tbuckley/cabot-search huggingface dataset:
Persistence of microsatellite arrays in finite populations
Authors: W. Stephan, Y. Kim
Journal: Molecular Biology and Evolution (1998)

Given that most microsatellite arrays are of no obvious functional significance, it is natural to ask how long these sequences persist during evolution. The expected persistence time was calculated for microsatellite arrays undergoing replication slippage and random genetic drift using diffusion theory and Monte Carlo simulation. In each of the three models of replication slippage compared, copy number changes involve only single steps. In one model, the rates of addition or loss of repeat units are constant; in the other two models, they are dependent on array length in a linear or quadratic way. For all three models, it was found that persistence time of microsatellite loci increases with population size in a sublinear fashion. A heuristic argument is presented as to why this result holds true for a more general class of mutation mechanisms, including models that incorporate base substitutions in addition to replication slippage. This suggests that the approximately 30% deficiency of microsatellite loci on chromosome X (relative to autosomes) that has been well documented for several mammalian species cannot be explained by the fact that the X chromosome has a smaller effective population size than do autosomes, as has been hypothesized.
Designer infant formulas: making a killing
Authors: H. Gunasekera
Journal: Journal of the Royal Society of Medicine (2005)

December is an advertiser's dream but who stops to reflect on how marketing affects our health? Consider the impact of the pictures of adorable, thriving babies looking down at us beckoningly from the supermarket infant formula section. There are choices for every maternal anxiety: formulas for newborns; young infants; older infants; the lactose-intolerant and those with gastro-oesophageal reflux disease.1 The marketing gurus offer ‘casein-dominant’ or ‘whey-dominant’ proteins, iron fortification or even special supplements such as ‘omega-3 acids’, ‘omega-6 acids’, ‘probiotics’ or ‘prebiotics’. How did the human race survive before these designer formulas?
DETECTION OF A PRIOR EPISODE OF MYOCARDIAL ISCHEMIA USING THE METABOLIC TRACER TC99M-ETHYLENEDICYSTEINE D-GLUCOSAMINE (ECDG) IN A CANINE MODEL OF ISCHEMIC MEMORY
Authors: Alexis Broisat, Mirta Ruiz, Norman C. Goodman, Julien Dimastromatteo, David K. Glover
Journal: Journal of the American College of Cardiology (2011)
Abstract LB-339: Increase in tumor-associated macrophages (TAMs) after antiangiogenic therapy is associated with poor survival in recurrent glioblastoma (GBM) patients.
Authors: Christine Lu-Emerson, Matija Snuderl, Nathaniel D. Kirkpatrick, Jermaine Goveia, Jennie Taylor, Christian Davidson, Yuhui Huang, Lars Riedemann, S. Percy Ivy, G. Dan Duda, Marek Ancukiewicz3, Scott R. Plotkin, Andrew Chi, Elizabeth R. Gerstner, April F. Eichler, Jorg Dietrich, Anat O. Stemmer-Rachamimov, Tracy T. Batchelor, Rakesh K. Jain
Journal: Cancer Research (2013)

