tbuckley/cabot-search huggingface dataset:
Abstract S6-8: Hedgehog Ligand Overexpression Predicts Poor Outcome in Breast Cancer and Is a Potential Therapeutic Target for Metastatic Disease
Authors: SA O'Toole, D Machalek, R Shearer, EKA Millar, R Nair, L Martelotto, D McLeod, C Cooper, M Ru Qiu, RL Sutherland, DN Watkins, A. Swarbrick
Journal: Cancer Research (2010)

Abstract Background: The Hh signalling pathway plays an important role in a number of malignancies, and accumulating data suggest it contributes significantly to the development and progression of breast cancer. However, there is scant data regarding the clinical significance of its dysregulation in breast cancer and its functional effects in breast cancer models. Methods: We investigated the clinical significance of the expression of Hh pathway components using immunohistochemistry in a well-characterised cohort of 279 patients with invasive ductal carcinoma (IDC) to determine its prognostic significance. A murine mammary cancer allograft model based on the M6 cell line, derived from the C3/SV40T transgenic mouse was used to determine the effects of Shh overexpression on tumour growth in vitro and in vivo. Finally, the therapeutic potential of Hh blockade using the monoclonal antibody 5E1 was also explored in two mouse mammary carcinoma models; the M6 allograft model and the highly metastatic 4T1 cell line in immunocompetent Balb/C mice. Results: High Hh ligand expression was observed in 34% of IDC and was associated with increased risk of breast cancer recurrence (HR 1.95, p=0.0004) and breast cancer specific death (HR 2.3, p=0.0002). High Hh expression was also associated with the basal-like subtype (p=0.004). Overexpression of Hh ligand in M6 cells transplanted to fat pads of immunodeficient mice resulted in a 4 fold increase in tumor volume (p= 0.006) and was associated with upregulation of the canonical Hh target genes Gli1 and HHIP. However, Shh promoted peritumoral lymphatic invasion in 4/5 mice compared to only 1/5 in the vector control group and was associated with a significantly shorter time to the development of metastatic disease (p=0.0004). M6 cells overexpressing Hh ligand showed no change in proliferation, self renewal or migration in vitro, suggesting a requirement for stromal interaction in Hh-dependent tumor promotion. Finally, we found that the enhanced tumor growth conferred by Hh ligand overexpression could be blocked by administration of a neutralizing antibody to Hh ligand. Furthermore, using a metastatic mammary carcinoma isograft model (4T1) that endogenously expresses Hh ligand, we demonstrate that Hh blockade resulted in smaller lung metastatic deposits (p=0.045). Conclusions: We found that high Hh ligand is associated with a poor prognosis in IDC. Overexpression of Hh ligand promotes murine mammary tumor growth, which requires stromal interaction, as well as lymphatic vessel invasion. Finally, we demonstrate that blockade of the Hh ligand is a potential therapy in metastatic breast carcinoma. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr S6-8.
Tackling HIV in resource poor countries
Authors: J S Mukherjee
Journal: BMJ (2003)

Focusing on prevention of HIV will not prevent the deaths of the millions already infected. The international community must adopt a strategy that links treatment and prevention Despite recent proposals to expand access to antiretroviral treatment for people with HIV in resource poor settings, debate continues about the cost effectiveness of prevention and treatment strategies. This debate delays the urgent action needed to implement a comprehensive global AIDS strategy. To underscore the need to link prevention with treatment, we review the effect of HIV on economic and human development, the ways in which HIV prevention and treatment are mutually reinforcing, and the requirements for scaling up the response. Prevention of HIV infection is often promoted as the only feasible option in resource poor settings despite the existence of drugs to treat it. As recently as 2002, experts argued that prevention should take priority over treatment for AIDS in Africa based on cost effectiveness.1 2 However, cost effectiveness analyses fail to take into account the most important reason for implementing widespread HIV treatment–treating sick people. Prevention strategies do nothing to improve the quality or length of life of the millions of people living with HIV. Moreover, the unchecked spread of HIV is resulting in indirect costs, ranging from orphaning to famine and from stigma to professional burnout, that are damaging already heavily burdened societies. A poignant example of the shortcomings of the focus on prevention is the practice of prioritising the use of antiretroviral therapy for prevention of mother to child transmission without giving the drugs to mothers who are sick. Although this strategy protects babies, their untreated mothers develop AIDS and die. Clearly, both prevention of mother to child transmission and treatment of HIV positive parents are needed to protect the family and community.
Metabolic Syndrome Is Also a Risk Factor for Primary Liver Cancer in Patients Younger than 65 Years of Age?
Authors: Maurizio Montella, Jerry Polesel, Renato Talamini, Anna Crispo, Aldo Giudice, Francesco Izzo, Carlo La Vecchia
Journal: Hepatology (2010)

