tbuckley/cabot-search huggingface dataset:
Breast Cancer in Young Women: The University of New Mexico Cancer Center (UNMCC) Experience.
Authors: S. Movva, L. Ballinger, J. Saiki, M. Royce
Journal: Cancer Research (2009)

Abstract Background: While only a small proportion of breast cancer is attributable to hereditary susceptibility, identifying high-risk individuals is essential for appropriate medical management. Furthermore, identifying individuals with inherited breast cancers have significant impact on both patient and their family. Beyond early age of onset, family history of multiple cancers may warrant a referral to cancer genetics professional. However, in a busy oncology practice, documentation of a full family history can be time consuming and referral opportunities for genetic counseling may be missed. In this study, we evaluated the strength of family history documentation in breast cancer patients' charts, and whether or not appropriate referrals to the Hereditary Cancer Assessment Program (HCAP) were made. Racial differences in these referral patterns were also assessed.Materials and Methods: All charts of patients last known to be living as of 03/29/06 per the UNMCC Tumor Registry with an invasive breast cancer who were 40 years old or younger at the time of diagnosis were reviewed. Baseline data included patient age at diagnosis, self-reported ethnicity, histology, bilaterality and cancer status. The presence or absence of family history of breast and other cancers, and referral to the HCAP was documented. Descriptive statistics were performed on baseline data. Correlative analyses were conducted to note any racial differences in referral to HCAP.Results: A total of 211 women met inclusion criteria. Patients in the Tumor Registry were seen at diagnosis at UNMCC from 01/01/67 through 12/31/04. Mean age was 35. Racial distribution was similar to that of the New Mexican population: 44% Caucasian, 41% Hispanic, 10% Native American (NA) and 3% African American. Predominant histology was infiltrating ductal carcinoma (79%); 10% of women had a second breast primary. 63% of women had a positive family history of cancer; however, family history was not recorded in 17%. After HCAP was established, 109 women were eligible for referral, yet 68 (62%) of women had not been referred for genetic counseling. Only 39% of Caucasian, 40% of Hispanic and 34% of NA eligible women were referred.Discussion: Women under the age of 40 at time of breast cancer diagnosis are more likely to have a hereditary cancer syndrome. In our population, 17% of women had no documentation of family history, and almost 70% were never referred for hereditary counseling. There was no difference in referral patterns among different racial/ethnic backgrounds. On the basis of this review, quality improvement initiatives were undertaken to improve referral patters of young women with breast cancer for genetic counseling and potential genetic testing. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4079.
Today’s allergic rhinitis patients are different: new factors that may play a role
Authors: R. Mösges, L. Klimek
Journal: Allergy (2007)

Most of today’s patients suffering from allergic rhinitis (AR) are sensitized to more than one trigger and suffer from persistent and moderate/severe symptoms, which severely impair their quality of life (QOL). The objective of this article was to review the data on the effect of increased air pollution, changes in indoor environment/lifestyle/affluence, exposure to new allergens and psychologically stressful lifestyles, as also to explore their potential in the development of this more ‘aggressive’ form of disease. Increased fossil fuel‐generated air pollution may increase the risk of allergic sensitization, airway responsiveness to allergens, and allergenicity and the bioavailability of airborne allergens. Changes in indoor environment/lifestyle/affluence appear to have led to more time being spent indoors and resulted in perennial exposure to indoor allergens, changes in sensitization patterns, and polysensitization to a variety of novel cross‐reacting exotic food and pet allergens. Although evidence suggests an association between psychological stress and increased risk for atopy and allergic disease, further studies are required to demonstrate this unequivocally. The more persistent and moderate/severe nature of the disease suggests a need for modification of current treatment strategies and advocacy of the use from the outset of agents, which are both efficacious and safe in managing severe and persistent AR symptoms and in improving the QOL of affected individuals.
Cochrane reviews <i>v</i> industry supported meta-analyses: We should read all reviews with caution
Authors: James C Coyne
Journal: BMJ (2006)

EDITOR—That industry sponsored meta-analyses differ in conclusions from Cochrane reviews does not mean that industry sponsorship is the only source of bias or that Cochrane reviews should be uncritically accepted.1

Allegiances of authors of meta-analyses are not only associated with selective attention to relevant studies and more positive conclusions in the case of industry ties.2 We should be sceptical about …
Itraconazole in opportunistic mycoses: Cryptococcosis and aspergillosis
Authors: David W. Denning, Richard M. Tucker, Linda H. Hanson, David A. Stevens
Journal: Journal of the American Academy of Dermatology (1990)

