tbuckley/cabot-search huggingface dataset:
A Comparison of Amphotericin B Alone and Combined with Flucytosine in the Treatment of Cryptoccal Meningitis
Authors: John E. Bennett, William E. Dismukes, Richard J. Duma, Gerald Medoff, Merle A. Sande, Harry Gallis, John Leonard, Branch T. Fields, Major Bradshaw, Hubert Haywood, Zell A. McGee, Thomas R. Cate, C. Glenn Cobbs, John F. Warner, David W. Alling
Journal: New England Journal of Medicine (1979)

We compared amphotericin B therapy for cryptococcal meningitis with a newer regimen containing both amphotericin B and flucytosine. In 50 patients with 51 courses of therapy adherent to the protocol, 27 courses were with amphotericin B and 24 with the combination. Even though the combination regimen was given for only six weeks and amphotericin B for 10 weeks, the combination cured or improved more patients (16 vs. 11), produced fewer failures or relapses (three vs. 11), more rapid sterilization of the cerebrospinal fluid (P<0.001) and less nephrotoxicity (P<0.05) than did amphotericin B alone. The number of deaths was the same (five) with each regimen. Adverse reactions to flucytosine occurred in 11 of 34 patients but were not life threatening. We conclude that combined flucytosine-amphoericin B therapy is the regimen of choice in cryptococcal meningitis. (N Engl J Med 301:126–131, 1979)
Blood Pressure and Calcium Supplementation-Reply
Authors: Roseann M. Lyle
Journal: JAMA (1987)

<h3>In Reply.—</h3> The comments and questions of Drs Cappuccio and Strazzullo are appreciated. We, too, believe that rigorously designed and carefully presented studies are needed to answer basic questions about the relationship between oral calcium intake and blood pressure. Our choice of a normotensive population was justified by our interest in nonpharmacologic approaches to the primary prevention of hypertension as well as the treatment of established hypertension. The entire range of the blood pressure distribution should be examined with respect to proposed interventions to determine their potential for prevention and treatment of hypertension. Only two previously reported studies<sup>1,2</sup>have examined the impact of increased calcium intake in normotensives and none have specifically addressed the possibility of racial differences in blood pressure response to calcium supplementation. It is a matter of opinion whether covariance is appropriate when a randomized design is employed and baseline values are not significantly different between
BLOOD PRESSURE STUDIES OF FIVE HUNDRED MEN
Authors: BERTNARD SMITH
Journal: JAMA (1918)

The studies for this report were made on men who applied for examination for the American Army Aviation Service. It may readily be seen that a long period of study could not be given to each applicant without causing unwarranted delay to the applicant and also to the other examiners. A Tycos instrument, daily tested with a mercurial sphygmomanometer, was used for all blood pressure estimations. All readings were made by one examiner in order to reduce the personal factor to as small an error as possible. Readings were made with applicants in (1) the recumbent position; (2) standing, before exercise, and (3) standing, after measured exercise. The readings, in the first position, were made after the nervous excitement had become controlled as much as possible. This factor was commonly very prominent and often difficult to control, sometimes requiring the subject to return for a later reading. For the exercise
P4-17-01: Trastuzumab Does Not Increase the Incidence of Central Nervous System (CNS) Relapses in HER2−Positive Early Breast Cancer: The HERA Trial Experience.
Authors: B Pestalozzi, E Holmes, O Metzger, Azambuja E de, L Hogge, M Scullion, R Gelber, M Piccart-Gebhart, D Cameron
Journal: Cancer Research (2011)

