tbuckley/cabot-search huggingface dataset:
Adult Bone Marrow Cell Therapy Improves Survival and Induces Long-Term Improvement in Cardiac Parameters
Authors: Vinodh Jeevanantham, Matthew Butler, Andre Saad, Ahmed Abdel-Latif, Ewa K. Zuba-Surma, Buddhadeb Dawn
Journal: Circulation (2012)

Background— Despite rapid clinical translation and widespread enthusiasm, the therapeutic benefits of adult bone marrow cell (BMC) transplantation in patients with ischemic heart disease continue to remain controversial. A synthesis of the available data is critical to appreciate and underscore the true impact of this promising approach. Methods and Results— A total of 50 studies (enrolling 2625 patients) identified by database searches through January 2012 were included. Weighted mean differences for changes in left ventricular (LV) ejection fraction, infarct size, LV end-systolic volume, and LV end-diastolic volume were estimated with random-effects meta-analysis. Compared with control subjects, BMC-treated patients exhibited greater LV ejection fraction (3.96%; 95% confidence interval, 2.90–5.02; P &lt;0.00001) and smaller infarct size (−4.03%, 95% confidence interval, −5.47 to −2.59; P &lt;0.00001), LV end-systolic volume (−8.91 mL; 95% confidence interval, −11.57 to −6.25; P &lt;0.00001), and LV end-diastolic volume (−5.23 mL; 95% confidence interval, −7.60 to −2.86; P &lt;0.0001). These benefits were noted regardless of the study design (randomized controlled study versus cohort study) and the type of ischemic heart disease (acute myocardial infarction versus chronic ischemic heart disease) and persisted during long-term follow-up. Importantly, all-cause mortality, cardiac mortality, and the incidence of recurrent myocardial infarction and stent thrombosis were significantly lower in BMC-treated patients compared with control subjects. Conclusions— Transplantation of adult BMCs improves LV function, infarct size, and remodeling in patients with ischemic heart disease compared with standard therapy, and these benefits persist during long-term follow-up. BMC transplantation also reduces the incidence of death, recurrent myocardial infarction, and stent thrombosis in patients with ischemic heart disease.
Regulation of tissue noradrenaline in the rat myocardial infarction model of chronic heart failure
Authors: R. Zelis, B. Clemson, R. Baily, D. Davis
Journal: Cardiovascular Research (1992)

The aim was to evaluate mechanisms regulating tissue noradrenaline in congestive heart failure. Methods: Tissue noradrenaline was measured in the conscious post myocardial infarction rat model of congestive heart failure and in sham operated rats (1) under control conditions, (2) 6 h after inhibition of tyrosine hydroxylase by the intraperitoneal administration of α-methyl-paratyrosine (AMPT) (100 mg·kg−1 every 2 h), (3) 6 h after AMPT with desipramine pretreatment (0.3 mg·kg−), and (4) following exhaustive exercise after AMPT. Tissue noradrenaline was extracted with perchloric acid and measured by high performance liquid chromatography with electrochemical detection. Results: In control animals without drug, tissue noradrenaline concentration was lower in the following tissues in the rats with myocardial infarction compared with the sham operated group: left and right ventricles, spleen, soleus and white gastrocnemius muscles, kidney cortex, and tail artery. After AMPT, tissue noradrenaline concentration in the sham operated group was significantly lower than control; in the myocardial infarction group the fall in noradrenaline was only significant in the kidney, and group differences were no longer present. In the sham operated animals, coadministration of desipramine with AMPT attenuated the fall in tissue noradrenaline caused by AMPT in the heart and spleen. With exercise to exhaustion, cardiac noradrenaline was lower in rats with myocardial infarction than in sham operated rats, but higher in the soleus muscle. Conclusions: These data suggest that tissue noradrenaline depletion in congestive heart failure is not isolated to the heart, and it occurs despite activation of mechanisms that might be operating to conserve neuronal noradrenaline. One mechanism may be reduced organ blood flow to retard diffusion of noradrenaline into the circulation. If this increases interstitial noradrenaline concentration, it would facilitate prejunctional α2 receptor restraint on noradrenaline release. Metabolic coronary vasdilatation during exercise reverses this process, and makes the heart most susceptible to noradrenaline depletion in congestive heart failure. Cardiovascular Research 1992;26:933–938
Basic Electrocardiography and Vectorcardiography
Authors: I. Martin Grais
Journal: JAMA (1983)

