tbuckley/cabot-search huggingface dataset:
Innate immunity and cardiac preconditioning: a putative intrinsic cardioprotective program
Authors: R Smith
Journal: Cardiovascular Research (2002)

Ischemic preconditioning is thought to evoke cell survival programs in the heart in large part via the activation of GI-protein coupled receptor signal transduction pathways. However, the identification and characterization of GI-protein coupled receptor independent pathways would enable researchers to pursue novel cellular events that could direct or promote preconditioning. In this regard recent work has begun to explore the role of the innate immune system in intrinsic cardioprotection against both viral myocarditis and ischemia. Interestingly, cytokines such as TNFα, IL-1β and leukemia inhibitory factor, which are components of innate immunity, have been shown to mimic ischemic preconditioning. Thus as the innate immune system functions via a diverse array of GI-protein independent receptors, the study of this immunological system in the heart may provide new insight into mechanisms driving and promoting ischemic preconditioning. We propose that innate immunity is indeed an integral part of ischemic preconditioning. In this review, we provide an overview of the innate immune system, describe the studies whereby cytokines mimic ischemic preconditioning and finally postulate some mechanisms whereby innate immunity may promote cardioprotection as a component of preconditioning.
[231] CEREBRAL MAGNETIC RESONANCE IMAGING REVEALS FINDINGS COMPATIBLE WITH GRAY AND WHITE MATTER LOSS IN PATIENTS WITH CIRRHOSIS
Authors: M.E. Baccaro, M. Guevara, B. Gomez-Anson, C. Testa, G.B. Frisoni, A. Torre, G.C. Monte-Rubio, M.N. Pepin, M. Martin-Llahi, C. Terra, V. Arroyo, P. Gines
Journal: Journal of Hepatology (2007)
Dendritic-Cell-Based Therapeutic Cancer Vaccines
Authors: Karolina Palucka, Jacques Banchereau
Journal: Immunity (2013)

The past decade has seen tremendous developments in novel cancer therapies through the targeting of tumor-cell-intrinsic pathways whose activity is linked to genetic alterations and the targeting of tumor-cell-extrinsic factors, such as growth factors. Furthermore, immunotherapies are entering the clinic at an unprecedented speed after the demonstration that T cells can efficiently reject tumors and that their antitumor activity can be enhanced with antibodies against immune-regulatory molecules (checkpoint blockade). Current immunotherapy strategies include monoclonal antibodies against tumor cells or immune-regulatory molecules, cell-based therapies such as adoptive transfer of ex-vivo-activated T cells and natural killer cells, and cancer vaccines. Herein, we discuss the immunological basis for therapeutic cancer vaccines and how the current understanding of dendritic cell and T cell biology might enable the development of next-generation curative therapies for individuals with cancer.
Spinal Cord Involvement in Acute Bacterial Meningitis
Authors: Glen G. Glista
Journal: JAMA (1980)

A 25-month-old boy had the development of respiratory arrest and quadriplegia with a T-10 sensory level during the acute phase of<i>Haemophilus influenzae</i>meningitis. The sequelae of spinal cord involvement of bacterial meningitis are reviewed. A possible mechanism of the spinal cord involvement in this case is discussed with reference to known pathology of<i>H influenzae</i>meningitis. (<i>JAMA</i>243:1362-1363, 1980)
Detection of Monocyte Chemoattractant Protein-1 Receptor Expression in Experimental Atherosclerotic Lesions
Authors: Katsuichi Ohtsuki, Motoya Hayase, Koichi Akashi, Susan Kopiwoda, H.William Strauss
Journal: Circulation (2001)

