tbuckley/cabot-search huggingface dataset:
Hormone Replacement Therapy and Incidence of Alzheimer Disease in Older Women&lt;SUBTITLE&gt;The Cache County Study&lt;/SUBTITLE&gt;
Authors: Peter P. Zandi
Journal: JAMA (2002)

ContextPrevious studies have shown a sex-specific increased risk of Alzheimer disease (AD) in women older than 80 years. Basic neuroscience findings suggest that hormone replacement therapy (HRT) could reduce a woman's risk of AD. Epidemiologic findings on AD and HRT are mixed.ObjectiveTo examine the relationship between use of HRT and risk of AD among elderly women.Design, Setting, and ParticipantsProspective study of incident dementia among 1357 men (mean age, 73.2 years) and 1889 women (mean age, 74.5 years) residing in a single county in Utah. Participants were first assessed in 1995-1997, with follow-up conducted in 1998-2000. History of women's current and former use of HRT, as well as of calcium and multivitamin supplements, was ascertained at the initial contact.Main Outcome MeasureDiagnosis of incident AD.ResultsThirty-five men (2.6%) and 88 women (4.7%) developed AD between the initial interview and time of the follow-up (3 years). Incidence among women increased after age 80 years and exceeded the risk among men of similar age (adjusted hazard ratio [HR], 2.11; 95% confidence interval [CI], 1.22-3.86). Women who used HRT had a reduced risk of AD (26 cases among 1066 women) compared with non-HRT users (58 cases among 800 women) (adjusted HR, 0.59; 95% CI, 0.36-0.96). Risk varied with duration of HRT use, so that a woman's sex-specific increase in risk disappeared entirely with more than 10 years of treatment (7 cases among 427 women). Adjusted HRs were 0.41 (95% CI, 0.17-0.86) for HRT users compared with nonusers and 0.77 (95% CI, 0.31-1.67) compared with men. No similar effect was seen with calcium or multivitamin use. Almost all of the HRT-related reduction in incidence reflected former use of HRT (9 cases among 490 women; adjusted HR, 0.33 [95% CI, 0.15-0.65]). There was no effect with current HRT use (17 cases among 576 women; adjusted HR, 1.08 [95% CI, 0.59-1.91]) unless duration of treatment exceeded 10 years (6 cases among 344 women; adjusted HR, 0.55 [95% CI, 0.21-1.23]).ConclusionsPrior HRT use is associated with reduced risk of AD, but there is no apparent benefit with current HRT use unless such use has exceeded 10 years.
Metabolic and Therapeutic Effects of Hydroxyurea in Chronic Myeloid Leukemia
Authors: B. J. Kennedy
Journal: JAMA (1966)

Hydroxyurea (Hydrea) is a compound currently employed in clinical trials in malignant disease. It has produced bone marrow suppression, megaloblastosis, and antitumor effects in animals and man. Hydroxyurea was first synthesized by Dresler and Stein in 1869.<sup>1</sup>Its empirical formula is CH<sup>4</sup>N<sup>2</sup>O<sup>2</sup>and its structural formula is shown in Fig 1. Hydroxyurea was employed in biological studies in 1928 by Rosenthal and co-workers who demonstratedthe development of anemia and megaloblastosis in rabbits during treatment with large doses. They also observed a depression of leukocyte formation in the bone marrow (Table 1).<sup>2</sup>Further biological studies were reported in 1958,<sup>3</sup>and in 1960 antitumor activity was reported in animal screening studies.<sup>4</sup> Hydroxyurea has antitumor activity against transplantable L1210 leukemia in mice and against L1210 strains that were resistant to methotrexate (Amethopterin), 2-amino-6-purinethiol or 8-aza-guanine. It was also active against the solid tumor
Cancer of the Prostate-Reply
Authors: Joseph E. Oesterling
Journal: JAMA (1992)

In Reply.  —The above Letters to the Editor touch on many important issues that I will address in the following comments.  The prevalence of incidental, clinically insignificant prostate cancer is undoubtedly quite high; the overall estimated value for men 50 years of age or older is 30% to 40%. 1 These are microscopic lesions that most physicians would argue are not of clinical importance, and thus, do not need to be identified or treated. However, neither PSA testing, DRE, nor transrectal ultrasonography (TRUS) possess the sensitivity to detect such small, clinically insignificant lesions. Depending on the series, 38% to 45% of patients with organ-confined prostate cancer—the ideal candidates for definitive treatment and the most likely ones to be cured—have a serum PSA value within the reference range. 2 Thus, with such low sensitivity, it is unlikely that the routine use of PSA testing will increase our detection rate of these
Treatment of Herpetic Pain and Postherpetic Neuralgia with Intravenous Procaine
Authors: Edward Shanbrom
Journal: JAMA (1961)

