tbuckley/cabot-search huggingface dataset:
Clinical pharmacology as a cornerstone of orphan drug development
Authors: Edward D. Bashaw, Shiew-Mei Huang, Timothy R. Coté, Anne R. Pariser, Christine E. Garnett, Gilbert Burckart, Lei Zhang, Angela Y. Men, Christine D. Le, Rosane Charlab, Jogaro V. Gobburu, Lawrence J. Lesko
Journal: Nature Reviews Drug Discovery (2011)
Is Antimicrobial Prophylaxis of Urinary Tract Infections Cost Effective?
Authors: WALTER E. STAMM
Journal: Annals of Internal Medicine (1981)

Antimicrobial prophylaxis prevents recurrent urinary tract infections in susceptible women, but its cost effectiveness has not been studied. In a recent placebo-controlled trial of urinary prophylaxis, we also assessed cost effectiveness using a decision analysis model. In our hospital the direct cost of 1 patient year of urinary prophylaxis approximates the cost of treating one episode of cystitis. In women with a baseline infection rate of three per patient year, the annual cost of prophylaxis ($85.82) was less than treatment of acute episodes of infection ($392.30). Sensitivity analyses showed that in women with three infections per year, prophylaxis became cost effective when charges per episode exceeded $42.00. In women with frequent episodes of cystitis, prophylaxis will be cost effective in most practice settings.
Death in heat waves: Beware of fans...
Authors: R. M Wolfe
Journal: BMJ (2003)

Editor—In his editorial Keatinge referred to fans as a prevention for heat injury.1 However, in severe heat, fans can add to the level of heat stress.

Writing about the fatal heat wave of 1995 in Chicago, the US Centers for Disease Control and Prevention noted that fans should not be used for preventing heat related illness in areas with high humidity because increased air movement (such as from fans) is associated with heat stress when the ambient temperature exceeds approximately 100°F (37.8°C) and because fans are not protective at temperatures greater than 90°F (greater than 32.3°C) with humidity greater than 35% (the exact temperature varies with the humidity).2

Fans can be extremely effective when combined with the use of a fine water mist in areas of normal or low humidity, but if the temperature and humidity are high, even water mist plus fanning is not reliable for cooling. In such cases people at risk of heat injury are advised to take a cool shower or bath, or seek shelter in an air-conditioned building.
Duodenal Diverticulum Presenting as a Hypermetabolic Mass on F-18 FDG PET/CT
Authors: Michael Piesman, Inku Hwang, Frank M. Moses, Thomas W. Allen
Journal: Clinical Nuclear Medicine (2005)

F-18 FDG PET/CT has been proven to be an accurate test for the diagnosis and staging of a wide variety of primary and metastatic malignancies, including those of the gastrointestinal tract. However, false-positive results can be encountered on PET/CT examinations with certain inflammatory and infectious conditions. We present a case of a duodenal diverticulum with markedly increased F-18 FDG activity. The hypermetabolic diverticulum showed progressive increasing radiotracer accumulation on dual time point FDG PET imaging. High rate of glucose utilization by inflammatory cells within the diverticulum or accumulation of physiologically excreted FDG within the diverticulum may explain the abnormal findings.
Induction of cardiac nerve sprouting and sympathetic hyperinnervation by subthreshold electrical stimulation of the left stellate ganglion in dogs
Authors: Moshe Swissa, Shengmei Zhou, Che-Ming Chang, Angela C. Lai, Adam Cates, Michael C. Fishbein, Hrayr S. Karaguezian, Peng-Sheng Chen, Lan S. Chen
Journal: Journal of the American College of Cardiology (2002)
Risk of Leukemia after Chemotherapy and Radiation Treatment for Breast Cancer
Authors: Rochelle E. Curtis, John D. Boice, Marilyn Stovall, Leslie Bernstein, Raymond S. Greenberg, John T. Flannery, Ann G. Schwartz, Peter Weyer, William C. Moloney, Robert N. Hoover
Journal: New England Journal of Medicine (1992)

Few studies have evaluated the late effects of adjuvant chemotherapy for breast cancer. Moreover, the relation between the risk of leukemia and the amount of drug given and the interaction of chemotherapy with radiotherapy have not been described in detail.
Dangerous Potentiation of Meperidine Hydrochloride by Pargyline Hydrochloride
Authors: I. Myron Vigran
Journal: JAMA (1964)