Abstract Background: Retrospective studies of HER2−positive metastatic breast cancer (BC) showed an incidence of CNS metastases of 21% to 34%. We investigated the incidence and clinical aspects of CNS relapse (CNS-R) in patients (pts) enrolled in the HERA trial, a prospectively randomized adjuvant trial in node + or high-risk node - HER2−positive early BC pts. Methods: 3401 pts were randomized into the 1-year trastuzumab (1yT) or the observation (obs) arms of HERA (Piccart-Gebhart et al, 2005, Gianni et al, 2011). The cumulative incidences of first disease-free survival (DFS) events in the CNS vs other sites were estimated using competing risk analysis. The database of the main study had a clinical cut-off date of 9th June 2008. To obtain additional information regarding CNS-R (including occurrence of CNS-R after first DFS event), a specific CNS-directed questionnaire was sent to investigators of pts who were deceased as of July 2009. Information collected included the date of CNS-R, whether it was symptomatic, the type of CNS-R (brain metastases (BM) or meningeal carcinomatosis (MC)), methods of diagnosis, and treatments at the time of CNS-R. Results: 1yT significantly reduced the risk of other DFS events (p=0.000017, Gray's test), but not of CNS-R (p=0.55) as first event (see table). During the first year of follow up, CNS-R accounted for 15 (14.9%) of the 101 first DFS events in the 1yT arm and 15 (7.7%) of the 194 first DFS events in the obs arm. The analysis of baseline patient and tumor characteristics associated with CNS-R as first event confirmed known risk factors such as young age (&amp;lt;35y), T3 tumor, ≥ 4 + LN, ER neg, and G3. 413 of the 481 questionnaires (85.9%) were returned. 217 of the 413 deceased pts had a CNS-R diagnosed prior to death (52.5%), with more events occurring in the 1yT arm (see table). By contrast, the incidence of CNS-R as first DFS event was balanced across the arms. Based on the survey data, CNS-R was symptomatic in 189 pts (87.1%) with no differences between arms. BM were present in 211 pts (97.2%), absent in 5 (2.3%), and missing information in 1 (0.5%). MC was diagnosed in 25 pts (11.5%), absent in 187 (86.2%), missing information in 5 (2.3%). Frequencies for BM and MC were very similar in both arms. Conclusion: This retrospective analysis of a prospective large study shows more than 50% incidence of clinically diagnosed CNS-R in HER2−positive BC pts who have died. CNS-R was symptomatic in most pts. CNS-R at any time was less frequent in the 1yT arm (88 vs 129). There is no evidence that adjuvant trastuzumab increases the incidence of CNS-R. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-17-01.
Clinical Aspects of Aging: A Comprehensive Text Prepared Under the Direction of the American Geriatrics Society
Authors: C. A. Hedberg
Journal: JAMA (1978)

Presently, there are more than 22 million Americans older than 65 years, with 1.2 million in long-term care facilities, yet the medical school curriculums and standard textbooks are often devoid of information relative to the care of the aged. As if to mirror our youth-oriented society, there is neglect of the concept that geriatric care requires a special body of psychological, social, and scientific knowledge. This multiauthored volume, prepared under the auspices of the Public Health Service and the American Geriatric Society, is an ambitious and successful attempt to improve this situation. The subject is comprehensively covered, so that the book becomes a resource of information for family practitioners, internists, nurses, social workers, and all others involved with the care of the elderly. Chapters devoted to diagnosis and treatment span the entire range of medical and surgical specialties and focus on modifying the clinical approach so that it will accord
Clinical measurement of myocardial infarct size. Modification of a method for the estimation of total creatine phosphokinase release after myocardial infarction.
Authors: R M Norris, R M Whitlock, C Barratt-Boyes, C W Small
Journal: Circulation (1975)

A modified method for the measurement of total creatine phosphokinase release from venous blood samples taken four-hourly after myocardial infarction has been used in 43 patients admitted to a Coronary Care Unit. The fractional decay rate (Kd) of enzyme activity has been measured by a standardized method in each patient, and accuracy of the calculation of total enzyme release has been improved by allowance for individual variations in decay rate, and discarding of data from which decay rates cannot be measured within confidence limits of less than plus or minus 15 per cent. Total enzyme release was greater in cases of transmural infarction than in patients with subendocardial infarction, and showed a good positive correlation with clinical indices of the extent of myocardial damage. As noted by previous workers, this method allows for the measurement of the rate as well as the extent of enzyme release, and so should prove useful in the clinical evaluation of therapeutic agents which might accelerate or retard the rate of myocardial necrosis in patients with acute myocardial infarction.
Early detection of gastric cancer.
Authors: M T Hallissey, W H Allum, A J Jewkes, D J Ellis, J W Fielding
Journal: BMJ (1990)

