tbuckley/cabot-search huggingface dataset:
Pharmacokinetics of 5-Azacitidine Administered With Phenylbutyrate in Patients With Refractory Solid Tumors or Hematologic Malignancies
Authors: Michelle A. Rudek, Ming Zhao, Ping He, Carol Hartke, Jill Gilbert, Steven D. Gore, Michael A. Carducci, Sharyn D. Baker
Journal: Journal of Clinical Oncology (2005)

Purpose To characterize the pharmacokinetic behavior of 5-azacitidine (5-AC), a cytidine nucleoside analog, when given with phenylbutyrate, a histone deaceytlase inhibitor. Patients and Methods Pharmacokinetic data were obtained from two trials involving patients with solid tumor and hematologic malignancies. 5-AC at doses ranging from 10 to 75 mg/m 2 /d was administered once daily as a subcutaneous injection for 5 to 21 days in combination with phenylbutyrate administered as a continuous intravenous infusion for varying dose and duration every 28 or 35 days. Serial plasma samples were collected up to 24 hours after 5-AC administration. 5-AC was quantitated using a validated liquid chromatograph/tandem mass spectrometry method. Results 5-AC was rapidly absorbed with the mean T max occurring at 0.47 hour. Average maximum concentration (C max ) and area under the curve (AUC 0-∞ ) values increased in a dose-proportionate manner with increasing dose from 10 to 75 mg/m 2 /d; the mean ± SD C max and AUC 0-∞ at 10 mg/m 2 /d were 776 ± 459 nM and 1,355 ± 1,125 h*nM, respectively, and at 75 mg/m 2 /d were 4,871 ± 1,398 nM and 6,582 ± 2,560 h*nM, respectively. Despite a short terminal half-life of 1.5 ± 2.3 hours, inhibition of DNA methyl transferase activity in tumors of patients receiving 5-AC has been documented. Conclusion 5-AC is rapidly absorbed and eliminated when administered subcutaneously. Sufficient 5-AC exposure is achieved to produce pharmacodynamic effects in tumors.
Maxillary Brown Tumor of Secondary Hyperparathyroidism in a Hemodialysis Patient
Authors: Robert R. Weiss, Morris J. Schoeneman, William Primack, Danuta Rozycki, Boyce Bennett, Ira Greifer
Journal: JAMA (1980)

HYPERPARATHYROIDISM of any etiology may result in a focal lesion of bone called a "brown tumor."<sup>1</sup>This mass occurs most often in the ribs, clavicle, and pelvic girdle. We describe an adolescent hemodialysis patient with severe secondary hyperparathyroidism in whom a mass lesion of the maxilla developed, which histologically was a brown tumor. This unusual manifestation of secondary hyperparathyroidism can be expected to occur more often with increased longevity of patients with chronic renal failure and illustrates the need to include brown tumor in the differential diagnosis of any bony mass. Although parathyroidectomy is said to be curative,<sup>2</sup>our patient demonstrated an unexplained rapid tumor growth after parathyroid surgery. <h3>Report of a Case</h3> An 18-year-old woman with chronic renal failure caused by chronic glomerulonephritis showed the development of a maxillary mass (Fig 1) after two years of maintenance hemodialysis. Histological examination showed a brown tumor of hyperparathyroidism (Fig
Structural Transformations of the Sciences and the End of Peer Review
Authors: Horace Freeland Judson
Journal: JAMA (1994)