Abstract Antiangiogenic therapy is associated with increased radiographic responses in glioblastomas (GBMs), but tumors invariably recur. Because tumor-associated macrophages (TAMs) have been shown to mediate escape from antiangiogenic therapy in preclinical models, we examined the role of TAMs in recurrent glioblastoma (rGBM) patients. We compared autopsy brain specimens from 20 rGBM patients who received antiangiogenic treatment and chemoradiation (AAT+) to 8 patients who received chemotherapy and/or radiotherapy without antiangiogenic therapy, or no treatment (AAT-). TAMs were morphologically and phenotypically analyzed using flow cytometry and immunohistochemistry (IHC) for CD68, CD14, CD163, and CD11b expression. Flow cytometry showed an increase in TAMs in the AAT+ patients. IHC analysis demonstrated an increase in CD68+ TAMs in the tumor bulk (p&amp;lt;0.01) and infiltrative areas (p=0.02) in AAT+ patients. We also observed an increase in CD11b+ cells in the tumor bulk (p&amp;lt;0.01) and an increase in CD163+ TAMs in infiltrative tumor (p=0.02). Of note, an increased number of CD11b+ cells in bulk and infiltrative tumor (p=0.05 and p=0.05, respectively) correlated with poor overall survival in patients who first received antiangiogenic therapy at recurrence. In summary, rGBMs showed an increased infiltration in myeloid populations in the tumor bulk and in the infiltrative regions after antiangiogenic therapy. Higher numbers of CD11b+ cells correlated with poor survival in rGBM patients. These data suggest that TAMs may participate in escape from antiangiogenic therapy and may represent a potential biomarker of resistance and a potential therapeutic target in rGBM. Citation Format: Christine Lu-Emerson, Matija Snuderl, Nathaniel D. Kirkpatrick, Jermaine Goveia, Jennie Taylor, Christian Davidson, Yuhui Huang, Lars Riedemann, S. Percy Ivy, G. Dan Duda, Marek Ancukiewicz3, Scott R. Plotkin, Andrew Chi, Elizabeth R. Gerstner, April F. Eichler, Jorg Dietrich, Anat O. Stemmer-Rachamimov, Tracy T. Batchelor, Rakesh K. Jain. Increase in tumor-associated macrophages (TAMs) after antiangiogenic therapy is associated with poor survival in recurrent glioblastoma (GBM) patients. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-339. doi:10.1158/1538-7445.AM2013-LB-339
High‐titer acquired factor V inhibitor responsive to corticosteroids and cyclophosphamide in a patient with two malignant tumors
Authors: Nazanine Bayani, Michel Rugina, Laurence Haddad‐Vergnes, Françoise Lelong
Journal: American Journal of Hematology (2002)

Abstract We report a 79‐year‐old man with two simultaneous malignant tumors (buccal epidermoid carcinoma and prostatic adenocarcinoma) who developed a severe bleeding complication at the site of the buccal tumor as well as a massive cerebral hematoma after a skull trauma. Laboratory findings showed the presence of a high‐titer specific factor V inhibitor. The patient failed to respond to intravenous immunoglobulins, but both clinical and laboratory improvement was obtained after treatment with corticosteroids and cyclophosphamide. Am. J. Hematol. 71:33–36, 2002. © 2002 Wiley‐Liss, Inc.
HS1 has a central role in the trafficking and homing of leukemic B cells
Authors: Cristina Scielzo, Maria T. S. Bertilaccio, Giorgia Simonetti, Antonis Dagklis, Elisa ten Hacken, Claudia Fazi, Marta Muzio, Valeria Caiolfa, Daisuke Kitamura, Umberto Restuccia, Angela Bachi, Martina Rocchi, Maurilio Ponzoni, Paolo Ghia, Federico Caligaris-Cappio
Journal: Blood (2010)
Geriatrics in the United States — Baby Boomers' Boon?
Authors: Leslie S. Libow
Journal: New England Journal of Medicine (2005)

The graying of America, a triumph of medical and cultural advances, has caught us unprepared. Our economic system, burdened with Social Security, Medicare, and extended retirement years, is shaking. Our legal system may be overwhelmed by the choosing of surrogates to make health care and end-of-life decisions, evaluations of competence, and the issuing of advance directives. Our health care system is challenged by the sheer number of elderly people and the demands of providing cost-effective care to those who are frail.For the elderly, health is the foundation of a good quality of life — the obvious reason that the . . .
Abstract PR2: Therapeutic intervention targeting a Hedgehog-dependent barrier to drug delivery in pancreatic cancer
Authors: Kenneth P. Olive, Michael Jacobetz, Aarthi Gopinathan, Mae Goldgraben, Heather Ireland, Stefanie Reichelt, William J. Howat, Nigel Whitebread, Karen McGovern, Julian Adams, Christine Iacobuzio-Donahue, John Griffiths, David Tuveson
Journal: Clinical Cancer Research (2010)