To see whether investigation of dyspeptic patients aged over 40 after their first consultation with the general practitioner would increase the proportions with early and operable gastric cancers.Prospective study of gastric cancer in dyspeptic patients aged over 40 from a defined population.10 General practices (six in central Birmingham, four in Sandwell); the Queen Elizabeth Hospital, Birmingham; and Sandwell District General Hospital.2659 Patients aged 40 or over referred with dyspepsia.Increase in early and operable gastric cancers detected in middle aged patients with dyspepsia.Disease was identified in 1992 patients (75%). Fifty seven were found to have gastric cancer, 36 being treated by potentially curative resection, including 15 with early cancer.The investigation of dyspeptic patients over 40 at first attendance can increase the proportion of early gastric cancers detected to 26% and the proportion of operable cases to 63%. Such a policy has the potential to reduce mortality from gastric cancer in the population.
Eosinophils in chronically inflamed human upper airway tissues express transforming growth factor beta 1 gene (TGF beta 1).
Authors: I Ohno, R G Lea, K C Flanders, D A Clark, D Banwatt, J Dolovich, J Denburg, C B Harley, J Gauldie, M Jordana
Journal: Journal of Clinical Investigation (1992)

Transforming growth factor beta (TGF beta) is a multifunctional protein which has been suggested to play a central role in the pathogenesis of chronic inflammation and fibrosis. Nasal polyposis is a condition affecting the upper airways characterized by the presence of chronic inflammation and varying degrees of fibrosis. To examine the potential role of TGF beta in the pathogenesis of this condition, we investigated gene expression and cytokine production in nasal polyp tissues as well as in the normal nasal mucosa. By Northern blot analysis using a porcine TGF beta 1 cDNA probe, we detected TGF beta 1-specific mRNA in nasal polyp tissues, as well as in the tissue from a patient with allergic rhinitis, but not in the normal nasal mucosa. By the combination of tissue section staining with chromotrope 2R with in situ hybridization using the same TGF beta 1 probe, we found that approximately 50% of the eosinophils infiltrating the polyp tissue express the TGF beta 1 gene. In addition, immunohistochemical localization of TGF beta 1 was detected associated with extracellular matrix as well as in cells in the stroma. These results suggest that in nasal polyposis where eosinophils are the most prevalent inflammatory cell, TGF beta 1 synthesized by these cells may contribute to the structural abnormalities such as stromal fibrosis and basement membrane thickening which characterize this disease.
An Unusual Case of a False-Positive lodine-131 Whole Body Scan in a Patient with Papillary Thyroid Cancer
Authors: CLAUDIA CECCARELLI, FURIO PACINI, FRANCESCO LIPPI, ALDO PINCHERA
Journal: Clinical Nuclear Medicine (1988)

A false-positive I-131 whole body scan (WBS) for lung uptake in a patient with papillary thyroid cancer, with replacement of his infiltrated esophagus with a left colon graft, is presented. The I-131 image, seen in the upper right lung field, was due to the contaminated colon graft lacking normal peristaltic movements, which was located in the right paramediastinal region. This finding was demonstrated by imaging the upper digestive tract with orally administered Tc-99m DTPA and by a barium x-ray.
Abstract 2710: KSHV-induced PDGF signaling dyregulation drives a Rac1 and ROS-mediated paracrine tumorigenic mechanism necessary for Kaposi's sarcoma
Authors: Lucas E. Cavallin, Qi Ma, Pascal J. Goldschmidt-Clermont, Enrique A. Mesri
Journal: Cancer Research (2011)

