tbuckley/cabot-search huggingface dataset:
Hyperthermia in the Treatment of Cancer
Authors: DAVID S. SHIMM
Journal: Annals of Internal Medicine (1984)

ExcerptHyperthermia for the treatment of cancer was first used by Coley (1) in this country in 1893. After a period of eclipse, hyperthermia has enjoyed a recent surge in interest on the part of engineers, biologists, and clinicians. Research into the biology of hyperthermia has concentrated on the physiologic conditions that alter response to hyperthermia, and the phenomenon of thermo-tolerance, whereby cells surviving an initial heat treatment sustain transient resistance to subsequent heat treatments. The response to hyperthermia is increased in the presence of combined acute hypoxia and glucose deprivation (2), chronic hypoxia alone (3), or low pH (4). Cells...
Tuberculosis through the rose tinted spectacles of the EBUS endoscopist: be aware of the bias
Authors: Kurt Tournoy
Journal: Thorax (2011)

I read with interest the article on the utility of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in tuberculous intrathoracic lymphadenopathy by Navani et al .1

EBUS-TBNA has been validated for the assessment of mediastinal nodes in lung cancer2 and to obtain a diagnosis in (presumed) centrally located lung cancer3 or sarcoidosis.4 In addition to a recent report,5 the study by Navani et …
Tales of a Shaman's Apprentice: An Ethnobotanist Searches for New Medicines in the Amazon Rain Forest
Authors: Byron J. Bailey
Journal: JAMA (1995)

This is the first major publication by Mark Plotkin, a talented scientist who is also a gifted storyteller. He has made numerous, extensive trips into the rain forests of South America over the past two decades in a quest to uncover important elements of the native knowledge of pharmacology and the medical practice of the tribal shamans. His observations and conclusions are compelling, and if you only have time to read one book about the vital connection between the protection of the tropical rain forests, the preservation of a disappearing culture, and the pharmaceuticals that you use in your daily practice, this is the book to read. Plotkin is an ethnobotanist, a scientist engaged in the systematic study of how the native people in a geographic region use their local plants. His work takes him into remote areas in search of tribal shamans, the special people who hold this knowledge
New Directions for Rabbit Antithymocyte Globulin (Thymoglobulin®) in Solid Organ Transplants, Stem Cell Transplants and Autoimmunity
Authors: Mohamad Mohty, Andrea Bacigalupo, Faouzi Saliba, Andreas Zuckermann, Emmanuel Morelon, Yvon Lebranchu
Journal: Drugs (2014)

In the 30 years since the rabbit antithymocyte globulin (rATG) Thymoglobulin(®) was first licensed, its use in solid organ transplantation and hematology has expanded progressively. Although the evidence base is incomplete, specific roles for rATG in organ transplant recipients using contemporary dosing strategies are now relatively well-identified. The addition of rATG induction to a standard triple or dual regimen reduces acute cellular rejection, and possibly humoral rejection. It is an appropriate first choice in patients with moderate or high immunological risk, and may be used in low-risk patients receiving a calcineurin inhibitor (CNI)-sparing regimen from time of transplant, or if early steroid withdrawal is planned. Kidney transplant patients at risk of delayed graft function may also benefit from the use of rATG to facilitate delayed CNI introduction. In hematopoietic stem cell transplantation, rATG has become an important component of conventional myeloablative conditioning regimens, following demonstration of reduced acute and chronic graft-versus-host disease. More recently, a role for rATG has also been established in reduced-intensity conditioning regimens. In autoimmunity, rATG contributes to the treatment of severe aplastic anemia, and has been incorporated in autograft projects for the management of conditions such as multiple sclerosis, Crohn's disease, and systemic sclerosis. Finally, research is underway for the induction of tolerance exploiting the ability of rATG to induce immunosuppresive cells such as regulatory T-cells. Despite its long history, rATG remains a key component of the immunosuppressive armamentarium, and its complex immunological properties indicate that its use will expand to a wider range of disease conditions in the future.
Ga-67 Imaging of Bronchial Metastatic Melanoma
Authors: S. SOLFANELLI, P. FAZZI, M. FREDIANI, C. ADAMO, F. RICAGNA, A. IANNI, M. URBANO, C. A. ANGELETTI, C. GIUNTINI
Journal: Clinical Nuclear Medicine (1991)

A solitary bronchial metastasis from a malignant melanoma was identified on Ga-67 imaging.
Molecular Genetics of Chronic Myelogenous Leukemia
Authors: Arthur L. Hooberman
Journal: Annals of Internal Medicine (1990)

