·NO and tumor cell cytotoxicity were inhibited by 1400W, a more specific inhibitor of inducible nitric oxide synthase (iNOS or NOS II). Both fluvastatin and simvastatin increased iNOS mRNA and protein expression. Stimulation of iNOS by statins via inhibition of geranylgeranylation by GGTI-298, but not via inhibition of farnesylation by FTI-277, enhanced the proapoptotic effects of statins in MCF-7 cells. Statin-mediated antiproliferative and proapoptotic effects were exacerbated by sepiapterin, a precursor of tetrahydrobiopterin, an essential cofactor of ·NO biosynthesis by NOS. We conclude that iNOS-mediated ·NO is responsible in part for the proapoptotic, tumoricidal, and antiproliferative effects of statins in MCF-7 cells. [Cancer Res 2007;67(15):7386–94]
Measurement of trypsin in duodenal juice by radioimmunoassay.
Authors: G Lake-Bakaar, S McKavanagh, C E Rubio, O Epstein, J A Summerfield
Journal: Gut (1980)

Trypsin in duodenal aspirate and pure pancreatic juice samples has been measured by both radioimmunoassay and enzymatic mathods. The radioimmunossay has been shown to be specific and to detect trypsin in the presence of aprotinin (Trasylol). In duodenal juice samples from control subjects and from patients with primary biliary cirrhosis a good correlation was obtained between both immunoreactive trypsin concentration and trypsin activity. The immunoreactive trypsinogen concentration in pure pancreatic juice also correlated well with activated trypsin activity. The mean immunoreactive trypsin concentration and the concentration of enzymatically inert immunoreactive trypsin in duodenal juice samples from patients with primary biliary cirrhosis were significantly lower than controls, suggesting pancreatic hyposecretion in this disease. After five duodenal juice samples had been stored for three months at -70 degrees C, immunoreactive trypsin concentration in samples stored without Trasylol were reduced by 12 . 0 +/- 4 . 2 (mean +/- SD) times the concentration of samples stored in Trasylol. Trypsin autodegradation continues even at -70 degrees C; Trasylol protects against this. Radioimmunoassay is a reliable method of trypsin estimation in duodenal juice and has advantages over conventional enzymatic analysis.
Acute Gaseous Cholecystitis
Authors: John F. Gowdey, N. Newell Copeland
Journal: New England Journal of Medicine (1950)

THE preoperative diagnosis of gaseous cholecystitis has been comparatively rare, and in the absence of surgical or post-mortem examination, its detection is only possible by roentgenographic examination of the gall-bladder region. There is no way to distinguish gaseous or emphysematous cholecystitis from other cases of cholecystitis without such a procedure.Kirchmayr1 first drew attention to this interesting entity in 1925, describing the operative finding of a gangrenous gall bladder, distended with gas and pus, the walls of which showed emphysematous blebs. Hegner,2 in 1931, reported a case of gaseous pericholecystitis with cholecystitis and cholelithiasis, diagnosed radiographically, evidently the first preoperatively . . .
Rubbish in the Red Cell
Authors: David G. Nathan
Journal: New England Journal of Medicine (1969)

The role of the erythrocyte is simple and uncomplicated: it transports oxygen and carbon dioxide in the blood. To accomplish this gaseous transfer, the erythrocyte must traverse capillaries no greater than its own diameter and sometimes even smaller. Passage through some of these straitened gates requires that the cell fold upon itself, elongate or assume the form of a parachute.1 Obviously, the cell must remain plastic and flexible to achieve these alterations in shape without rupture. Therefore, the flow characteristics of the intracellular solution of hemoglobin and enzymes must not be disturbed by the presence of concretions. The membrane itself . . .
Pressure-Volume Changes in the Forearm Veins of Man During Hyperventilation12
Authors: John W. Eckstein, William K. Hamilton, John M. McCammond
Journal: Journal of Clinical Investigation (1958)

Peripheral venous pressure is known to fall duringvoluntaryhyperventilation (2).Mean (3) found this pressure reduction to be accompanied by a decrease in the volume of small segments of superficial forearm veins.He regarded the vol- ume change as a mechanical phenomenon sec- ondary to the fall in venous pressure and the as- pirating effect of the ventilatory efforts.In more recent studies (4, 5) the pressure in temporarily isolated forearm veins was found to rise during overbreathing, indicating an increase in venous tone.From these reports it is evident that the forearm venous volume may decrease during hy- perventilation and that the change may be at- tributed to two factors-a fall in intraluminal pressure and active venous constriction.The ex- periments reported here were designed to assess the importance of each of these factors in the in- tact human forearm and to determine if the venous responses to hyperventilation with associated hy- pocapnia are different from the responses to hyperventilation when carbon dioxide is added to the inspired air. METHOD AND PROCEDUREForearm venous pressure-volume curves were obtained by the plethysmographic method of Litter, Wood, and Wilkins (6, 7).In this procedure the forearm is en- closed in a tall plethysmograph and water is added to a level such that the external pressure on the arm is greater than venous pressure but less than diastolic ar- terial pressure.The arterial inflow continues and drives venous pressure in the segment of limb within the plethysmograph to a height greater than that of the water col-
STANDARDIZATION OF DIGITALIS-Reply
Authors: Robert L. Levy
Journal: JAMA (1934)

