tbuckley/cabot-search huggingface dataset:
Questions about dexamethasone use for the prevention of anti-SSA related congenital heart block
Authors: N Costedoat-Chalumeau
Journal: Annals of the Rheumatic Diseases (2003)

Mothers with anti-SSA/Ro antibodies who have had a previous fetus with congenital heart block (CHB) have a risk of recurrence estimated to be up to 16%.To improve the management of these "high risk patients" by determining (a) whether or not prophylactic treatment is efficient; (b) whether or not fluorinated steroids (betametasone and dexamethasone) that do cross the placenta in an active form are safe for the fetus; and (c) which prophylactic treatment should be used.Retrospective study performed on seven mothers sent to a university hospital owing to a past history of one (six mothers) or two children (one mother) with CHB.13 subsequent pregnancies occurred. No CHB was observed. All four pregnancies in women treated with 10 mg/day prednisone were uneventful. Three pregnancies in women receiving no steroids resulted in two early spontaneous abortions and one live birth. The six pregnancies in women treated with dexamethasone (4-5 mg/day) ended in one early and one late spontaneous abortion, two stillbirths, and two live births with intrauterine growth restriction and mild adrenal insufficiency. A histological study of one stillbirth disclosed intrauterine growth restriction and marked adrenal hypoplasia.Adverse obstetric outcomes were often seen here and major concerns have been raised by paediatricians about the safety of fluorinated steroids, owing to the results of animals studies, retrospective data, and randomised trials. Because fluorinated steroids have not been shown to improve prophylactic treatment of CHB in pregnant women at high risk, their use is questionable.
How Does the Patient Benefit from Clinical PET?
Authors: Jens Sörensen
Journal: Theranostics (2012)

Clinical molecular imaging by use of PET and PET/CT is increasingly important in routine oncological practice worldwide. A vast majority of clinical PET investigations are performed with [(18)F]-fluorodeoxyglucose (FDG), but there is a growing interest in novel molecular probes among scientists and clinicians. Beyond FDG, a small number of different tracers have been shown to be of clinical value. With a growing commercial interest in tracer development, many more are under investigation. This review provides some examples of clinical situations where tracers other than FDG have been found useful and an outlook towards technical and regulatory development needed to allow the full impact of clinical PET to benefit the individual patient.
Anatomic-Electrophysiological Correlations Concerning the Pathways for Atrioventricular Conduction
Authors: Todor N. Mazgalev, Siew Yen Ho, Robert H. Anderson
Journal: Circulation (2001)

Abstract —The remarkable success of radiofrequency ablation in recent decades in curing atrioventricular nodal reentrant tachycardias has intensified efforts to provide a solid theoretical basis for understanding the mechanisms of atrioventricular transmission. These efforts, which were made by both anatomists and electrophysiologists, frequently resulted in seemingly controversial observations. Quantitatively and qualitatively, our understanding of the mysteries of propagation through the inhomogeneous and extremely complex atrioventricular conduction axis is much deeper than it was at the beginning of the past century. We must go back to the initial sources, nonetheless, in an attempt to provide a common ground for evaluating the morphological and electrophysiological principles of junctional arrhythmias. In this review, we provide an account of the initial descriptions, which still provide an appropriate foundation for interpreting recent electrophysiological findings.
Loss of Dnmt3b function upregulates the tumor modifier Ment and accelerates mouse lymphomagenesis
Authors: Ryan A. Hlady, Slavomira Novakova, Jana Opavska, David Klinkebiel, Staci L. Peters, Juraj Bies, Jay Hannah, Javeed Iqbal, Kristi M. Anderson, Hollie M. Siebler, Lynette M. Smith, Timothy C. Greiner, Dhundy Bastola, Shantaram Joshi, Oksana Lockridge, Melanie A. Simpson, Dean W. Felsher, Kay-Uwe Wagner, Wing C. Chan, Judith K. Christman, Rene Opavsky
Journal: Journal of Clinical Investigation (2011)

