tbuckley/cabot-search huggingface dataset:
A 40-Year Journey in Search of Selective Antiviral Chemotherapy*
Authors: Erik De Clercq
Journal: The Annual Review of Pharmacology and Toxicology (2011)

My search for a selective antiviral chemotherapy started more than 40 years ago with interferon inducers, then shifted to nucleoside analogs with the discovery of BVDU (brivudin), a highly selective anti-HSV-1 and anti-VZV agent, and to dideoxynucleoside analogs such as d4T (stavudine), anti-HIV agents. The search culminated in the discovery of acyclic nucleoside phosphonates (ANPs) (in collaboration with Antonin Holý), a key class of compounds active against HIV, hepatitis B virus, and DNA viruses at large; the best known of these compounds is tenofovir. Along the way, the principle of the non-nucleoside reverse transcriptase inhibitors (NNRTIs) was established. This work, initiated in collaboration with the late Paul A.J. Janssen, eventually led to the identification of rilpivirine as perhaps an "ideal" NNRTI.
THE SANATORIUM TREATMENT OF CONSUMPTION.
Authors: S. G. BONNEY
Journal: JAMA (1902)

There is no problem of more absorbing interest to the profession from a medical and humanitarian aspect, and to the public from a social and economic standpoint, than the comprehensive management of pulmonary tuberculosis. Any discussion bearing directly on this question should be inspired solely by its relation to two central thoughts, the ultimate welfare of the consumptive class and the permanent preservation of the community. <h3>THE FUNDAMENTAL PRINCIPLES OF TREATMENT.</h3> The welfare of the consumptives, especially among the poorer classes, includes an intelligent aid rendered to those in early stages, affording a reasonable prospect of success, and adequate provision for the care of the enormous class of incurables. The interests of the community pertain to the removal from its very midst of destitute invalids constituting an oppressive burden to their families, if not to society, and who, through their ignorance and inability to observe precautions, become a constant menace
Jet Hypodermic Injectors For Use in Diabetes
Authors: Frank S. Perkin
Journal: JAMA (1966)

<h3>To the Editor:—</h3> The availability on the market for general use of the jet dermal injector has raised many questions in the minds of the medical profession and lay individuals who have either purchased such instruments or are contemplating doing so. This applies particularly to use in the administration of insulin. Unfortunately, the only published work on the comparative efficiency of needle vs. jet administration of insulin was done in 1949 to 1950<sup>1</sup>and appeared to show no significant difference in the effect or dosage between the two methods. In the succeeding five years, approximately 35 diabetics received their insulin by jet injection with generally satisfactory results, although a few were unable to master the necessary technique satisfactorily. These diabetics were composed of three groups for whom this type of injection has special advantages or appeal: (1) children in the 10 to 16 years of age group who were
Personality and fatal diseases.
Authors: A J Pelosi, L Appleby
Journal: BMJ (1993)

clinical judgment.4Following head injury the mecha- nism of injury, including estimated forces, should play a part in selecting patients for radiography.In addition, while it is desirable to minimise waiting times for children in accident and emergency departments, too rapid a passage through the department may prevent repeated clinical examination and can thus lead to premature discharge of patients with potential intracranial complications.
Hemolytic Uremic Syndrome — Then and Now
Authors: Keith N. Drummond
Journal: New England Journal of Medicine (1985)

In our editorial in the Journal in 1978,1 Kaplan and I discussed the observations of Koster et al.2 on shigella-associated hemolytic uremic syndrome, which suggested that endotoxin damaged vascular endothelium and set in motion events leading to the full-blown syndrome. We were concerned that others had not observed endotoxemia in this syndrome and that this pathogenetic mechanism might apply in a limited number of cases.We emphasized that in parallel with the nephrotic syndrome, the hemolytic uremic syndrome could be seen as a constellation of clinical and laboratory findings occurring in many different settings and resulting from a variety of . . .
1,N(2)-propanodeoxyguanosine adduct formation in aortic DNA following inhalation of acrolein.
Authors: A Penn, R Nath, J Pan, L Chen, K Widmer, W Henk, F L Chung
Journal: Environmental Health Perspectives (2001)