<h3>To the Editor:—</h3> The suggestion of Dr. McGuigan that the cat be "left in the laboratory" is, unfortunately, not feasible. The dosage of any form of medication must be gaged by its potency. When the chemical composition of a drug is known, the dose can be expressed in terms of weight or volume. But equivalent weights or volumes of digitalis preparations are not necessarily equal in potency. In the case of biologically standardized products there must be some unit of strength by which the effects on man may be estimated. The term "unit" is one with which the practitioner is already familiar and which he employs daily in prescribing insulin, diphtheria antitoxin and the vitamin products. A unit there must be; and since, in the assay of digitalis, various methods are still in use, accuracy of definition makes it necessary to refer to the "cat unit."
Competition and Cost Containment
Authors: Eli Ginzberg
Journal: New England Journal of Medicine (1980)

Over two years have passed since Prof. Alain Enthoven of Stanford University described in nontechnical language the rationale of his Consumer-Choice Health Plan (CCHP).1 The proposal, developed initially at the request of Secretary Califano, of the Department of Health, Education, and Welfare, failed to win the Administration's support, but in the months since it began to circulate, it has won adherents in the Congress2 3 4 and among businessmen and has informed a growing number of economists and other social scientists concerned with the formulation of public policy for health care and regulation.With rising health-care expenditures likely to exceed $240 billion . . .
Measurement of fibrinogen-fibrin-related antigen in serum as aid to diagnosis of deep vein thrombosis in outpatients.
Authors: D A Tibbutt, C N Chesterman, M J Allington, E W Williams, T Faulkner
Journal: BMJ (1975)

A study of serum levels of fibrinogen-fibrin-related antigen (F.R.-antigen) in outpatients presenting with clinical features suggesting deep vein thrombosis was undertaken. A raised serum level of this antigen (greater than 12 mg/1) is strong evidence in favour of the diagnosis of deep vein thrombosis. It is virtually conclusive evidence if other known causes of a raised level of the antigen are absent. On the other hand, a normal serum level of F.R.-antigen does not exclude even extensive thrombosis, and other objective techniques are required to substantiate the diagnosis.
Methods of hysterectomy: systematic review and meta-analysis of randomised controlled trials
Authors: Neil Johnson, David Barlow, Anne Lethaby, Emma Tavender, Liz Curr, Ray Garry
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objective</b> To evaluate the most appropriate surgical method of hysterectomy (abdominal, vaginal, or laparoscopic) for women with benign disease. <b>Design</b> Systematic review and meta-analysis. <b>Data sources</b> Cochrane Menstrual Disorders and Subfertility Group Trials Register, Cochrane Central Register of Controlled Trials, Medline, Embase, and Biological Abstracts. <b>Selection of studies</b> Only randomised controlled trials were selected; participants had to have benign gynaecological disease; interventions had to comprise at least one hysterectomy method compared with another; and trials had to report primary outcomes (time taken to return to normal activities, intraoperative visceral injury, and major long term complications) or secondary outcomes (operating time, other immediate complications of surgery, short term complications, and duration of hospital stay). <b>Results</b> 27 trials (total of 3643 participants) were included. Return to normal activities was quicker after vaginal than after abdominal hysterectomy (weighted mean difference 9.5 (95% confidence interval 6.4 to 12.6) days) and after laparoscopic than after abdominal hysterectomy (difference 13.6 (11.8 to 15.4) days), but was not significantly different for laparoscopic versus vaginal hysterectomy (difference −1.1 (−4.2 to 2.1) days). There were more urinary tract injuries with laparoscopic than with abdominal hysterectomy (odds ratio 2.61 (95% confidence interval 1.22 to 5.60)), but no other intraoperative visceral injuries showed a significant difference between surgical approaches. Data were notably absent for many important long term patient outcome measures, where the analyses were underpowered to detect important differences, or they were simply not reported in trials. <b>Conclusions</b> Significantly speedier return to normal activities and other improved secondary outcomes (shorter duration of hospital stay and fewer unspecified infections or febrile episodes) suggest that vaginal hysterectomy is preferable to abdominal hysterectomy where possible. Where vaginal hysterectomy is not possible, laparoscopic hysterectomy is preferable to abdominal hysterectomy, although it brings a higher chance of bladder or ureter injury.
Gamma Globulin in Hepatitis
Authors: Saul Krugman
Journal: JAMA (1961)