Abstract Ductal pancreatic tumors are unusually resistant to chemotherapy, exhibiting primary resistance to each of the numerous regimens tested to date. These tumors are also unusually desmoplastic and harbor a sparse and inefficient vasculature. The resulting lack of perfusion appears to play a role in the inefficient delivery of numerous chemotherapeutic agents to the parenchyma of pancreatic tumors. Recent evidence has implicated the sonic hedgehog pathway in promoting desmoplasia through a paracrine signaling mechanism active in pancreatic tumors of both humans and the Kras/p53/PdxCre (KPC) mouse model. We sought to evaluate the dependence of stromal desmoplasia on Hedgehog (Hh) pathway signaling and, by extension, assess the effects of Hh pathway inhibition on drug delivery and chemoresistance. Using IPI-926, a semisynthetic inhibitor of the Smoothened protein, we found that stromal contribution was markedly diminished within 10 days of inhibition of the Hh pathway. Paradoxically, the depletion of stromal cells was coincident with an increase in microvessel density, despite previous data indicating a pro-angiogenic role for the Hh pathway. These non-cell autonomous changes resulted in an increase in the delivery of small molecules to KPC pancreatic tumors and an increase in apoptosis when administered in combination with gemcitabine. Ultimately, mice treated with both IPI-926 and gemcitabine had a significant extension of survival and a decrease in the incidence of liver metastases. We conclude that the Hh pathway plays an important role in the maintenance of pancreatic tumor stroma and that this contributes to the primary chemoresistance of pancreatic tumors. These data also support the clinical evaluation of agents that target the stroma in pancreatic cancer. Citation Information: Clin Cancer Res 2010;16(14 Suppl):PR2.
Raising the Safety Bar — The FDA's Coxib Meeting
Authors: Susan Okie
Journal: New England Journal of Medicine (2005)

After sitting through three days of testimony and debate last month, a panel of experts advising the Food and Drug Administration (FDA) rendered an ambivalent verdict on the future of the cyclooxygenase-2 (COX-2) inhibitors. On the one hand, the 32 members of the advisory committee agreed that these drugs for pain and arthritis pose serious hazards. They voted unanimously that the available evidence on the three approved "coxibs" — rofecoxib, celecoxib, and valdecoxib — supports the conclusion that each of the drugs significantly increases users' risk of cardiovascular events, including heart attacks and strokes. Nonetheless, the committee also voted, by . . .
Ecology and Tugboat Annie
Authors: John G. Deaton
Journal: JAMA (1971)

<h3>To the Editor.—</h3> Greenwald's letter (<b>217</b>:1705, 1971), in which he asked that the give-away medical journals be policed for, among other things, the sake of ecology, reminded me of the story about the guy who, hearing of LBJ's war on poverty, rushed out and shot a beggar. As one of the medical journalists who is guilty of doing some writing for the give-aways, I felt after reading Dr. Greenwald's letter that I should rush out and give away the $425 my last article netted me. (A red-neck looks at a black face.<i>Hospital Physician</i>, to be published; $250 of the $425 was for placing second in the annual writing contest.) But, I could not decide whether to give the money to the University of Texas, which has oil wells strung out all the way to New Mexico, or to my local hospital so that they could reduce the room
Idiopathic Pulmonary Haemosiderosis in a Young Adult
Authors: N. A. J. Hamer
Journal: BMJ (1955)

MITRAL VALVOTOMYin its intensity.His blood pressure was 108/70.The lungs were clear.He could now be classified as grade I. CommentThe diagnosis of dextrocardia with mitral stenosis was well established from physical findings, electrocardiographic studies, and angiocardiography.The aetiology of mitral stenosis was only presumptive before operation, but was established 'beyond doubt from histological study of the atrial wall.Dextrocardia of the mirror type with situs inversus is probably not as rare as is commonly believed; but unless the condition is associated with other congenital cardiac anomalies or cardiac disease no symptoms are produced.These symptoms, when they do appear, are those of the associated abnormality and not due to the dextrocardia per se.The signs in the heart are, of course, found on the right chest instead of on the left.It is claimed by some workers that the condition is common in white persons.It is worth noting, however, that the case reported prior to this was in a negro (Bleyer and Saphir, 1953), and our case is in an Indian. SummaryA case of pure mitral stenosis due to rheumatic infection in a true dextrocardiac (with situs inversus) is described.The successful performance of valvotomy in such a case is reported.
Enterogastric Reflux Detection with Technetium-99m IDA
Authors: A GARCIA, J PAVIA, F LOOMENA, R ABELL??, R. HERRANZ, J SETOAIN
Journal: Clinical Nuclear Medicine (1985)