AS SO OFTEN OCCURS in diseases for which have no specific treatment, a great number of therapeutic measures have been recommended in the treatment of herpes zoster and postherpetic neuralgia. Since herpes zoster is a self-limiting disorder which usually clears without complication, it is difficult to carry out controlled studies or to evaluate the results of any specific form of treatment. An excellent review of 916 patients with herpes zoster seen at the Mayo Clinic reveals clearly that therapeutic measures can best be evaluated if studied in the older-age group.<sup>1</sup>While pain persisting for a month or more was a rare occurrence in those under the age of 30, the percentage of patients with postherpetic neuralgia increased in direct proportion to age, so that over 80% of the patients beyond the age of 40 suffered this complication. In the age group of 70 years or more, 45.5% of the
Abstract 4761: Regulation of TNFα-induced cell death of primary human brain microvessel endothelial cells by integrins
Authors: M R Sandhya Rani, Ping Huang, Richard Prayson, Hirad Hedayat, Andrew E. Sloan, Amy Nowacki, Robert Weil, Manmeet S. Ahluwalia, Russell Tipps, Candece L. Gladson
Journal: Cancer Research (2011)

Abstract TNFα induces cell death of primary human brain microvessel endothelial cells (MvEC) in a dose-dependent manner through TNF-R1 activation. To determine whether TNF-R1 was available to be therapeutically manipulated on tumor-associated endothelial cells in glioblastoma tumors, we evaluated its expression on the endothelial cells in 50 human glioblastoma and 38 normal brain samples by immunohistochemistry. A significantly increased expression of TNF-R1 and TNFα was detected on the endothelial cells in the tumor biopsies as compared to the normal brain samples. We then investigated whether integrins regulate TNF-R1 pro-apoptotic signaling in MvEC isolated from normal brain; these cells proliferate in culture and resemble reactive endothelial cells. TNFα stimulation readily induced cell death of the brain MvEC when plated on collagen or fibronectin (attachment mediated by integrins α2β1 and α5β1, respectively), but the cells were protected from this pro-death signal when plated on laminin (mediated by integrin α6β1). In the cells plated on collagen (not on laminin) a time-dependent increase in the phosphorylation of p38 MAP kinase was detected with TNFα stimulation and knockdown of p38 MAP kinase blocked the TNFα-induced cell death suggesting p38 MAP kinase is a downstream effector for TNFα-induced apoptosis. We then examined whether engagement of a particular integrin signaled for expression of an anti-apoptotic protein and found expression of cFLIP when the MvEC were plated on laminin, but not when the cells were plated on collagen. Furthermore, down-regulation of cFLIP using siRNA restored the pro-apoptotic signal of TNFα in MvEC plated on laminin. To substantiate the clinical relevance of these findings, we examined the effect of TNFα stimulation on endothelial cells isolated from two different glioblastoma tumors, and found that TNFα induced cell death was similarly regulated by the ECM or integrins. Our data suggest that TNF-R1 on tumor-associated endothelial cells in glioblastoma tumors is available to be therapeutically manipulated as part of an anti-angiogenic therapy, and that the effectiveness of such a therapy maybe in part dependent on the activity of specific integrins expressed on the tumor endothelial cells. 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 4761. doi:10.1158/1538-7445.AM2011-4761
Incidence of Type 1 Diabetes in Sweden Among Individuals Aged 0–34 Years, 1983–2007
Authors: Gisela G. Dahlquist, Lennarth Nyström, Christopher C. Patterson
Journal: Diabetes Care (2011)