We read with great interest the article by Welzel et al.1 The study reported a positive association between metabolic syndrome and hepatocellular carcinoma (HCC), but the results were restricted to people aged ≥65 years of age. Although the incidence of obesity and/or metabolic syndrome is showing no sign of decline, the epidemic of hepatitis B (HBV) and C (HCV) viruses is at its peak, thus increasing the incidence of HCC.2, 3 To provide further insights on the association of HCC and metabolic syndrome on the interaction with HBV/HCV infection, we report data from an Italian case–control study on HCC. The study was conducted between 1999 and 2002 in the province of Pordenone, Northeastern Italy, and in Naples, Southern Italy.4 Cases comprised 185 patients aged 43-84 years (50% below age 65 years) with incident HCC, who had not yet received any cancer treatment at study entry. The control group included 412 cancer-free patients from the same areas as the cases.4 Metabolic syndrome was associated with a four-fold higher risk of HCC. The association was confirmed among hepatitis B surface antigen (HBsAg)-negative and antibody to HCV (anti-HCV)-negative subjects (odds ratio [OR] = 4.00; 95% confidence interval [CI] = 1.30-12.27). According to the individual preexisting medical condition, only diabetes was significantly associated with HCC risk (OR = 3.75; 95% CI = 1.66-8.44; Table 1). This result was in agreement with a recent study.5 Our results are therefore in agreement with the study by Welzel et al.1; in particular, our study confirms that metabolic syndrome is also a risk factor for HCC in people younger than 65 years (50% of our study population). Our results on metabolic syndrome, together with heavy drinking (in the North) and high HCV prevalence (in the South), contribute to explain the high incidence of and mortality rates from HCC in Italy.3, 6 In order to reduce the burden of liver cancer, actions to control the recent epidemic of metabolic syndrome should be promoted. The authors gratefully acknowledge The Italian League Against Cancer (LILT), Project n. 11/2008. Maurizio Montella M.D.*, Jerry Polesel Sc.D. , Renato Talamini M.D. , Anna Crispo Sc.D.*, Aldo Giudice Sc.D.*, Francesco Izzo M.D. , Carlo La Vecchia Ph.D.§ ¶, * Unità di Epidemiologia, stituto Nazionale dei Tumori Fondazione "G. Pascale" Naples, Italy, Dipartimento di Epidemiologia e Biostatistica, Centro di Riferimento Oncologico—IRCCS, Aviano, Italy, Divisione di Chirurgia "D", Istituto Nazionale dei Tumori Fondazione "G. Pascale," Naples, Italy, § Istituto di Ricerche Farmacologiche "Mario Negri," Milan, Italy, ¶ Istituto di Statistica Medica e Biometria "G. A. Maccacaro," Università degli Studi di Milano, Milan, Italy.
Hyperparathyroid Neuromuscular Disease.
Authors: Bernard M. Patten
Journal: Annals of Internal Medicine (1973)

