tbuckley/cabot-search huggingface dataset:
Phase I Trial of Taxotere: Five-Day Schedule
Authors: R. Pazdur, R. A. Newman, B. M. Newman, A. Fuentes, J. Benvenuto, B. Bready, D. Moore, I. Jaiyesimi, F. Vreeland, M. M. G. Bayssas, M. N. Raber
Journal: JNCI Journal of the National Cancer Institute (1992)

Background : Taxotere, a semisynthetic compound structurally related to taxol, has a broad spectrum of activity in murine transplantable tumors; in the B16 melanoma model, it caused a total log cell kill 2.5 times greater than that caused by taxol at equitoxic doses. Purpose : We conducted a phase I study of Taxotere ( a ) to determine its qualitative and quantitative toxic effects and a starting dose for phase II trials, ( b ) to investigate its clinical pharmacology, and ( c ) to document its antitumor activity. Methods : Taxotere was given as a 1-hour infusion at a starting dose of 1 mg/m 2 per day for 5 consecutive days. The 5-day course of therapy was repeated every 21 days. Thirty-nine cancer patients with advanced disease were entered in the study; at least three patients were entered at each dose level. Initial dose escalations were planned at 100% increments until biologic activity was observed; subsequent escalations were planned at 50% increments until grade 2 toxicity (the National Cancer Institute's Common Toxicity Criteria) occurred and then at 25% increments until the maximum tolerated dose was established. Results : Thirtynine patients were entered in the study. Successive dose levels used were 1, 4, 8, 16, 12, and 14 mg/m 2 per day. The dose-limiting toxic effects were granulocytopenia and concurrent mucositis. Grade 4 granulocytopenia associated with grade 3 mucositis developed in six of 12 patients treated at a dose of 16 mg/m 2 per day, two of 10 treated at 12 mg/m 2 per day, and two of eight treated at 14 mg/m 2 per day. Because these toxic effects occurred concurrently, all patients so affected developed neutropenic fevers and required hospitalization. Neither cardiac nor neurologic toxic effects were noted. Antitumor activity was observed in six patients with ovarian cancer and in one with breast carcinoma. Although pharmacokinetic parameters were consistent between day 1 and day 5 for individual patients, considerable variation existed among those treated at the same dose level. A relationship was observed between the area under the curve for plasma concentration of drug × time (AUC) on day 1 and the percentage decrease in absolute granulocyte counts. Conclusion : Granulocytopenia associated with oral mucositis is the dose-limiting toxicity of this schedule. We recommend a starting dose of 14 mg/m 2 per day for phase II studies of this 5-day schedule. Dose modifications on days 2–5 based on the day-1 AUC may allow individualized dosing. [J Natl Cancer Inst 84:1781–1788, 1992]
High smoking rates in 1940s, 1950s and 1960s in US explain comparatively lower life expectancy of older Americans
Authors: B. Roehr
Journal: BMJ (2011)

High levels of cigarette smoking in the past and rising rates of obesity are the primary reasons why US citizens older than 50 do not live as long as citizens in other industrialised nations. The study by the National Research Council, part of the National Academy of Sciences, was released on 25 January.

Although life expectancy has risen in the US over the last 25 years, it had done so at a slower pace than most other high income countries, despite the fact that the US spends far more on healthcare per person than any other nation.

“Fifty years ago, smoking was much more widespread in the …
A Colour Atlas of Clinical Orthopaedics
Authors: A. J. Hall
Journal: Annals of the Rheumatic Diseases (1981)