Recent reports indicate that many of the cytotoxic and health-threatening components of environmental tobacco smoke (ETS) reside in the vapor phase of the smoke. We have reported previously that inhalation of 1,3-butadiene, a prominent vapor phase component of ETS, accelerates arteriosclerotic plaque development in cockerels. In this study we asked whether inhaled acrolein, a reactive aldehyde that is also a prominent vapor-phase component of ETS, damages artery-wall DNA and accelerates plaque development. Cockerels inhaled 0, 1, or 10 ppm acrolein mixed with HEPA-filtered air for 6 hr. Half were killed immediately (day 1 group) for detection of the stable, premutagenic 1,N(2)-propanodeoxyguanosine acrolein adduct (AdG3) in aortic DNA via a (32)P-postlabeling/HPLC method, and half were killed after 10 days (day 10 group) for indirect assessment of adduct repair. In the day 1 group, acrolein-DNA adducts were 5 times higher in the 1 and 10 ppm groups than in HEPA-filtered air controls. However, in the day 10 group, adduct levels in the 1 and 10 ppm acrolein groups were reduced to the control adduct level. For the plaque studies, cockerels inhaled 1 ppm acrolein (6 hr/day, 8 weeks), mixed with the same HEPA-filtered air inhaled by controls. Plaque development was measured blind by computerized morphometry. Unlike butadiene inhalation, acrolein inhalation did not accelerate plaque development. Thus, even though repeated exposure to acrolein alone has no effect on plaque size under the exposure conditions described here, a single, brief inhalation exposure to acrolein elicits repairable DNA damage to the artery wall. These results suggest that frequent exposure to ETS may lead to persistent artery-wall DNA damage and thus provide sites on which other ETS plaque accelerants can act.
Guidelines are often based on evidence not relevant to primary care, study finds
Authors: J. Wise
Journal: BMJ (2014)

Almost two thirds of research cited in support of primary care recommendations is based on higher risk populations and could lead to overtreatment, say researchers.

A study published in the Journal of Clinical Epidemiology analysed 22 guidelines from the National Institute for Health and Care Excellence (NICE) that were relevant to primary care.1 These contained 1185 recommendations, of which 495 were evidence based and …
Mortality in Cigarette Smokers and Quitters
Authors: Gary D. Friedman, Diana B. Petitti, Richard D. Bawol, A. B. Siegelaub
Journal: New England Journal of Medicine (1981)

THE health benefits of quitting cigarette smoking have usually been inferred from the differences in morbidity and mortality experienced by smokers and ex-smokers.1 2 3 When formal observation of these groups begins, the ex-smokers have quit smoking at various times in the past; thus, it is not usually possible to assess their health-related characteristics at a time when they were smoking. Consequently, it is difficult to be certain that quitting itself and not some other difference or differences between quitters and persistent smokers has been responsible for the apparently better health outcome.In an earlier study4 longitudinal data derived from three or . . .
Radiogallium Accumulation in Heterotopic Bone
Authors: JOHN J. SZIKLAS, JOHN A. VENTO, RICHARD P. SPENCER, RONALD J. ROSENBERG
Journal: Clinical Nuclear Medicine (1985)

Images from two cases are presented in which heavy soft tissue deposition of Ga-67 citrate occurred due to previously unrecognized heterotopic bone formation. Failure to recognize this cause of gallium uptake may result in misleading interpretation and inappropriate therapy.
Proposals of Donaldson report are “not evidence based,” says Scottish health department
Authors: Bryan Christie
Journal: BMJ (2006)

The health department in Scotland has strongly rejected many of the proposals put forward in July by England's chief medical officer to reform the way UK doctors are regulated. The key complaint of the Scottish Executive Health Department is that many of the recommendations are not evidence based and are “unlikely to result in improvements in patient safety.” 

In a response to Liam Donaldson's report Good Doctors, Safer Patients ( BMJ 2006;333:163), Harry Burns, Scotland's chief medical officer, and Paul Martin, the …
Juvenile rheumatoid arthritis with rice bodies: light and electron microscopic studies.
Authors: C R Wynne-Roberts, J T Cassidy
Journal: Annals of the Rheumatic Diseases (1979)