To clarify whether the increase in childhood type 1 diabetes is mirrored by a decrease in older age-groups, resulting in younger age at diagnosis.We used data from two prospective research registers, the Swedish Childhood Diabetes Register, which included case subjects aged 0-14.9 years at diagnosis, and the Diabetes in Sweden Study, which included case subjects aged 15-34.9 years at diagnosis, covering birth cohorts between 1948 and 2007. The total database included 20,249 individuals with diabetes diagnosed between 1983 and 2007. Incidence rates over time were analyzed using Poisson regression models.The overall yearly incidence rose to a peak of 42.3 per 100,000 person-years in male subjects aged 10-14 years and to a peak of 37.1 per 100,000 person-years in female subjects aged 5-9 years and decreased thereafter. There was a significant increase by calendar year in both sexes in the three age-groups <15 years; however, there were significant decreases in the older age-groups (25- to 29-years and 30- to 34-years age-groups). Poisson regression analyses showed that a cohort effect seemed to dominate over a time-period effect.Twenty-five years of prospective nationwide incidence registration demonstrates a clear shift to younger age at onset rather than a uniform increase in incidence rates across all age-groups. The dominance of cohort effects over period effects suggests that exposures affecting young children may be responsible for the increasing incidence in the younger age-groups.
Dedication symposium. I. Comments
Authors: C. D. Leake
Journal: JAMA (1965)

The development of the Institute for Biomedical Research represents a return to the purposes, it seems to me, that were so clearly expressed in the founding of the American Medical Association in 1847—to improve the standards of medical training and of medical practice. We realize now as the founders did then that those standards are dependent upon verifiable information about ourselves and our environment. That leads me to make a philosophical comment about Dr. Page, who is a pragmatist. He represents the best in skeptical scientific advance in biomedical affairs, recognizing always that the verifiable truth we may learn about ourselves and our environment is always tentative, always subject to revision, and ever to be approached in the spirit expressed by Professor Conklin many years ago: "Unwelcome truth is better than cherished error." It is the self-critical, self-corrective approach which has always been so characteristic of the medical advance that
Cooperation between Rb and Arf in suppressing mouse retinoblastoma
Authors: Karina Conkrite, Maggie Sundby, David Mu, Shizuo Mukai, David MacPherson
Journal: Journal of Clinical Investigation (2012)

Retinoblastoma is a pediatric cancer that has served as a paradigm for tumor suppressor gene function. Retinoblastoma is initiated by RB gene mutations, but the subsequent cooperating mutational events leading to tumorigenesis are poorly characterized. We investigated what these additional genomic alterations might be using human retinoblastoma samples and mouse models. Array-based comparative genomic hybridization studies revealed deletions in the CDKN2A locus that include ARF and P16INK4A, both of which encode tumor suppressor proteins, in both human and mouse retinoblastoma. Through mouse genetic analyses, we found that Arf was the critical tumor suppressor gene in the deleted region. In mice, inactivation of one allele of Arf cooperated with Rb and p107 loss to rapidly accelerate retinoblastoma, with frequent loss of heterozygosity (LOH) at the Arf locus. Arf has been reported to exhibit p53-independent tumor suppressor roles in other systems; however, our results showed no additive effect of p53 and Arf coinactivation in promoting retinoblastoma. Moreover, p53 inactivation completely eliminated any selection for Arf LOH. Thus, our data reveal important insights into the p53 pathway in retinoblastoma and show that Arf is a key collaborator with Rb in retinoblastoma suppression.
PARALYSIS OF THE SIXTH CRANIAL NERVE ASSOCIATED WITH OTITIS MEDIA
Authors: JOHN M. WHEELER
Journal: JAMA (1918)

In the routine practice of ophthalmology when patients present themselves with extra-ocular muscle paralyses which have developed suddenly, one is inclined to be content with inferring probable syphilitic etiology or some toxic cause, in case there is no history of traumatism. This habit of practice has led too often to the neglect of a careful search for a definite underlying cause and a definite pathologic lesion. There are many conditions that may be responsible for paralysis or paresis of the third, fourth and sixth cranial nerves, and the whole subject is full of interest; but I wish at this time to call attention definitely to paralyses of a single nerve, namely, the abducens, which occur rarely but unmistakably in the course of purulent otitis media. In 1904, Gradenigo<sup>1</sup>described a symptom complex which is now known as Gradenigo's syndrome or triad. It is characterized by (<i>a</i>) acute otitis media
Endocrine Disorders: A Guide to Diagnosis
Authors: John T. Garland
Journal: JAMA (1984)