Letters1 December 1990Molecular Genetics of Chronic Myelogenous LeukemiaArthur L. Hooberman, MDArthur L. Hooberman, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-113-11-898 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editors:The editorial by Epner and Koeffler (1) about molecular genetic analysis of chronic myelogenous leukemia contains some misleading points. First, the youngest age for a Philadelphia-chromosome (Ph1)-positive patient with acute lymphocytic leukemia who has a chromosome 22 breakpoint within the breakpoint cluster region (bcr) is not 14 years as they stated, but 12 years (2). Further, because relatively few pediatric patients with acute lymphocytic leukemia have had molecular studies, it seems to be premature to make absolute statements about the age limit under which bcr rearrangements are not seen. Second, they state that Ph1-positive patients with acute...References1. Epner D and Koeffler H. Molecular genetic advances in chronic myelogenous leukemia. Ann Intern Med. 1990;113:3-5. LinkGoogle Scholar2. Hooberman A, Rubin C, Barton K, and Westbrook C. Detection of the Philadelphia chromosome in acute lymphoblastic leukemia by pulsed-field gel electrophoresis. Blood. 1988;74:1101-7. CrossrefGoogle Scholar3. Hirsch-Ginsberg C, Childs C, and Chang K. Phenotypic and molecular heterogeneity in Philadelphia chromosome-positive acute leukemia. Blood. 1988;71:186-95. CrossrefMedlineGoogle Scholar4. Turhan A, Eaves C, Kalousek D, Eaves A, and Humphries R. Molecular analysis of clonality and bcr rearrangements in Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood. 1988;71:1495-8. CrossrefMedlineGoogle Scholar5. Seeker-Walker L, Cooke H, and Browett P. Variable Philadelphia breakpoints and potential lineage restriction of bcr rearrangement in acute lymphoblastic leukemia. Blood. 1988;72:784-91. CrossrefMedlineGoogle Scholar1. Epner D and Koeffler H. Molecular genetic advances in chronic myelogenous leukemia. Ann Intern Med. 1990;113:3-5. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Arthur L. Hooberman, MD PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byA 3′-Transcribed Region of the HLA-A2 Gene Mediates Posttranscriptional Stimulation by IFN-γ 1 December 1990Volume 113, Issue 11Page: 898-899KeywordsChromosomesChronic myelogenous leukemiaMolecular biologyPrecursor cells ePublished: 1 December 2008 Issue Published: 1 December 1990 PDF downloadLoading ...
Sildenafil treatment for portopulmonary hypertension
Authors: F. Reichenberger, R. Voswinckel, E. Steveling, B. Enke, A. Kreckel, H. Olschewski, F. Grimminger, W. Seeger, H. A. Ghofrani
Journal: European Respiratory Journal (2006)

Portopulmonary hypertension (POPH) is regarded as a subtype of pulmonary arterial hypertension (PAH); however, established PAH therapies have not been evaluated for this condition. The current authors treated 14 patients (four male, 10 female; mean (range) age 55 (39-75) yrs) with moderate (n = 1) or severe (n = 13) POPH caused by alcoholic liver disease (n = 7), chronic viral hepatitis (n = 3), autoimmune hepatitis (n = 3), and hepatic manifestation of hereditary haemorrhagic teleangiectasia (n = 1) with oral sildenafil. Eight patients were newly started on pulmonary vasoactive treatment, while six patients were already on treatment with inhaled prostanoids (iloprost, n = 5; treprostinil, n = 1). During treatment with sildenafil, mean +/- sd 6-min walk distance increased from 312 +/- 111 m to 397 +/- 99 m after 3 months, and 407 +/- 97 m after 12 months. Mean +/- sd pro-brain natriuretic peptide levels decreased from 582 +/- 315 ng x mL(-1) to 230 +/- 278 ng x mL(-1), and to 189 +/- 274 ng x mL(-1) after 3 and 12 months, respectively. Two patients died after 1 and 2 months from liver failure and cardiac failure, respectively. There was a similar response to sildenafil treatment after 3 and 12 months in patients on monotherapy and those on combination therapy. In conclusion, sildenafil might be effective in monotherapy and in combination therapy with inhaled prostanoids in portopulmonary hypertension, leading to significant improvement by 3 months and sustained response over 12 months.
Monitoring the allergic inflammation
Authors: P. Venge
Journal: Allergy (2003)