It was Sherlock Holmes, that practitioner of scalpel-sharp observation, who said, in A Case of Identity, Never trust to general impressions... but concentrate yourself upon   Since selective attention to details is essential to electrocardiographic interpretation, one problem I've had with the pattern-reading approach is its blunt dissection of the ECG. The vector approach sharpens that dissection, and spatial vectorcardiographic correlation using spatial loops focuses on details. The late Dr Beckwith has sought to instruct both the beginning and more advanced reader of ECGs in these vector terms.  The text is well organized and well written, elucidating the normal and abnormal ECG through the use of spatial vectorcardiographic concepts and loops. There are explanations of when and how vectorcardiography (VCG) can aid in the differential diagnosis of ECG problems. The appendix provides many examples with clinical correlations, and there is a well-selected, annotated bibliography.  Unfortunately, and not unexpectedly for a
Duration of cardiopulmonary bypass and risk of perioperative stroke in coronary artery bypass surgery operations
Authors: Ronald M. Weintraub, Donald S. Likosky, Cathy S. Ross, Bruce J. Leavitt, Charles A. Marrin, David J. Malenka, Louis R. Caplan, Yvon R. Baribeau, David C. Charlesworth, Felix Hernandez, Gerald T. O'Connor
Journal: Journal of the American College of Cardiology (2003)
Occupational asthma due to soft corrosive soldering fluxes containing zinc chloride and ammonium chloride.
Authors: D C Weir, A S Robertson, S Jones, P S Burge
Journal: Thorax (1989)

Two cases of occupational asthma due to soft corrosive soldering fluxes used in metal jointing are described in which the diagnosis was based on work related deterioration in daily peak expiratory flow rate and positive responses in bronchial provocation tests. Both fluxes contained ammonium chloride and zinc chloride. Occupational asthma provoked by these agents has not previously been reported.
Heparinization vs Surgery for Small Bowel Infarction
Authors: John J. Bergan, James G. Hoehn
Journal: JAMA (1964)

<h3>To the Editor:—</h3> The brief clinical presentation by Frajndlich and Taylor on the use of heparin in small bowel infarction (<i>JAMA</i><b>189</b>:327 [July 27] 1964) is the first recorded report of such treatment. With the history of heart disease, acute onset of catastrophic abdominal symptoms, colicky pain, and vomiting, the case is typical of acute embolic occlusion of the superior mesenteric artery. The findings at exploratory laparotomy are absolutely diagnostic, since they indicate sparing of the upper jejunal circulation by the ischemic process. This anatomic distribution is quite different from that of nonorganic occlusion of the mesenteric artery, which the authors discuss. Readers should be aware that one case treated successfully with heparin does not have the significance of the 20 reported cases treated successfully with embolectomy. It should be emphasized that heparinization is not the preferred treatment for this condition, that leaving a clot within the mesenteric arborization
Thirty Years of Bone Marrow Transplantation for Severe Combined Immunodeficiency
Authors: Alain Fischer
Journal: New England Journal of Medicine (1999)

It has been 30 years since the first patient with combined T-cell and B-cell immunodeficiency was successfully treated with transplantation of bone marrow from an HLA-identical sibling.1 Since then, hundreds of patients with severe combined immunodeficiency have been cured by the transplantation of hematopoietic progenitor cells from either a sibling or a parent who was HLA-haploincompatible (also called HLA-haploidentical, meaning that one of the two HLA haplotypes of the parent matches one of the child's, but the other parental HLA haplotype does not). Many of these patients are now long-term survivors. During the same period, the molecular basis for most . . .
The future of the NHS
Authors: C. Ham
Journal: BMJ (1996)

ers, and to a lesser extent midwives, often had reservations about the safety of home birth and tended to discourage it.General practitioners and midwives have responsibility for creating the right circumstances for safe and satisfying home births.This means, firstly, selecting women who are not at high risk of complications; secondly, establishing an infrastructure for safe obstetric interventions-such as providing elevated beds and ensuring adequate hygiene; thirdly, providing support during,labour and in the days after delivery, for which maternity home care assistants are important; and, finally, allowing access to hospital facilities-this is vital, as serious complications during labour can never be excluded.Transfer during labour can be safe,6 7 but safety must not be assumed, and the availability of obstetric care must be established beforehand.Coordinated planning between primary care practitioners and obstetricians is crucial, and much will depend on local conditions: hospital facilities are usually avail- able within 15 minutes in densely populated Holland, but transfer will take much longer in remote areas of North 1 Department of Health Expert Maternity Group.Changing childbirth. 1.The Cumberlege report
Ian Murray Lawson
Authors: N. Mackenzie
Journal: BMJ (2009)

Ian Murray Lawson qualified in 1947 from Edinburgh University and after army medical service in Hong Kong started anaesthesia training in Liverpool. He returned to his native Dundee in 1951, where he remained, latterly as consultant in administrative charge from 1972 to 1984 and head of the university department until his retirement in 1989.