THREE great structural transformations are now taking place in the sciences. The<i>structures</i>are the conditions, the building plan, the institutional relationships that underlie and shape the way sciences are done today.<i>Transformations</i>affect the structures radically yet systematically—in ways that preserve many of the original elements while creating a set of relationships fundamentally different. Structural transformations are probably impossible to resist. Their consequences are hard to predict. The first and most familiar of the transformations we can think of as internal to research and publishing: it comprises the declining standards and the growing, built-in tendency toward corruption of the peer-review and refereeing processes. The other two transformations we can describe as external to peer review<i>sensu stricto</i>: they are the transition from exponential growth of the sciences to a steady state, and the appearance and development of electronic publishing and electronic collaboration more generally. The three overlap and interact.
An Investigation into Causative Factors in Patients with Bronchiectasis
Authors: MARK C. PASTEUR, SHARON M. HELLIWELL, SALLY J. HOUGHTON, SUSANNAH C. WEBB, JULIET E. FOWERAKER, RICHARD A. COULDEN, CHRISTOPHER D. FLOWER, DIANA BILTON, MARY T. KEOGAN
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Bronchiectasis is a pathologic description of lung damage characterized by inflamed and dilated thick-walled bronchi. These findings may result from a number of possible causes and these may influence treatment and prognosis. The aim of this study was to determine causative factors in 150 adults with bronchiectasis (56 male, 94 female) identified using high-resolution computerized tomography. Relevant factors were identified in the clinical history; cystic fibrosis gene mutation analysis was performed; humoral immune defects were determined by measuring immunoglobulins, IgG subclasses and functional response to Pneumovax II vaccine; assessment was made of neutrophil function (respiratory burst, adhesion molecule expression, and chemotaxis); ciliary function was observed and those likely to have allergic bronchopulmonary aspergillosis (ABPA) were identified. Causes identified were: immune defects (12 cases), cystic fibrosis (4), Young's syndrome (5), ciliary dysfunction (3), aspiration (6), panbronchiolitis (1), congenital defect (1), ABPA (11), rheumatoid arthritis (4), and early childhood pneumonia, pertussis, or measles (44). Intensive investigation of this population of patients with bronchiectasis led to identification of one or more causative factor in 47% of cases. In 22 patients (15%), the cause identified had implications for prognosis and treatment.
Antiarrhythmic drug therapy in survivors of prehospital cardiac arrest: comparison of effects on chronic ventricular arrhythmias and recurrent cardiac arrest.
Authors: R J Myerburg, C Conde, D S Sheps, R A Appel, I Kiem, R J Sung, A Castellanos
Journal: Circulation (1979)

We studied the long-term effects of membrane-active antiarrhythmic agents on chronic ventricular arrhythmias in patients who have survived prehospital cardiac arrest. Among 16 patients treated with a dose-adjusted, plasma level-monitored antiarrhythmic regimen, eight have survived for longer than 12 months and eight have had recurrent cardiac arrests (RCAs). Monthly Holter monitor tapes (HM) recorded during the 4 months before the eight RCAs were compared with monthly HM tapes matched for time of entry and duration of follow-up in the eight patients who did not have RCAs. Transient or persistent complex ventricular ectopic depolarizations (VEDs) have been recorded on 47 of the 63 monthly HM tapes (75%). The difference between VEDs in the RCA patients (mean 153 VEDs/hr, median 19 VEDs/hr) and VEDs in the patients who have not had RCA (mean 122 VEDs/hr, median 8 VEDs/hr) was not significant (p less than 0.2); nor was there a predictable relationship between therapeutic plasma levels of antiarrhythmic agents and the frequency and complexity of chronic asymptomatic VEDs (therapeutic levels--mean 104 VEDs/hr, median 6 VEDs/hr; subtherapeutic levels--mean 184 VEDs/hr, median 21 VEDs/hr). Differences were not significant (p greater than 0.1). In contrast, all eight RCA patients had unstable plasma levels (21 of 31 determinations subtherapeutic) while six of the eight patients who have not had RCA had consistently therapeutic levels (p less than 0.01). Thus, adequate plasma levels of antiarrhythmic agents may protect against RCA, despite failure to suppress VEDs predictably. The apparent dissociation between predictable suppression of chronic VEDs and protection against RCA suggests that clinical effectiveness of these agents may not be best measured by their effect on chronic VEDs.
A Case of Poisoning by Mushrooms
Authors: J. Sedgwick
Journal: BMJ (1874)

founded in I824, it is as nearly as possible six months older than I am.It is something astounding to know what progress has been made since that time.I happened to take up to-day the syllabus of your sessional work here, and I turn, not unnaturally, to the class of Practical Physio- logy and Histology, and, on looking over the various doings of this course of instruction, it struck me that, thirty years ago, when I began my medical studies, there certainly was nobody in London-nay, nobody
Diagnosing at the Mall
Authors: James M. Cerletty
Journal: Annals of Internal Medicine (1995)