The preface promises "a practical guide to diagnosis [with] accessible information on the applications, interpretation and limitations of the various diagnostic tests... of interest... to endocrinologists, undergraduate and postgraduate students in internal medicine, and nursing and technical staff who carry out endocrine tests." Herein lies the problem. In staking out such a broad field and identifying that diverse audience, the editor has promised more than his writers deliver. Chapters 1 through 18 review the methods of clinical measurement, hormone assays, microscopic diagnosis, and body imaging. Some (eg, Tanner's chapter entitled "Growth Charts and Pubertal Staging") provide useful information and a thoughtful perspective that will be helpful for medical students. Others seem too general and of little interest to most medical readers—yet too elementary for those interested in detailed laboratory methods. Chapters 19 through 35 present endocrine pathophysiology and discuss the relevance of investigational procedures. Most of this is informative, although
DNA sequencing helped to limit spread of MRSA in a neonatal unit
Authors: K. Chinthapalli
Journal: BMJ (2012)

Researchers have used whole genome sequencing to trace the spread of an outbreak of meticillin resistant Staphylococcus aureus (MRSA) in an NHS hospital’s special care baby unit. Prospective sequencing then led them to screen staff and identify the potential source of infection, says a study in Lancet Infectious Diseases .1

Speaking at press briefing on the study, Sharon Peacock, professor of clinical microbiology at the University of Cambridge and one of the study’s authors, said, “Our study indicates the considerable potential of sequencing for the rapid identification of MRSA outbreaks.” 

She said that this was the first time she knew that DNA sequencing had been used to follow an outbreak in real time and help to contain it.

Previously her group had shown that …
Abstract 3740: Prognostic Significance of Plasma Osteopontin Levels in Patients Undergoing Percutaneous Coronary Intervention
Authors: Yukihiko Momiyama, Nobukiyo Tanaka, Reiko Ohmori, Ryuichi Kato, Hiroaki Taniguchi, Koh Arakawa, Haruo Nakamura, Fumitaka Ohsuzu
Journal: Circulation (2007)

Osteopontin (OPN) mRNA was shown to be highly expressed in atherosclerotic plaques. We reported plasma OPN levels to be high in patients (pts) with coronary artery disease. Moreover, OPN levels were recently shown to be high in acute coronary syndrome. Increased OPN mRNA expression was also shown in rat arteries after balloon injury. OPN transgenic mice showed markedly increased neointimal formation after arterial injury. OPN may play a role in the development of restenosis after percutaneous coronary intervention (PCI). Methods: We investigated the prognostic value of pre-procedural plasma OPN levels by ELISA on restenosis and clinical outcome in 130 pts undergoing PCI, of whom 89 (68%) had bare metal stent. Pts with AMI were excluded. Restenosis was defined as &gt;50% diameter stenosis at follow-up angiography. Pts were followed up for 3 years for major adverse cardiovascular events (MACE) (death, MI, unstable angina, stroke). Results: At 7±3 months after PCI, re-angiography was performed in 91 (70%) pts, of whom 40 had restenosis. Between 40 pts with restenosis and 51 without it, plasma OPN (492±200 vs 482±224 ng/ml) and C-reactive protein (CRP) (median 0.78 vs 0.70 mg/l) levels did not differ. In multivariate analysis, reference diameter and smoking were independent predictors for angiographic restenosis, but OPN or CRP levels were not. During the 3-year follow-up, MACE occurred in 21 pts. Compared with 109 pts without MACE, 21 with it had higher OPN (586±230 vs 438±195 ng/ml, P&lt;0.005) and CRP (1.30 vs 0.70 mg/l, P&lt;0.002) levels. Pts with MACE more often had OPN level &gt;500 ng/ml (62% vs 35%) and CRP &gt;3.0 mg/l (33% vs 12%) than without it (P&lt;0.05). OPN did not correlate with CRP levels. To clarify the association between MACE and OPN, pts were divided into 2 groups by OPN levels. Kaplan Meier analysis showed a lower event-free survival rate in pts with OPN level &gt;500 ng/ml than those without it (P&lt;0.05). In multivariate analysis, both OPN and CRP levels were independent predictors for MACE. Hazard ratios for MACE were 2.9 (95%CI=1.3–5.5) for OPN &gt;500 ng/ml and 4.3 (1.3–14.0) for CRP &gt;3.0 mg/l. Conclusion: Plasma levels of OPN as well as CRP were found to be independent predictors for cardiovascular events in pts undergoing PCI, but they were not predictors for restenosis.
Abstract 4567: Urine biomarkers outperform serum biomarkers in the diagnosis of various human cancers
Authors: Brian M. Nolen, Aleksey Lomakin, Robert Bast, Karen Lu, William E. Grizzle, Nirag C. Jhala, Mohamad A. Eloubeidi, John D. Christein, Juan P. Arnoletti, Denise K. Oelschlager, Selwyn M. Vickers, Adele Marrangoni, Anna Lokshin
Journal: Cancer Research (2010)