Abstract Kaposi's sarcoma (KS), caused by the Kaposi's sarcoma-associated herpesvirus (KSHV), is a major AIDS-associated malignancy characterized by angiogenesis and proliferation of spindle cells. KSHV-infected KS lesions are composed of latently-infected cells and a minority of cells expressing lytic genes such as vGPCR, which are implicated the development of KS angioproliferative phenotype via a paracrine mechanism. A key unsolved question is how this minor population of lytically-infected cells expressing vGPCR transduce an angio-proliferative phenotype to latently-infected cells. Here, we describe a Rac1 and ROS driven mechanism of paracrine amplification of viral oncogenesis in the KSHV-induced tumor model mECK36. It is triggered by vGPCR-induced PDGF secretion, which in the presence of high expression of PDGF receptors and NADPH oxidase family members caused by latent KSHV infection, leads to STAT3-mediated transcriptional activation of c-Myc, VEGF and KSHV latent genes. This paracrine loop, driven by PDGF signaling and regulated by Rac1 and ROS, amplifies vGPCR oncogenesis by driving proliferation and angiogenesis in latently-infected cells. Inhibtion of this molecular pathway by either the antioxidant N-acetylcysteine (NAC) or PDGF receptor tyrosine kinase inhibitors impair KSHV-induced tumorigenesis, angiogenesis and lymphangiogenesis, further validating this paracrine oncogenesis mechanism and its components as anti-KS tumor targets. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2710. doi:10.1158/1538-7445.AM2011-2710
Crohn's Disease and Cancer
Authors: David D. Weedon, Roy G. Shorter, Duane M. Ilstrup, Kenneth A. Huizenga, William F. Taylor
Journal: New England Journal of Medicine (1973)

A follow-up study of 449 patients with Crohn's enteritis, enterocolitis or colitis showed the incidence of colonorectal cancer to be 20 times greater in these cases than in a control population. Life-table methods were used for analysis, and complete follow-up observation was achieved in 442 (98.4 per cent) of the patients. (N Engl J Med 289:1099–1103, 1973)
Abstract 5038: Why is rapamycin effective against Kaposi sarcoma? An analysis of molecular pathways reveals posttranslational silencing of PTEN
Authors: Dirk Dittmer, Debasmita Roy, Susan E. Krown, Blossom Damania
Journal: Cancer Research (2011)

Abstract Background: Rapamycin (RAPA) and its derivatives target the mTOR kinase within the PI3K/Akt/mTOR pathway. RAPA induced regression of transplant-associated Kaposi sarcoma (KS), but it is unclear why this cancer and selected others are responsive to mTOR inhibitors, whereas many others are not. KS requires infection with the KS-associated herpesvirus (KSHV). We hypothesized that because of its viral etiology, the PI3K/Akt/mTOR pathway in KS would be activated post-translationally and reversibly rather than by mutation and thus more responsive to small molecule inhibitors. Material and methods: The AMC conducted a pilot study of RAPA in HIV-associated KS and several partial responses were observed. We used immuno- histochemistry and molecular methods to study the PI3K/Akt/mTOR pathway in sequential biopsies from patients on this trial, as well as in a larger collection of KS biopsies assembled into a TMA, tumor cell lines and tumors from RAPA-treated mice bearing KS xenografts. Results: Ribosomal protein S6 and Akt were consistently phosphorylated in KS. At the same time PTEN was expressed. We found no evidence for PTEN mutations, rather it was phosphorylated. RAPA inhibited mTORC1 signaling in HIV-KS patients and murine xenografts as determined by loss of S6 phosphorylation. Akt remained consistently activated and we saw no changes in phosphorylation at either the mTORC-independent S308 or mTORC2-dependent T473, i.e. there was no evidence for compensatory upregulation of mTORC2. Conclusions: Rapamycin inhibits the mTORC1 pathway in HIV-KS. KS can be considered representative of tumors in which PTEN is epigenetically inactivated and which may be most susceptible to mTOR inhibition. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5038. doi:10.1158/1538-7445.AM2011-5038
Obesity in the US: what is the best role for primary care?
Authors: J. Ard
Journal: BMJ (2015)

