tbuckley/cabot-search huggingface dataset:
Impact of a Managed-Medicare Physical Activity Benefit on Health Care Utilization and Costs in Older Adults With Diabetes
Authors: Huong Q. Nguyen, Ronald T. Ackermann, Ethan M. Berke, Allen Cheadle, Barbara Williams, Elizabeth Lin, Matthew L. Maciejewski, James P. LoGerfo
Journal: Diabetes Care (2006)

The purpose of this article was to determine the effects of a managed-Medicare physical activity benefit on health care utilization and costs among older adults with diabetes.This retrospective cohort study used administrative and claims data for 527 patients from a diabetes registry of a staff model HMO. Participants (n = 163) were enrolled in the HMO for at least 1 year before joining the Enhanced Fitness Program (EFP), a community-based physical activity program for which the HMO pays for each EFP class attended. Control subjects were matched to participants according to the index date of EFP enrollment (n = 364). Multivariate regression models were used to determine 12-month postindex differences in health care use and costs between participants and control subjects while adjusting for age, sex, chronic disease burden, EFP attendance, prevention score, heart registry, and respective baseline use and costs.Participants and control subjects were similar at baseline with respect to age (75 +/- 5.5 years), A1C levels (7.4 +/- 1.4%), chronic disease burden, prevention score, and health care use and costs. After exposure to the program, there was a trend toward lower hospital admissions in EFP participants compared with control subjects (13.5 vs. 20.9%, P = 0.08), whereas total health care costs were not different (P = 0.39). EFP participants who attended > or = 1 exercise session/week on average had approximately 41% less total health care costs compared with those attending <1 session/week (P = 0.03) and with control subjects (P = 0.02).Although elective participation in a community-based physical activity benefit at any level was not associated with lower inpatient or total health care costs, greater participation in the program may lower health care costs. These findings warrant additional investigations to determine whether policies to offer and promote a community-based physical activity benefit in older adults with diabetes can reduce health care costs.
Programmed Necrosis, Not Apoptosis, in the Heart
Authors: Gloria Kung, Klitos Konstantinidis, Richard N. Kitsis
Journal: Circulation Research (2011)

It is well known that apoptosis is an actively mediated cell suicide process. In contrast, necrosis, a morphologically distinct form of cell death, has traditionally been regarded as passive and unregulated. Over the past decade, however, experiments in Caenorhabditis elegans and mammalian cells have revealed that a significant proportion of necrotic death is, in fact, actively mediated by the doomed cell. Although a comprehensive understanding of necrosis is still lacking, some key molecular events have come into focus. Cardiac myocyte apoptosis and necrosis are prominent features of the major cardiac syndromes. Accordingly, the recognition of necrosis as a regulated process mandates a reexamination of cell death in the heart. This review discusses pathways that mediate programmed necrosis, how they intersect with apoptotic pathways, roles of necrosis in heart disease, and new therapeutic opportunities that the regulated nature of necrosis presents.
The evolution of field neurosurgery in the British Army
Authors: P. H Schurr
Journal: Journal of the Royal Society of Medicine (2005)

During the First World War there were no special facilities for the treatment of head injuries until it was realized that early operation and the avoidance of slow and distressing evacuation gave much better results and less infection of the wounds. Hospitals located a few miles from the front were therefore designated for the reception of head-wounded soldiers, and postoperative cases were held there for two or three weeks before being sent on. The principles of what came to be known as neurosurgery were formulated by Harvey Cushing, an American working in Boston. There were very few surgeons with expertise in the treatment of war wounds of the head; however, the need for a thorough exploration and the removal of all bone fragments was slowly appreciated and, when it was possible, primary wound closure soon after injury avoided herniation of brain into the skull defect and scalp wound—a very undesirable condition known as brain fungus. The postoperative mortality was about 50% but many died before reaching a surgeon. The work of these pioneers was reported in several papers that were a valuable record,1-7 though unfortunately not all their experience was remembered twenty years later. There were great advances in technique and equipment in the years between the two World Wars but neurosurgery remained a very small specialty practised by men who had also to care for general cases.
Peyer’s patch organogenesis—cytokines rule, OK?
Authors: GRAHAM MAYRHOFER
Journal: Gut (1997)