Meeting Abstracts1 May 1973Hyperparathyroid Neuromuscular Disease.Bernard M. Patten, M.D., John Belizikian, M.D., Lawrence Mallette, M.D., Alan Prince, M.D., Gerald Aurbach, M.D., W. King Engel, M.D.Bernard M. Patten, M.D.Search for more papers by this author, John Belizikian, M.D.Search for more papers by this author, Lawrence Mallette, M.D.Search for more papers by this author, Alan Prince, M.D.Search for more papers by this author, Gerald Aurbach, M.D.Search for more papers by this author, W. King Engel, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-78-5-815_4 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptWe report the first detailed study of the neurological, electromyographic, and muscle biopsy findings in patients with hyperparathyroidism.Over 80% of our 16 patients presented with a distinct syndrome consisting of easy fatigability; weakness and atrophy of proximal muscles, particularly of the leg; tongue tremors; and normal or hyperactive reflexes. The presence or severity of weakness bore no relationship to the alteration of any serum ion measured, including calcium. The electromyograms showed short-duration, low-amplitude complex and, sometimes, polyphasic potentials mingled with high-amplitude, long-duration motor units. Motor and sensory nerve conduction times were normal. Muscle biopsies showed neurogenic atrophy of both... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Bernard M. Patten, M.D.; John Belizikian, M.D.; Lawrence Mallette, M.D.; Alan Prince, M.D.; Gerald Aurbach, M.D.; W. King Engel, M.D.Affiliations: Bethesda, Maryland. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1973Volume 78, Issue 5Page: 815-816KeywordsAtrophyCalciumElectromyographyHyperparathyroidismMuscle biopsiesMusclesNervesNeuromuscular diseasesReflexesTongue ePublished: 1 December 2008 Issue Published: 1 May 1973 PDF downloadLoading ...
IS THE RAT DERMATITIS CONSEQUENT ON VITAMIN B2 (G) DEFICIENCY TRUE PELLAGRA?
Authors: Samuel S. Gurin, Walter H. Eddy
Journal: The Journal of Experimental Medicine (1931)

1. Isolated cases of a dermatitis resembling histologically that of human pellagra have occurred in rats supplied with sufficient vitamin B(2) (G) in the form of beef extract or neutral autoclaved yeast to produce good growth. 2. Other rats on basal diets containing similarly prepared nutrients but deprived of any known source of vitamin B(2) (G) develop a dermatitis similar in appearance to that described by other workers, but this skin effect differs in histological picture from that found in human pellagra or in black tongue of dogs. These rats showed growth failure which supports the view that they lacked growth-promoting vitamin B(2) (G). 3. It is suggested that dermatitis in rats may be of diverse type; one resulting from vitamin B(2) (G) deficiency quite different histologically from human pellagra, and one closely allied to human pellagra and black tongue in dogs due to lack of some at present unidentified factor.
Circulating Antinuclear Antibody and Rheumatoid Factor in Coal Pneumoconiosis
Authors: C. A. Soutar, M. Turner-Warwick, W. R. Parkes
Journal: BMJ (1974)

Circulating antinuclear antibody and rheumatoid factor have been measured in 109 coal miners with pneumoconiosis whose chest radiograph showed a range of abnormalities varying from simple pneumoconiosis of mild degree to advanced progressive massive fibrosis.At a screening dilution of 1/10 the overall incidence of antinuclear antibody was 17%. In almost half of the positive cases the titre was 1/40 or greater.The prevalence of antinuclear antibody was lowest in those with simple pneumoconiosis (9%) and highest in those with category C progressive massive fibrosis (27%). A similar but less striking trend was seen with rheumatoid factor, ranging from 6% in simple pneumoconiosis to 18% in category C progressive massive fibrosis. The trend of increasing frequency of autoantibodies with advancing radiographic category was most marked when the frequencies of antinuclear antibody and rheumatoid factor were combined. These autoantibodies were found in 13% of the miners with simple pneumoconiosis and 45% of those with category C progressive massive fibrosis (P for the trend=0.01).
Exercise Thallium Stress Testing Compared with Coronary Angiography in Patients Without Exclusions for Suboptimal Exercise or Cardioactive Medications
Authors: NORMAN R. VINCENT, LEONARD DENIS
Journal: Clinical Nuclear Medicine (1986)