DNA methyltransferase 3B (Dnmt3b) belongs to a family of enzymes responsible for methylation of cytosine residues in mammals. DNA methylation contributes to the epigenetic control of gene transcription and is deregulated in virtually all human tumors. To better understand the generation of cancer-specific methylation patterns, we genetically inactivated Dnmt3b in a mouse model of MYC-induced lymphomagenesis. Ablation of Dnmt3b function using a conditional knockout in T cells accelerated lymphomagenesis by increasing cellular proliferation, which suggests that Dnmt3b functions as a tumor suppressor. Global methylation profiling revealed numerous gene promoters as potential targets of Dnmt3b activity, the majority of which were demethylated in Dnmt3b-/- lymphomas, but not in Dnmt3b-/- pretumor thymocytes, implicating Dnmt3b in maintenance of cytosine methylation in cancer. Functional analysis identified the gene Gm128 (which we termed herein methylated in normal thymocytes [Ment]) as a target of Dnmt3b activity. We found that Ment was gradually demethylated and overexpressed during tumor progression in Dnmt3b-/- lymphomas. Similarly, MENT was overexpressed in 67% of human lymphomas, and its transcription inversely correlated with methylation and levels of DNMT3B. Importantly, knockdown of Ment inhibited growth of mouse and human cells, whereas overexpression of Ment provided Dnmt3b+/+ cells with a proliferative advantage. Our findings identify Ment as an enhancer of lymphomagenesis that contributes to the tumor suppressor function of Dnmt3b and suggest it could be a potential target for anticancer therapies.
Atypical neurological complications of ipilimumab therapy in patients with metastatic melanoma
Authors: Bing Liao, Sheetal Shroff, Carlos Kamiya-Matsuoka, Sudhakar Tummala
Journal: Neuro-Oncology (2014)

Ipilimumab is a novel FDA-approved recombinant human monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4 and has been used to treat patients with metastatic melanoma. Immune-related neurological adverse effects include inflammatory myopathy, aseptic meningitis, posterior reversible encephalopathy syndrome, Guillain-Barré syndrome, myasthenia gravis–type syndrome, sensorimotor neuropathy, and inflammatory enteric neuropathy. To date, there is no report for ipilimumab-induced chronic inflammatory demyelinating polyneuropathy (CIDP), transverse myelitis (TM), or concurrent myositis and myasthenia gravis–type syndrome. Our objective is to raise early recognition of atypical neurological adverse events and to share our therapeutic approach. We report 3 cases of metastatic melanoma treated with ipilimumab in which the patients developed CIDP, TM, and concurrent myositis and myasthenia gravis–type syndrome, respectively, at the MD Anderson Cancer Center between July 2012 and June 2013. Patients consented to release of medical information for publication/educational purposes. Our 3 cases of metastatic melanoma treated with ipilimumab developed CIDP, TM, and concurrent myositis and myasthenia gravis–type syndrome, respectively. The median time to onset of immune-related adverse events following ipilimumab treatment ranged from 1 to 2 weeks. Ipilimumab was discontinued due to the severe neurological symptoms. Plasmapheresis was initiated in the patients with CIDP and concurrent myositis and myasthenia gravis–type syndrome; high-dose intravenous steroids were given to the patient with TM, and significant clinical response was demonstrated. Ipilimumab could induce a wide spectrum of neurological adverse effects. Our findings support the standard treatment of withholding or discontinuing ipilimumab. Plasmapheresis or high-dose intravenous steroids may be considered as the initial choice of treatment for severe ipilimumab-related neurological adverse events. Improvement of neurological symptoms may be seen within 2 weeks.
Attenuated cardioprotection by ischemic preconditioning in coronary stenosed heart and its restoration by carvedilol
Authors: K WATANABE, H YAOITA, K OGAWA, M OIKAWA, K MAEHARA, Y MARUYAMA
Journal: Cardiovascular Research (2006)

Infarct size (IS) reduction by ischemic preconditioning (IPC) has been assessed in the heart in which coronary stenosis (CS)-induced chronic ischemia was not present. The aim of this study is to assess whether and how IS reduction by IPC is modified in the heart in which CS has occurred, and how further therapeutics, if any, modify it.We assessed the IS produced by a 30-minute acute coronary occlusion and a 24-hour reperfusion (COR) in rat hearts in which CS had developed for 1-12 weeks. Modifications of IS by IPC and the mitochondrial KATP channel (mitoKATP) opener and blocker, and the effects of daily beta-blocker treatment with carvedilol on them, were also assessed. Myocardial protein kinase C (PKC)-epsilon activities in the risk areas were measured by Western blotting.One to 4 weeks after CS induction, myocardial PKC-epsilon was activated in the risk area of CS even without IPC, but such CS-induced PKC activation as well as that by IPC was attenuated 8-12 weeks after CS. The IS reductions by the mitoKATP opener as well as by IPC were attenuated 8-12 and 4-12 weeks after CS, respectively. Daily carvedilol treatment after inducing CS restored the malfunctioning PKC-mitoKATP signal cascade and the attenuated IPC and mitoKATP effect on IS.CS activates the PKC-mitoKATP signal cascade, mimicking the IPC effect, whereas this cardioprotective effect is attenuated late after CS via their downregulation. Restoration of these changes may be a novel mechanism for cardioprotection by carvedilol in the CS-induced ischemic heart.
Inhibition of Phosphatidylserine Recognition Heightens the Immunogenicity of Irradiated Lymphoma Cells In Vivo
Authors: Attilio Bondanza, Valérie S. Zimmermann, Patrizia Rovere-Querini, Javier Turnay, Ingrid E. Dumitriu, Christian M. Stach, Reinhard E. Voll, Udo S. Gaipl, Wolf Bertling, Ernst Pöschl, Joachim R. Kalden, Angelo A. Manfredi, Martin Herrmann
Journal: The Journal of Experimental Medicine (2004)