Striking results were obtained with oral itraconazole therapy in two opportunistic mycoses. Of 28 patients with cryptococcal meningitis, 18 achieved complete responses, including 16 of 24 patients with acquired immunodeficiency syndrome. Other manifestations of cryptococcosis were similarly responsive. In aspergillosis 12 of 15 patients responded, including 8 of 10 immunocompromised hosts. These patients included those with invasive pulmonary disease (4/5), skeletal disease (2/2), pleural disease (1/2), and pericardial, sinus, mastoid, hepatosplenic, or nail disease (1/1). These results with itraconazole compare favorably to conventional (parenteral) therapy, and toxicity was minimal. This suggests that comparative trials are now in order. Striking results were obtained with oral itraconazole therapy in two opportunistic mycoses. Of 28 patients with cryptococcal meningitis, 18 achieved complete responses, including 16 of 24 patients with acquired immunodeficiency syndrome. Other manifestations of cryptococcosis were similarly responsive. In aspergillosis 12 of 15 patients responded, including 8 of 10 immunocompromised hosts. These patients included those with invasive pulmonary disease (4/5), skeletal disease (2/2), pleural disease (1/2), and pericardial, sinus, mastoid, hepatosplenic, or nail disease (1/1). These results with itraconazole compare favorably to conventional (parenteral) therapy, and toxicity was minimal. This suggests that comparative trials are now in order.
Labour promises to abolish competition in NHS and promote "true integration"
Authors: M. Limb
Journal: BMJ (2015)

Labour’s first NHS priority if elected will be to abolish competition and the internal health market, the shadow health secretary, Andy Burnham, has said.

He also said that Labour’s plan to raise an extra £2.5bn (€3.5bn; $3.7bn) in health funding would radically reform payment systems to underpin better integration of physical healthcare, mental healthcare, and social care. The party would also bring in a new workforce plan later this year to increase training places for doctors and other clinical staff.

Burnham gave an interview to The BMJ at the Labour Party’s spring rally in Birmingham on Saturday 14 March. “I have made a very clear judgment,” he said. “The market is not the answer to 21st century health and care. My plan is about true integration, allowing professionals to merge, to collaborate, to partner without the artificial requirements of the competition regime in the way.”

Burnham said that the NHS was “teetering on the brink right now” and was at risk of losing financial control and that the market had delivered “dangerous” fragmentation. He said that Labour was already working …
Role of protein kinases in stimulation of human polymorphonuclear leukocyte oxidative metabolism by various agonists. Differential effects of a novel protein kinase inhibitor.
Authors: C Gerard, L C McPhail, A Marfat, N P Stimler-Gerard, D A Bass, C E McCall
Journal: Journal of Clinical Investigation (1986)

Isoquinoline sulfonamides have recently been shown to exert novel inhibitory effects on mammalian protein kinases by competitively binding to the ATP substrate site (Hidaka, H., M. Inagaki, S. Kawamoto, and Y. Sasaki, 1984, Biochemistry, 23: 5036-5041). We synthesized a unique analog of the previously reported compounds, 1-(5-isoquinolinesulfonyl) piperazine (C-I), in order to assess the role of protein kinases in modulating the agonist-stimulated oxidative burst of human polymorphonuclear leukocytes (PMN). Compound C-I, at micromolar concentration, markedly inhibited the release of superoxide anion from human PMN stimulated with phorbol myristate acetate or the synthetic diacylglycerol, 1-oleoyl-2-acetyl glycerol. These data are consonant with previously reported data which indicate that the calcium and phospholipid-dependent protein kinase, protein kinase C, serves as the intracellular receptor for these agonists. In contrast, superoxide anion production stimulated by the complement anaphylatoxin peptide C5a or the synthetic chemotaxin formyl-methionyl-leucyl-phenylalanine were not inhibited by C-I. These data suggest that parallel pathways exist for the agonist-stimulated respiratory burst of human neutrophils, only one of which utilizes the calcium and phospholipid-dependent protein kinase.
Association of two loci on chromosome 2q with nodal osteoarthritis.
Authors: G D Wright, A E Hughes, M Regan, M Doherty
Journal: Annals of the Rheumatic Diseases (1996)