Individual symptoms of allergy such as asthma, dermatitis, rhinitis have many different underlying mechanisms. The detailed characterization of the inflammatory mechanisms underlying symptom development in the individual patient is important in order to optimally control treatment. Measurement of eosinophil cationic protein (ECP) in sputum or blood and eosinophil protein X/eosinophil derived neurotoxin (EPX/EDN) in urine may be used to read the involvement of the eosinophil granulocyte in the process. An important information as eosinophil dominated processes seem to be particularly sensitive to corticosteroid treatment. The possibilities to measure the involvement of other inflammatory cells exist today, but are only used to a small extent. The dream would be that every patient with an inflammatory disease is characterized with respect to the profile of involving cells and mediators. Such information would provide us with a unique understanding of the underlying mechanisms of the development of disease symptoms and the possibilities of treating these.
Talking about Spirituality in the Clinical Setting: Can Being Professional Require Being Personal?
Authors: Mark G. Kuczewski
Journal: The American Journal of Bioethics (2007)

Spirituality or religion often presents as a foreign element to the clinical environment, and its language and reasoning can be a source of conflict there. As a result, the use of spirituality or religion by patients and families seems to be a solicitation that is destined to be unanswered and seems to open a distance between those who speak this language and those who do not. I argue that there are two promising approaches for engaging such language and helping patients and their families to productively engage in the decision-making process. First, patient-centered interviewing techniques can be employed to explore the patient's religious or spiritual beliefs and successfully translate them into choices. Second, and more radically, I suggest that in some more recalcitrant conflicts regarding treatment plans, resolution may require that clinicians become more involved, personally engaging in discussion and disclosure of religious and spiritual worldviews. I believe that both these approaches are supported by rich models of informed consent such as the transparency model and identify considerations and circumstances that can justify such personal disclosures. I conclude by offering some considerations for curbing potential unprofessional excesses or abuses in discussing spirituality and religion with patients.
Gradual weight loss is no better than rapid weight loss for long term weight control, study finds
Authors: Z. Kmietowicz
Journal: BMJ (2014)

A new study has challenged the common belief that losing weight gradually is better in the long term than rapid weight loss. The findings showed that regaining weight was just as common regardless of the speed of weight loss.

Over the past decade dietary experts have recommended gradual weight loss for obese people—probably because they believe that the longer people spend losing weight, the more likely they are to establish healthier eating habits.

To test this hypothesis Australian researchers randomised 204 obese adults (body mass index 30-45 kg/m²) to either a 12 week rapid weight loss programme on a very low calorie diet (450-800 kcal/day) or a 36 week gradual weight loss programme, which reduced participants’ daily energy intake by about 500 …
Chronic changes in skeletal muscle histology and function in peripheral arterial disease.
Authors: J G Regensteiner, E E Wolfel, E P Brass, M R Carry, S P Ringel, M E Hargarten, E R Stamm, W R Hiatt
Journal: Circulation (1993)

BACKGROUND Peripheral arterial disease (PAD) is associated with an impairment in exercise performance and muscle function that is not fully explained by the reduced leg blood flow during exercise. This study characterized the effects of PAD on muscle function, histology, and metabolism. METHODS AND RESULTS Twenty-six patients with PAD and six age-matched control subjects were studied. Ten of the PAD patients had unilateral disease, which permitted paired comparisons between their diseased and nonsymptomatic legs. All PAD patients had a lower peak treadmill walking time and peak oxygen consumption than controls. Vascular disease (diseased leg in unilateral patients and the most severely diseased leg in bilateral patients) was associated with decreased calf muscle strength compared with control values. In patients with unilateral disease, the diseased legs had a greater percentage of angular fibers (indicating chronic denervation) and a decreased type II fiber cross-sectional area (expressed as percent of total fiber area) compared with the nonsymptomatic, or control, legs. In diseased legs, gastrocnemius muscle strength was correlated with the total calf cross-sectional area (r = 0.78, p &lt; 0.05) and type II fiber cross-sectional area (r = 0.63, p &lt; 0.05). Activities of citrate synthase, phosphofructokinase, and lactate dehydrogenase in all 26 PAD patients (most diseased leg) did not differ from control values. Despite a wide range in citrate synthase activity in PAD patients, activity of this enzyme was not correlated with muscle strength or treadmill exercise performance. CONCLUSIONS In patients with PAD, gastrocnemius muscle weakness is associated with muscle fiber denervation and a decreased type II fiber cross-sectional area. In contrast, the PAD patients displayed substantial heterogeneity in muscle enzyme activities that was not associated with exercise performance. Denervation and type II fiber atrophy may contribute to the muscle dysfunction in patients with PAD and further confirm that the pathophysiology of chronic PAD extends beyond arterial obstruction.
Effect of intravenous pamidronate on bone mineral density in adults with cystic fibrosis
Authors: C S Haworth
Journal: Thorax (2001)