From 1293 patients who underwent thallium stress testing and 1099 patients who had coronary angiography, a consecutive series of 122 who had both studies is evaluated. This group includes suboptimally exercised patients and those receiving one or several cardiovascular drugs that were not discontinued prior to exercise. When compared with the EKG stress test, thallium stress imaging was superior in sensitivity (80% vs 68%), specificity (84% vs 49%), accuracy (81% vs 62%), positive predictive value, (92% vs 75%), and negative predictive value (65% vs 45%) in this group, with 71% prevalence of angiographically significant coronary artery disease.
Current Developments in Cancer Vaccines and Cellular Immunotherapy
Authors: Antoni Ribas, Lisa H. Butterfield, John A. Glaspy, James S. Economou
Journal: Journal of Clinical Oncology (2003)

This article reviews the immunologic basis of clinical trials that test means of tumor antigen recognition and immune activation, with the goal to provide the clinician with a mechanistic understanding of ongoing cancer vaccine and cellular immunotherapy clinical trials. Multiple novel immunotherapy strategies have reached the stage of testing in clinical trials that were accelerated by recent advances in the characterization of tumor antigens and by a more precise knowledge of the regulation of cell-mediated immune responses. The key steps in the generation of an immune response to cancer cells include loading of tumor antigens onto antigen-presenting cells in vitro or in vivo, presenting antigen in the appropriate immune stimulatory environment, activating cytotoxic lymphocytes, and blocking autoregulatory control mechanisms. This knowledge has opened the door to antigen-specific immunization for cancer using tumor-derived proteins or RNA, or synthetically generated peptide epitopes, RNA, or DNA. The critical step of antigen presentation has been facilitated by the coadministration of powerful immunologic adjuvants, the provision of costimulatory molecules and immune stimulatory cytokines, and the ability to culture dendritic cells. Advances in the understanding of the nature of tumor antigens and their optimal presentation, and in the regulatory mechanisms that govern the immune system, have provided multiple novel immunotherapy intervention strategies that are being tested in clinical trials.
Quality Improvement Organizations and Hospital Care
Authors: S. F. Jencks
Journal: JAMA (2005)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
Abrupt Vomiting and Pain With Abdominal Mass
Authors: Yoshitaka Furuya, Hiroshi Yasuhara
Journal: JAMA Surgery (2014)

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 Surgery HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Surgery journal
Prophylaxis of infection after appendicectomy: a survey of current surgical practice.
Authors: W B Campbell
Journal: BMJ (1980)

Two hundred and eighty questionnaires were sent to junior surgical staff throughout England inquiring about their use of systemic antibiotic prophylaxis, topical antibacterial agents, and surgical drainage in appendicectomy. One hundred and seventy-five (63%) replies were received from 81 of the 87 hospitals included in the survey. Prophylactic systemic antibiotics were used by 78 surgeons (46%) when operating on a normal appendix but by 168 (99%) when the organ had perforated. Most surgeons started antibiotics before operation, but proportionately fewer did so when the appendix was gangrenous or perforated. Patients with severe contamination tended to receive longer courses of antibiotics, although the duration of administration varied considerably. Metronidazole was included in over 95% of all the prophylactic regimens and was often combined with other drugs when the appendix was gangrenous and perforated. Topical antibacterial agents were applied to the wound routinely by only 45 surgeons (26%), although 106 (61%) used them sometimes. Povidone-iodine was the agent most commonly used. Only 98 surgeons (56%) ever drained appendicectomy wounds, while 135 (77%) sometimes drained the peritoneal cavity. Evidence suggests that present methods of giving systemic antibiotic prophylaxis should continue, but that topical agents and surgical drainage are perhaps unnecessary when surgeons are confident of the efficacy of the systemic treatment used.
Health of the nation
Authors: J. Hinnie, J. J Jankowski
Journal: BMJ (1991)