Rice bodies obtained from a young man with juvenile rheumatoid arthritis were found by light and electron microscopy to contain cells that appeared viable. The majority of these cells closely resembled type B synovial lining cells. Type A-like cells were also seen. The cells contained few mitochondria but often much lipid and glycogen, observations which suggested a dependence on anaerobic metabolic pathways in the avascular synovial fluid environment. Cells within the rice bodies lay in a matrix of collagen fibres, fibrin, and amorphous material. The source of the collagen appeared to be the cells themselves. The relatively normal appearance of the cells suggested that they were protected from many of the inflammatory stimuli present in rheumatoid synovia. This 'reversion' towards a normal appearance suggested that the stimuli inducing chronic rheumatoid inflammation might not originate in the synovial lining.
Priorities for development of research methods in occupational cancer.
Authors: Elizabeth M Ward, Paul A Schulte, Steve Bayard, Aaron Blair, Paul Brandt-Rauf, Mary Ann Butler, David Dankovic, Ann F Hubbs, Carol Jones, Myra Karstadt, Gregory L Kedderis, Ronald Melnick, Carrie A Redlich, Nathaniel Rothman, Russell E Savage, Michael Sprinker, Mark Toraason, Ainsley Weston, Andrew F Olshan, Patricia Stewart, Sheila Hoar Zahm
Journal: Environmental Health Perspectives (2003)

Occupational cancer research methods was identified in 1996 as 1 of 21 priority research areas in the National Occupational Research Agenda (NORA). To implement NORA, teams of experts from various sectors were formed and given the charge to further define research needs and develop strategies to enhance or augment research in each priority area. This article is a product of that process. Focus on occupational cancer research methods is important both because occupational factors play a significant role in a number of cancers, resulting in significant morbidity and mortality, and also because occupational cohorts (because of higher exposure levels) often provide unique opportunities to evaluate health effects of environmental toxicants and understand the carcinogenic process in humans. Despite an explosion of new methods for cancer research in general, these have not been widely applied to occupational cancer research. In this article we identify needs and gaps in occupational cancer research methods in four broad areas: identification of occupational carcinogens, design of epidemiologic studies, risk assessment, and primary and secondary prevention. Progress in occupational cancer will require interdisciplinary research involving epidemiologists, industrial hygienists, toxicologists, and molecular biologists.
Surface expression of a T cell receptor beta (TCR-beta) chain in the absence of TCR-alpha, -delta, and -gamma proteins.
Authors: J A Punt, R T Kubo, T Saito, T H Finkel, S Kathiresan, K J Blank, Y Hashimoto
Journal: The Journal of Experimental Medicine (1991)

The antigen receptor expressed by mature T cells has been described as a disulfide-linked alpha/beta or gamma/delta heterodimer noncovalently associated with CD3, a complex of transmembrane proteins that communicates signals from the T cell receptor (TCR) to the cell interior. Studies suggest that all component chains must assemble intracellularly before surface expression can be achieved. We described, however, a CD4+/CD8+ transformed murine thymocyte, KKF, that expresses surface TCR-beta chains in the absence of gamma, delta, and alpha proteins; these beta chains are only weakly associated with CD3-epsilon and CD3-zeta. Furthermore, KKF responds differently to stimulation through TCR-beta and CD3-epsilon, a functional dissociation that has been ascribed to a CD4+/CD8+ subpopulation of normal thymocytes. KKF's unique TCR structure may offer an explanation for the functional anomalies observed.
Mouse Model of Multiple System Atrophy α-Synuclein Expression in Oligodendrocytes Causes Glial and Neuronal Degeneration
Authors: Ikuru Yazawa, Benoit I. Giasson, Ryogen Sasaki, Bin Zhang, Sonali Joyce, Kunihiro Uryu, John Q. Trojanowski, Virginia M.-Y. Lee
Journal: Neuron (2005)
Phenylbutazone and acute leukemia.
Authors: N. S. Stenhouse, J. A. Sims, L. Dougan, H. J. Woodliff
Journal: BMJ (1966)