His career spanned a time of immense changes, advances, and growth in …
Enoxaparin thrombophylaxis did not reduce mortality in acutely ill medical patients
Authors: David Feinbloom, Kenneth A. Bauer
Journal: Annals of Internal Medicine (2012)

Source Citation Kakkar AK, Cimminiello C, Goldhaber SZ, et al; LIFENOX Investigators. Low-molecular-weight heparin and mortality in acutely ill medical patients. N Engl J Med. 2011;365:2463-72. 22204723
Human hypervariable sequences in risk assessment: rare Ha-ras alleles in cancer patients.
Authors: T G Krontiris, N A DiMartino, H D Mitcheson, J A Lonergan, C Begg, D R Parkinson
Journal: Environmental Health Perspectives (1987)

A variable tandem repeat (VTR) is responsible for the hyperallelism one kilobase 3' to the human c-Ha-ras-1 (Ha-ras) gene. Thirty-two distinct restriction fragments, comprising 3 allelic classes by frequency of occurrence, have thus far been detected in a sample size of approximately 800 caucasians. Rare Ha-ras alleles, 21 in all, are almost exclusively confined to the genomes of cancer patients (p less than 0.001). From our data we have computed the relative cancer risk associated with possession of a rare Ha-ras allele to be 27. To understand the molecular basis for this phenomenon, we have begun to clone Ha-ras fragments from nontumor DNA of cancer patients. We report here the weak activation, as detected by transfection and transformation of NIH 3T3 mouse cells, of two Ha-ras genes which were obtained from lymphocyte DNA of a melanoma patient. We have mapped the regions that confer this transforming activity to the fragment containing the VTR in one Ha-ras clone and the fragment containing gene coding sequences in the other.
Doing better, looking worse
Authors: C. Douglas
Journal: BMJ (2002)

The portrayal of doctors in art, literature, and television

In Luke Fildes' memorable Victorian painting The Doctor a child lies ill. Her father looks helplessly on, while a far more imposing male figure gazes intently at his patient. The doctor broods, and in truth there was very little more he could do; we know now that he was almost as helpless as the parent, only six feet and three or four social classes away. So his manner is all, and Fildes captures it for ever: the furrowed brow; the hand propping the firm bearded chin; the calm, concerned authority.

For all their professional powerlessness, whole generations of our predecessors enjoyed similar esteem in the media of their day. The doctors of 18th and 19th century fiction offer many more heroes than villains: Tobias Smollett's ebullient protagonist in Roderick Random ; the kindly Dr Lydgate in Middlemarch —idealistic and progressive, marrying upwards (in an age when medical men still used the tradesman's entrance) then driven to commercial practice by his wife's extravagance. And in Charles Dickens's Bleak House the decent young Dr Woodcourt—an altruist in the slums …
Pregnancy and Travel: The Risks of Hepatitis and Scuba Diving
Authors: Frank L. Mannino
Journal: JAMA (1989)

<h3>To the Editor. —</h3> I read with interest the timely and informative article on pregnancy and travel by Drs Barry and Bia.<sup>1</sup>However, a common error was made in explaining the effects of high altitude exposure of the mother on fetal oxygenation. The oxygen tension values for umbilical artery and vein were reversed. Umbilical venous blood, which is<i>returning from</i>the placenta, has the highest oxygen content in the fetus, with a PO<sub>2</sub>of 32 mm Hg. In a sense, the umbilical vein is similar to the pulmonary vein in the adult circulation. This better oxygenated blood flows preferentially to the ascending aorta (via right atrium, foramen ovale, and left atrium), allowing greater oxygen delivery to the fetal heart and brain. Blood in the descending aorta comes from systemic venous return to the right side of the heart (via pulmonary artery and ductus arteriosus) and has a much
Is This Patient Dead, Vegetative, or Severely Neurologically Impaired?
Authors: Christopher M. Booth, Robert H. Boone, George Tomlinson, Allan S. Detsky
Journal: JAMA (2004)