Research in human subjects is very important.Apart from the study of disease there is now a widespread acceptance of the view that treatment can be shown to be effective only by controlled clinical trials.This brings physicians to give their patients dummy tablets, to deny them active treatment, and to fail to tell them what is going on.What patient would continue to take dummy tablets if he knew what they were?The surface of this important subject is gently stroked but not scratched in this little book, and it is probably good to remind clinical investigators of their moral obligations from time to time.Relations with regulatory authorities are also discussed, and the British investigator will be pleased to know, from an inside source, that the FDA will not reject his 'foreign data' just because they are 'foreign'.They may not be regarded as 'pivotal,' since it appears that 'foreign' investigators are reluctant to supply case records or report forms to support the honesty and integrity of their work.A continued deep suspicion of foreigners, and their work is clearly justified.Jargon abounds in this publication.Could FDA, for example, give NDA, or could CSM grant NPL in NIH funded REC approved NHLBI CT of BO under HEW regulations using SSN for FECA at RBH? Words do not necessarily help.Once paper concludes that 'multicentre clinical trials require a synthesis of the scientific method and the precepts of modern management.'Among a few very enjoyable and stimulating contributions is a paper on randomised controlled trials of nonpharmacological treatment.This would be enormously helpful to a young physician who wanted to do some research but could not think of a worthwhile project.Much of what physicians and surgeons do is empirical but could be randomised and documented.Though there
Damaged interlobular bile ducts in primary biliary cirrhosis show reduced expression of glutathione-S-transferase-pi and aberrant expression of 4-hydroxynonenal
Authors: Koichi Tsuneyama, Kenichi Harada, Naoko Kono, Motoko Sasaki, Takahito Saito, M.Eric Gershwin, Mamoru Ikemoto, Hiroyuki Arai, Yasuni Nakanuma
Journal: Journal of Hepatology (2002)
PRELIMINARY RESULTS FROM A RANDOMIZED TRIAL ON GLUCOSE-INSULIN-POTASSIUM AND N-ACETYL-CYSTEINE IN PREVENTION OF CONTRAST-INDUCED NEPHROPATHY IN DIABETIC AND/OR WITH CHRONIC RENAL FAILURE PATIENTS UNDERGOING PERCUTANEOUS CORONARY INTERVENTION
Authors: Annunziata Nusca, Cosimo Marco Campanale, Rocco Contuzzi, Giuseppe Patti, Andrea D'Ambrosio, Germano Di Sciascio
Journal: Journal of the American College of Cardiology (2011)
Levamisole Potentiation of Fluorouracil Antiproliferative Activity Mimicked by Orthovanadate, an Inhibitor of Tyrosine Phosphatase
Authors: J. S. Kovach, P. A. Svingen, D. J. Schaid
Journal: JNCI Journal of the National Cancer Institute (1992)

Background : Levamisole is an effective antihelminthic drug with immunomodulatory and anticancer activities in model systems. Combined with fluorouracil (5-FU) as adjuvant treatment following resection of Dukes' stage C colon carcinomas, levamisole significantly reduces mortality. However, neither 5-FU nor levamisole alone has a significant effect on survival in this patient group. Previously, we noted that in vitro levamisole potentiated the antiproliferative activity of 5-FU. Purpose: Because levamisole is known to inhibit alkaline phosphatases and has been reported to inhibit dephosphorylation of some membrane phosphoproteins, we studied the effects of levamisole analogues and of chemically unrelated inhibitors of phosphatases for their ability to potentiate 5-FU inhibition of tumor cell line proliferation in vitro. Methods: Human cancer cell lines were exposed to drugs alone or in combination with 5-FU. Antiproliferative activity was measured by determining the extent of reduction of colony formation by the cell lines in test plates compared with control plates. Results: We found that potentiation of 5-FU cytotoxicity by levamisole and by phydroxytetramisole, a metabolite of levamisole, is mimicked by orthovanadate, an inhibitor of tyrosine phosphatases, but not by okadaic acid, an inhibitor of serine and threonine phosphatases. Furthermore, l- p -bromotetramisole, a synthetic analogue of levamisole that is 10-fold more potent in inhibition of alkaline phosphatase than levamisole, potentiates the antiproliferative activity of 5-FU to a greater extent than d- p -bromotetramisole, a stereoisomer of l-p-bromotetramisole with little antiphosphatase activity. Conclusion: Inhibition of tyrosine phosphatases may be responsible for the potentiation by levamisole of the inhibitory activity of 5-FU in vitro. Implications: Inhibition of dephosphorylation of regulatory phosphoproteins may be related to the therapeutic efficacy of the combination of levamisole and 5-FU in the adjuvant treatment of colon carcinoma and may underlie at least some of the multiple effects of levamisole on immune parameters. [J Natl Cancer Inst 84: 515–519, 1992]
Abhorrent weapons and "superfluous injury or unnecessary suffering": from field surgery to law
Authors: R. M Coupland
Journal: BMJ (1997)