Strategies to enhance the immunogenicity of tumors are urgently needed. Although vaccination with irradiated dying lymphoma cells recruits a tumor-specific immune response, its efficiency as immunogen is poor. Annexin V (AxV) binds with high affinity to phosphatidylserine on the surface of apoptotic and necrotic cells and thereby impairs their uptake by macrophages. Here, we report that AxV preferentially targets irradiated lymphoma cells to CD8+ dendritic cells for in vivo clearance, elicits the release of proinflammatory cytokines and dramatically enhances the protection elicited against the tumor. The response was endowed with both memory, because protected animals rejected living lymphoma cells after 72 d, and specificity, because vaccinated animals failed to reject unrelated neoplasms. Finally, AxV–coupled irradiated cells induced the regression of growing tumors. These data indicate that endogenous adjuvants that bind to dying tumor cells can be exploited to target tumors for immune rejection.
Mushroom worker's lung-two outbreaks
Authors: C. J. Stewart
Journal: Thorax (1974)

<b>Stewart, C. J. (1974).</b><i>Thorax</i>, <b>29</b>, 252-257. <b>Mushroom worker9s lung—two outbreaks.</b> The clinical picture, immunological findings, and working environment of six mushroom farm workers who developed the characteristic features of mushroom worker9s lung while handling pasteurized compost are reported and discussed. A specific antigen has not been identified. The sporadic occurrence of the condition suggests that the antigen is present only intermittently in the working environment in sufficient concentrations to cause alveolitis. Until such time as the constitutional, immunological, and environmental factors predisposing to the development of alveolitis are better understood preventive measures must be empirical.
Older Breast Cancer Survivors: Factors Associated With Change in Emotional Well-Being
Authors: Kerri M. Clough-Gorr, Patricia A. Ganz, Rebecca A. Silliman
Journal: Journal of Clinical Oncology (2007)

Purpose During the 5 years after primary breast cancer diagnosis for women ≥ 65 years old, we examined factors associated with change in emotional well-being. Patients and Methods We identified women diagnosed with primary breast cancer and selected women with stage I to IIIa disease, age ≥ 65 years, and for whom we had permission from the attending physician to contact. Data were collected during 5 years of follow-up from consenting patients' medical records and telephone interviews with patients. Outcomes included a five-question Mental Health Inventory general measure of emotional health (MHI5) and two cancer-specific measures: breast cancer–specific emotional health (BCSEH) and Cancer Rehabilitation Evaluation System–Short Form (CARES-SF) Psychosocial Summary Scale. Results During 5 years of follow-up of older breast cancer survivors, 57% had less than a ± 10-point change in MHI5, 38% had less than a ± 10-point change in BCSEH, and 52% had less than a ± 10-point change in CARES-SF Psychosocial Summary Scale. Women with less than 12 years of education were at greatest risk for having negative changes in both general and breast cancer–specific emotional health. Moreover, we also found that women who perceived themselves as never being cured had greater negative changes in all outcomes. Conversely, those who had better physical function, emotional social support, and positive ratings regarding the quality of medical interactions at baseline were less likely to have poor emotional health during follow-up. Conclusion For the majority of older breast cancer survivors, cancer-specific well-being and general emotional health do not change substantially after a breast cancer diagnosis. Among those in whom change occurs, risk factors are similar and may be related to other age-related diseases.
Nonspecific Immunotherapy of Murine Solid Tumors With &lt;italic&gt;Corynebacterium granulosum&lt;/italic&gt;&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: L Milas, B Hunter, K Mason, D Grdina, H Withers
Journal: JNCI Journal of the National Cancer Institute (1975)