Most survivors of cardiac arrest are comatose after resuscitation, and meaningful neurological recovery occurs in a small proportion of cases. Treatment can be lengthy, expensive, and often difficult for families and caregivers. Physical examination is potentially useful in this clinical scenario, and the information obtained may help physicians and families make accurate decisions about treatment and/or withdrawal of care.To determine the precision and accuracy of the clinical examination in predicting poor outcome in post-cardiac arrest coma.We searched MEDLINE for English-language articles (1966-2003) using the terms coma, cardiac arrest, prognosis, physical examination, sensitivity and specificity, and observer variation. Other sources came from bibliographies of retrieved articles and physical examination textbooks. Studies were included if they assessed the precision and accuracy of the clinical examination in prognosis of post-cardiac arrest coma in adults. Eleven studies, involving 1914 patients, met our inclusion criteria.Two authors independently reviewed each study to determine eligibility, abstract data, and classify methodological quality using predetermined criteria. Disagreement was resolved by consensus.Summary likelihood ratios (LRs) were calculated from random effects models. Five clinical signs were found to strongly predict death or poor neurological outcome: absent corneal reflexes at 24 hours (LR, 12.9; 95% confidence interval [CI], 2.0-68.7), absent pupillary response at 24 hours (LR, 10.2; 95% CI, 1.8-48.6), absent withdrawal response to pain at 24 hours (LR, 4.7; 95% CI, 2.2-9.8), no motor response at 24 hours (LR, 4.9; 95% CI, 1.6-13.0), and no motor response at 72 hours (LR, 9.2; 95% CI, 2.1-49.4). The proportion of individuals' dying or having a poor neurological outcome was calculated by pooling the outcome data from the 11 studies (n = 1914) and used as an estimate of the pretest probability of poor outcome. The random effects estimate of poor outcome was 77% (95% CI, 72%-80%). The highest LR increases the pretest probability of 77% to a posttest probability of 97% (95% CI, 87%-100%). No clinical findings were found to have LRs that strongly predicted good neurological outcome.Simple physical examination maneuvers strongly predict death or poor outcome in comatose survivors of cardiac arrest. The most useful signs occur at 24 hours after cardiac arrest, and earlier prognosis should not be made by clinical examination alone. These data provide prognostic information, rather than treatment recommendations, which must be made on an individual basis incorporating many other variables.
Chemical Mediators of the Muscle Ergoreflex in Chronic Heart Failure
Authors: Adam C. Scott, Roland Wensel, Constantinos H. Davos, Michael Kemp, Agnieszka Kaczmarek, James Hooper, Andrew J.S. Coats, Massimo F. Piepoli
Journal: Circulation (2002)

Background — The overactivity of ergoreceptors (intramuscular afferents sensitive to products of skeletal muscle work) may be responsible for the abnormal responses to exercise and symptoms of exercise intolerance in chronic heart failure (CHF); however, little is known of the chemical nature of the stimuli involved. We investigated biochemical factors (H + , V̇ co 2 , V̇ o 2 , H co 3 , K + , phosphate, lactate, PGE 2 , PGF 1α , and bradykinin) potentially involved in ergoreceptor activation. Methods and Results — Sixteen stable patients with CHF (64.9±2.7 years, peak V̇ o 2 15.8±0.7 mL/kg per min) and 10 age-matched controls were studied. The ergoreceptor test involved two 5-minute handgrip exercises. On one occasion, the subjects recovered normally (control recovery), whereas on the other a posthandgrip regional circulatory occlusion was induced in the exercising arm, isolating the stimulation of the ergoreceptor after exercise. The ergoreflex was quantified as the difference in ventilation between the posthandgrip regional circulatory occlusion and the control recovery periods. During the protocol, the local muscular blood effluent concentrations of metabolic mediators were assessed. Patients had an ergoreflex effect on ventilation greater than controls (4.8±1.4 versus 0.4±0.1 L/min, P &lt;0.01). During the ergoreflex test in patients, the following metabolites were elevated with respect to resting values in comparison with controls: PGE 2 (3.7±0.7 versus 1.1±0.2 pg/mL), PGF 1α (16.2±2.8 versus 7.2±1.2 pg/mL), and bradykinin (2.1±0.3 versus 1.0±0.1 pg/mL), P &lt;0.05 for all comparisons. Only the increases in prostaglandins were predictors of the ergoreflex response ( r &gt;0.41, P &lt;0.01). Conclusions — Although multiple metabolites are concentrated in exercising muscle in CHF, only prostaglandins correlated with ergoreflex activity, suggesting these factors as potential triggers to the exaggerated ergoreflex, which is characteristic of CHF. This may have important implications for novel therapies to improve exercise tolerance.
Abstract 3859: Multivalency of non-peptide integrin <i>αVβ</i> <i>3</i> antagonist slows tumor growth
Authors: Yoo-Shin Kim, Feng Li, Brian E. O'neill, King CP Li, Zheng Li
Journal: Cancer Research (2012)