To search for genetic association between microsatellite marker loci and sibling pairs with nodal osteoarthritis (NOA).Using the affected sibling pair method of analysis, genomic DNA from 66 sib pairs with NOA was analysed for association with highly polymorphic microsatellite marker loci. The microsatellite markers were amplified using polymerase chain reaction and typed on polyacrylamide gels.A significant association (p < 0.05) was identified between NOA and two loci on the short arm of chromosome 2 (2q 23-35). Candidate genes for osteoarthritis in this region include: fibronectin, a glycoprotein present in the extracellular matrix of normal cartilage; the alpha 2 chain of collagen type V, a major constituent of bone; and the interleukin-8 receptor, important in the regulation of neutrophil activation and chemotaxis.The chromosomal region 2q 23-35 requires further detailed study in NOA. Confirmation of these findings in large independent data sets and further analysis of candidate genes in this region will be important in unravelling the molecular basis for this common disease.
Enhanced detection of the evolution of tissue changes after acute myocardial infarction using color-encoded two-dimensional echocardiography.
Authors: A F Parisi, M Nieminen, J E O'Boyle, P F Moynihan, S F Khuri, R A Kloner, E D Folland, F J Schoen
Journal: Circulation (1982)

Acute myocardial infarction was produced in 26 dogs by ligation of the left anterior descending coronary artery. Two-dimensional echocardiograms (2-D echoes) were performed through the chest wall before and serially after coronary ligation. The dogs were then killed in four groups at the following intervals: 24-48 hours, 1-2 weeks, 3 weeks and 6-8 weeks. Each 2-D echo was processed through a video quantizer, which encoded echo amplitudes progressively into eight regions of color. The myocardium was graded with respect to color composition in regions that showed any abnormally contracting segment (ACS). The ACS exhibited a progressive increase in echo intensity that became maximal 6-8 weeks after coronary ligation. Histopathologic and histochemical studies verified that these increases in echo amplitude correlated with the evolution of healing and myocardial scar formation. At 6-8 weeks, the mean collagen content of infarcted myocardium had increased by a factor of 4; concurrently, ACS echo amplitude had increased two- to threefold. These observations suggest that color-encoded 2-D echo promotes facile perception of serial changes in tissue characteristics that result from acute myocardial infarction.
Educators Say MD-PhD Degree Programs Make Sense, But Prove It
Authors: Elisa Krill
Journal: JAMA (1990)

ORGANIZERS of the first national symposium on the education of physician-scholars have released preliminary recommendations that call for a study of the success of medical-scholar training programs in preparing the nation's future medical leaders. The symposium held last November at the University of Illinois College of Medicine, Urbana-Champaign, included medical educators, MD-PhD-degree candidates, and government and corporate representatives. Among the issues discussed at the meeting, one especially nagging question remains unanswered: Are combined degree programs better than sequential degree programs in developing medical researchers, educators, and leaders? While the participants concurred on the need for well-trained physician-scientists, many questioned whether sufficient data exist to evaluate these programs. Most of the existing data that favor the combined programs are anecdotal, they say. James Blankenship, PhD, director of the MD-PhD program at the University of Texas Medical School, Galveston, however, says he has observed that concurrent-degree students become especially successful researchers. He
Gallium-67 Imaging in Dilated Cardiomyopathy Secondary to Viral Infection
Authors: Tsau-Yuen Huang
Journal: Clinical Nuclear Medicine (1985)

A 16-year-old white boy developed congestive heart failure following an upper respiratory tract viral infection. Chest x-ray showed marked cardiomegaly and prominent pulmonary vasculature. Gallium images revealed an increased radionuclide activity in the entire heart at 6- and 24-hour postinjection. Despite digitalization and diuresis, he died two months after the onset of symptoms. Autopsy revealed marked cardiomegaly (heart weight 500 g) with biventricular dilatation and interstitial myocardial fibrosis consistent with dilated cardiomyopathy secondary to viral infection. Gallium images may be helpful in the diagnosis and follow-up studies of inflammatory cardiomyopathy.
3. Effects of the cHS4 Insulator Elements on Transgene Expression and Biological Titer of Lentiviral Vector
Authors: Hideki Hanawa, Takashi Shimada
Journal: Molecular Therapy (2005)