BMJORL 16of the facilities provided, all general practi- tioners, paediatricians, and district medical officers in the county were circularized.They were informed of the existing provisions for the mentally handicapped in the county, and were advised that if they wished to refer such patients, and their parents, to the county medical officer, arrangements would be made for them to be seen at their county health clinic by the medical officer for mental health.In addition, discussions have been held with groups of health visitors to help them recognize mental subnormality.Since this service commenced there have been 29 referrals, 18 from general practi- tioners, eight from district medical officers, and three from paediatricians.Seventeen (iore than half the total) were children aged 5 years or less, of whom six were 2 years or less.
Regulation of Hypoxia-induced Pulmonary Hypertension by Vascular Smooth Muscle Hypoxia-Inducible Factor-1α
Authors: Molly K. Ball, Gregory B. Waypa, Paul T. Mungai, Jacqueline M. Nielsen, Lyubov Czech, V. Joseph Dudley, Lauren Beussink, Robert W. Dettman, Sara K. Berkelhamer, Robin H. Steinhorn, Sanjiv J. Shah, Paul T. Schumacker
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Chronic hypoxia induces pulmonary vascular remodeling, pulmonary hypertension, and right ventricular hypertrophy. At present, little is known about mechanisms driving these responses. Hypoxia-inducible factor-1α (HIF-1α) is a master regulator of transcription in hypoxic cells, up-regulating genes involved in energy metabolism, proliferation, and extracellular matrix reorganization. Systemic loss of a single HIF-1α allele has been shown to attenuate hypoxic pulmonary hypertension, but the cells contributing to this response have not been identified.We sought to determine the contribution of HIF-1α in smooth muscle on pulmonary vascular and right heart responses to chronic hypoxia.We used mice with homozygous conditional deletion of HIF-1α combined with tamoxifen-inducible smooth muscle-specific Cre recombinase expression. Mice received either tamoxifen or vehicle followed by exposure to either normoxia or chronic hypoxia (10% O2) for 30 days before measurement of cardiopulmonary responses.Tamoxifen-induced smooth muscle-specific deletion of HIF-1α attenuated pulmonary vascular remodeling and pulmonary hypertension in chronic hypoxia. However, right ventricular hypertrophy was unchanged despite attenuated pulmonary pressures.These results indicate that HIF-1α in smooth muscle contributes to pulmonary vascular remodeling and pulmonary hypertension in chronic hypoxia. However, loss of HIF-1 function in smooth muscle does not affect hypoxic cardiac remodeling, suggesting that the cardiac hypertrophy response is not directly coupled to the increase in pulmonary artery pressure.
Conversion of External Arteriovenous Hemodialysis Shunt to Internal Fistula
Authors: Allan B. Schwartz
Journal: JAMA (1978)

The preservation of arteriovenous (AV) access site is important to long-term survival of patient's requiring maintenance hemodialysis life-support therapy. Patients with chronic renal failure and uremia who are not suited for immediate application of a subcutaneous AV fistula or arteriovenous graft and who require an initial Teflon-Silastic AV shunt to initiate urgent hemodialysis need not lose these vessels when the AV shunt is removed. After venous maturation, these patients should have a subcutaneous AV fistula created from the uninfected, unclotted shunt before infection or clotting would cause loss of these vessels.
Risk to frontline medical care
Authors: S. D Ford
Journal: BMJ (1983)

We agree with Dr Serjeant that a controlled prospective assessment of prophylactic regi- mens of intensive blood transfusions during pregnancy in women with sickle cell disease is urgently required.The advantage of such treatment over equally careful supervision of the pregnancy but with a more conservative use of blood transfusions has been questioned."9 Multiple transfusions are not with- out certain dangers, including the induction of atypical red cell antibodies, which occurred in 14°(? of the transfused patients in our United Kingdom series.4If prophylactic transfusions are expected to have any appre- ciable impact on the rate of abortion and severe fetal growth retardation they would clearly need to be started much earlier than the suggested 28 weeks.In collaboration with colleagues at St Thomas's and certain other London hospitals we are about to start a study of the efficacy of transfusions that we hope will help to answer these questions.
Serum biomarker analysis in a phase II study of irinotecan in refractory metastatic breast cancer (MBC).
Authors: A Moreno-Aspitia, KS Anderson, MM Reinholz, A Lipton, W Carney, AC Dueck, JM Lafky, TR Fitch, DW Hillman, EA Perez
Journal: Cancer Research (2009)