Gerhard Rose, one of Germany's most respected physicians, stood in the prisoner's dock at the Palace of Justice in Nuremberg, Germany, awaiting his sentence for "murders, tortures, and other atrocities committed in the name of medical science."Dr Rose, the department head for tropical medicine of the Robert Koch Institute, was on trial along with 22 of his medical colleagues, for perpetrating "ghastly" and "hideous" experiments on concentration camp prisoners during the war. 1 At one point in the trial when the chief prosecution witness, Dr Andrew C Ivy of the medical school of the University of Illinois, underscored the basic principle "that human experimental subjects must be volunteers," Dr Rose and his defence counsel vigorously objected, arguing that the United States was guilty of similar medical practices and giving several examples to support this contention.
A novel MHC-associated Proteinase 3 peptide isolated from primary chronic myeloid leukaemia cells further supports the significance of this antigen for the immunotherapy of myeloid leukaemias
Authors: A J Knights, A O Weinzierl, T Flad, B-a Guinn, L Mueller, G J Mufti, S Stevanovic, G Pawelec
Journal: Leukemia (2006)
Abstract P025: Trying to Lose Weight: The Effect of Income and Age on Weight Loss Strategies in NHANES 1999-2010
Authors: Lisa Kakinami, Lise Gauvin, Tracie Barnett, Gilles Paradis
Journal: Circulation (2013)

Background: Two-thirds of the general US population is overweight or obese; those living in poverty are disproportionately affected. Although 30-50% of Americans report currently trying to lose weight, some strategies can be counterproductive. Even though increased physical activity and decreased fat consumption were recently reported to be among the most successful weight-loss strategies for obese persons, little is known about how income may be associated with the type of strategies used to lose weight. Objective: determine the association between income and types of weight-loss strategies. Methods: Analyses included the 1999-2010 National Health and Nutrition Examination Survey participants that reported trying to lose weight in the last year and were stratified by age (youth: aged 8-19, n=3184; adults: 20+, n=5643) due to availability of covariates and different weight-loss questions. Annual household income was categorized as: &lt;$20K, $20K-45K, $45-75K, and compared to the referent ($75K+). Multivariable models included sampling weights, and adjusted for sex, age, ethnicity, and whether the person was overweight or obese (body mass index &gt; 25 for adults, or &gt; 85th percentile for youth according to the CDC growth curves). Analyses among adults also adjusted for marital status and education. Multivariable logistic regression assessed the likelihood of using healthy weight-loss strategies (e. g., exercising) and unhealthy weight-loss strategies (e. g., skipping meals). Results: Compared to the referent, adults with lower household incomes were less likely to use healthy weight-loss strategies (Fig. 1) but unhealthy strategies were not associated; youth from lower income households were more likely to utilize unhealthy weight-loss strategies, and less likely to use healthy strategies. Conclusions: Weight-loss strategies differ based on income and age. Education efforts and environmental strategies should be done in tandem to increase use of healthy weight-loss strategies to curb the obesity epidemic.
Common variants in DGKK are strongly associated with risk of hypospadias
Authors: Loes F M van der Zanden, Iris A L M van Rooij, Wout F J Feitz, Jo Knight, A Rogier T Donders, Kirsten Y Renkema, Ernie M H F Bongers, Sita H H M Vermeulen, Lambertus A L M Kiemeney, Joris A Veltman, Alejandro Arias-Vásquez, Xufeng Zhang, Ellen Markljung, Liang Qiao, Laurence S Baskin, Agneta Nordenskjöld, Nel Roeleveld, Barbara Franke, Nine V A M Knoers
Journal: Nature Genetics (2010)
Adult T-cell Leukemia Presenting a IIa + IIc-like Lesion in the Stomach on Endoscopic Examination
Authors: S. Obata, A. Tsukamoto, K. Kimura, K. Maeda, R. Kawamura
Journal: Endoscopy (1990)

A patient with gastric involvement of adult T-cell leukemia is reported. Endoscopically, it mimicked an early gastric cancer IIa + IIc, but had the nature of a submucosal tumor, and could be distinguished from carcinoma. It is very important to distinguish it from carcinoma because of the different mode of therapy.
RISK FOR PERSISTENT RENAL DYSFUNCTION IN PATIENTS WITH CONTRAST–INDUCED NEPHROPATHY AFTER PRIMARY PCI
Authors: Per Thayssen, Henrik Steen Hansen, Anne Kaltoft, Jan Ravkilde, Knud Noerregaard Hansen, Hans Erik Bøtker, Hans–Henrik Tilsted, Anders Junker, Leif Thuesen, Karsten T. Veien, Lisette Okkels Jensen
Journal: Journal of the American College of Cardiology (2013)
Hospital Variation in Intrapartum Use of Zidovudine
Authors: Marta Gwinn
Journal: JAMA (1997)