A Tc-99m IDA scan was performed in a patient with severe alkaline esophagitis subsequent to a Bilroth I gastroenterostomy. The scan showed enterogastric reflux simultaneously with gastroesophageal reflux of bile. The study was recorded in a computer and the reflux quantitated.
Clinical trials update from the American Heart Association Meeting 2010: EMPHASIS-HF, RAFT, TIM-HF, Tele-HF, ASCEND-HF, ROCKET-AF, and PROTECT
Authors: John G.F. Cleland, Alison P. Coletta, Laszlo Buga, Renjith Antony, Pierpaolo Pellicori, Nick Freemantle, Andrew L. Clark
Journal: European Journal of Heart Failure (2011)
A CULTURE MEDIUM FOR THE ISOLATION OF STREPTOCOCCUS EPIDEMICUS OF SEPTIC SORE THROAT
Authors: Isadore Pilot
Journal: JAMA (1930)

In the original report<sup>1</sup>on<i>Streptococcus epidemicus</i>as the cause of septic sore throat in a milk borne epidemic, it was noted that on blood agar the colonies of this streptococcus were more moist, often mucoid and somewhat less hemolytic than those of ordinary hemolytic streptococci. For purposes of differentiation, these properties together with other features were emphasized by Brown, Frost and Shaw<sup>2</sup>and by Frost, Gumm and Thomas<sup>3</sup>in the isolation and identification of<i>Streptococcus epidemicus</i>from milk. In a study of hemolytic streptococci from the throats and ears of patients with epidemic septic sore throat at Baraboo, Wis., these characteristics were noted on ordinary blood agar. On slants of meat infusion agar the colonies were slightly larger than those of ordinary streptococci and were distinctly more moist and ameboid. It was noted that these differences on ordinary blood agar, however, while constant, might be overlooked
Ratio of waist circumference to height is strong predictor of intra-abdominal fat
Authors: M. Ashwell, T. J Cole, A. K Dixon
Journal: BMJ (1996)

necessary.A national waiting list policy that guarantees access according to agreed criteria, rather than simply guaranteeing maximum wait- ing times, could facilitate contracts between pur- chasers and providers on the basis of agreed criteria for the prioritisation of waiting lists.Points could be assigned to patients by consultants to reflect, for example, current health status, assessed using the EuroQoL or SF36 health status measures; expected gain in quality of adjusted life years (QALY)3 from treatment; or some combination of clinical factors such as rate of deterioration and social factors reflecting dysfunction in usual activities.This is being pursued by New Zealand's Health Commission4 and in the United Kingdom is being piloted at Salisbury District Hospital.5Points schemes could help establish thresholds for entry on to elective waiting lists and help standardise general practitioners' referral prac- tice for routine procedures.If rationing in the NHS is inevitable, waiting list points schemes could help to ensure that patients with similar need, somehow reflected by their points allocation, could be assured of simi- lar access to treatment, regardless of clinical specialty, geographical location, or general practitioner's status.Points schemes could provide a redefinition of the principle on which the NHS was founded within the constraints of resource limitation.
Disulfiram-Alcohol Skin Reaction to Beer-Containing Shampoo
Authors: David Stoll
Journal: JAMA (1980)

<h3>To the Editor.—</h3> Disulfiram, an inhibitor of acetaldehyde metabolism, is used to discourage alcohol consumption by inducing nausea, vomiting, flushing, and hypotension whenever alcohol is ingested.<sup>1</sup>The same symptoms may be produced if a disulfiramtreated patient absorbs alcohol through the skin from colognes, aftershave lotions, sunscreen lotions, and alcohol-based tar gels.<sup>2</sup>The following case history illustrates that a commonly available, alcohol-containing shampoo may produce the aldehyde cutaneous reaction in a patient receiving disulfiram. <h3>Report of a Case.—</h3> A 56-year-old man was admitted to the Nashville (Tenn) Veterans Administration Medical Center Alcohol Treatment Program because of chronic alcohol abuse. Except for a contact dermatitic reaction to squash four months before admission, the patient had no skin problems or allergies. Physical examination and admission laboratory values were all unremarkable before starting disulfiram therapy, 250 mg daily at bedtime. Eleven days after disulfiram treatment was started, the patient noted a generalized
Unemployment rate as predictor of rate of psychiatric admission.
Authors: R M Kammerling, S O'Connor
Journal: BMJ (1993)