The increasing prevalence of obesity together with projected increases in diabetes over the next 20-30 years will put a substantial strain on the finances and resources of the US healthcare system. The best opportunity for broad scale treatment of obesity may lie in the primary care setting. This review assesses the evidence on the efficacy of treatment for obesity delivered in primary care in the United States. It summarizes an earlier systematic review, recent obesity treatment guidelines, and subsequent US based trials with a minimum follow-up of six months in which at least one member of a primary care team helped deliver comprehensive behavioral obesity treatment to adults with overweight or obesity. Overall, the evidence suggests that obesity treatment delivered in primary care has limited effectiveness. Questions remain about the optimal role of the primary care provider in the treatment of obesity and the prevention of weight gain, as well as potential systems approaches to the treatment of obesity.
Value of plasma fibrin D-dimers for detection of acute aortic dissection
Authors: Holger Eggebrecht, Christoph K. Naber, Christian Bruch, Knut Kröger, Clemens von Birgelen, Axel Schmermund, Marc Wichert, Thomas Bartel, Klaus Mann, Raimund Erbel
Journal: Journal of the American College of Cardiology (2004)
Increased Risk for Anaphylactoid Reaction from Contrast Media in Patients on β-Adrenergic Blockers or with Asthma
Authors: David M. Lang, Michael B. Alpern, Paul F. Visintainer, Stephen T. Smith
Journal: Annals of Internal Medicine (1991)

Objective: To determine whether greater risk for anaphylactoid reaction from intravenous urographic contrast media exists in patients receiving β-adrenergic blockers or in asthmatic patients. Design: Case-control study. Setting: Tertiary care, referral-based medical center. Patients: Of 28 978 intravenous urographic contrast media procedures done from July 1987 to June 1988, 49 patients experienced moderate to severe anaphylactoid reaction. Medical records from these 49 reactors were compared with those from a control group matched for gender, age, and date and type of contrast study who received intravenous urographic contrast media without adverse reaction. Main Results: Patients exposed to β-adrenergic blockers or with asthma comprised 39% (19 of 49) of reactors, compared to 16% (13 of 83) of matched controls (odds ratio, 3.43; 95% Cl, 1.45 to 8.15; P = 0.005). Exposure to β-blockers was 27% among reactors and 12% in matched controls (odds ratio, 2.67; Cl, 1.01 to 7.05; P = 0.036). Asthma was found in 12% of reactors and 4% of controls; after correction for β-blocker use, asthma was also associated with increased risk for anaphylactoid reaction (odds ratio, 4.54; Cl, 1.03 to 20.05; P = 0.046). Compared with nonasthmatic patients not taking β-blockers, asthmatic patients were at greater risk for anaphylactoid reaction with bronchospasm (P = 0.02). Five of 13 reactors receiving β-blockers became hypotensive, and three needed hospitalization. Compared with nonasthmatic patients not taking β-blockers, patients exposed to β-blocking drugs were almost nine times (odds ratio, 8.7; Cl, 0.81 to 93.5; P = 0.075) more likely to be hospitalized after an anaphylactoid reaction. Conclusion: Increased risk for moderate to severe anaphylactoid reaction from intravenous urographic contrast media exists in patients receiving β-adrenergic blockers or with asthma. These patients are appropriate target populations for efforts to reduce risk before intravenous urographic contrast media are administered.
The sympathetic nervous system regulates the three glycerol-3P generation pathways in white adipose tissue of fasted, diabetic and high-protein diet-fed rats
Authors: Danúbia Frasson, Renata Polessi Boschini, Valéria Ernestânia Chaves, Maria Emília Soares Martins dos Santos, Sílvia de Paula Gomes, Rafael Rossi Valentim, Maria Antonieta Rissato Garófalo, Luiz Carlos Carvalho Navegantes, Renato Hélios Migliorini, Isis do Carmo Kettelhut
Journal: Metabolism (2012)
Systemic Hypothermia — A “Cool” Therapy for Neonatal Hypoxic–Ischemic Encephalopathy
Authors: Lu-Ann Papile
Journal: New England Journal of Medicine (2005)

Hypoxic–ischemic encephalopathy is an important cause of death and disability in full-term infants. The incidence of moderate or severe hypoxic–ischemic encephalopathy has remained essentially unchanged over the past 20 years, at 1.5 to 2 per 1000 live births in the United States. Approximately 15 to 20 percent of these infants will die, and 20 to 25 percent of those who survive will be disabled.1,2 Prevention is problematic, as the initiating event may occur before the onset of labor, and there are no proven effective therapies.Brain injury is a process that begins with a hypoxic–ischemic event and evolves after . . .