Abstract Abstract #6074 Objective: To analyze blood-serum biomarkers (HER2, EGFR, uPA, and TIMP-1) for prediction of response to treatment in conjunction with Study 96-32-55, a multicenter phase II trial assessing the efficacy and tolerability of two irinotecan schedules in anthracycline- or taxane-refractory MBC patients.&amp;#x2028; Methods: MBC patients who experienced disease progression after one to three chemotherapy regimens, including at least one anthracycline- or taxane-based regimen, were randomly assigned to irinotecan in 6-week cycles comprising 100 mg/m2 weekly for 4 weeks, then a 2-week rest or 240 mg/m2 every 3 weeks. During this study the serum samples from each patient were collected at a possibility of three time points; prior to treatment, at the first occurrence of response, and at completion of or withdrawal from treatment. Response prediction was analyzed using predetermined elevated/non-elevated serum biomarker cutoffs. Percentage changes from baseline to first response and disease progression were analyzed.&amp;#x2028; Results: In the weekly arm, the objective response (CR+PR) rate was 23% (95% CI, 13% to 37%), and in the every-3-weeks arm, the objective response rate was 14% (95% CI, 6% to 26%). Serum biomarker levels were determined for HER2, EGFR, uPA, and TIMP-1 prior to treatment for 91 patients. Of these 91 patients, 17 had serum measurements at first response, and 38 had serum measurements at their completion of study due to disease progression. Only 7 patients had serum-levels collected at all three event-points. The baseline levels of sHER2, EGFR, uPA, and TIMP-1 were not different among responders and non-responders (Fisher's Exact p=0.41, 0.26, 0.68, 0.75). sHER2 level increased by 20.6% from baseline to disease progression (p=0.01). TIMP-1 level was 15.2% lower than baseline at first response (p=0.03), 16.5% higher than baseline at disease progression (p=0.01), and for 7 patients with all three event-point measures, TIMP-1 was 21.8% lower than baseline at first response and was 22.3% higher than baseline at disease progression (p=0.02, 0.04).&amp;#x2028; Conclusions: In this study, serum levels of HER2, EGFR, uPA, and TIMP-1 do not appear to be predictive of response. However, interpretation of the data is compromised due to limited availability of serum at all 3 points. Serum HER2 appears higher at disease progression than at baseline. Serum TIMP-1 appears to decrease from baseline to first response, and then appears to increase at disease progression. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6074.
Alcohol Consumption and Withdrawal in New-Onset Seizures
Authors: K.C. Ng Stephen, W. Allen Hauser, John CM. Brust, Mervyn Susser
Journal: New England Journal of Medicine (1988)

We studied alcohol use before the onset of a first seizure in 308 patients with seizures and 294 controls. The risk of seizures increased with increasing current alcohol use. For unprovoked seizures (i.e., seizures occurring without an antecedent event, such as a recent stroke), the adjusted odds ratios rose from 3-fold at intakes of 51 to 100 g of ethanol per day (95 percent confidence limits, 1.3 and 6.3), to 8-fold at 101 to 200 g per day (95 percent confidence limits, 3.3 and 18.7), and to almost 20-fold at 201 to 300 g per day (95 percent confidence limits, 6.1 and 62). For provoked seizures, the odds ratios were lower and statistically significant only above 200 g per day (odds ratio, 10.1; 95 percent confidence limits, 2.3 and 43.8 at 201 to 300 g per day; odds ratio, 7.4; 95 percent confidence limits, 1.8 and 30.5 above 300 g per day). Among exdrinkers (abstention ≥1 year), no increased risk was detected. Alcohol withdrawal was not associated with the onset of seizures in this study; 16 percent of first seizures in drinkers fell outside the conventionally defined withdrawal period, and the remainder exhibited a seemingly random timing after the last drink. We conclude that the relation of seizures to alcohol use is dose dependent and appears to be causal, and that seizures can be interpreted as a disorder induced by the ingestion of alcohol, independently of alcohol withdrawal. (N Engl J Med 1988; 319:666–73.)
Child consultation patterns in general practice comparing "high" and "low" consulting families.
Authors: P D Campion, J Gabriel
Journal: BMJ (1984)

All children's consultations with their general practitioner over a 12 month period in a small urban practice were analysed. Overall consultation rates ranged from 2.2 per child a year for 8 to 11 year olds, to 6.8 for those under 2. Families were grouped according to their average rate of new consultation for children, standardised for age. Families with higher consulting rates scored higher on an index of economic disadvantage, with mothers who scored higher on a test of "tendency to consult" and who were less educated than those in lower consulting families. The presence of any doctor-defined "significant disease" in any child was highly correlated with the family's consultation rate.
Psychiatric Complications of Heart Transplants
Authors: DONALD T. LUNDE
Journal: American Journal of Psychiatry (1969)

As the psychiatric consultant to a cardiac transplant team, this author faced a unique challenge. He discusses the factors involved in the psychiatric screening of potential candidates for the operation and describes the preoperative and postoperative psychiatric complications observed among nine patients who have received heart transplants at his medical center. As surgery progresses in the direction of organ replacement, he concludes, psychiatrists must prepare to meet the increasing need for their services in this area.