Targeted inactivation of genes in the tumor necrosis factor (TNF)/lymphotoxin (LT) ligand and receptor system has recently revealed essential roles forthese molecules in lymphoid tissue development and organization. Lymphotoxin-alpha beta (LT alpha beta)/lymphotoxin-beta receptor (LT beta-R) signaling is critical for the organogenesis of lymph nodes and Peyer's patches and for the structural compartmentalization of the splenic white pulp into distinct B and T cell areas and marginal zones. Moreover, an essential role has been demonstrated for TNF/p55 tumor necrosis factor receptor (p55TNF-R) signaling in the formation of splenic B lymphocyte follicles, follicular dendritic cell networks, and germinal centers. In contrast to a previously described essential role for the p55TNF-R in Peyer's patch organogenesis, we show in this report that Peyer's patches are present in both TNF and p55TNF-R knockout mice, demonstrating that these molecules are not essential for the organogenesis of this lymphoid organ. Furthermore, we show that in the absence of TNF/p55TNF-R signaling, lymphocytes segregate normally into T and B cell areas and a normal content and localization of dendritic cells is observed in both lymph nodes and Peyer's patches. However, although B cells are found to home normally within Peyer's patches and in the outer cortex area of lymph nodes, organized follicular structures and follicular dendritic cell networks fail to form. These results show that in contrast to LT alpha beta signaling, TNF signaling through the p55TNF-R is not essential for lymphoid organogenesis but rather for interactions that determine the cellular and structural organization of B cell follicles in all secondary lymphoid tissues.
Whither Art Thou, SCN10A, and What Art Thou Doing?
Authors: Barry London
Journal: Circulation Research (2012)

Barry LondonS ince its initial cloning in 1992, SCN5A (Nav1.5)has become known as "the" cardiac sodium channel. 1 SCN5A encodes a tetrodotoxin (TTX)-resistant channel that is responsible for the inward sodium current (I Na ), which initiates the cardiac action potential.Its RNA and protein expression dominate the sodium channel landscape in the ventricle, atrium, and specialized conduction system.Mice heterozygous for a targeted Scn5a deletion (Scn5a ϩ/Ϫ mice) have slowed conduction along with atrial and ventricular arrhythmias, whereas homozygous targeted deletion in mice is embryonic lethal. 2 In humans, pharmacological agents that block SCN5A such as flecainide, developed as antiarrhythmics, are proarrhythmic and increase mortality in patients with structural heart disease. 3In addition, SCN5A mutations cause a potpourri of diseases that lead to sudden cardiac death including long-QT syndrome type 3 (LQT3, gain-of-function mutations that slow inactivation and increase late sodium current, I Na,L ), Brugada syndrome (BRS1, loss of function mutations that decrease peak I Na ), conduction disease, atrial fibrillation, and dilated cardiomyopathy. 4More recently, changes in SCN5A (expression, splicing, posttranslational modifications including CaMKII phosphorylation) and/or its ␤-subunits that decrease peak I Na or increase I Na,L have been implicated as potential contributing factors for more common types of sudden death from acquired heart diseases such as heart failure.
A RASSF1A Polymorphism Restricts p53/p73 Activation and Associates with Poor Survival and Accelerated Age of Onset of Soft Tissue Sarcoma
Authors: Karen S. Yee, Lukasz Grochola, Garth Hamilton, Anna Grawenda, Elisabeth E. Bond, Helge Taubert, Peter Wurl, Gareth L. Bond, Eric O'Neill
Journal: Cancer Research (2012)

RASSF1A (Ras association domain containing family 1A), a tumor suppressor gene that is frequently inactivated in human cancers, is phosphorylated by ataxia telangiectasia mutated (ATM) on Ser131 upon DNA damage, leading to activation of a p73-dependent apoptotic response. A single-nucleotide polymorphism located in the region of the key ATM activation site of RASSF1A predicts the conversion of alanine (encoded by the major G allele) to serine (encoded by the minor T allele) at residue 133 of RASSF1A (p.Ala133Ser). Secondary protein structure prediction studies suggest that an alpha helix containing the ATM recognition site is disrupted in the serine isoform of RASSF1A (RASSF1A-p.133Ser). In this study, we observed a reduced ability of ATM to recruit and phosphorylate RASSF1A-p.133Ser upon DNA damage. RASSF1A-p.133Ser failed to activate the MST2/LATS pathway, which is required for YAP/p73-mediated apoptosis, and negatively affected the activation of p53, culminating in a defective cellular response to DNA damage. Consistent with a defective p53 response, we found that male soft tissue sarcoma patients carrying the minor T allele encoding RASSF1A-p.133Ser exhibited poorer tumor-specific survival and earlier age of onset compared with patients homozygous for the major G allele. Our findings propose a model that suggests a certain subset of the population have inherently weaker p73/p53 activation due to inefficient signaling through RASSF1A, which affects both cancer incidence and survival.
ACE Gene Insertion/Deletion Polymorphism Associated With 1998 World Health Organization Definition of Metabolic Syndrome in Chinese Type 2 Diabetic Patients
Authors: Yau-Jiunn Lee, Jack C.R. Tsai
Journal: Diabetes Care (2002)

