tbuckley/cabot-search huggingface dataset:
Medicine at Harvard: The First 300 Years
Authors: Lester S. King
Journal: JAMA (1977)

Henry Beecher was indeed one of the outstanding physicians of the mid-20th century. For the last several years, he worked on a history of the Harvard Medical School, but he died while the work was still in progress. Mark Altschule, Beecher's classmate, also a fruitful investigator and prolific author, undertook to complete the work. Those acquainted with Altschule's writings will find many passages that bear the unmistakable stamp of his prose—witty, terse, but not always reliable when it asserts opinion as fact. I would guess that Beecher laid out the plan of the whole, wrote most of the first two parts, much of the third, and portions of the last, while Altschule revised the whole and, I would imagine, contributed heavily to the latter part of the book. The Harvard Medical School had its formal beginning in 1782, but the whole period from earliest colonial medicine to 1869 is compressed
Imaging of human atherosclerotic lesions with In-111 Z2D3 antibody specific for proliferating smooth muscle cells in human atheroma
Authors: Pierluigi Pieri, Ignasi Carrió, Jagat Narula, Giovanni Moscatelli, Lourdes Prat, Luciano Pedrini, Vicens Riambau, Chris Pak, Francis Chen, Ban-An Khaw
Journal: Journal of the American College of Cardiology (1996)
The Biological and Therapeutic Importance of Gastrin Gene Expression in Pancreatic Adenocarcinomas
Authors: Joseph C. Harris, Andrew D. Gilliam, Andrew J. McKenzie, Sean A. Evans, Anna M. Grabowska, Philip A. Clarke, Daniel F. McWilliams, Sue A. Watson
Journal: Cancer Research (2004)

The gastrin gene is expressed widely in pancreatic adenocarcinomas and the study aimed to assess its role in both the resistance of cancer cells to apoptosis and the sensitivity of cells to chemotherapeutic agents. Two human pancreatic cell lines, PAN1 and BXPC3, expressed gastrin at both the RNA and protein levels and are shown to be representative of human pancreatic adenocarcinomas in terms of gastrin expression. Inhibition of endogenous gastrin production by tumor cells was achieved with neutralizing gastrin antiserum and transfection with a gastrin antisense plasmid. Gastrin antiserum synergized with both taxotere and gemcitabine in inhibiting the in vitro growth of the PAN1 cell line with the inhibitory effect of the antiserum increasing from 12.7% to 70.2% with taxotere (P < 0.05) and 28.6% with gemcitabine (P < 0.01) after controlling for the effects of the cytotoxics. Synergy was only achieved with taxotere in BXPC3 cells with the inhibitory effect of gastrin antiserum increasing from 22.9% to 50.0% (P < 0.005). Cells transfected with gastrin antisense had reduced in vitro growth in low serum conditions and were poorly tumorigenic in nude mice at an orthotopic site. Gastrin antisense-transfected PAN1 cells had increased sensitivity to the antiproliferative effects of both gemcitabine (IC50 of > 100 microg/ml reduced to 0.1 microg/ml) and taxotere (IC50 of 20 microg/ml reduced to < 0.01 microg/ml) when compared with vector controls. The increased sensitivity of PAN1 antisense coincided with increased caspase-3 activity and reduced protein kinase B/Akt phosphorylation in response to both gemcitabine and taxotere. Gastrin gene circumvention may be an optimal adjunct to chemotherapeutic agents, such as taxotere and gemcitabine, in pancreatic adenocarcinoma.
726. Effect of G-CSF-Mediated Mobilization on Tumor Homing of Genetically Modified, Bone Marrow Derived Cells
Authors: Zong-Yi Li, Shaoheng Ni, Hans-Peter Kiem, Andre Lieber
Journal: Molecular Therapy (2005)

