tbuckley/cabot-search huggingface dataset:
Morphometric study of early postnatal development in the left and right ventricular myocardium of the rat. I. Hypertrophy, hyperplasia, and binucleation of myocytes.
Authors: P Anversa, G Olivetti, A V Loud
Journal: Circulation Research (1980)

We reviewed the absolute amd differential growths of the myocyte populations in the left (L) and right (R) ventricular myocardium morphometrically from 1 to 5 days and from 5 to 11 days after birth.From 1 to 11 days hypertrophy of the average myocyte in the ventricles was (L) 2.7-and (R) 2.4-fold, and myocyte proliferation was (L) 2.0-and (R) 1.2-fold.Mean cell volume, cell length, and percent binucleation of cardiac myocytes were similar in both ventricles at 1, 5, and 11 days of age.During this period, average myocyte length increased 2-fold (12 sarcomere lengths), and the percentage of binucleate myocytes increased approximately from 2.7 to 17 to 48%.Myocyte hypertrophy from 1 to 5 days resulted mainly from an increase in the volume of cytoplasm per nucleus and from 5 to 11 days from the accumulation of binucleate cells.No differences were observed in the characteristics of epicardial and endocardial myocytes in either ventricle up to 11 days of age.The 61% greater proliferation of myocytes in the left ventricle was the principal basis for the development of a 2-fold difference in ventricular weight gains: (L) 6.2-and (R) 3.4-fold.No increase in right ventricular midwall thickness was observed, in contrast to a 2.7-fold increase of the left ventricle.It was concluded that, as a result of the circulatory changes occurring shortly after birth, right ventricular growth is analogous to eccentric hypertrophy, whereas left ventricular growth represents a combination of eccentric and concentric hypertrophy.Circ Res 46: 495-502, 1980 GROWTH of the myocardium during the early postnatal period must accommodate not only the increasing demands of the rapidly growing animal but also the relatively abrupt changes in the patterns of blood flow and circulatory resistance occuring shortly after birth.Work required of the left and right ventricles is approximately equal as they pump in parallel during fetal life (Heymann and Rudolph, 1973;Rudolph, 1974).With closure of the foramen ovale and ductus arteriosus after birth, blood flow is henceforth in series through the right and left ventricles, resulting in a greater volume work load on each ventricle.In the same period, pulmonary resistance is lowered by expansion of the collapsed lungs (Klopfenstein and Rudolph, 1978;Rudolph, 1979), peripheral resistance increases with loss of the placental circulation (Rudolph, 1970), and the pressure load on the left ventricle becomes significantly greater than that on the right ventricle (Assali et al., 1965).The combi-
Reparative properties of a commercial fish protein hydrolysate preparation
Authors: A J Fitzgerald
Journal: Gut (2005)

<b>Background:</b> A partially hydrolysed and dried product of pacific whiting fish is currently marketed as a health food supplement to support "intestinal health". However, there has been only limited scientific study regarding its true biological activity. <b>Aims:</b> We therefore tested its efficacy in a variety of models of epithelial injury and repair. <b>Methods:</b> Effects on proliferation were determined using [<sup>3</sup>H] thymidine incorporation into epithelial rat intestinal RIE-1 and human colonic HT29 cells. Effects on restitution (cell migration) were analysed using wounded HT29 monolayers and its ability to influence gastric injury analysed using a rat indomethacin restraint model. Partial characterisation of bioactive agents was performed using mass spectroscopy, high pressure liquid chromatography, and gas chromatography. <b>Results:</b> Both cell proliferation and cell migration were increased by about threefold when added at 1 mg/ml (p&lt;0.01). Gastric injury was reduced by 59% when gavaged at 25 mg/ml (p&lt;0.05), results similar to using the potent cytoprotective agent epidermal growth factor at 12.5 μg/ml. The vast majority of biological activity was soluble in ethanol, with glutamine in its single, di-, and tripeptide forms probably accounting for approximately 40% of the total bioactivity seen. Fatty acid constituents may also have contributed to cell migratory activity. <b>Conclusions:</b> Fish protein hydrolysate possesses biological activity when analysed in a variety of models of injury and repair and could provide a novel inexpensive approach for the prevention and treatment of the injurious effects of non-steroidal anti-inflammatory drugs and other ulcerative conditions of the bowel. Further studies appear justified.
Social inequalities and health: ecological study of mortality in Budapest, 1980-3 and 1990-3
Authors: P Jozan, D P Forster
Journal: BMJ (1999)

joint registration category, and these cannot be identified separately from published sources.This form of misclassification has probably not changed over the study period in a way that would affect the interpretation of trends.Secondly, the status of the baby at death may be different from that at birth, but this is unlikely to be an issue for most of the deaths occurring within 1 month of birth.The research highlights the need for lone and unsupported mothers to be given every possible help after the birth of their babies, not just in the neonatal period but on a sustained basis.We thank Jeremy Schuman, Office for National Statistics, for help in extracting the data on deaths.Contributors: MW and FD jointly developed the idea for this study and worked on its design.FD
Revalidation needs proper testing before adoption throughout UK
Authors: Lisa Hitchen
Journal: BMJ (2008)