Background — Monocytes, a common component of atheroma, are attracted to the lesion site in response to chemotactic signals, particularly expression of monocyte chemoattractant peptide 1 (MCP-1). This study assessed the feasibility of using radiolabeled MCP-1 to identify monocytes and macrophages that have localized at sites of experimental arterial lesions. Methods and Results — The biodistribution of radiolabeled MCP-1 was determined in normal mice, and localization in experimental atheroma was determined in cholesterol-fed rabbits 4 weeks after arterial injury of the iliac artery (9 rabbits) and the abdominal aorta (1 rabbit). Vessels were harvested and autoradiographed after intravenous administration of 125 I-labeled MCP-1 and Evans blue dye. The arteries were evaluated histologically by hematoxylin and eosin staining and immune staining with a monoclonal antibody specific for rabbit macrophages (RAM-11). 125 I-MCP-1 has a blood clearance half-time of ≈10 minutes and circulates in association with cells. The liver, lungs, and kidneys had the highest concentration of 125 I-MCP-1 at 5 and 30 minutes after tracer administration. Autoradiograms revealed accumulation of 125 I-MCP-1 in the damaged artery wall, with an average ratio of lesion to normal vessel of 6:1 (maximum 45:1). The accumulation of 125 I-MCP-1 in the reendothelialized (plaque formation) areas was greater than in the deendothelialized (Evans blue-positive) areas (6.55±2.26 versus 4.34±1.43 counts/pixel, P &lt;0.05). The uptake of 125 I-MCP-1 correlated with the number of macrophages per unit area ( r =0.85, P &lt;0.0001). Conclusions — Radiolabeled MCP-1 may be a useful tracer for imaging monocyte/macrophage-rich experimental atherosclerotic lesions.
Quantification of apolipoprotein A-I and B messenger RNA in heavy drinkers according to liver disease
Authors: P Mathurin, D Vidaud, M Vidaud, P Bedossa, V Paradis, V Ratziu, J Chaput, T Poynard
Journal: Hepatology (1996)

It has previously been shown that, in heavy drinkers, serum apolipoprotein A-I (ApoA-I) levels are closely related to the degree of liver injury: they are at a maximum in patients with steatosis, begin to decrease in patients with fibrosis, and reach a minimum in patients with severe cirrhosis. In contrast with serum ApoA-I variations, serum apolipoprotein B (ApoB) levels are stable. The assessment of messenger RNA (mRNA) levels of ApoA-I and ApoB using a quantitative competitive polymerase chain reaction (PCR) method was performed in 18 alcoholic patients: 8 with normal livers or steatosis (group I), 6 with fibrosis or nonsevere cirrhosis (group II), and 4 with severe cirrhosis (group III). For ApoA-I, group I had higher serum levels (208.4 ± 37.6 mg/dL mean ± SE) and mRNA levels (0.51 ± 0.12) than group II (serum 116 ± 19 mg/dL, P &lt; .01, mRNA 0.40 ± 0.11, P &lt; .09) or group III (serum 56.5 ± 28.6 mg/dL, P &lt; .01, mRNA 0.27 ± .02, P = .008). For ApoB, the three groups had similar serum ApoB levels: 129.9 ± 37.7, 121 ± 51, 120.7 ± 57.4 mg/dL. Group I presented higher levels of ApoB mRNA than those of group III (0.68 ± 0.21 vs. 0.41 ± 0.18, P &lt; .06). There was a significant correlation between serum and mRNA levels of ApoA-I ( r = .65, P = .003) but no correlation between serum and mRNA levels of ApoB ( r = .19, NS). We suggest that (1) steatosis is associated with increased ApoA-I mRNA; (2) fibrosis is associated with decreased serum ApoA-I, probably caused by a posttranscriptional mechanism; (3) severe alcohol-induced cirrhosis is associated with a nonspecific decrease in ApoA-I and ApoB mRNA; and (4) in contrast to ApoA-I mRNA, the ApoB mRNA level makes a slight contribution to the ApoB serum concentration.
Necrolytic Migratory Erythema
Authors: Laura McGevna, Zarry Tavakkol
Journal: New England Journal of Medicine (2010)

This 63-year-old woman with diabetes mellitus presented with an ulcerating rash on the shins, groin, and face. It had been worsening for 4 years despite specialized wound care. Given her history, abdominal CT was performed and glucagon levels were measured.
Association between thyroid autoantibodies and miscarriage and preterm birth: meta-analysis of evidence
Authors: S. Thangaratinam, A. Tan, E. Knox, M. D. Kilby, J. Franklyn, A. Coomarasamy
Journal: BMJ (2011)