Because ACE insertion/deletion (I/D) polymorphism has been shown to be associated with diabetes, hypertension, coronary artery diseases, and diabetic nephropathy, and because plasma ACE concentration has been found to be associated with plasma triglyceride and total cholesterol levels in patients with type 2 diabetes, the goal of this study was to investigate whether ACE gene I/D polymorphism is associated with metabolic syndrome in Chinese subjects with type 2 diabetes.A total of 711 patients with type 2 diabetes and 750 control subjects were studied. The ACE I/D polymorphism was determined by PCR. The definition and criteria of metabolic syndrome used in this study matched those proposed in the 1998 World Health Organization classification.Of 711 patients with type 2 diabetes, 534 (75.1%) fulfilled the criteria for metabolic syndrome. The prevalence of metabolic syndrome in control subjects with II, ID, and DD genotype was 9.4, 11.5, and 15.4%, respectively, and in patients with type 2 diabetes, it was 68.6, 79.2, and 86.1%, respectively. The ACE I/D polymorphism was significantly associated with the syndrome in patients with type 2 diabetes (P = 0.001). When pooling the control subjects with diabetic patients, the prevalence of metabolic syndrome in the whole study group with II, ID, and DD genotype was 37.9, 44.5, and 51.0%, respectively, and ACE I/D polymorphism was still significantly associated with metabolic syndrome (P = 0.003). Diabetic patients with DD genotype were also found to have a higher prevalence of dyslipidemia (II/ID/DD = 43.1/53.1/65.8%, P < 0.001) and albuminuria (36.0/44.6/50.6%, P = 0.018) and to have higher serum triglyceride levels (II, ID, and DD = 155 +/- 114, 170 +/- 140, and 199 +/- 132 mg/dl, respectively, P < 0.05). Control subjects with DD genotype were also found to have a higher prevalence of albuminuria or more advanced nephropathy (II/ID/DD = 5.7/14.0/15.4%, P = 0.001), whereas the prevalence of dyslipidemia was not found to be statistically different in the control group. When pooling control with diabetic subjects, ACE genotype could still be significantly associated with dyslipidemia (II/ID/DD = 34.7/41.3/52.2%, P < 0.001) and albuminuria or more advanced nephropathy (20.3/28.9/33.1%, P < 0.001). Diabetic patients with metabolic syndrome were found to have higher serum uric acid levels than those without metabolic syndrome (6.4 +/- 1.8 vs. 5.3 +/- 1.4 mg/dl, P < 0.01).The ACE I/D polymorphism was found to be associated with metabolic syndrome in Chinese patients with type 2 diabetes. This finding may provide genetic evidence to explain the clustering of metabolic syndrome and suggests that the renin-angiotensin system is involved in the pathophysiology of metabolic derangement in patients with type 2 diabetes.
The Heritage of Hepatitis B Vaccine
Authors: R. Gordon Douglas
Journal: JAMA (1996)

Pioneering development of the plasma-derived and yeast-derived recombinant hepatitis B vaccines represents a major contribution to preventive health care of this century. Current and expanding worldwide application of hepatitis B vaccine promises to eliminate and eventually eradicate hepatitis B infection from the human population and, with it, many cases of cirrhosis and cancer of the liver.
Androgen-Independent Prostate Cancer Is a Heterogeneous Group of Diseases
Authors: Rajal B. Shah, Rohit Mehra, Arul M. Chinnaiyan, Ronglai Shen, Debashis Ghosh, Ming Zhou, Gary R. MacVicar, Soorynarayana Varambally, Jason Harwood, Tarek A. Bismar, Robert Kim, Mark A. Rubin, Kenneth J. Pienta
Journal: Cancer Research (2004)