<h3>BACKGROUND</h3> Low bone mineral density (BMD) is prevalent in adults with cystic fibrosis. The aim of this study was to assess the effect of intravenous pamidronate on BMD in these subjects. <h3>METHODS</h3> Patients were invited to participate if they had a BMD Z score of –2 or less in the lumbar spine, proximal femur, or distal forearm. Patients were randomised to receive either 30 mg intravenous pamidronate every 3 months + 1 g calcium daily (pamidronate group) or 1 g calcium daily (control group). All pancreatic insufficient patients were prescribed oral vitamin D supplements. <h3>RESULTS</h3> After 6 months of treatment the pamidronate group (n=13) showed a significant increase in absolute BMD compared with the control group (n=15) in the lumbar spine (mean difference 5.8% (CI 2.7% to 8.9%)) and total hip (mean difference 3.0% (CI 0.3% to 5.6%)). However, the pamidronate group showed a reduction in BMD compared with the control group in the distal forearm (mean difference –1.7% (CI –3.7% to 0.3%)). The use of pamidronate was associated with a high incidence of bone pain in non-corticosteroid treated individuals. <h3>CONCLUSION</h3> Intravenous pamidronate increases axial BMD in adults with cystic fibrosis, but the high incidence of bone pain associated with this treatment might limit its use.
Allocation of Subjects in Medical Experiments
Authors: Milton C. Weinstein
Journal: New England Journal of Medicine (1974)

Abstract Randomized clinical trials have been a subject of much controversy for ethical reasons. When alternative experimental designs are judged on the basis of expected outcomes to the entire patient population, including the experimental subjects, it can be demonstrated that classical randomized designs need not be optimal. Consideration of individual patient preferences in a decision-analytic framework may lead to rejection of randomized trials in favor of alternative, perhaps nonrandomized, designs. Moreover, the ethical problems of experimentation can be rendered less severe if adaptive designs are used — i.e., designs that make use of information obtained during the investigation, thus permitting meaningful inferences to be drawn while exposing fewer patients to the inferior treatment. For both statistical and ethical reasons, adaptive designs should be used more often, and strictly randomized designs should be used sparingly. (N Engl J Med 291:1278–1285, 1974)
Influence of Achlorhydria on Aspirin-induced Occult Gastrointestinal Blood Loss: Studies in Addisonian Pernicious Anaemia
Authors: D. J. B. St. John, F. T. McDermott
Journal: BMJ (1970)

The effect of aspirin (acetylsalicylic acid) ingestion on occult gastrointestinal blood loss has been studied in patients with treated Addisonian pernicious anaemia and proved achlorhydria and in control patients able to secrete hydrochloric acid. A highly significant increase in gastrointestinal blood loss (1.9 ml./day of treatment) occurred with aspirin ingestion in the achlorhydric patients. The control group had a significantly greater increase in blood loss (4.29 ml./day of treatment). Thus aspirin can produce occult gastrointestinal blood loss by a mechanism unrelated to hydrochloric acid. Half of the control patients had losses of similar magnitude to those in the pernicious anaemia group, and the degree of blood loss in individual control patients appeared unrelated to gastric acidity. Differences in gastric mucosal characteristics, in the rate of gastric emptying, or in systemic effects of aspirin may explain the variation between individuals in the degree of occult gastrointestinal blood loss after aspirin.
CHRONIC ULCER OF THE STOMACH AND FIRST PORTION OF THE DUODENUM, WITH ESPECIAL REFERENCE TO THE SURGICAL TREATMENT.
Authors: WILLIAM J. MAYO
Journal: JAMA (1905)