On Being a Doctor1 September 1995Diagnosing at the MallJames M. Cerletty, MDJames M. Cerletty, MDMedical College of Wisconsin, Milwaukee, WI 53226Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-123-5-199509010-00011 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Physicians, nurses, and others who work in the medical profession love to make snap diagnoses. We pride ourselves on our clinical astuteness and the rapidity with which we arrive at the exact diagnosis of a disorder. A story was in circulation some years ago that illustrates this point. It seems that two clinicians were standing at a window on a lower floor of a Chicago skyscraper when a body, soon to be that of a suicide victim, plummeted by. With hardly a pause, one of the observers said “myxedema” and went on with his conversation.Come on, admit it. You ... Author, Article, and Disclosure InformationAffiliations: Medical College of Wisconsin, Milwaukee, WI 53226Corresponding Author: James M. Cerletty, MD, Department of Medicine, Medical College of Wisconsin, John L. Doyne Hospital, 8700 West Wisconsin Avenue, Milwaukee, WI 53226. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited bySynthesis and antimicrobial activity of new functionalized derivatives of [1,2,4]triazolo[4,3-a]pyrimidin-5(1H)-one 1 September 1995Volume 123, Issue 5Page: 387KeywordsAcromegalyDiagnostic radiologyHabitsPenisPituitary glandPituitary tumorsRadiologistsSuicideSurgeryThorax Issue Published: 1 September 1995 Copyright & PermissionsCopyright © 1995 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Gunshot Injuries in the Late Grecoturkish War, with Remarks upon Modern Projectiles
Authors: H. J. Davis
Journal: BMJ (1897)

National Fund for Greek Wounded, and late House Surgeon to St Thomas's Hospital.IT is almost true to say that all bullet wounds, except those limited to the soft structures, result in fracture of bones.If there is any breach of surface it is of necessity a compound fracture, and is the most unfavourable form of any kind of bone injury, for (i) the wound is an infected one, (2) it is devoid of drainage owing to the long sinus left by the track of the bullet, and (3) the hygienic surroundings are invari- ably bad.When a joint is opened by a bullet it communi- cates with the exterior, and being exposed to all the sources of ordinary infective processes it suppurates.A fractured ole- cranon, a fractured patella, and an impacted Colles's fracture are fractujres into the joint, but suppuration does not occur unless contamination is admitted to the seat of injury.It is not my intention in this paper to give a routine description of bullet wounds, but I will confine my remarks to examples of projectile wounds that I saw in the late Greco- Turkish war.Definitions never cover all the ground, but I remember Sir William Mac Cormac's excellent definition of a bullet wound as " an extreme form of contused wound com- bined with the dangerous depths of a punctured wound."Shell wounds, of course, differ in the respect that they usually result in extensive lacerations of the soft tissues, with perhaps comminution of the bones as well.M ODERN BULLETS AND THE WOUNDS THEY PRODUCE.Practically only three kinds of rifle bullets were employed in the war.The Greeks used the Le Gras French rifle with a Chassepot lever action.In Fig. 2 is shown one of the cart-
Developing new drugs from annals of Chinese medicine
Authors: Zhaoxiang Bian, Shilin Chen, Chungwah Cheng, Jun Wang, Haitao Xiao, Hongyan Qin
Journal: Acta Pharmaceutica Sinica B (2012)

Developing new pharmaceuticals requires massive amounts of time, money and efforts. The key step is how to find a safe and effective entity for a disease condition and how to develop it as new drug effectively. Unfortunately, the FDA's rate of approving new entities has declined dramatically in the last three decades. There is a strong need to review the current strategy and to optimize process in developing new drugs, both to shorten the process and increase the success rate. Chinese medicine has used natural products to treat patients for thousands of years, and Chinese medicine practitioners have chronicled the patients and treatment methods for thousands of years. There is much information that has not yet been used. The success stories of artimisinin and arsentic trioxide are wonderful examples of how the annals of Chinese medicine can provide leads for discovering new drugs. This paper argues that the annals of Chinese medicine are valuable and describes how they can be used in modern drug discovery. The major topics addressed are: (i) why Chinese medicine is a rich resource for finding new drugs; (ii) how to identify a potential valuable record from Chinese medicine annals; (iii) when a potential valuable record is identified from annals, how to proceed; and (iv) both why and how the approach used for chemical drugs should be revised for drugs based on the historical documents related to herbal medicine. In conclusion, we argue here that the annals of Chinese medicine offer not only a rich resource for new drugs, but also several centuries of patient data with regard to safety and efficacy, that in effect represent pilot studies. Acknowledging and using these data can shorten new drug discovery time and improve efficiency of the drug development process, bringing more effective, safe drugs to market much more quickly and cheaply.
Meningococcus and Gonococcus: Never the Twain... Well, Hardly Ever
Authors: Harry A. Feldman
Journal: New England Journal of Medicine (1971)

Among the more intriguing unanswered questions related to infectious diseases are not only how illness and death are induced, but why some of their causative organisms have predilections for certain areas of the host. So accustomed do we become to the latter that we often tend to dismiss a particular organism's possible role in a clinical problem because of the seeming location of the infectious process. Good and pertinent examples of this in relation to the Neisseriae are provided by two papers in this issue of the Journal (Taubin and Landsberg, and Keys et al.). One deals with a case . . .
South Africa withdraws TB drugs because of quality concerns
Authors: P. Sidley
Journal: BMJ (2008)

South African health authorities have withdrawn two generic drugs widely used in the country to treat tuberculosis, amid concerns about their quality.