INTEREST IN the role of monoamine oxidase (MAO) inhibitors in the treatment of hypertensive disease has been stimulated by the widely noted observation that therapy with potent monoamine oxidase inhibitors produces marked orthostatic hypotension. Originally a troublesome side reaction, this property has since been utilized in the treatment of hypertension. Recently, the introduction of a new drug, pargyline hydrochloride (Eutonyl), with powerful MAO inhibiting properties and antihypertensive effects, has been used as a therapeutic agent in the treatment of hypertension. Little known is the fact that the effects of meperidine (Demerol) hydrochloride are markedly potentiated when administered to patients concurrently taking MAO inhibitors. To my knowledge, this has not been reported in the American literature with the exception of a precaution concerning the drug,<sup>1</sup>although it has been discussed by the British.<sup>2-6</sup>It is felt that a timely warning of the danger of meperidine administration to patients being
THE PHAGOCYTOSIS AND INACTIVATION OF STAPHYLOCOCCI BY MACROPHAGES OF NORMAL RABBITS
Authors: G. B. Mackaness
Journal: The Journal of Experimental Medicine (1960)

The phagocytosis and survival of staphylococci in the presence of rabbit macrophages has been studied quantitatively. The method permitted an independent measurement to be made of intracellular and extracellular bacteria during the course of phagocytosis. It was found that S. aureus was relatively resistant to phagocytosis. In the presence of specific immune serum, however, it was ingested at a rate comparable with that of S. albus in normal serum; under these conditions more than 90 per cent of bacteria of either strain were inactivated within 60 minutes. Since immune serum did not alter the susceptibility of S. aureus to inactivation within macrophages, it is concluded that S. aureus and S. albus are similar in respect to their ability to survive within macrophages. The inactivation of staphylococci occurred more slowly, and a greater percentage survived incubation for 180 minutes, in macrophages than in polymorphonuclear leucocytes. Moreover, they retained their morphology for many hours within the former cell, but disappeared rapidly from the cytoplasm of granulocytes. It is suggested that the antibacterial mechanisms of the two cell types are fundamentally different. When studied over a prolonged period the staphylococci which survived early inactivation within macrophages were observed to die slowly over many hours. When they were recovered from cells and exposed to fresh macrophages, however, they were ingested and inactivated as readily as bacteria of the original population. It is suggested, therefore, that the prolonged survival in vitro of some staphylococci is due to variation in the efficiency of the antibacterial mechanism of exudative mononuclear phagocytes.
VOLUNTEER MEDICAL SERVICE CORPS
Authors: William Brady
Journal: JAMA (1918)

FROM ELMIRA, N. Y.  To the Editor:  —The  Medical Service  merits much plainer discussion thanThe Journalhas seen fit to devote to it.  In Elmira, for example, we had only a handful of doctors in the Medical Reserve Corps, U. S. Army. We needed stimulation or something. So Major C. A. L. Reed was sent here to enable any physicians so inclined to be examined for commissions without inconvenience to themselves. The local representatives of the Volunteer Medical Service Corps gave out to the press, and there was duly published, a statement that all physicians were compelled to apply for commission or enroll in the stay-at-home-and-wear-a-button corps. The chairman of the local committee of the Volunteer Medical Service Corps called a meeting of physicians, and in his address stated emphatically that the matter of applying for a commission or enrolling in the organization was not an invitation,
DNA — Structure and Enzymatic Synthesis
Authors: Gerald Medoff, Morton N. Swartz
Journal: New England Journal of Medicine (1967)

IN the past ten years there has been a phenomenal increase in knowledge of the mechanism of synthesis of deoxyribonucleic acid (DNA) in bacterial, mammalian and virus–infected cell systems. The introduction of new technics and instrumentation has led to further eludication of DNA structure and physical properties, and essentially complete confirmation of the double-helical model of DNA proposed by Watson and Crick thirteen years ago.1 Investigations of the interrelations among the 3 major biologic macromolecules, the so-called "holy trinity," — consisting of DNA, ribonucleic acid (RNA) and protein, — have partially answered fundamental questions concerning gene structure, replication, and mutation . . .
Diet and Exercise Training Restore Blood Pressure and Vasodilatory Responses During Physiological Maneuvers in Obese Children
Authors: Maurício M. Ribeiro, Alexandre G. Silva, Nelson S. Santos, Isabel Guazzelle, Luciana N.J. Matos, Ivani C. Trombetta, Alfredo Halpern, Carlos E. Negrão, Sandra M.F. Villares
Journal: Circulation (2005)