Modification of retroviral vector to minimize the chance of insertional mutagenesis is the urgent require for stem cell gene therapy. A possible approach is the use of an insulator element identified in the 1.2 Kb fragment from chicken |[beta]|-globin hypersensitivity site 4 (cHS4). When the gene is flanked by the element, both enhancer blocking effect and stable gene expression independent of chromosomal positional effect are observed. One of the problems of the insulator element in the case of HIV-1 vector is the decrease in biological titer, which is thought to be attributed to the increase in the vector RNA size (Blood 101: 4717|[ndash]|4724, 2003). The other possible reason is the characteristic of HIV-1 reverse transcriptase (RT). To form DNA flap during reverse transcription, HIV-1 RT aborts at central termination sequence when it is already double stranded. Retroviral RT have to go through already double stranded LTR for successful reverse transcription, therefore HIV-1 LTR can be a weak point when it is modified. To test the hypothesis, we constructed a series of HIV-1 based vectors. The parent vector carries the EGFP marker gene under the control of U3 from MSCV oncoretroviral vector. The 1.2 Kb cHS4 element or the 0.5 Kb core insulator element was inserted into the parent vector at various positions with either orientation. The relative orientation of cHS4 element against |[beta]|-globin genes and INS1R vector genome is identical. The values shown are the relative biological titer measured on HeLa cells (TU/ml) and the relative biological titer normalized using p24 level measured by ELISA (TU/ng) against those of parental vector, and these are average of four independent experiments (Exp.1) or three independent experiments (Exp.2). The actual titers of parental vector are 2.7|[times]|107 TU/ml and 7.6|[times]|104 TU/ng in Exp.1, and 1.9|[times]|107 TU/ml and 4.0|[times]|104 TU/ng in Exp.2.
Intracutaneous eotaxin and eotaxin-2 induces mRNA expression of IL-4, IL-5, eotaxin and eotaxin-2 in human atopic and non-atopic subjects
Authors: Qiu Meng, Andrew Menzies-Gow, Simon Phipps, richard Stillion, A Barry Kay, Sun Ying
Journal: Journal of Allergy and Clinical Immunology (2002)
Developmental paediatrics in primary care: what should we teach?
Authors: G Baird, D M Hall
Journal: BMJ (1985)

There is little agreement about what constitutes good developmental paediatric practice at the level of primary care. Many of the available screening tests are intrinsically unsatisfactory or badly performed, but screening is only a small part of developmental paediatrics. Every primary care doctor should be familiar with the scientific basis of the subject even if a decision is made not to embark on a formal screening programme.
The Tipping Point
Authors: K. Thomas
Journal: BMJ (2010)

The 1990s saw a dramatic increase in the incidence of syphilis in Baltimore. Epidemiologists at the US Centers for Disease Control noted that the use of crack cocaine had risen among the patients, while doctors from the local sexual health clinics wondered whether a reduction in their staff numbers was the cause of this outbreak. A possible third factor was the relocation of patients as part of a public housing programme. Malcolm Gladwell began his first book, The Tipping Point , with this case study from Baltimore. He points out that all the above factors or “agents of change,” as he calls them, may have caused this epidemic. However, he goes on to emphasise that the changes in the agents themselves …
Systemic <scp><scp>FasL</scp></scp> neutralization increases eosinophilic inflammation in a mouse model of asthma
Authors: S. K. Sharma, F. A. Almeida, S. Kierstein, L. Hortobagyi, T. Lin, A. Larkin, J. Peterson, H. Yagita, J. G. Zangrilli, A. Haczku
Journal: Allergy (2011)