When the health minister, Manto Tshabalala-Msimang, announced the withdrawal earlier this month she said that her department had received information suggesting that the ingredients in the two combination drugs, called Antib-4 and Ebsar, “were not at the level stated in the label after storage.”

Antib-4 combines pyrazinamide, ethambutol, isoniazid, and rifampicin. Ebsar is a combination of isoniazid and rifampicin.

Both drugs are manufactured in India by Rusan Pharma and imported into South Africa, where they are …
High-density and low-density lipoproteins and prevalence of vascular disease in diabetes mellitus.
Authors: J P Reckless, D J Betteridge, P Wu, B Payne, D J Galton
Journal: BMJ (1978)

The prevalence of vascular disease among 154 diabetic patients was analysed in relation to the serum concentrations of individual lipoproteins. Overal the presence of vascular disease (59 cases) was positively associated with serum cholesterol and low-density-lipoprotein cholesterol but negatively associated with high-density-lipoprotein (HDL) cholesterol. The negative relation between HDL and vascular disease was not observed in all subgroups of diabetics. We conclude that there may be no overriding association between HDL and vascular disease in diabetics as proposed for some non-diabetic populations.
Investigations editor's reply to Sawka and Hargreaves
Authors: D. Cohen
Journal: BMJ (2012)

<h3>Background</h3> A 2015, Hockey Calgary body checking (BC) policy change disallowed BC from non-elite Bantam (ages 13–14, lower 60% of divisions). This was informed by evidence that disallowing BC in Pee Wee (ages 11–12) reduced the risk of injury, specifically concussion, by &gt;3-fold. <h3>Objective</h3> To compare the frequency of type and intensity of player-to-player contacts (PC) and head contact in non-elite Bantam ice hockey games in leagues allowing BC (2014–15) compared with leagues disallowing BC (2015–16). <h3>Design</h3> Cohort study. <h3>Setting</h3> Ice-hockey arenas in Calgary, Canada. <h3>Participants</h3> Non-elite Bantam players in 2014–15 (n=348 players) and 2015–16 (n=309 players) seasons. <h3>Interventions</h3> In the 2014–15 season, non-elite Bantam leagues allowed BC. In 2015–2016, BC was disallowed. <h3>Main Outcome Measurements</h3> Thirteen games pre-policy change (2014–2015) and 13 post-policy change were video recorded. Analysis using validated methodology was used to compare the frequency, type (i.e., trunk, head and other types of PC with limb/head/stick), and intensity (trunk contacts level 1–5 with increasing intensity) of PCs. Incidence rate ratios (IRR) were estimated using Poisson regression (controlling for cluster by team, offset by player minutes). <h3>Results</h3> There were a total of 3485 trunk contacts and 1395 other contacts in 26 games. The overall risk of trunk PCs was lower post-policy change (IRR=0.50, 95% CI; 0.45–0.56). Post-policy change, high intensity (body checking - level 4,5) contacts decreased (IRR<sub>4</sub>=0.19, 95% CI; 0.13–0.26 IRR<sub>5</sub>=0.11, 95% CI; 0.03–0.51), lower intensity (level 2,3) PCs were less frequent (IRR<sub>2</sub>=0.45, 95% CI; 0.40–0.50 and IRR<sub>3</sub>=0.47, 95% CI; 0.35–0.63), and other contacts made with the limb/stick also decreased (IRR=0.60, 95% CI; 0.48–0.73). Head contact decreased (IRR=0.40, 95% CI; 0.25–0.61). <h3>Conclusions</h3> Post-policy change disallowing BC in non-elite Bantam, incidence of high intensity (level 4,5) PCs decreased 82%. Head contact decreased 60% and stick/limbs contact decreased 40%. These findings inform the mechanisms of injury explaining concussion risk reduction post-BC policy change.
Long term care of older people
Authors: E. Dickinson
Journal: BMJ (1996)

Car manufacturers have responded radically to the challenge of global competition; they have revolutionised assembly through technology, just-in-time inventories, team working, and a focus on quality; they have optimised component supply by forging long term contracts based on mutual help and trust; they have introduced customer focus into relationships with car purchasers. This exemplifies how industry has recognised the need for effective strategic management when crisis looms. Why then, when Britain faces the unprecedented strategic challenge of the long term care of older people, is there increasing evidence of strategic drift? Two issues are of particular concern and may lead to increased costs: they are the poor assessment of eligibility of older people for long term care, and poor quality of care.