Tumor stromal cells represent important targets for gene transfer in the context of tumor gene therapy. We previously reported that intraportal transplantation of MDA-MB435 human breast cancer cells (MDA cells) results in liver metastases surrounded by stroma and that stromal cells are bone marrow derived. We further showed that upon ex vivo transduction of bone marrow cells with a lentivirus vector and subsequent transplantation into tumor-bearing mice, genetically modified donor cells can be found within the tumor stroma. In this study, we tested whether the recruitment of genetically modified cells to tumor stroma can be increased by mobilization of myeloid progenitor cells with G-CSF. Human CD34 (+) cells were isolated from human umbilical cord blood and infected with RD114-pseudotyped lentivirus vectors expressing GFP under the control of the EF1alpha promoter. Infected CD34+cells (3|[times]|10e5 cells/mouse) were transplanted into sublethally irradiated NOD-SCID mice. Four weeks after CD34+cell transplantation, mice received an intraportal injection of 2|[times]|10e6 MDA cells. After tumor cell transplantation, mice were divided into two groups. One group received subcutaneous G-CSF injection daily for 2 weeks and another group was mock-injected. G-CSF injection resulted in a 4 fold increase in the number of leukocytes in peripheral blood. Seven weeks after transplantation, analysis of bone marrow aspirates for human CD45 cells by flow cytometry showed varying engraftment rates with 40|[ndash]|50% of human donor cells expressing GFP. Livers of mice were examined 3 weeks after tumor cell transplantation. Immunohistochemistry revealed human-derived CD45+cells and GFP (+) cells in mouse livers. Human derived cells were mostly located in vicinity of blood vessels or around tumor nests. The ratio of GFP+cells to CD45+cells was consistent with the transduction rate shown in bone marrow. The human derived cells were mostly of monocyte lineage. There was no significant increase in human derived cells in the livers of the mice that received G-CSF injection when the human derived cells numbers were normalized to the level of engraftment. This indicates that the number of myeloid progenitors present in peripheral blood is not a limiting factor for their efficient engraftment in tumor stroma.
Diabetes Mellitus in Patients With Gout
Authors: Fred W. Whitehouse
Journal: JAMA (1966)

About 10% of patients with gout will have diabetes mellitus. Of our 89 patients with both diseases, 74 (83%) have insulin-independent diabetes and in two of three gout developed first. Obesity is a frequent concomitant (65 patients, 73%), and perhaps represents the common etiologic basis for both metabolic abnormalities in this type of patient. The excessive use of food and drink probably heightens the chances of one or both disorders developing. Physicians should be aware of this concomitance and attempt the early detection of diabetes in appropriate cases of gout. Insulin-dependent diabetes was uncommon in our patients (15 patients, 17%). One need not expect the frequent development of gout in patients with diabetes. Only one in 100 of our patients with diabetes has gout.
99m TECHNETIUM DIMERCAPTOSUCCINIC ACID (99m Tc-DMSA) SINGLE PHOTON EMMISSON COMPUTED TOMOGRAPHY (SPECT) RENAL IMAGING PROCESSED ACCORDING TO BODY ORIENTATION VS. KIDNEY ORIENTATION
Authors: SRA G.M. Hewitt, A. Ramos-Gabatin, J. Morrison, MAJ G. Lonergan
Journal: Clinical Nuclear Medicine (1995)

Hewitt, SRA G.M. CNMT, RT(N); Ramos-Gabatin, A. MD, TSG G.Reyes, CNMT, RT(N), COL.; Morrison, J. MD, LTC J. Brown, MD; Lonergan, MAJ G. MD Author Information
Comparison of the clinical characteristics of diabetic and non-diabetic women with community-acquired acute pyelonephritis: A multicenter study
Authors: Yeonjae Kim, Seong-Heon Wie, U-Im Chang, Jieun Kim, Moran Ki, Young Kyun Cho, Seung-Kwan Lim, Jin Seo Lee, Ki Tae Kwon, Hyuck Lee, Hee Jin Cheong, Dae Won Park, Seong Yeol Ryu, Moon-Hyun Chung, Hyunjoo Pai
Journal: Journal of Infection (2014)
Identifying men at high risk of heart attacks: Authors' reply
Authors: A G Shaper, S J Pocock, A N Phillips, M Walker
Journal: BMJ (1986)

strategy aimed at reducing coronary heart disease.This high risk approach is complementary to the population strategy.More information is needed concerning the best means of identifying men and women who are at high risk of coronary heart disease because of factors that can be usefully modified.The data from Professor Shaper and colleagues could usefully contribute to this dis- cussion if multivariate analysis were performed which examined the effect of such factors rather than one which included several irreversible attributes.In particular it would be helpful to have comparable estimates of the sensitivity of the prediction of coronary heart disease in their data, if cholesterol had been included in the risk score and some irreversible indices had been excluded.
Politicians vie to support access to talking therapies on NHS
Authors: P. Gray
Journal: BMJ (2015)