To examine the relation between rates of psychiatric admissions and both the rate of unemployment and the underprivileged area score within small areas.Calculation of correlation coefficients and explanatory power by using data on psychiatric admissions from April 1990 to March 1992. Crude and age standardised rates were used based on all admissions and also on the number of people admitted regardless of the number of times each person was admitted.Sectors with an average population of 45,000 consisting of aggregations of neighbouring wards in Bristol and District Health Authority and electoral wards with an average population of 9400 in the city of Bristol.Unemployment rates explained 93% of the variation in the crude person based admission rates standardised for age for those aged under 65 in the sectors. Person based rates correlated more strongly with unemployment than did rates based on all separate admissions. Inclusion of people aged 65 and over weakened the relation. Within electoral wards unemployment rates explained only about 50-60% of the variation but were still more powerful than the underprivileged area score. There was a significant negative correlation between average length of stay and readmission rates--that is, sectors with short lengths of stay were more likely to have patients readmitted (r = -0.64, 95% confidence interval -0.25 to -0.85).Unemployment rates are an extremely powerful indicator of the rates of serious mental illness that will need treatment in hospital in those aged under 65. This should be considered in the process of resource allocation, particularly to fundholders in general practice, or people with serious mental illness living in areas of high unemployment could be considerably disadvantaged.
Introduction/overview on clinical registries
Authors: D D Gladman
Journal: Annals of the Rheumatic Diseases (2005)

Patient registries have become an important instrument in epidemiological studies in chronic disease. There are several types of registry (table 1). Administrative registries have been developed to identify patients with particular conditions, and these are then used in epidemiological studies to identify prevalence of certain conditions. For administrative registries, a limited amount of primarily demographic information is required as the purpose is only to identify patients rather than to learn as much as possible about an individual patient. Such registries exist in Europe, where patient information is recorded in common registries at each encounter with a physician or a healthcare facility.1–3 Such registries have been used to identify associations between the primary disease and other complications such as the development of cancer among patients with psoriasis.4

View this table:

 Table 1  
 Purpose of registries



Clinical registries have been developed specifically for drug trials. Some registries have been set up to identify patients who might be suitable for drug trials, whereas others have been developed for the management of the drug trial itself. Registries have also been set up as a surveillance mechanism to follow patients treated with particular medications.5 For the latter type of registry, more than simple demographic information, such as previous medications and level of disease activity, is gathered for individual patients.6

For a longitudinal observational cohort much more detailed information is required. Here …
THE ETHICS OF PHARMACY.
Authors: H. W. WILEY
Journal: JAMA (1905)

It is rather a peculiar feature of life that some of the best advice we get is from those who know the least of what we do. The charming sarcasm of Pinafore in the representation of Sir Joseph Porter, K.C.G., at the head of the British Admiralty is only excused by the truthfulness of the application. Many of our great secretaries of war and of the navy have been ignorant of the principles of land and sea warfare. Some of our great presidents have known nothing of statecraft on their accession to office; great lawyers often do not know how to draw a will, and great physicians have been among the most distinguished legislators of the world. It is perhaps, therefore, not entirely amiss to have an address on the ethics of pharmacy from one who is not in the profession. A man who stands by at a game of
Serum methylmalonic acid and total homocysteine in patients with suspected cobalamin deficiency: A clinical study based on gastrointestinal histopathological findings
Authors: Anders Lindgren, Birgitta Swolin, Ola Nilsson, Kurt W. Johansson, Anders F. Kilander
Journal: American Journal of Hematology (1997)

We compared the sensitivity and specificity of the two metabolite tests, methylmalonic acid (MMA) and total homocysteine (Hcy) in serum, and serum cobalamin (Cbl) in patients referred to our hospital because of suspected cobalamin deficiency and a serum cobalamin value at the referring unit <200 pmol/L. All 111 patients included were investigated using upper gastrointestinal endoscopy with biopsy specimens taken from the gastric and duodenal mucosa to find a morphological basis for cobalamin malabsorption as well as the Schilling test for the validation of the serum tests. All patients were treated with cobalamin and new blood samples were taken after 4 weeks. We found no difference in sensitivity and specificity between serum MMA, Hcy, and Cbl in identifying patients with and without conditions compatible with cobalamin malabsorption. Elevated serum MMA and Hcy were also found in about 15% of the group of patients with normal Schilling tests and without a morphological basis for cobalamin malabsorption. Moreover, most patients in this group responded with decreased values of the metabolite tests following cobalamin treatment, suggesting that neither elevated metabolites nor a decrease in these values following cobalamin treatment are specific for cobalamin deficiency.