Thorough trials of revalidation are needed to test the new system for assessing doctors’ fitness to practise before it is introduced everywhere, says the Department of Health.

Bruce Keogh, the NHS medical director, said, “This needs to be piloted. A big bang approach is going to be an utter disaster.” He said that a “whole system trial” is needed that tests the system in a number of different specialties and settings.

He was speaking at a conference of the British Association of Medical Managers and Healthcare Events on the topic in London last week.

Una Lane, assistant director for revalidation at the General Medical Council, agreed that a phased approach was needed. A recent audit by the company KPMG showed that the current appraisal system was patchily implemented geographically and in …
Effect of lidocaine on atrioventricular response via the accessory pathway in patients with Wolff-Parkinson-White syndrome.
Authors: M Akhtar, C J Gilbert, M Shenasa
Journal: Circulation (1981)

Electrophysiologic effects of i.v.lidocaine were evaluated in 10 patients with Wolff-Parkinson-White (WPW) syndrome during atrial fibrillation (AF) (eight of 10) or programmed atrial stimulation (nine of 10).The shortest RR intervals during AF were 190-415 msec (mean 271.8 ± 64.5 msec) before lidocaine and decreased to 250.0 i 85.4 msec (range 180-435 msec, p = NS) after the drug.In six of eight patients, the shortest RR interval decreased and in the remaining two patients it increased by 20 msec after lido- caine.After lidocaine, the average RR intervals during AF for all eight patients decreased from 351.1 ± 45.9 msec to 335.6 ± 68.0 msec (p = NS).After lidocaine, the RR inverval shortened in five of eight patients, lengthened in two and did not change In one.In two of eight patients, acceleration of ventricular rate after lidocaine was accompanied by hemodynamic deterioration, necessitating DC cardioversion in one.The control effective refractory period of the accessory pathway (ERP-AP) was 300 msec or less in all patients, and lidocaine prolonged this variable in only one case.In the remaining patients, after lidocaine the ERP-AP either shortened (two of nine), did not change (two of nine) or atrial refractoriness precluded its determination.Similarly, during incremental pacing, the atrial cycle length that produced block in the AP shortened in five patients, lengthened in one and did not change in the others.In patients with WPW syndrome and relatively short ERP-AP (i.e., 300 msec), lidocaine generally has no significant effect or produces acceleration of ventricular response during AF.In patients with AF and a rapid ventricular rate due to antegrade conduction over the AP, lidocaine is unlikely to have beneficial effects and may be deleterious.
Oxygen Therapy Equipment
Authors: Howard L. Zauder
Journal: JAMA (1961)

<h3>To the Editor:—</h3> We were quite distressed to see the article by Barach et al. (<i>JAMA</i><b>174</b>:1276 [Nov. 5] 1960) in which it is suggested that the oxygen therapy equipment described might be refilled by the user. While we have little doubt that such transfilling is reasonably safe in the hands of those as experienced in oxygen therapy as Dr. Barach and his associates, the general practice is to be discouraged, if not condemned. We know of one experienced anesthesiologist who was killed during this procedure when his apparatus exploded. When transfilling is performed by casual practitioners, unacquainted with the hazards of handling compressed gases at high pressure, the risk is greatly increased. The National Fire Protection Association has recommended that "transfer of gas from one cylinder to another on the hospital site or by hospital personnel shall be prohibited."
Does the evidence support the use of mild hypothermia after cardiac arrest? Yes
Authors: J. P. Nolan, J. Soar
Journal: BMJ (2011)

Several guidelines recommend hypothermia for comatose patients who have had a cardiac arrest outside hospital. <b>Jerry Nolan </b>and<b> Jasmeet Soar </b>believe the data support this advice, but <b>Andrew Walden</b>, <b>Niklas Nielsen,</b> and <b>Matt Wise </b>(doi:10.1136/bmj.d5889) question the quality of the evidence
PRECAUTIONS ON THE PART OF PHYSICIANS TO AVOID INFLUENZA INFECTION
Authors: B. Franklin Royer
Journal: JAMA (1918)