<h3>To the Editor.</h3> —In August 1994, the US Public Health Service issued recommendations for administering zidovudine to pregnant women infected with the human immunodeficiency virus (HIV) and their newborns to reduce the risk of perinatal HIV transmission.<sup>1</sup>We conducted an anonymous, population-based study to estimate the proportion of HIV-infected women giving birth in Florida from October 1994 through March 1995 who received perinatal treatment with zidovudine. We used a modified radioimmunoassay for serum zidovudine to test dried-blood specimens that had been collected from newborns for routine metabolic screening. These specimens had been tested anonymously for maternal HIV antibody as part of a nationwide HIV serosurvey conducted under an existing protocol that had institutional review board approval. Performance characteristics of the modified assay are described elsewhere,<sup>2</sup>and studies are now in progress to develop a confirmatory test. The metabolism of zidovudine is delayed in neonates, resulting in
Bird-Mite Infestation
Authors: Tak K Kong, Wing K To
Journal: New England Journal of Medicine (2006)

A 46-year-old woman and her husband had their sleep disturbed by pruritus, waking up to find similar, itchy papular lesions over their finger webs (Panel A), axillae, groins, and buttocks. They found small (less than 1 mm) mites (Panel B) moving across their skin, which light microscopy revealed to be Ornithonyssus bursa (Panel C), bloodsucking bird mites commonly found in pigeons' nests. Their pruritus improved after the application of crotamiton to their lesions and after the pigeon's nest hidden under the air conditioner above their bedroom was cleaned. When unexplained scabies-like illness occurs in humans during late spring or early . . .
The Unborn Patient: Prenatal Diagnosis and Treatment
Authors: Joshua A. Copel
Journal: JAMA (1991)

The second edition of<i>The Unborn Patient</i>is, as indicated in the preface, an outgrowth of the first edition. The first edition was a monograph based primarily on the personal experiences of those working at one of the most active centers of experimental fetal treatment. The second edition is intended to be more comprehensive and generally succeeds. The volume is divided into four slightly artificial parts. The first, "The Fetus as Patient," includes a valuable overview of the field by Harrison, as well as chapters on ethical, legal, and economic considerations. The remaining three parts, "Fetal Diagnosis," "Fetal Treatment," and "Fetal Diseases and Their Management," contain chapters similar to those found in several current texts, but this is not just another text-book of fetal diagnosis, for several reasons. It is inevitable that the lag time between writing and publishing makes some information obsolete, but this is rarely significant in this
Crisis Intervention and Prevention of Psychiatric Disability: A Follow-Up Study
Authors: J. BARRY DECKER, J. M. STUBBLEBINE
Journal: American Journal of Psychiatry (1972)

Two groups of young adults were followed for two and a half years after their first psychiatric hospitalizations. The first group received traditional modes of treatment; the second group was hospitalized after the institution of a crisis intervention program. The authors compared the outcomes of the two groups to test whether crisis intervention could reduce long-term hospital dependency without producing alternate forms of psychological or social dependency. They found that crisis intervention did reduce hospitalization throughout the second group's follow-up period without an increase in other indices of disability.
Cellular basis of wall remodeling in long-term pressure overload-induced right ventricular hypertrophy in rats.
Authors: G Olivetti, R Ricci, C Lagrasta, E Maniga, E H Sonnenblick, P Anversa
Journal: Circulation Research (1988)

To determine the effects of long-term pressure overload on the structural mechanisms implicated in wall remodeling of the right ventricle, a mild pulmonary artery banding was applied to rats approximately 2 months old, and the animals were killed 150 days later. The surgical procedure resulted in a 60% reduction in the cross-sectional area of the constricted vessel and a 52% increase in the weight of the right ventricle. The hypertrophic myocardial response was associated with an elevation in right ventricular systolic pressure (from 33 +/- 11 mm Hg to 71 +/- 12 mm Hg), right ventricular end-diastolic pressure (from 3 +/- 1 mm Hg to 10 +/- 3 mm Hg), and central venous pressure (from 2 +/- 0.2 mm Hg to 10 +/- 3 mm Hg). The 76% increase in wall thickness after pulmonary artery stenosis was the result of a 24% lateral expansion of cardiac muscle cells and a 44% increase in the number of myocytes across the ventricular wall. The intermyocyte distance was also increased by 22%. These cellular adaptations occurred with no alterations in total myocyte length, average sarcomere length, and volume composition of the myocardium. Ventricular wall area was decreased by 14%, which suggests a small reduction in chamber volume. Myocyte growth was accompanied by proportional expansions of mitochondrial and myofibrillar components, so that the ratio of mitochondria to myofibrils in the cytoplasm remained essentially constant. In conclusion, ventricular remodeling in this model of chronic pressure hypertrophy is characterized by increases in cellular diameter and number that would both tend to decrease the magnitude of systolic and diastolic stresses on a per cell basis and thus improve the myocardial response to a prolonged and sustained mechanical load.
US company designs gun for people with arthritic hands
Authors: R. Dobson
Journal: BMJ (2008)