Abstract Understanding the biology of prostate cancer metastasis has been limited by the lack of tissue for study. We studied the clinical data, distribution of prostate cancer involvement, morphology, immunophenotypes, and gene expression from 30 rapid autopsies of men who died of hormone-refractory prostate cancer. A tissue microarray was constructed and quantitatively evaluated for expression of prostate-specific antigen, androgen receptor, chromogranin, synaptophysin, MIB-1, and α-methylacylCoA-racemase markers. Hierarchical clustering of 16 rapid autopsy tumor samples was performed to evaluate the cDNA expression pattern associated with the morphology. Comparisons were made between patients as well as within the same patient. Metastatic hormone-refractory prostate cancer has a heterogeneous morphology, immunophenotype, and genotype, demonstrating that “metastatic disease” is a group of diseases even within the same patient. An appreciation of this heterogeneity is critical to evaluating diagnostic and prognostic biomarkers as well as to designing therapeutic targets for advanced disease.
Foxp3 and microsatellite stability phenotype in colorectal cancer
Authors: C. Loddenkemper, D. Nagorsen, M. Zeitz
Journal: Gut (2008)

Colorectal tumourigenesis is in the majority of cases regarded as a multistep process resulting in chromosomal instability.1 High-frequency microsatellite instability (MSI-H) can be detected in ∼15–20% of all sporadic colorectal cancers (CRCs) and represents the hallmark of the hereditary non-polyposis colorectal cancer (HNPCC) syndrome. CRCs with MSI-H are caused by inactivation of DNA mismatch repair (MMR) genes leading to hundreds of insertion or deletion mutations in short segments of repeated nucleotide sequences, but no chromosomal instability. It has been speculated that abnormal peptides are generated as a consequence of these frameshift mutations, and one would expect a stimulation of the antitumour response by these tumour-associated antigens (TAAs).2 3 In fact, CRCs with MSI-H are associated with a markedly increased number of tumour-infiltrating lymphocytes (TILs) as compared with microsatellite-stable (MSS) tumours, and the favourable prognosis of patients with MSI-H cancer has been attributed to the high content of cytotoxic T cells.4

Over the past few years, CD4+CD25+ regulatory T cells (Treg cells) expressing the transcription factor forkhead box P3 (Foxp3) have been demonstrated to suppress T cell-mediated immunity to TAAs in various human tumours—for example, ovarian cancer.5 In mouse models, depletion of Treg cells using treatment with CD25-, GITR- or CTLA4-specific antibodies has resulted in improved antitumour immunity.6 In human CRC tissue samples, increased numbers of Treg cells as compared with normal mucosa have also been described, with a Treg cell infiltration rate slightly higher in patients without a systemic TAA-specific immune reaction.7 Despite successful induction of an immunological response, current protocols of immunotherapy and vaccination in CRC are not satisfactory.8 The poor response rate in patients with CRC may in part be due to the fact that immunosuppressive mechanisms conferred by Treg cells outweigh the beneficial effects of …
Time Course of Late Preconditioning Against Myocardial Stunning in Conscious Pigs
Authors: Xian-Liang Tang, Yumin Qiu, Seong-Wook Park, Jian-Zhong Sun, Anantharam Kalya, Roberto Bolli
Journal: Circulation Research (1996)

We have recently found in conscious pigs that a sequence of brief coronary occlusions induces severe myocardial stunning, but when the same sequence is repeated 24 hours later, the severity of stunning is markedly reduced (≈50%) (“late preconditioning against stunning”). As an initial step toward elucidating the mechanism and potential clinical significance of this powerful cardioprotective response, the present study was conducted to define the time course of late preconditioning against myocardial stunning. Conscious pigs underwent a sequence of ten 2-minute coronary occlusion/2-minute reperfusion cycles and then a second identical sequence at 6 hours (group I, n=7), 12 hours (group II, n=6), 24 hours (group III, n=10), 3 days (group IV, n=10), or 6 days (group V, n=11) after the first. Systolic wall thickening (WTh) in the ischemic/reperfused region remained significantly depressed for at least 3 hours after the 10th reperfusion of the first sequence, indicating myocardial stunning. When the second sequence of coronary occlusions was performed 6 hours after the first (group I), the recovery of WTh was similar to the first. In contrast, when the second sequence was repeated 12 hours after the first (group II), the recovery of WTh was improved, though not consistently, and the total deficit of WTh decreased by 41% ( P &lt;.05) compared with the first sequence. When the second sequence was repeated 24 hours (group III) and 3 days (group IV) after the first, the recovery of WTh was substantially enhanced, with 52% and 49% reductions in the total deficit of WTh, respectively ( P &lt;.01 versus the first sequence). When the second sequence was repeated 6 days later (group V), the recovery of WTh was indistinguishable from the first sequence. Thus, late preconditioning against myocardial stunning requires &gt;6 hours to develop, lasts for at least 60 hours after its appearance (with the most effective protection present at 24 hours and 3 days), and disappears within 6 days after the preconditioning ischemia, a time course that is consistent with the synthesis and degradation of cardioprotective proteins. In view of its sustained duration, this endogenous cardioprotective mechanism is of potential clinical importance.
Incidence of multiple myeloma in Olmsted County, Minnesota: 1978 through 1990, with a review of the trend since 1945.
Authors: R A Kyle, C M Beard, W M O'Fallon, L T Kurland
Journal: Journal of Clinical Oncology (1994)