Background— The effects of diet and diet plus exercise training on muscle vasodilatation during physiological maneuvers in obese children are unknown. We tested the hypothesis that (1) blood pressure (BP) and forearm vascular conductance (FVC) responses during handgrip exercise and mental stress would be altered in obese children and (2) diet plus exercise training would restore BP and FVC responses during exercise and mental stress in obese children. Methods and Results— Thirty-nine obese children (aged 10±0.2 years) were randomly divided into 2 groups: diet plus exercise training (n=21; body mass index [BMI]=28±0.5 kg/m 2 ) and diet (n=18; BMI=30±0.4 kg/m 2 ). Ten age-matched lean control children (BMI=17±0.5 kg/m 2 ) were also studied. Forearm blood flow was measured by venous occlusion plethysmography. BP was monitored noninvasively. Handgrip exercise was performed at 30% maximal voluntary contraction for 3 minutes. Stroop color word test was performed for 4 minutes. Baseline BP was significantly higher and FVC was significantly lower in obese children. During exercise and mental stress, BP responses were significantly higher and FVC responses were significantly lower in obese children. Diet and diet plus exercise training significantly reduced body weight. Diet and diet plus exercise training significantly decreased BP levels during exercise and mental stress. Diet plus exercise training, in contrast to diet alone, significantly increased FVC responses during exercise (3.7±0.3 versus 5.6±0.4 U; P =0.01) and mental stress (3.5±0.5 versus 4.5±0.4 U; P =0.02). After diet plus exercise training, BP and FVC responses during exercise and mental stress were similar between obese children and the control group. Conclusions— Obesity exacerbates BP responses and impairs FVC responses during exercise and mental stress in children. Diet and exercise training restore BP and FVC responses in obese children.
Absence of the platelet receptor for drug-dependent antibodies in the Bernard-Soulier syndrome.
Authors: T J Kunicki, M M Johnson, R H Aster
Journal: Journal of Clinical Investigation (1978)

The platelet membrane receptor for quinidine- and quinine-dependent antibodies was studied in three patients with the Bernard-Soulier syndrome (BSS) and in normal subjects with immunologic techniques based on the release of 51Cr from labeled platelets. The receptor could not be detected on BSS platelets but was present on platelets from each of 180 normal subjects. BSS platelets reacted normally with other allo- and autoantibodies. In confirmation of previous reports, BSS platelets were found to be deficient in glycoproteins Ib and Is. However, after apparently total cleavage of these proteins from the membrane of normal platelets by controlled hydrolysis with trypsin or chymotrypsin, 80% of the drug-dependent antibody receptor activity was retained. These observations suggest the existence of an additional, hitherto unrecognized membrane defect in Bernard-Soulier platelets.
Atlas of Ultrasound-Guided Procedures in Interventional Pain Management
Authors: Matthias Karst
Journal: JAMA (2012)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Effect of the ACE Inhibitor Lisinopril on Mortality in Diabetic Patients With Acute Myocardial Infarction
Authors: Giulio Zuanetti, Roberto Latini, Aldo P. Maggioni, MariaGrazia Franzosi, Luigi Santoro, Gianni Tognoni
Journal: Circulation (1997)