ABSTRACT. Balloon angioplasty (PTA) is an established treatment modality for stenosis in dysfunctional arteriovenous fistulae (AVF), although most studies showing efficacy have been retrospective, uncontrolled, and nonrandomized. In addition, it is unknown whether correction of stenosis not associated with significant hemodynamic, functional, and clinical abnormality may improve survival in AVF. This study was a prospective controlled open trial to evaluate whether prophylactic PTA of stenosis not associated with access dysfunction improves survival in native, virgin, radiocephalic forearm AVF. Sixty-two stenotic, functioning AVF, <i>i.e.</i>, able to provide adequate dialysis, were enrolled in the study: 30 were allocated to control and 32 to PTA. End points of the study were either AVF thrombosis or surgical revision due to reduction in delivered dialysis dose. Kaplan-Meier analysis showed that PTA improved AVF functional failure-free survival rates (<i>P</i> = 0.012) with a fourfold increase in median survival and a 2.87-fold decrease in risk of failure. Cox proportional hazard model identified PTA as the only variable associated with outcome (<i>P</i> = 0.012). PTA induced an increase in access blood flow rate (Qa) by 323 (236 to 445) ml/min (<i>P</i> &lt; 0.001), suggesting that improved AVF survival is the result of increased Qa. PTA was also associated with a significant decrease in access-related morbidity by approximately halving the risk of hospitalization, central venous catheterization, and thrombectomy (<i>P</i> &lt; 0.05). This study shows that prophylactic PTA of stenosis in functioning forearm AVF improves access survival and decreases access-related morbidity, supporting the usefulness of preventive correction of stenosis before the development of access dysfunction. It also strongly supports surveillance program for early detection of stenosis. E-mail: nicola.tessitore@mail.azosp.vr.it
Diagnosis of Diabetic Eye Disease-Reply
Authors: Elliot J. Sussman
Journal: JAMA (1982)

<h3>In Reply.—</h3> Dr Kutner suggested the possibility of a study to be performed under usual rather than optimal clinical conditions. Since under ideal conditions the nonophthalmologists missed 50% of treatable eye disease, there is every reason to believe that under usual clinical conditions, the missed diagnosis rate would increase even more. We appreciate Dr Fier's comments.
Mothers' Preference in Confinement
Authors: E. Zadik
Journal: BMJ (1960)

<b>1222</b> <b>Objectives</b>: Alzheimer’s disease (AD) is the most common cause of dementia in the elderly. Many studies revealed that early intervention may be helpful in the clinical course. Therefore, early detection is of particular importance as strategies for the management of AD. The clinical role of Single Photon Emission Tomography (SPECT) in the diagnosis and prognostication of dementing illnesses has been confirmed by many studies. The typical abnormality in AD is bilateral posterior temporal/parietal hypoperfusion, which often correlates with mental status, and can be asymmetrical. The question has been arisen whether SPECT would be also helpful in subjects with mild cognitive impairment (MCI) to predict who will progress to dementia. The aim of this SPECT study was to determine the initial abnormality in regional cerebral blood flow (rCBF) in questionable dementia (QD) using statistical parametric mapping (SPM). <b>Methods</b>: Sixty patients with questionable dementia (QD) and 17 normal volunteers were matched with age, education, and sex. Each patient received the test of mini-mental state examination (MMSE) and the Tc-99m HMPAO SPECT examination. SPECT acquisitions were performed at 30 minutes after injection of iv injection of 740 MBq of freshly prepared Tc-99m HMPAO. Parametric images were generated by grand mean scaling each scan to 50 ml/min/dL. The images were then transformed into standard stereotactic space using statistical parametric mapping 2 (SPM 2). The regional cerebral blood flow (rCBF) images were analyzed by SPM2. <b>Results</b>: There was no significantly statistical difference between two groups in age, education, and and sex. And there was no correlation between duration of illness, MMSE scores and rCBF in patients with questionable dementia. As compared to normal volunteers, the rCBF of patients with questionable dementia was diffusely decreased in bilateral hemispheres, significantly. The first involving region was bilateral insula (Brodmann area 13). The second decreased rCBF region was located at bilateral parietal and temporal lobes. The third area was located at precental gyrus and middle frontal gyrus of bilateral frontal lobe (Brodmann area 4 and 6). The thalamus area passed the criteria at voxel level but failed at cluster level. There was no increased rCBF area in patients with QD as compared to normal volunteers. <b>Conclusions</b>: In the current study, we prospectively demonstrated the pattern of defective rCBF of questionable dementia. Although it can not be detected visually, we can make the diagnosis as early as possible by measuring the changes of rCBF of certain brain area using SPM.
A Procedure for the Quantitative Determination of Protein of the Rat Heart
Authors: HARRY SOBEL, SARA M. MYERS, JESSIE MARMORSTON
Journal: Circulation Research (1955)