PURPOSE Incidence rates of multiple myeloma appear to have increased in recent decades, but it is difficult to compare the incidence rates over time because of changes in laboratory procedures, differences in diagnostic criteria, and variations in indexing of medical records. However, Olmsted County, Minnesota, provides a rare opportunity to minimize these limitations, because the medical care has been provided mainly by the Mayo Clinic. PATIENTS AND METHODS Records of Olmsted County residents with a diagnosis of multiple myeloma from January 1, 1978 through December 31, 1990 were reviewed. Criteria for diagnosis and residency were the same as in previous Olmsted County studies. RESULTS The incidence rate per 100,000 age-adjusted to the 1950 United States white population was 5.4 for males and 2.8 for females; the overall rate was 4.1. The rates were age-adjusted to the 1950 United States population for comparison with earlier data from this population. The rates increased with age for both sexes. There was no significant change in incidence rates from 1945 through 1990. A comparison of the median age for Olmsted County patients with the age of those referred to the Mayo Clinic from elsewhere indicated that the local patients were appreciably older (74 v. 62 years, respectively). Thirty-two of 55 patients (58%) with multiple myeloma from 1978 through 1990 had a monoclonal plasma-cell proliferative process before the diagnosis of multiple myeloma. CONCLUSION The incidence rate of multiple myeloma in Olmsted County, Minnesota, has not changed significantly during the past 46 years. We believe that reports of increasing rates over time are mainly due to improved case ascertainment.
The E-SCREEN assay as a tool to identify estrogens: an update on estrogenic environmental pollutants.
Authors: A M Soto, C Sonnenschein, K L Chung, M F Fernandez, N Olea, F O Serrano
Journal: Environmental Health Perspectives (1995)

Estrogens are defined by their ability to induce the proliferation of cells of the female genital tract. The wide chemical diversity of estrogenic compounds precludes an accurate prediction of estrogenic activity on the basis of chemical structure. Rodent bioassays are not suited for the large-scale screening of chemicals before their release into the environment because of their cost, complexity, and ethical concerns. The E-SCREEN assay was developed to assess the estrogenicity of environmental chemicals using the proliferative effect of estrogens on their target cells as an end point. This quantitative assay compares the cell number achieved by similar inocula of MCF-7 cells in the absence of estrogens (negative control) and in the presence of 17 beta-estradiol (positive control) and a range of concentrations of chemicals suspected to be estrogenic. Among the compounds tested, several
The best time to go around
Authors: G. E. Elfarouki
Journal: BMJ (2009)

As a surgical trainee, I am usually given little choice as to when to carry out a ward round. Yet, I often wonder whether there is an ideal time in the day when the encounter between doctor and in-patient would be most effective.

Recently, after a fairly busy and varied day, I felt the urge to stick around the hospital when only those …
Pulmonary function abnormalities in Sjogren's syndrome and the sicca complex.
Authors: I Segal, G Fink, I Machtey, V Gura, S A Spitzer
Journal: Thorax (1981)

The frequency of pulmonary involvement in a group of 20 patients with Sjögren9s syndrome or the sicca complex was evaluated with pulmonary function studies. In 12 patients pulmonary functional abnormalities were demonstrated. The most common abnormality was airway obstruction. Nine out of 13 patients with the limited variant of the disease (sicca complex) and three out of seven patients with the complete syndrome had abnormal pulmonary function.