Background Mortality of diabetic patients with acute myocardial infarction (MI) remains high despite recent improvement in their management. There is a need to evaluate efficacy and safety of novel treatments of MI in this high-risk population. We evaluated whether treatment with an ACE inhibitor begun within 24 hours from the onset of symptoms is able to decrease mortality and morbidity of diabetic patients with acute MI. Methods and Results A retrospective analysis of the data of the GISSI-3 study in patients with and without a history of diabetes was performed. Patients with suspected acute MI were randomized to treatment with lisinopril (2.5 to 5 up to 10 mg/d) with or without nitroglycerin (5 to 20 μg IV then 10 mg/d) begun within 24 hours and continued for 6 weeks. The main end point was mortality at 6 weeks, and the secondary end point was a combined evaluation of mortality and severe left ventricular dysfunction. Information on diabetic status was available for 18 131 patients (≈94% of the total population enrolled), of whom 2790 patients had a history of diabetes. Treatment with lisinopril was associated with a decreased 6-week mortality in diabetic patients (8.7% versus12.4%; OR, 0.68; 95% CI, 0.53 to 0.86; 37±12 lives saved per 1000 treated patients), an effect that was significantly ( P &lt;.025) higher than that observed in nondiabetic patients. The survival benefit in diabetics was mostly maintained at 6 months despite withdrawal from treatment at 6 weeks (12.9% versus 16.1%; OR, 0.77; 95% CI, 0.62 to 0.95). Conclusions Early treatment with the ACE inhibitor lisinopril in diabetic patients with acute MI is associated with a decreased 6-week mortality. This beneficial effect supports a widespread and early use of ACE inhibitors in diabetic patients with acute MI. The burden of mortality plus morbidity for ventricular dysfunction in diabetics remains clinically important and warrants further testing of novel therapeutic approaches.
The High-Dose Aldesleukin “Select” Trial: A Trial to Prospectively Validate Predictive Models of Response to Treatment in Patients with Metastatic Renal Cell Carcinoma
Authors: David F. McDermott, Su-Chun Cheng, Sabina Signoretti, Kim A. Margolin, Joseph I. Clark, Jeffrey A. Sosman, Janice P. Dutcher, Theodore F. Logan, Brendan D. Curti, Marc S. Ernstoff, Leonard Appleman, Michael K.K. Wong, Nikhil I. Khushalani, Leslie Oleksowicz, Ulka N. Vaishampayan, James W. Mier, David J. Panka, Rupal S. Bhatt, Alexandra S. Bailey, Bradley C. Leibovich, Eugene D. Kwon, Fairooz F. Kabbinavar, Arie S. Belldegrun, Robert A. Figlin, Allan J. Pantuck, Meredith M. Regan, Michael B. Atkins
Journal: Clinical Cancer Research (2014)

Purpose: High-dose aldesleukin (HD IL2) received FDA approval for the treatment of metastatic renal cell carcinoma (MRCC) in 1992, producing a 14% objective response rate (ORR) and durable remissions. Retrospective studies suggested that clinical and pathologic features could predict for benefit. The Cytokine Working Group conducted this prospective trial to validate proposed predictive markers of response to HD IL2.Experimental Design: Standard HD IL2 was administered to prospectively evaluate whether the ORR of patients with mRCC with "good" predictive pathologic features based on an "integrated selection" model [ISM (e.g., clear-cell histology subclassification and carbonic anhydrase-9 (CA-9) IHC staining] was significantly higher than the ORR of a historical, unselected population. Archived tumor was collected for pathologic analysis including tumor programmed death-ligand 1 (PD-L1) expression.Results: One hundred and twenty eligible patients were enrolled between June 11 and September 7; 70% were Memorial Sloan Kettering Cancer Center (New York, NY) intermediate risk, 96% had clear cell RCC, and 99% had prior nephrectomy. The independently assessed ORR was 25% (30/120, 95% CI, 17.5%–33.7%, P = 0.0014; 3 complete responses, 27 partial responses) and was higher than a historical ORR. Thirteen patients (11%) remained progression free at 3 years and the median overall survival was 42.8 months. ORR was not statistically different by ISM classification ("good-risk" 23% vs. "poor-risk" 30%; P = 0.39). ORR was positively associated with tumor PD-L1 expression (P = 0.01) by IHC.Conclusions: In this prospective, biomarker validation study, HD IL2 produced durable remissions and prolonged survival in both "good" and "poor-risk" patients. The proposed ISM was unable to improve the selection criteria. Novel markers (e.g., tumor PD L1 expression) appeared useful, but require independent validation. Clin Cancer Res; 21(3); 561–8. ©2014 AACR.
Frequent genital herpes simplex virus 2 shedding in immunocompetent women. Effect of acyclovir treatment.
Authors: A Wald, L Corey, R Cone, A Hobson, G Davis, J Zeh
Journal: Journal of Clinical Investigation (1997)