Abstract Background: The measurement of biomarkers present in the bodily fluids of cancer patients represents an important avenue for the development of minimally invasive tests to predict tumorigenesis, disease recurrence, or treatment response. A great deal of work along these lines has already been devoted to blood, given its systemic exposure and extensive availability through tissue banks. However, blood is a dynamic biofluid with a proteome under continuous metabolic and homeostatic regulation. Alternatively, urine represents a biofluid that is inherently quiescent in that all molecular and proteolytic activity is largely complete upon sampling. Additional characteristics of urine including its high level of temperature stability and low-complexity matrix resulting from renal filtration have led many to propose urine as an alternative or companion to blood for biomarker studies. Methods: We performed an analysis of biomarkers present in the urine and serum of patients diagnosed with ovarian, pancreatic, and breast cancer utilizing multiplexed bead-based immunoassays developed for the Luminex® xMAP® platform. Ovarian and breast cancer patients were compared to matched healthy controls while the pancreatic cancer patients were compared to a group of patients diagnosed with benign pancreatic conditions. Each case/control group was tested for 10-15 biomarkers identified as informative for each cancer type through previous population-based analyses of serum biomarkers. Results: In our analysis, nearly all of the tested biomarkers were detectable in urine and many of the biomarkers exhibited mean relative differences of greater magnitude in urine versus serum. Our multivariate analysis identified several urine multimarker panels capable of discriminating the cancer from the control groups with high sensitivity and specificity. The use of a 4-biomarker panel comprised of 3 urine biomarkers and one serum biomarker resulted in the discrimination of ovarian cancer patients from healthy controls with a sensitivity of 100% at 95% specificity. For the ovarian and pancreatic cancer comparisons, urine/serum multimarker panels outperformed the best serum biomarker panels identified. A urine 5-biomarker panel was identified in the breast cancer comparison that demonstrated a high discriminatory power in both training and validation sample sets. Conclusions: Our results support the use of urine biomarkers as alternatives and/or companions to serum biomarkers for the diagnosis of selected human cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4567.
Nutrition and Cancer
Authors: Robert B. McGandy
Journal: JAMA (1985)

As a biomedical area, the association between diet and cancer is at about the same stage of development as was diet and atherosclerotic vascular disease 20 years ago. We have tantalizing epidemiologic observations, which, along with dietary studies utilizing experimental animals, suggest that a variety of dietary components may modulate the transformation and promotion stages of carcinogenesis. Among these are the energy nutrients, several vitamins and minerals, and nonnutrient substances, which are both natural and inadvertent constituents of the food supply. This diversity of agents, as well as the observations that many individual factors are site-specific in their effect on target organs, makes this a complex field indeed. The first chapter of this book presents an overview of the entire field and is a good summary of the scope of the problem. The subsequent sections are based on the several categories of individual nutrients. Each furnishes an extensive and technical,
Political Campaign Pinpoints `Stigma Hurdle' Facing Nation's Mental Health Community
Authors: Chris Anne Raymond
Journal: JAMA (1988)

THE CAMPAIGN to overcome cultural stigma attached to depression (JAMA1988;260:309-310) has received a boost from another campaign, the one for President of the United States. Candidate Michael S. Dukakis has been obliged to respond to allegations that he received professional treatment for depression. Although this was not the case; much of the reaction among the news media and elsewhere has been: What's wrong with being treated for a usually curable problem experienced by millions of persons?  In recent presidential campaigns, perhaps in reaction to postmortem disclosures of serious illnesses of some past Presidents, the willingness or reluctance of a candidate to reveal medical history has in itself become a public issue. Candidates are now under pressure to disclose the minutiae of their personal health, from hemorrhoids to allergies. Personal physicians are being instructed to respond in detail to news media questions about their prominent patient's ailments and therapies.  Greater