To the Editor:  —I believeThe Journalwould do service by suggesting precaution that should be practiced by physicians and others in the sick room with influenza patients.  Large numbers of Pennsylvania's physicians are sickening, I am sure, because they are indifferent to danger and careless about protecting themselves from the spray of moisture from the mouth of the patient.  I am getting stories every day by the score of physicians examining the chests of influenza patients in the old careless fashion, leaning over the bed with the patient talking constantly and with no attempt to have the patient cover the cough or sneeze with a towel or handkerchief. The sick rate among physicians and the death rate are appalling, and I believe physicians are needlessly sacrificing themselves because of their failure to fully appreciate what they ought to do.  I have not had time to prepare an article and
Abstract 1255: Protein kinase C epsilon (PKCε) as a target for lung cancer treatment: Essential role of PKCε in tumor growth and metastatic dissemination of non-small cell lung cancer (NSCLC) cells
Authors: M. Cecilia Caino, Cynthia C. Lopez Haber, Jeewon Kim, Marcelo G. Kazanietz
Journal: Cancer Research (2010)

Abstract Protein Kinase C epsilon (PKCε), a member of the PKC family of phorbol ester/diacylglycerol receptors, has been recently shown to be highly overexpressed in non-small cell lung carcinomas (NSCLCs) compared to normal lung epithelium. The fact that several of the most common genetic alterations in lung cancer, such as EGFR, K-Ras, or PI3K mutations, could signal through PKCs, led us to hypothesize that PKCε may contribute to lung tumorigenesis. We found that the expression of PKCε was markedly up-regulated in NSCLC cell lines (H358, H441, H322, H1299, and A459) relative to immortalized non-tumorigenic cells (HBEC-3). Stable knockdown of PKCε in NSCLC cells using shRNA lentiviruses impaired cell survival in response to serum starvation, as well as it increased the sensitivity to senescence induction by phorbol esters. Moreover, anchorage-dependent and -independent growth were markedly reduced in PKCε-depleted NSCLC cells. Notably, silencing of PKCε-expression in NSCLC impaired motility in response to PMA, FBS or TGFα. Treatment of NSCLC cells with PMA led to a significant enhancement in cell motility as well as it promoted ruffle formation. Both ruffle formation and migration were mediated by PKCε. Moreover, PMA caused a marked enhancement in Rac1-GTP levels in NSCLC cells, but this effect was lost when PKCε was knocked down using RNAi. To address the relevance of our findings in an in vivo setting, we examined the requirement of PKCε in tumorigenesis and metastasis. Remarkably, PKCε-depleted H358 cells have impaired tumorigenic potential when inoculated into nude mice. At early time points during tumor formation (6-15 days) we observed a significant increase in apoptotic cells in PKCε-depleted H358 xenografts compared to controls, as determined by TUNEL. These in vivo results were validated pharmacologically by means of a specific inhibitor of PKCε translocation/activation. Indeed, delivery of the specific PKCε inhibitor εV1-2 by osmotic minipumps greatly reduced the rate of tumor growth in nude mice. Finally, we sought to study whether PKCε is implicated in tumor dissemination. Using a tail vein injection assay, we found that stable depletion of PKCε essentially impaired the appearance of lung metastatic foci in nude mice. In summary, our results established PKCε as a key mediator of lung tumorigenesis and provided strong evidence that elevated PKCε levels in NSCLC cells play a key role in metastatic dissemination. We speculate that PKCε is an attractive pharmacological target for lung cancer treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1255.
Hydrophobic poly (amino acid) modified PEI mediated delivery of rev-casp-3 for cancer therapy
Authors: Chunling Fu, Lin Lin, Hengliang Shi, Daxue Zheng, Wei Wang, Shiqian Gao, Yifei Zhao, Huayu Tian, Xiaojuan Zhu, Xuesi Chen
Journal: Biomaterials (2012)
Acute Pelvic Inflammatory Disease in Outpatients: Association with Chlamydia trachomatis and Neisseria gonorrhoeae
Authors: WILLIAM R. BOWIE
Journal: Annals of Internal Medicine (1981)