A procedure has been developed for the quantitative determination of the extractable proteins of the rat heart. Utilizing extraction with a sucrose-versene solution and employing differential centrifugation, followed by extraction with a phosphate-pyrophosphate buffer, low-ionic-strength extractives, a mitochondrial fraction, and high-ionic-strength extractives have been obtained. Electrophoretic analysis has shown five subfractions to be present in the low-ionic-strength extractives and three sub-fractions in the high-ionic-strength extractives.
Transient Anterior Electrocardiographic Changes Simulating Acute Anterior Myocardial Infarction in Diabetic Ketoacidosis
Authors: Peter J Fuller, Peter G Colman, Richard W Harper, Jan R Stockigt
Journal: Diabetes Care (1982)

In two patients with severe diabetic ketoacidosis, electrocardiography showed transient anterior changes suggestive of acute transmural infarction without subsequent evidence of myocardial necrosis. While the mechanism of these and other temporary electrocardiographic changes in diabetic ketoacidosis remains unclear, appreciation of their transient nature is essential if misdiagnosis of myocardial infarction and possible inappropriate delay in intravenous fluid administration are to be avoided. When electrocardiographic abnormalities are present early in diabetic ketoacidosis, the full 12-lead electrocardiogram should be repeated after adequate resuscitation.
WHO report shows progress in efforts to reduce malaria incidence
Authors: S. Mayor
Journal: BMJ (2008)

Efforts to reduce the incidence of malaria are increasing significantly, says a major report published on 18 September by the World Health Organization. Parts of Africa that have made aggressive use of a combination of preventive measures over the past few years have seen dramatic falls in the number of cases, WHO says.

The World Malaria Report 2008 found an estimated 247 million cases of malaria and 881 000 deaths from the disease, mostly among children in Africa, meaning that it remains one of the world’s leading causes of death. However, several countries had achieved a sharp fall in the number of people affected by malaria after increasing control measures.

Eritrea, Rwanda, Sao Tome and Principe, and Zanzibar (in Tanzania) each reported reductions of 50% or more in the number of malaria cases and deaths between 2000 and 2006 or 2007. 

These areas had achieved high coverage of …
Ceftazidime improves hemodynamics and oxygenation in ovine smoke inhalation injury and septic shock
Authors: Marc O Maybauer, Dirk M Maybauer, John F Fraser, Lillian D Traber, Martin Westphal, Robert A Cox, Ruksana Huda, Yoshimitsu Y Nakano, Perenlei Enkhbaatar, Hal K Hawkins, David N Herndon, Daniel L Traber
Journal: Intensive Care Medicine (2007)
In Defense of Tinkers
Authors: Harry Beckman
Journal: New England Journal of Medicine (1962)

Atinker is one who strives to improve a thing through mending or altering it. To alter a drug in the hope of improving it is therefore to tinker with it. I am writing this brief article in defense of such tinkering because aspersions were cast upon the process in the recent Congressional Subcommittee investigations.Analysis of tinkering of this sort falls very easily into a natural pattern. Why would anyone want to alter a drug molecule, what have been the results of such alterations in the past, and what is the relation of the resultant new products to the realities . . .
The mechanism of elevated alkaline phosphatase activity after bile duct ligation in the rat
Authors: Shakuntla Seetharam, Norman L. Sussman, Tsugikazu Komoda, David H. Alpers
Journal: Hepatology (1986)