<b>Objectives</b> To evaluate the association between thyroid autoantibodies and miscarriage and preterm birth in women with normal thyroid function. To assess the effect of treatment with levothyroxine on pregnancy outcomes in this group of women. <b>Design</b> Systematic review and meta-analysis. <b>Data sources</b> Medline, Embase, Cochrane Library, and SCISEARCH (inception-2011) without any language restrictions. We used a combination of key words to generate two subsets of citations, one indexing thyroid autoantibodies and the other indexing the outcomes of miscarriage and preterm birth. <b>Study selection</b> Studies that evaluated the association between thyroid autoantibodies and pregnancy outcomes were selected in a two stage process. Two reviewers selected studies that met the predefined and explicit criteria regarding population, tests, and outcomes. <b>Data synthesis</b> Odds ratios from individual studies were pooled separately for cohort and case-control studies with the random effects model. <b>Results</b> 30 articles with 31 studies (19 cohort and 12 case-control) involving 12 126 women assessed the association between thyroid autoantibodies and miscarriage. Five studies with 12 566 women evaluated the association with preterm birth. Of the 31 studies evaluating miscarriage, 28 showed a positive association between thyroid autoantibodies and miscarriage. Meta-analysis of the cohort studies showed more than tripling in the odds of miscarriage with the presence of thyroid autoantibodies (odds ratio 3.90, 95% confidence interval 2.48 to 6.12; P&lt;0.001). For case-control studies the odds ratio for miscarriage was 1.80, 1.25 to 2.60; P=0.002). There was a significant doubling in the odds of preterm birth with the presence of thyroid autoantibodies (2.07, 1.17 to 3.68; P=0.01). Two randomised studies evaluated the effect of treatment with levothyroxine on miscarriage. Both showed a fall in miscarriage rates, and meta-analysis showed a significant 52% relative risk reduction in miscarriages with levothyroxine (relative risk 0.48, 0.25 to 0.92; P=0.03). One study reported on the effect of levothyroxine on the rate of preterm birth, and noted a 69% relative risk reduction (0.31, 0.11 to 0.90). <b>Conclusion</b> The presence of maternal thyroid autoantibodies is strongly associated with miscarriage and preterm delivery. There is evidence that treatment with levothyroxine can attenuate the risks.
Home Nasoenteric Feeding for Malabsorption and Weight Loss Refractory to Conventional Therapy
Authors: STEVEN B. HEYMSFIELD
Journal: Annals of Internal Medicine (1983)

Two patients with malabsorption syndrome and weight loss refractory to conventional pharmacologic and dietary therapy were evaluated on a metabolic ward. Baseline studies indicated moderate to severe protein-energy malnutrition, and severe energy, fat, and nitrogen malabsorption. Metabolic balance studies on low-fat elemental formulas infused nasoenterally over 18-hour periods indicated improved retention of nitrogen, phosphorus, calcium, magnesium, and energy when compared with a solid food diet. Because this dietary modification appeared to correct their malabsorption, both patients learned to insert the nasoenteral tube themselves, and a low-calorie solid-food diet combined with nocturnal tube feedings was continued at home. During the next 9 to 12 months, both patients had increases in body weight, and in the mass of fat-free tissue, skeletal muscle, and fat. This therapeutic approach may correct life-threatening semistarvation in selected patients.
Early detection of mediastinal spread of pulmonary carcinoma by mediastinoscopy
Authors: M. Hajek, J. N. H. Van Der Heide
Journal: Thorax (1970)

To the great disappointment of all concerned, too many operations performed for pulmonary carcinoma still prove to be exploratory thoracotomies or non-curative resections, in spite of careful preoperative investigations. A follow-up study of 168 patients operated upon for pulmonary carcinoma clearly shows that such non-curative procedures yield very disappointing results. To reduce this number of unnecessary and often harmful operations mediastinoscopy was introduced as an aid in detecting mediastinal spread of the tumour. It was thought that such knowledge would make preoperative assessment more accurate and so make easier the decision whether to operate.
How Best to Train Physician-Managers
Authors: Robert D. Gillette
Journal: JAMA (1987)

To the Editor.—  A recent Letter to the Editor by Dr Henry, 1 outlining a proposal for combined MD-MBA educational programs, highlights a need that has received insufficient attention heretofore. Physicians sometimes move into positions of responsibility in our increasingly complex health care system with inadequate managerial skills and orientation. This may lead to unnecessary interpersonal conflicts and inadequate executive performance in many areas.  There is, however, a danger that the model proposed by Dr Henry (concurrent medical and MBA training starting with medical students or first-year residents) will create a class of leaders with inadequate acculturation into the physician role—executives fluent in medical jargon but lacking the perspective, judgment, and dedication to patient needs that come from years of clinical experience. The result would be a cluster of managers with MD degrees who had acquired reasonable amounts of textbook medical knowledge but only superficial familiarity with the realities of
The Burn-Prone Society
Authors: Francis D. Moore
Journal: JAMA (1975)