<h3>To the Editor:—</h3> Thank you for affording me the opportunity to reply to Doctor Albrecht whose views deserve serious consideration. I have received correspondence from other public health officers who share Doctor Albrecht's concern about our recommendations for increasing the dose of gamma globulin in the prevention of infectious hepatitis. Our suggestion for increasing the dose of gamma globulin from 0.01 ml. to 0.06 ml. per pound of body weight was based on our personal evaluation of (1) the results of our studies (<i>JAMA</i><b>174</b>:823, 1960) and (2) the results of controlled studies reported in the literature. Unfortunately, controlled observations on the efficacy of intermediate doses between 0.01 ml. and 0.06 ml. are not available. It is possible that a dose of 0.02 ml. or 0.04 ml. of gamma globulin per pound of body weight may prove to be as effective as the 0.06-ml. dose. The data to support
Does peritransplantation use of rituximab reduce the risk of EBV reactivation and PTLPD?
Authors: Bipin N. Savani, Paula R. Pohlmann, Madan Jagasia, Wichai Chinratanalab, Adetola Kassim, Brian Engelhardt, John Greer, Friedrich Schuening, Stacey Goodman
Journal: Blood (2009)
Teenage Pregnancy and Educational Opportunity
Authors: Neal Devitt
Journal: JAMA (1991)

<h3>To the Editor.</h3> —In his commentary on our high infant mortality rate, Dr Hein<sup>1</sup>recommends an intensive educational program about sexuality and responsible parenthood as a solution to our high teenage pregnancy rate. He makes the assumption that an unplanned pregnancy is an undesired pregnancy. In my experience as the medical director of a community health center serving a predominantly Hispanic and indigent population with a high proportion of teenage pregnancies, many of these pregnancies are not really unplanned. Many young women have told me that while they did not actively seek to become pregnant, they were not disappointed with the result. In analyzing this issue, one must look at the alternatives from the viewpoint of the teenage woman. One must ask whether her life will be appreciably better if she chooses to plan to avoid pregnancy. All too often, coming from a broken family in a substandard educational
THE TREATMENT OF DIPHTHERIA.Read in the Section on Diseases of Children at the Forty-fourth Annual Meeting of the American Medical Association.
Authors: F. E. WAXHAM
Journal: JAMA (1893)

It is to be hoped that in the not far distant future the inoculation treatment of diphtheria will supersede or largely displace all other treatments. The researches in the field of bacteriology; the discovery of the Klebs-Löffler bacillus and the various experiments with ptomaines and anti-toxines are most assuring. Yet notwithstanding the fact that Bering and Kitasato have clearly demonstrated that cultures, which will invariably kill susceptible animals in very small amounts, have their toxic properties entirely destroyed by the addition of the blood of an immune animal; and while the experiments upon animals have been such as to give us confidence in the future treatment of the disease by inoculation, yet for the present we must rely upon the well-tried methods of to-day. While mice inoculated with a virulent filtrate, neutralized by the addition of immune blood have remained immune to diphtheria for forty or fifty days, yet this
Migraine and cardiovascular disease: systematic review and meta-analysis
Authors: M. Schurks, P. M Rist, M. E Bigal, J. E Buring, R. B Lipton, T. Kurth
Journal: BMJ (2009)

To evaluate the association between migraine and cardiovascular disease, including stroke, myocardial infarction, and death due to cardiovascular disease.Systematic review and meta-analysis.Electronic databases (PubMed, Embase, Cochrane Library) and reference lists of included studies and reviews published until January 2009. Selection criteria Case-control and cohort studies investigating the association between any migraine or specific migraine subtypes and cardiovascular disease. Review methods Two investigators independently assessed eligibility of identified studies in a two step approach. Disagreements were resolved by consensus. Studies were grouped according to a priori categories on migraine and cardiovascular disease.Two investigators extracted data. Pooled relative risks and 95% confidence intervals were calculated.Studies were heterogeneous for participant characteristics and definition of cardiovascular disease. Nine studies investigated the association between any migraine and ischaemic stroke (pooled relative risk 1.73, 95% confidence interval 1.31 to 2.29). Additional analyses indicated a significantly higher risk among people who had migraine with aura (2.16, 1.53 to 3.03) compared with people who had migraine without aura (1.23, 0.90 to 1.69; meta-regression for aura status P=0.02). Furthermore, results suggested a greater risk among women (2.08, 1.13 to 3.84) compared with men (1.37, 0.89 to 2.11). Age less than 45 years, smoking, and oral contraceptive use further increased the risk. Eight studies investigated the association between migraine and myocardial infarction (1.12, 0.95 to 1.32) and five between migraine and death due to cardiovascular disease (1.03, 0.79 to 1.34). Only one study investigated the association between women who had migraine with aura and myocardial infarction and death due to cardiovascular disease, showing a twofold increased risk.Migraine is associated with a twofold increased risk of ischaemic stroke, which is only apparent among people who have migraine with aura. Our results also suggest a higher risk among women and risk was further magnified for people with migraine who were aged less than 45, smokers, and women who used oral contraceptives. We did not find an overall association between any migraine and myocardial infarction or death due to cardiovascular disease. Too few studies are available to reliably evaluate the impact of modifying factors, such as migraine aura, on these associations.