Abstract To date, more than 200 angiogenesis inhibitors have been reported. These include only a few antiangiogenic peptide drugs. In addition, many molecules upregulated on angiogenic endothelial cells have been explored in the past decades. One of these is integrin αvβ3, which recognizes RGD (Arg-Gly-Asp) motifs in extracellular protein components. Targeting the αvβ3 integrin with drugs may provide an opportunity to destroy tumor vessels without harmful effects on microvessels of normal tissues. Multivalency is a strategy for increasing the binding affinity of compounds ostensibly to increase their potency or imaging potential. Surprisingly, multivalent versions of successful drugs showing enhanced binding have not always demonstrated enhanced therapeutic efficacy. For example, multivalent RGDs have not generally shown better therapeutic efficacy. In our study, we prepared a multivalent nonpeptide integrin αvβ3 antagonist (multivalent IA, 4-[2-(3,4,5,6-tetrahydropyrimidine-2-ylamino)ethyloxy]benzoyl-2-(S)-aminoethylsulfonyl-amino-halanine monomer, dimer and trimer) for anti-tumor therapy. The anti-tumor efficacies of the IA multivalent compounds were evaluated in B16F10 melanoma tumor-bearing mice. Tumors were inoculated subcutaneously and allowed to progress before treating. IA compounds were given by intraperitoneal injection every 12 hours for 14 days. It was observed that 30 mg/kg of IA-trimer showed higher antitumor efficacy and lower toxicity compared to IA-Monomer and IA-Dimer, as shown by changes in tumor volume against control group (IA-Trimer, 32.05 % &amp;gt; IA-Dimer, 45.33 % &amp;gt; IA-Monomer 59.29 %). Based on these results, we conclude that the success of a multivalent strategy depends on the details of the individual components and how they are put together. This may be the first αvβ3 multivalent ligand showing clear enhancement in anti-tumor effectiveness. 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 3859. doi:1538-7445.AM2012-3859
849. Transduction of Mouse Dendritic Cells Is Enhanced by Repetitive Infection with Self-Complementary Adeno-Associated Virus 6 Combined with Immunostimulatory Ligands
Authors: Wayne A. Aldrich, Changchun Ren, AprilF. White, Shang-Zhen Zhou, Sanjay Kumar, Connie B. Jenkins, Denise R. Shaw, Theresa V. Strong, Pierre L. Triozzi, Selvarangan Ponnazhagan
Journal: Molecular Therapy (2005)

The potential of adeno-associated virus (AAV)-based vectors in human gene therapy is being explored for several diseases. Although sustained transgene expression and low vector-associated cellular immunity are attractive features of recombinant (r) AAV, the wider application rAAV vectors encapsidated in serotype 2 capsid, the most commonly applied rAVV, is hampered by poor transduction efficiency in many target tissues. These include ex vivo generated dendritic cells (DC), which have demonstrated promising immunotherapeutic activity. We report here that efficient transduction of mouse bone marrow-derived DC can be achieved with self-complementary (sc) rAAV encapsidated in serotype 6 capsid. Sequential exposure of DC precursor cultures to IL-4 and GM-CSF with sc rAAV6 encoding the human tumor antigen, carcinoembryonic antigen (CEA), for seven days followed by activation with CpG oligodeoxynucleotides (ODN) and anti-mouse CD40 antibody resulted in highly efficient transduction of DC. DC surface markers as determined by flow cytometry analysis of sc rAAV6-transduced DC were comparable to non-transduced DC. Efficiency of vector transduction and transgene expression were confirmed by immunostaining and real-time PCR. Microarray analysis of RNA from CpG-ODN and CD40 antibody stimulated sc AAV6-transduced DC revealed upregulation of transcription factors and cytokines involved in immune activation and down-regulation of inhibitory factors, suggesting a possible role of transcriptional activation in the observed effect. The adoptive transfer into syngeneic mice of the ex vivo transduced and activated DC resulted in the development of CEA-specific antibody. Immunized mice also developed antibody to AAV-6 capsid protein which did not cross-react with AAV-2 capsid protein. These studies demonstrate the potential utility of sc rAAV serotype 6-based vectors in transduction of DC for genetic vaccination approaches.