Among 830 women attending a clinic for sexually transmitted disease, Chlamydia trachomatis was isolated from 180 (22%) and Neisseria gonorrhoeae from 84 (10%). Retrospective analysis showed that 43 of the women were given outpatient treatment for acute pelvic inflammatory disease because they had low abdominal pain, deep dyspareunia, or unusual vaginal bleeding, or all of these, for less than 2 months in association with cervical motion or adnexal tenderness, or both. None had adnexal masses. C. trachomatis was isolated from 22 and N. gonorrhoeae from 15 of this subgroup of 43 women. This presentation of pelvic inflammatory disease occurred in 10 of the 37 women in the whole study with both C. trachomatis and N. gonorrhoeae, 12 of 143 women with C. trachomatis alone, five of 47 women with N. gonorrhoeae alone, and 16 of 603 women with neither organism. Thus, in North America, C. trachomatis is associated with a syndrome usually diagnosed as mild pelvic inflammatory disease and managed on an outpatient basis.
Toll-like receptor 9 inhibition reduces mortality in polymicrobial sepsis
Authors: George Plitas, Bryan M. Burt, Hoang M. Nguyen, Zubin M. Bamboat, Ronald P. DeMatteo
Journal: The Journal of Experimental Medicine (2008)

The high rate of mortality in patients with sepsis results from an inappropriately amplified systemic inflammatory response to infection. Toll-like receptors (TLRs) are important for the activation of innate immunity against microbial pathogens. We demonstrate a critical role of TLR9 in the dysregulated immune response and death associated with sepsis. Compared with wild-type (WT) mice, TLR9−/− mice exhibited lower serum inflammatory cytokine levels, higher bacterial clearance, and greater survival after experimental peritonitis induced by cecal ligation and puncture (CLP). Protection of TLR9−/− mice after CLP was associated with a greater number of peritoneal dendritic cells (DCs) and granulocytes than in WT controls. Adoptive transfer of TLR9−/− DCs was sufficient to protect WT mice from CLP and increased the influx of peritoneal granulocytes. Subsequent experiments with a depleting antibody revealed that granulocytes were required for survival in TLR9−/− mice. Remarkably, a single injection of an inhibitory CpG sequence that blocks TLR9 protected WT mice, even when administered as late as 12 h after CLP. Our findings demonstrate that the detrimental immune response to bacterial sepsis occurs via TLR9 stimulation. TLR9 blockade is a potential strategy for the treatment of human sepsis.
Noninvasive Ventilation for Immunocompromised Patients
Authors: Nicholas S. Hill
Journal: New England Journal of Medicine (2001)

Immunocompromised patients with respiratory failure who require mechanical ventilation have notoriously poor prognoses, with mortality rates ranging from 60 to 100 percent, depending on the underlying diagnosis and factors such as age, functional status, the Acute Physiology and Chronic Health Evaluation score, the presence or absence of multiorgan failure, and the duration of neutropenia.1 Such patients' immunosuppression is most often a consequence of therapy for hematologic cancers, organ transplantation, the acquired immunodeficiency syndrome, or long-term treatment with high doses of corticosteroids. They usually die either from underlying illness or its complications or from the complications of mechanical ventilation.Although the . . .
Protagonist: Should we eradicate<i>Helicobacter pylori</i> in non-ulcer dyspepsia?
Authors: K E L McColl
Journal: Gut (2001)

The beneficial effects of fish oil on inflammation have been attributed to the content of eicosapentaenoic (EPA)/docosahexaenoic acid. EPA is also a substrate for arachidonic acid (AA) cascade enzymes, but it induces the production of alternative eicosanoids such as 3-series prostanoids and 5-series leukotrienes, which are considered to be less pro-inflammatory than AA metabolites. However, the molecular basis of this action is poorly understood. In this study, we compared the effects of PGE<sub>2</sub> and PGE<sub>3</sub> on endothelium permeability, and the effects of LTB<sub>4</sub> and LTB<sub>5</sub> on endothelium permeability and mononuclear adhesion and migration. In our study, both prostaglandins increased trans-endothelial Evans blue-albumin (EBA) permeability in a concentration-dependent manner. Interestingly, the effect of PGE<sub>3</sub> was significantly more pronounced than of PGE<sub>2</sub> and both were antagonized by EP<sub>1</sub> and EP<sub>2</sub> antagonists. LTB<sub>4</sub> and LTB<sub>5</sub> had a slight effect on EBA extravasation. However, we observed the enhancement of endothelial permeability in presence of polymorphonuclear (PMN), probably consequence of an interplay between leukotriene and prostanoid effects. LTB<sub>4</sub> caused significant increases in the number of PMN adhering to endothelial cells whereas LTB<sub>5</sub> did not induce a significant effect. This effect of LTB<sub>4</sub> appears BLT1 receptor dependent and was mediated through the enhancement of LFA-1, MAC-1, E-selectin and ICAM-1 expression. Finally, we observed that unlike LTB<sub>5</sub>, which had a weak effect, LTB<sub>4</sub> was a highly potent chemoattractant. An understanding of the differences in the effects of LTB<sub>4</sub>/LTB<sub>5</sub> on PMN adhesion and migration may help to explain the beneficial impact of ω-3 fatty acids in inflammatory processes.
AIDS and haemophilia: morbidity and morality in a well defined population.
Authors: P Jones, P J Hamilton, G Bird, M Fearns, A Oxley, R Tedder, R Cheingsong-Popov, A Codd
Journal: BMJ (1985)