Chronic ulcer of the stomach is certainly a more frequent disease than clinicians would lead us to believe. Compare for a moment the results of autopsy findings with the clinical diagnosis on hospital admission. Take three hospitals in Philadelphia—Blockley Hospital, giving 1.42 per cent. as the result of autopsy finding; University Hospital, clinical findings 0.48 per cent.; Pennsylvania Hospital, clinical findings 0.13 per cent. (Francine). In other words, in two hospitals of exactly the same character in the same city, ulcer is found clinically nearly four times as often as in the other, while both fall short of the postmortem from 3 to 11 times. Bettman finds that a diagnosis of gastric ulcer was<i>made</i>but 24 times in 27,567 Cincinnati hospital admissions (.08 per cent.) Howard, in comparative tables, shows that New York City autopsy records give 1.42 per cent. of gastric ulcers, while the records of clinical admissions
Abstract 1132: Identification of synthetic lethal genes to MYCN-amplified neuroblastoma.
Authors: Shuobo Zhang, J Yu, N Wei, J Silva, J J. Kandel, D J. Yamashiro
Journal: Cancer Research (2013)

Abstract Purpose. Despite the identification of MYCN amplification as an adverse prognostic marker in neuroblastoma, no drugs that target MYCN have yet been developed, in part due to the inherent difficulty in designing therapeutic molecules that can target transcription factors. An alternative approach is to identify genes that are essential for the growth of MYCN-amplified neuroblastoma. Methods. We have screened for MYCN synthetic lethal genes using a highly efficient microRNA-short-hairpin RNA (miRNA-shRNA) library that contains more than 200,000 shRNAs targeting almost all predicted genes in the human genome. If a shRNA leads to cellular death, this shRNA will diminish in the cell population. The level of each shRNA was measured both by hybridizing genomic PCR products to microarrays that contain complementary sequence to the shRNA region and by direct high-throughput sequencing of the shRNA region. Selected candidates were further validated in MYCN amplified and non-amplified neuroblastoma cell lines. Results. We have performed an shRNA screen utilizing the SHEP-21N cell line, which expresses MYCN under a tetracycline controlled promoter. 396 significantly (P&amp;lt;0.01) depleted or enriched genes by both best shRNA and integrated gene level were identified. Gene set enrichment analysis was performed utilizing the Pathway Commons data set. 25 potential synthetic lethal genes were examined by secondary screening utilizing Dharmacon SMARTpool siRNAs. The potential synthetic lethal gene transcription factor AP-4/activating enhancer binding protein (TFAP4) was further validated in three MYCN amplified cell lines and three MYCN non-amplified cell lines. Knocking down TFAP4 by siRNA inhibited cell growth in MYCN amplified cell lines (NGP, SKNDZ, and Be(2)c) by 30%-50%, 96 hours after transfection, while knocking down TFAP4 in MYCN non-amplified lines (CHP212, SKNSH, and SH-SY5Y) did not affect cell growth. Utilizing a tetracycline inducible shRNA system, knocking down TFAP4 significantly reduced colony formation of NGP by70% and Be(2)c by 25%. Conclusions. By the use of a genome wide RNAi screen, we identified potential synthetic lethal genes to MYCN amplification. The top candidate TFAP4 was validated to inhibit neuroblastoma cell growth and colony formation in a MYCN dependent manner. This may provide novel targets for the treatment of neuroblastoma. Citation Format: Shuobo Zhang, J Yu, N Wei, J Silva, J J. Kandel, D J. Yamashiro. Identification of synthetic lethal genes to MYCN-amplified neuroblastoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1132. doi:10.1158/1538-7445.AM2013-1132
False Positive Reactions in the Indirect Fluorescent Antibody Test for Legionnaires' Disease Eliminated by Use of Formolised Yolk-Sac Antigen
Authors: A. G. TAYLOR
Journal: Annals of Internal Medicine (1979)

The indirect fluorescent antibody (FA) technique for the diagnosis of Legionnaires' disease was used to investigate an outbreak of respiratory disease in a military population. The outbreak was later shown to be caused by an adenovirus. High titres were obtained using the ether-killed antigen supplied by the Center for Disease Control (CDC), Atlanta, but not with a formolised yolk-sac antigen prepared in our laboratory. The reactivity of these sera with the CDC antigen was removed by absorption with a partly identified gram-positive bacterium, whereas sera from persons with true Legionnaires' disease were unaffected by such treatment, suggesting that such reactivity is not specific for Legionnaires' disease. The lack of reactivity with negative control sera and strong reactivity from a small group of patients in whom seroconversion was demonstrated has led us to conclude that formolised yolk-sac antigen is a reliable antigen for the diagnosis of Legionnaires' disease by the indirect FA method. Measurement of the sensitivity and specificity of the formolised yolk-sac antigen is still in progress.