designed specifically to examine the efficacy of the step 1 diet in free living people and provide evidence that is relevant to current guidelines.' Thompson passes no comment on these trials, citing instead the "success" of diet in an uncon- trolled trial in 23 patients attending a lipid clinic, in which serum cholesterol concentration fell by 10% over six months.Readers must judge for themselves whether this estimate of efficacy, subject as it is to the error of small numbers and regression to the mean, should be preferred to unconfounded estimates of a reduction in cholesterol concentra- tion averaging 2% (range 0-4%) from five well designed prospective controlled trials of the step 1 diet.These trials were conducted in eight countries and studied 10 647 high risk people.We believe that Thompson, as a coauthor of a set of guidelines cited in our paper,4 is unwise to dismiss so quickly the evidence we have drawn together.We agree that it is absurd to believe that hyperlipidaemia will stop being a problem if it is ignored.It is equally absurd to expect that the problem will be resolved by guidelines that are patently flawed or by widespread implementation of dietary recommendations shown repeatedly to have little effect in sound, controlled trials.If experts who take it on themselves to provide guidance for ordinary doctors are unwilling to heed the scientific evidence available it is perhaps not surprising that the lay press takes an interest in the matter.
Born Again to Work Again
Authors: Harry S. Jacob
Journal: New England Journal of Medicine (1978)

The fascinating observation of Pearson and his coworkers, in this issue of the Journal, that traumatized spleen tissue may regrow (or be "reborn") into splenules after its spillage into the peritoneal cavity can probably be explained by the phenomenon of work-stimulated hypertrophy. That work does provoke spleen tissue to grow is suggested by the progressive splenomegaly that regularly accompanies chronic hemolytic disorders — particularly in patients in whom the spleen is the primary site of sequestration and destruction of abnormal red cells (e.g., in hereditary spherocytosis and the thalassemias). Conversely, splenic atrophy can be induced in some animals by . . .
A Sensitive Method for Detecting EGFR Mutations in Non-small Cell Lung Cancer Samples with Few Tumor Cells
Authors: Miguel A. Molina-Vila, Jordi Bertran-Alamillo, Noemí Reguart, Miquel Taron, Eva Castellà, Mariona Llatjós, Carlota Costa, Clara Mayo, Anna Pradas, Cristina Queralt, Mónica Botia, María Pérez-Cano, Esther Carrasco, Mireia Tomàs, Jose Luis Mate, Teresa Moran, Rafael Rosell
Journal: Journal of Thoracic Oncology (2008)
Breast vasculitis in association with breast gigantism in a pregnant patient with systemic lupus erythematosus.
Authors: D J Propper, D M Reid, L Stankler, C J Eastmond
Journal: Annals of the Rheumatic Diseases (1991)

A 24 year old woman with systemic lupus erythematosus (SLE) developed widespread necrotic skin ulceration and gigantism of both breasts during an exacerbation of SLE in the last trimester of her second pregnancy. Over the remainder of the pregnancy the ulceration was only controlled by high dose corticosteroids. After parturition, however, it was possible to reduce the steroid dose without recurrence of the ulceration.
Rubella
Authors: Frank L. Babbott
Journal: JAMA (1961)

A study of health records of 935 boys graduating from a college preparatory school between 1935 and 1959 revealed that approximately 90 per cent had a history of chickenpox and measles, 58 per cent had experienced mumps, and less than 50 per cent reported rubella by the time of graduation. In recent years, nearly all chickenpox, measles, and mumps occurred before high school, as did 56 per cent of reported rubella cases. Thus, these communicable diseases appear to to be moving from the adolescent into the preadolescent years, rubella more slowly than the others. Social forces of population increase, aggregation, and mobility were felt to account for this changing age distribution. However, the authors believe that rubella will require specific preventive measures, in addition to this natural shift, if adults are to attain a significant increase in immunity.