One hundred and forty-three multitransfused patients with hereditary haemostatic disorders were examined for evidence of disease related to the acquired immune deficiency syndrome (AIDS). Ninety-nine patients with severe haemophilia A were tested for anti-HTLV-III and 76 were found to be positive. All except one of these seropositive patients had received commercial factor VIII concentrates at some time. Eighteen patients with haemophilia B were tested and all were anti-HTLV-III negative. Three out of 36 sexual partners of patients with haemophilia A positive for anti-HTLV-III were also seropositive. One, who had recently received blood transfusions, had AIDS with Pneumocystis carinii pneumonia. Three patients with severe haemophilia A died from Aids. A further 30 haemophiliacs had AIDS related complex or lymphadenopathy that could be related to HTLV-III infection. There was a significant correlation between lymphadenopathy and anti-HTLV-III seropositivity. No evidence of casual spread of AIDS was found since all 68 health care staff tested were anti-HTLV-III negative, including three surgeons who regularly worked with patients positive for anti-HTLV-III. The resources devoted to counselling and laboratory support in centres treating people at risk and their families need to be urgently reassessed.
Cyclosporine therapy after cardiac transplantation causes hypertension and renal vasoconstriction without sympathetic activation.
Authors: D Kaye, J Thompson, G Jennings, M Esler
Journal: Circulation (1993)

Hypertension frequently complicates the use of cyclosporine A (CyA) therapy, and it has been suggested that sympathoexcitation may be the underlying mechanism in this form of hypertension.To further investigate the possibility of a neurogenic mechanism for this hypertensive effect, we studied the effects of CyA on renal blood flow (n = 11), forearm blood flow (n = 8), and sympathetic nervous system activity, assessed by renal and whole-body radiolabeled norepinephrine plasma kinetics and muscle sympathetic nerve firing (using microneurography) in cardiac transplant recipients receiving CyA and a reference group of healthy age-matched control subjects (n = 17). In 11 cardiac transplant patients (2 hours after cyclosporine dose), renal blood flow was significantly lower than that in 8 control subjects (680 +/- 88 vs 1285 +/- 58 mL/min, P < .001). In 5 of these transplant patients, renal blood flow was measured before and for 2 hours after oral cyclosporine and fell progressively over this period, by 37% (P < .01). Total body and renal norepinephrine spillover rates in transplant patients were similar to those in control subjects (3070 +/- 538 vs 2618 +/- 313 pmol/min and 579 +/- 124 vs 573 +/- 95 pmol/min, respectively), and there was no progressive effect in the 2 hours after cyclosporine dosing. Forearm blood flow was increased 2 hours after CyA administration (1.74 +/- 0.31 to 3.12 +/- 0.50 mL x 100 mL-1 x min-1, P < .001), whereas mean arterial blood pressure and noninvasively determined cardiac output (indirect Fick method) were unchanged. Muscle sympathetic nerve discharge rates recorded in 6 of these transplant patients were not different from those in 9 healthy control subjects (37.9 +/- 10.1 vs 41.3 +/- 2.3 bursts per 100 beats per minute). During 90 to 120 minutes of recording after cyclosporine dosing, nerve firing rates remained unchanged.CyA therapy causes acute renal vasoconstriction without accompanying systemic hemodynamic effects. These renal effects are nonneural, not being attributable to sympathoexcitation.
IS DOUBLE STENTING THE OPTIMAL TREATMENT FOR COMPLEX CORONARY BIFURCATION LESIONS?
Authors: Ricardo A. Costa, Fausto Feres, Rodolfo Staico, J. Ribamar Costa, Dimytri Siqueira, Alexandre Abizaid, Luiz F. Tanajura, Amanda Sousa, J. Eduardo Sousa, Antonio Colombo
Journal: Journal of the American College of Cardiology (2012)