Alkaline phosphatase activity in the liver and intestine increases after bile duct ligation, reportedly by increased enzyme synthesis. To ascertain the mechanism of this increased synthesis in the absence of a cDNA clone encoding the enzyme, we have estimated the concentration of liver and intestinal alkaline phosphatase mRNA by translational analysis. Monospecific antiserum to rat placental alkaline phosphatase was raised. The resulting antiserum precipitated two peptides of 53 and 56 kd after translation of liver poly(A) + RNA. The precipitation of both peptides was blocked by the single 64 kd placental alkaline phosphatase. Processing of the cell-free products by microsomal membranes produced peptides of 62 and 64 kd. Antiserum to rat intestinal alkaline phosphatase also identified two peptides as products of intestinal RNA translation. After bile duct ligation, we confirmed a transient 2-fold increase in alkaline phosphatase activity in the intestine and a more constant 7-fold increase in the liver. However, the alkaline phosphatase mRNA concentration remained unchanged in both organs. We conclude that increased alkaline phosphatase synthesis after bile duct ligation results from an enhanced rate of translation of mRNA.
Long‐term safety of fluticasone furoate nasal spray in adults and adolescents with perennial allergic rhinitis
Authors: A. Rosenblut, P. G. Bardin, B. Muller, M. A. Faris, W. W. Wu, M. F. Caldwell, W. J. Fokkens
Journal: Allergy (2007)

Background: Fluticasone furoate is a novel‐enhanced affinity glucocorticoid and its long‐term safety must be assessed. This study was designed to assess the safety and tolerability of 12‐month intranasal administration of fluticasone furoate in adult and adolescent patients with perennial allergic rhinitis (PAR). Methods: In this randomized, double‐blind, placebo‐controlled, parallel‐group study, 806 patients with PAR were randomized to once daily (od) fluticasone furoate nasal spray 110 μg ( n = 605) or vehicle placebo nasal spray ( n = 201) for 12 months, following a 7‐ to 14‐day screening period. Safety was assessed by monitoring adverse events (AEs), 24‐h urinary cortisol excretion, nasal and ophthalmic examinations, electrocardiograms and clinical laboratory tests. Plasma concentrations of fluticasone furoate were determined from blood samples. Results: Fluticasone furoate was well tolerated. The incidence of most AEs was similar to that observed with placebo, with the exception of epistaxis, which was more frequently reported on active treatment. There were no clinically meaningful differences between fluticasone furoate and placebo in terms of safety assessments, including mean changes in ophthalmic parameters and 24‐h urine cortisol excretion. Plasma concentrations of fluticasone furoate were not quantifiable in the majority of patients following intranasal administration. Conclusions: Long‐term (12‐month) administration of fluticasone furoate 110 μg od revealed an AE profile typical of the intranasal corticosteroid class in both adult and adolescent patients with PAR, with no evidence of clinically relevant systemic corticosteroid exposure.
Multiple self–healing squamous epitheliomata (ESS1) mapped to chromosome 9q22–q31 in families with common ancestry
Authors: David R. Goudie, Martin A.R. Yuille, Margaret A. Leversha, Robert A. Furlong, Nigel P. Carter, Michael J. Lush, Nabeel A. Affara, Malcolm A. Ferguson-Smith
Journal: Nature Genetics (1993)
Sulfasalazine
Authors: MARK A. PEPPERCORN
Journal: Annals of Internal Medicine (1984)

Sulfasalazine is metabolized by intestinal bacteria, resulting in the release of sulfapyridine and 5-aminosalicylate. The drug is useful in the treatment of active ulcerative colitis as well as in preventing relapses of the disease in remission. Although effective in active Crohn's disease as well, sulfasalazine appears to be of greater benefit to patients with colitis and ileocolitis than those with ileitis alone. 5-Aminosalicylate itself is efficacious when given in enema and suppository form; oral agents capable of delivering 5-aminosalicylate to distal disease sites are now under study. The drug's mechanism of action may relate to its effects on prostaglandin synthesis or interference with arachadonic acid metabolism by the lipoxygenase pathway. Common adverse reactions of sulfasalazine, including nausea, headache, and anorexia, as well as hemolysis, are associated with high serum sulfapyridine levels and often can be avoided by lowering the dose of sulfasalazine. Mild allergic reactions, such as rash and fever, may be overcome by gradual desensitization.