The care of a severely burned patient imposes a remarkable requirement on the supporting community for nurses, physicians, allied health personnel, special care facilities, and laboratory back-up as well as a large share of hospital beddays. Many hospitals that receive burn cases only occasionally have, quite wisely, adopted the policy of early transfer to units more suitably equipped by facilities and experience. Once the early respiratory threat has abated, and the early fluid therapy is judged satisfactory for transport, the patient is safely transportable. Far better to transport the patient to a burn center early in his course, rather than "hanging on" until sepsis and failure of skin grafting forces transfer. Wherever definitive treatment is given, the patient faces long months of intense physical suffering with the outcome long in doubt. Although many details of care have been improved in the past 25 years and rehabilitation accelerated for survivors, there
Aplastic anemia in Brazil: Incidence and risk factors
Authors: Eliane M.C.P. Maluf, Ricardo Pasquini, Jose N. Eluf, Judith Kelly, David W. Kaufman
Journal: American Journal of Hematology (2002)

Abstract This study is the first large‐scale epidemiological investigation of acquired aplastic anemia (AAA) in South America. The objective was to estimate the incidence and to identify risk factors for AAA in Brazil. A national case–control study was conducted to investigate the risk factors for the disease. One hundred twenty‐five cases and 129 controls were included. Multiple logistic regression was used in the estimation of odds ratios (OR) to control confounding. The size of Brazil made it unfeasible to estimate the incidence of AAA in the whole country, and we limited the calculation to the state of Parana. The annual incidence of AAA in Parana was 2.4 cases/10 6 inhabitants. There was no positive association between chloramphenicol use and AAA (OR 0.4; 95% CI: 0.1–2.9). The OR of AAA associated with household pesticides that include organophosphates in their composition was 2.7 (1.0–8.4). The OR for the usage of unspecified thinner and/or acetone for at least 7 days was 3.0 (1.2–7.3). Cases of AAA in Brazil seem to be associated with some factors traditionally related to this disease, such as certain solvents and the incidence is similar to what has been reported from Europe. Am. J. Hematol. 71:268–274, 2002. © 2002 Wiley‐Liss, Inc.
Abstract 4763: Targeting p300 for inhibiting triple negative breast cancer
Authors: Daiqing Liao, Heng Yang, Jian Luo
Journal: Cancer Research (2012)

Abstract Breast cancer (BC) can be classified into four main subtypes: normal-like, HER2 overexpressing, luminal A and B, and basal-like BC. Normal-like BC cells exhibit gene expression pattern resembling basal epithelial cells. Erb-B-2/HER2-positive BC cells display high levels of Her2 expression. Luminal tumors show heightened expression of luminal cytokeratins and genes specific to the luminal epithelial cells, and are generally ER positive. Basal-like BC is characterized by the lack of expression of ER, progesterone receptor (PgR), and HER2. Triple-negative BC (TNBC) is defined by the lack of expression of ER, PgR and HER2 with distinct molecular, histological and clinical characteristics. Among the four BC subtypes, TNBC shares many of the molecular features of basal-like BC. Patients with TNBC have worse prognosis than those with other types of BC due to residual diseases that are resistant to chemotherapy and display heightened tendency to disseminate to distant organs. Available targeted therapies are ineffective for TNBC. Interestingly, cells derived from TNBC contain an elevated proportion of tumor cells with stem cell traits. These cells, known as cancer stem cells (CSCs), can self renew, differentiate into other types of cells in the tumor bulks, and efficiently promote tumor regrowth. CSCs are highly resistant to chemotherapy due to the expression of antiapoptotic genes. Several highly active signaling pathways, including cytokine-JAK-STAT3, Wnt-β-catenin, and Hippo-TAZ cascades, support the survival and sustained self-renewal of CSCs. One remarkable feature of these diverse signaling pathways is the reliance on the functions of the coactivators and acetyltransferases p300 and its paralog CBP for the expression of the effector genes that underlie the CSC phenotypes. We therefore hypothesize that inhibition of p300/CBP is an effective strategy for treating TNBC. Using an unbiased ultra high-throughput screening, we have identified small chemical compounds that were highly toxic to TNBC cell line MDA-MB-231 and potently inhibited the enzymatic activity of p300. Validation experiments revealed that a specific compound, L002, with the IC50 of 1.98 µM against p300 in vitro suppressed histone acetylation at several known sites of p300 acetylation in cell-based assay. L002 was highly toxic to MDA-MB-231 cells but much less so to MCF7 derived from a luminal BC. Experiments are underway to examine the effects of L002 on the survival of breast CSCs. (This work was supported by Bankhead-Coley Cancer Research Program of the Florida Department of Health.) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4763. doi:1538-7445.AM2012-4763
Weight Cycling-Reply
Authors: Susan Zelitch Yanovski
Journal: JAMA (1995)