Evidence of the present inadequacy of eligibility assessment in Britain is beginning to emerge.1 A recent audit report disclosed a disturbing level of inappropriate placement, even after poor …
Administering Plasmid DNA Encoding Tumor Vessel–anchored IFN-α for Localizing Gene Product Within or Into Tumors
Authors: Ryan Craig, Jeffry Cutrera, Shiguo Zhu, Xueqing Xia, Yong-Hwan Lee, Shulin Li
Journal: Molecular Therapy (2008)

Tumor-targeted gene delivery has been intensively studied in the field of gene therapy, but no attention has been given to targeting the therapeutic gene products, which are transcribed and translated from the injected genes, into tumors. Targeting immune stimulatory gene products into tumors is the key to triggering tumor-specific CD8+ T-cell responses and reducing systemic toxicity. To target the gene products generated from the injected genes into tumors, genes encoding the tumor-targeted fusion gene product were generated and administered locally and systemically via electroporation. As anticipated, administration of a therapeutic gene encoding IFN-α and the tumor vessel-targeted peptide CDGRC fusion gene product minimizes the leakage of immunostimulatory cytokine from tumors into the blood circulation, increases the infiltration of CD8+ T cells into tumors, induces a high magnitude of cytotoxic T-cell lysis (CTL) activity, and reduces tumor vessel density. As a result, tumor growth was more significantly inhibited by administering the IFN-α-CDGRC gene than by administering the wild-type IFN-α gene. The same result was obtained with the systemic administration of the tumor-targeted IFN-α gene. This gene product-based tumor-targeted gene therapy approach could complement any other tumor-targeted gene delivery method for improving tumor-targeting efficiency.
Mortality in Geriatric Surgery
Authors: L. Carp
Journal: BMJ (1950)

SUPRANUCLEAR BULBAR PALSY IN MITRAL STENOSIS BDI Case 2 also had two acute cerebral attacks: the first resulted in a right hemiparesis, and the second, three weeks later, in a left hemiparesis.Supranuclear bulbar palsy developed with the second attack and disturbance of articulation was the most striking feature.In Case 3 it seems likely that several small cerebral emboli affected both sides of the brain almost simul- taneously.Typical supranuclear bulbar palsy immediately resulted and the spastic laughter and tears were very evident.Although emotional control improved considerably it was not complete six months later.All three cases had marked dysarthria and dysphagia and all were temporarily incontinent of urine.The onset of supranuclear bulbar palsy was in each case abrupt, but all three showed considerable improvement.In supranuclear bulbar palsy resulting from cerebral arteriosclerosis the vascular degenerative changes are likely to be diffuse and multiple.Bilateral pyramidal-tract signs are usually present and there may be a history of double hemiplegia, though there is often an interval of months or years between the involvement of the two sides.Some- times the supranuclear bulbar features are accompanied by only a hemiplegia or hemiparesis.More rarely there is no limb paralysis at all, though the plantar responses may be extensor.In addition to the involuntary laughter and crying, progressive dementia is seen in the arteriopathic group and occasional extrapyramidal features have been described.The course of the disease is irregular and may be prolonged.When supranuclear bulbar palsy is produced by bilateral cerebral embolism, however, there is usually a history suggesting sudden vascular occlusion on one side of the brain, followed quite rapidly by the same process on the opposite side, so that bilateral interference with the cortico- bulbar and cortico-spinal pathways immediately results.The embolic form of supranuclear bulbar palsy may occur in young subjects.Dementia is not a feature of the condi- tion, and, if the emboli are small, rapid resolution of symptoms may occur.Summary Supranuclear bulbar palsy (so-called pseudobulbar palsy) most often results from diffuse cerebral arteriosclerosis, with or without a history of double-that is, bilateral-hemiplegia.Three cases of mitral stenosis are described in which bilateral cerebral emboli resulted in the abrupt development of the characteristic syndrome of supranuclear bulbar palsy with bilateral pyramidal-tract signs.We should like to express our thanks to Professor E.