Abstract Background: Eosinophils and lymphocytes are pathogenically important in allergic inflammation and sensitive to F as‐mediated apoptosis. F as ligand ( FasL ) activity therefore should play a role in regulating the allergic immune response. We aimed to characterize the role of FasL expression in airway eosinophilia in A spergillus fumigatus ( A f )‐induced sensitization and to determine whether FasL neutralization alters the inflammatory response. Methods: Sensitized B alb/c mice were killed before (day 0) and 1, 7 and 10 days after a single intranasal challenge with A f . Animals received either neutralizing antibody to FasL (clone MFL 4) or irrelevant hamster I g G via intraperitoneal injection on days −1 and 5. FasL expression, BAL and tissue inflammatory cell and cytokine profile, and apoptosis were assessed. Results: Postchallenge FasL gene expression in BAL cells and TUNEL positivity in the airways coincided with the height of inflammatory cell influx on day 1, while soluble FasL protein was released on day 7, preceding resolution of the inflammatory changes. Although eosinophil numbers showed a negative correlation with soluble FasL levels in the airways, MBP + eosinophils remained TUNEL negative in the submucosal tissue, throughout the 10‐day period after A f challenge. Systemic FasL neutralization significantly enhanced BAL and tissue eosinophil counts. This effect was associated with increased activation of T cells and release of IL ‐5, IL ‐9, and GM ‐ CSF in the BAL fluid of mice, indicating an involvement of pro‐eosinophilic survival pathways. Conclusions: FasL activity may play an active role in resolving eosinophilic inflammation through regulating T cells and pro‐eosinophilic cytokine release during the allergic airway response.
V-AKT murine thymoma viral oncogene homolog/mammalian target of rapamycin activation induces a module of metabolic changes contributing to growth in insulin-induced hepatocarcinogenesis
Authors: Matthias Evert, Diego F. Calvisi, Katja Evert, Valentina De Murtas, Gioia Gasparetti, Sandra Mattu, Giulia Destefanis, Sara Ladu, Antje Zimmermann, Salvatore Delogu, Sara Thiel, Andrea Thiele, Silvia Ribback, Frank Dombrowski
Journal: Hepatology (2012)

Mounting epidemiological evidence supports a role for insulin-signaling deregulation and diabetes mellitus in human hepatocarcinogenesis. However, the underlying molecular mechanisms remain unknown. To study the oncogenic effect of chronically elevated insulin on hepatocytes in the presence of mild hyperglycemia, we developed a model of pancreatic islet transplantation into the liver. In this model, islets of a donor rat are transplanted into the liver of a recipient diabetic rat, with resulting local hyperinsulinism that leads to the development of preneoplastic lesions and hepatocellular carcinoma (HCC). Here, we investigated the metabolic and growth properties of the v-akt murine thymoma viral oncogene homolog/mammalian target of rapamycin (AKT/mTOR) pathway, a major downstream effector of insulin signaling, in this model of insulin-induced hepatocarcinogenesis. We found that activation of insulin signaling triggers a strong induction of the AKT/mTOR cascade that is paralleled by increased synthesis of fatty acids, cholesterol, and triglycerides, induction of glycolysis, and decrease of fatty acid oxidation and gluconeogenesis in rat preneoplastic and neoplastic liver lesions, when compared with the healthy liver. AKT/mTOR metabolic effects on hepatocytes, after insulin stimulation, were found to be mTORC1 dependent and independent in human HCC cell lines. In these cells, suppression of lipogenesis, glycolysis, and the pentose phosphate pathway triggered a strong growth restraint, despite insulin administration. Noticeably, metabolic abnormalities and proliferation driven by insulin were effectively reverted using the dual PI3K/mTOR inhibitor, NVP-BEZ235, both in vitro and in vivo.The present results indicate that activation of the AKT/mTOR cascade by unconstrained insulin signaling induces a defined module of metabolic alterations in hepatocytes contributing to aberrant cell growth. Thus, inhibition of AKT/mTOR and related metabolic changes might represent a novel preventive and therapeutic approach to effectively inhibit insulin-induced hepatocarcinogenesis.
Influence of dietary phosphorus on renal phosphate reabsorption in the parathyroidectomized rat.
Authors: T H Steele, H F DeLuca
Journal: Journal of Clinical Investigation (1976)

Inorganic phosphate (Pi) reabsorption was studied during Pi infusion, after acute or chronic thyroparathyroidectomy (TPTX), in rats stabilized on a high-phosphorus (1% P) or a low-phosphorus (0.02% P) diet. After acute TPTX, there were no consistent differences in Pi reabsorption between the high- and low-phosphorus dietary groups. After chronic TPTX, the rats stabilized on the low-phosphorus diet exhibited nearly complete Pi reabsorption at every plasma Pi level, while the animals receiving the high-phosphorus diet manifested a marked phosphaturic response to Pi infusion. In addition, Pi reabsorption was significantly increased in the chronic TPTX low-phosphorus rats which achieved the highest filtered Pi loads, while their urine remained essentially phosphate-free. Dietary phosphorus-dependent alterations in Pi reabsorption may play a significant role in establishing the rate of Pi excretion per nephron under certain circumstances and should be considered in the interpretation of studies investigating renal Pi handling. The ability of phosphorus-depleted animals to maintain a phosphate-free urine during Pi loading would favor the rapid repletion of body phosphorus stores.