US residents whose arthritic hands can no longer squeeze the trigger of a conventional gun may soon be able to start firing again.

A pistol, specifically designed for use by older people, disabled people, or others who may be at a physical disadvantage with potential attackers, is being offered for sale in the United States for about $300 (£200; €230). Described as an ergonomically innovative single shot double action defensive firearm that can be fired with either hand, its firing pin is released by the thumb instead of the index finger.

The developer, Constitutional Arms, says that it is seeking to obtain medical equipment coding from the Center for Medicare and Medicaid Services for the pistol. If successful, it is possible …
Activation of liver X receptors with T0901317 attenuates cardiac hypertrophy <i>in vivo</i>
Authors: Irma Kuipers, Jiang Li, Inge Vreeswijk‐Baudoin, Johan Koster, Pim van der Harst, Herman H.W. Silljé, Folkert Kuipers, Dirk J. van Veldhuisen, Wiek H. van Gilst, Rudolf A. de Boer
Journal: European Journal of Heart Failure (2010)
Liver biopsy as a day-case procedure
Authors: D Westaby, R Williams
Journal: BMJ (1981)

Tight lacing may have been made the scapegoat for chlorosis, just as holding the reins was for Dupuytren's contracture; but the association with pica suggests a deficiency state as a more likely cause.Dr Jenkins's idea of a chronic intoxication is not incompatible with this suggestion.
Long term safety of statins should be monitored
Authors: Steven J Haas, Rosana Hage-Ali, Brian G Priestly, Andrew Tonkin, Lisa Demos, John J McNeil, Mark Nelson
Journal: BMJ (2006)

Editor-Last year Hern et al published an editorial on knife crime and clearly the problem has not gone away. 1 A quick search of the Times website finds 90 hits on the single search term "stabbing" in the past three months alone.Several recent deaths have fuelled the perception that forensic knife injuries have become an epidemic, resulting in a knife amnesty and government discussion of new punitive measures.An increase in such injuries is supported by data from regional police forces and the Home Office, with 1200 reported attacks in London last year and 30% of homicides caused by knife injury. 2 Crimes defined as "more serious wounding or other act endangering life" almost doubled nationally from 1995 to 2005. 3 We audited forensic knife injuries at this hospital, one of Europe's busiest emergency departments, to establish the size of this problem in a representative urban area (east London).We extracted data on forensic knife injuries (excluding deliberate self harm) from a detailed prospectively recorded database of all trauma calls from July 2004 to June 2006 (these reflecting more severe injuries).Overall there were 309 forensic knife injuries; 259 patients were admitted, 184 were operated on, and eight died.The chest was the most common area injured (183/309 patients, 6/8 deaths).Most patients were men (297/309), and mean age was 28 (range 15-74).To give a measure of changing incidence over a longer time of a greater range of severity of injury, we also performed an audit of all cases coded as "stabbing" on the patient administration system during the 10 year period from July 1997 to June 2006 (figure).Over both periods, the data show an increase in the overall incidence of stabbings.Furthermore, increased need for surgical intervention in the prospective study may reflect increasing severity of injury.These data therefore seem to support the general perception that knife injuries are increasing.
652 DEVELOPMENT OF A FORMULA TO ESTIMATE GLOMERULAR FILTRATION RATE (GFR) IN PATIENTS WITH CIRRHOSIS
Authors: E. Tsochatzis, E. Theocharidou, M. Garcovich, E. Fatourou, G. Fede, G. Germani, P. Manousou, M. Rodriguez, E. Thalassinos, A.K. Burroughs
Journal: Journal of Hepatology (2012)