Reactivation of herpes simplex virus type 2 (HSV-2) occurs intermittently as perceived clinically and by viral culture. We performed a series of studies to evaluate the frequency and pattern of HSV-2 reactivation using both viral isolation and HSV PCR assay. Daily samples of genital secretions were obtained from 27 HSV-2 seropositive women; a subset of subjects obtained samples while receiving oral acyclovir 400 mg PO twice a day. HSV DNA was detected in genital swab specimens on 28% of 1,410 d compared with 8.1% of days by viral isolation. 11 of 20 women had HSV DNA detected on > 20% of days, 4 on > 50%, and 2 on > 75% of days; in contrast, none of the women shed on > 21% of days by viral isolation. The daily administration of oral acyclovir promptly reduced the frequency of HSV DNA detection by a median of 80%. Within 3-4 d of discontinuing daily acyclovir, HSV DNA again appeared in the genital area. HSV-2 shedding in the genital mucosa occurs much more frequently than previously appreciated. This frequent reactivation likely plays a role in the epidemic spread of genital herpes worldwide.
Myocardial lactate and adenosine metabolite production as indicators of exercise-induced myocardial ischemia in the dog.
Authors: T R Vrobel, C R Jorgensen, R J Bache
Journal: Circulation (1982)

To determine the value of lactate and the adenosine metabolites inosine and hypoxanthine as indicators of myocardial ischemia, we measured the levels of these metabolites in arterial and coronary sinus blood of nine chronically instrumented dogs subjected to exercise stress before and during reversible circumflex coronary artery occlusion. The degree of circumflex bed hypoperfusion was measured by 15-mu microspheres and the reduction in circumflex coronary flow was measured with a proximal flow probe. Adenosine metabolites, although below the level of accurate detection in our laboratory in arterial blood (i.e., 0.5 microM/l), were detected in coronary sinus blood (range 2.7--18.7 microM/l) in 26 of 33 studies with partial circumflex occlusion when circumflex flow was reduced to less than 80% of that seen during exercise without occlusion and when only subendocardial perfusion was reduced. Global left ventricular flow and transmural flow in nonischemic beds did not correlate with positive studies. Myocardial lactate extraction was a less accurate test for determining circumflex bed hypoperfusion. Thus, myocardial production of adenosine metabolites is a sensitive qualitative test of exercise-induced ischemia responding to a modest fall in coronary flow when only subendocardial hypoperfusion is present.
SHOCK, HEMORRHAGE AND SEPTCEMIA.
Authors: THOS. H. WAGNER
Journal: JAMA (1899)

In tabulating the symptoms of shock and hemorrhage, we usually note the following : An expressionless countenance, pallor, with corresponding coldness of face and mucous membrane, and clammy skin, often slight or profuse sweats, chilly sensations, irregular heart action, with weak, irregular, thready, often imperceptible pulse, and irregular sighing respiration. These two conditions, shock and hemorrhage, or rather their symptoms, are so intimately associated that I will not take time mentioning the slight variations or the local conditions found in hemorrhage alone. In the symptoms of septicemia we at first find the essential signs of fever, with often a full, bounding pulse; but later we get the feeble, less regular pulse, sighing respiration, clammy skin with slight or profuse sweats, countenance expressionless, or expressing great concern, the secretions from the bowels and kidneys scanty, and as regards these symptoms they are all due to a vasomotor paralysis, either
The development of the ICD-11 Clinical Descriptions and Diagnostic Guidelines for Mental and Behavioural Disorders
Authors: Michael B. First, Geoffrey M. Reed, Steven E. Hyman, Shekhar Saxena
Journal: World Psychiatry (2015)

The World Health Organization is in the process of preparing the eleventh revision of the International Classification of Diseases (ICD-11), scheduled for presentation to the World Health Assembly for approval in 2017. The International Advisory Group for the Revision of the ICD-10 Mental and Behavioural Disorders made improvement in clinical utility an organizing priority for the revision. The uneven nature of the diagnostic information included in the ICD-10 Clinical Descriptions and Diagnostic Guidelines (CDDG), especially with respect to differential diagnosis, is a major shortcoming in terms of its usefulness to clinicians. Consequently, ICD-11 Working Groups were asked to collate diagnostic information about the disorders under their purview using a standardized template (referred to as a "Content Form"). Using the information provided in the Content Forms as source material, the ICD-11 CDDG are being developed with a uniform structure. The effectiveness of this format in producing more consistent clinical judgments in ICD-11 as compared to ICD-10 is currently being tested in a series of Internet-based field studies using standardized case material, and will also be tested in clinical settings.