<h3>In Reply.</h3> —We agree with Drs Blackburn and Borrazzo that difficulties in the definition of weight cycling and other methodological considerations make meta-analysis an unacceptable method for determining the effects of weight cycling, based on currently available data. Therefore, we did not perform a meta-analysis; rather, we chose to critically review individual studies, noting the strengths and limitations of each. We agree with their conclusions that normal-weight individuals should focus on prevention of obesity, and that changes in lifestyle are essential; indeed, we tried to emphasize these points strongly in the article. Drs Ernsberger and Koletsky's assertion that seven of the nine scientific members are employed by weight-loss clinics is incorrect. In fact, none of the scientific members of the task force is employed by weight-loss clinics. All but one are employed as full-time university faculty. Dr Norma Goodwin is president of Healthwatch, a health-promotion organization that does not provide
A tale of two physicians: reflections on the Boston Marathon bombing
Authors: A. Rajabali, H. Caton
Journal: BMJ (2013)

On 15 April, I found myself thinking for the first time, “I wish I was a surgeon.” As a second year internal medicine resident, I am training to be a diagnostician. If a patient’s leg is red and swollen, I can differentiate between a clot and an infection. If a patient has abdominal pain, I can identify the culprit organ and determine if he needs medical or surgical intervention. If a patient has chest pain, I can decide if he is having a heart attack. But when disaster struck Boston on Monday afternoon and I saw a trauma victim point to a leg that had been ripped open, there was no diagnostic dilemma that needed my expertise. When the woman on the stretcher buckled over with pain lifted her hands for me to examine her, the third degree burns were explanation enough for her excruciating pain. And when the man with chest pain had a piece of shrapnel protruding from his chest, you didn’t need me to tell you why he was in pain. As our emergency department was inundated with victims, I started to think these patients needed a trauma physician and not an internal medicine doctor.

As a third year medicine pediatrics resident, I spent the night before the marathon reviewing the basics of treating hyponatremia. I was working in the emergency department and anticipated an influx of patients requiring careful sodium repletion after drinking too much water during the race. When the announcement that two bombs had exploded in Copley crackled over the emergency radios, there was a brief moment of stunned …
Leucocyte and erythrocyte counts during a multi-stage cycling race ('the Milk Race').
Authors: P Keen, D A McCarthy, L Passfield, H A Shaker, A J Wade
Journal: British Journal of Sports Medicine (1995)

Venous blood samples were taken from eight competitors in mid-evening after a racing day, and in the early morning before the next day's race, three times during the course of the Milk Race, 1992. These were used to gather information about the changes in circulating leucocyte levels in response to the exceptionally high sustained daily workload required during a major multi-stage race. The primary objective was to provide knowledge of 'normal' values against which future clinical judgements of abnormality might be made in these unusual circumstances. During the race, estimated energy output was about 25 MJ (6000 kCal)/day. The mean total circulating leucocyte numbers (per litre of blood), and those of individual leucocyte classes (neutrophil, lymphocyte, monocyte, eosinophil and basophil) were all inside the normal range both in the morning and in the evening. Evening counts were, however, 30-50% higher than morning counts, for all classes except eosinophils. We conclude that individual clinical decisions about leucocyte levels can best be made using normal (sedentary man) values if a morning sample is taken.
Libel case against Wilmshurst collapses as firm goes into liquidation
Authors: C. Dyer
Journal: BMJ (2011)

The long running libel action against cardiologist Peter Wilmshurst by the makers of a medical device has collapsed dramatically after the company suing him announced it was going into liquidation.

US based NMT Medical has pursued Dr Wilmshurst in the UK courts for more than three years over his comments alleging flaws in a clinical trial of the STARFlex septal repair implant, quoted on a US website for cardiologists. He was a lead investigator on the MIST (Migraine Intervention with STARFlex Technology) trial, carried out in the UK from 2004 to 2006.

Dr Wilmhurst, a …