A single intraperitoneal (ip) or intravenous (iv) injection of Corynebacterium granulosum into C3Hf/Bu mice shortly after subcutaneous (sc) injection of cells from a strongly antigenic syngeneic fibrosarcoma induced by 3-methylcholanthrene caused complete and lasting regressions of 100 and 70% of resulting tumors, respectively. Treatment with this bacterium sc only slightly inhibited the growth of some tumors. C. granulosum given iv to mice 3 days after the sc injection of fibrosarcoma cells caused complete regressions of 39 of 45 tumors; two iv injections with this immunostimulant given 1 month apart were no more effective than a single injection. Intralesional treatment of fibrosarcomas 8 mm in diameter induced complete regressions of tumors in 30% of the animals, whereas sc treatment contralateral to the growing tumor only slightly reduced tumor growth. Intraperitoneal growth of a fibrosarcoma was efficiently controlled (58-80% survival of mice) if C. granulosum was given ip, but not iv, 3 days after inoculation with tumor cells. Again, two injections of C. granulosum (given ip 4 days apart) were only as effective as a single injection. Treatment with C. granulosum iv at 3,7,14, or 21 days after sc inoculation of a weakly antigenic, spontaneously arising mammary carcinoma (MC-l) strongly inhibited tumor growth. Three complete but temporary tumor regressions were observed. The subcutaneous growth of another spontaneous mammary carcinoma (MC-2), which contained fairly strong tumor-specific antigen(s), was also significantly inhibited if C. granulosum was given 3, 7, or 14 days after, but not 7 days before, tumor cell inoculation. However, pretreatment of mice with the immunostimulant significantly protected the mice against artificially induced pulmonary metastases of this tumor
Carbon Disulfide Intoxication from Overdosage of Disulfiram
Authors: FRANCIS J. KANE
Journal: American Journal of Psychiatry (1970)

The author discusses a case of acute brain syndrome with depression, peripheral neuropathy, and transient parkinsonism following ingestion of large amounts of disulfiram. He reviews clinical and experimental evidence bearing on the relationship between disulfiram and its metabolite, carbon disulfide, and reviews similarities in the syndromes associated with the toxicity of each.
Th2 responses induced by epicutaneous or inhalational protein exposure are differentially dependent on IL-4
Authors: Christina A. Herrick, Heather MacLeod, Earl Glusac, Robert E. Tigelaar, Kim Bottomly
Journal: Journal of Clinical Investigation (2000)

Atopic individuals are predisposed to mounting vigorous Th2-type immune responses to environmental allergens. To determine the factors responsible, animal models that closely mimic natural modes of allergen exposure should prove most informative. Therefore, we investigated the role of IL-4, a known Th2-promoting cytokine, in generation of Th2 responses after exposure of either the skin or airway to soluble protein. Compared with wild-type (WT) mice, IL-4–deficient (IL-4–/–) mice showed markedly impaired Th2 activation after primary exposure to inhaled ovalbumin (OVA), with decreased OVA-specific IgG1 and IgE, and significantly fewer eosinophils in bronchoalveolar lavage (BAL) fluid after airway challenge. In contrast, IL-4–/– mice initially exposed to epicutaneous (e.c.) OVA mounted Th2 responses equivalent to responses in WT mice, with high numbers of eosinophils in BAL fluid. Because Th2 responses were not induced by e.c. OVA exposure in Stat6–/– mice (mice lacking signal transducer and activator of transcription 6), the role of IL-13 was tested. In vivo depletion of IL-13 prevented Th2 responses induced by e.c. OVA exposure in IL-4–/– mice. These data demonstrate a marked difference in the IL-4 dependence of Th2 responses generated at two anatomic sites of natural allergen encounter and identify the skin as a particularly potent site for Th2 sensitization.
Broken Heart: A Statistical Study of Increased Mortality among Widowers
Authors: C. M. Parkes, B. Benjamin, R. G Fitzgerald
Journal: BMJ (1969)

A total of 4,486 widowers of 55 years of age and older have been followed up for nine years since the death of their wives in 1957. Of these 213 died during the first six months of bereavement, 40% above the expected rate for married men of the same age. Thereafter the mortality rate fell gradually to that of married men and remained at about the same leveLThe greatest increase in mortality during the first six months was found in the widowers dying from coronary thrombosis and other arteriosclerotic and degenerative heart disease. There was also evidence of a true increase in mortality from other diseases, though the numbers in individual categories were too small for statistical analysis.In the first six months 22.5% of the deaths were from the same diagnostic group as the wife's death. Some evidence suggests that this may be a larger proportion than would be expected by chance association, but there is no evidence suggesting that the proportion is any different among widows and widowers who have been bereaved for more than six months.
Sequence variants in IL10, ARPC2 and multiple other loci contribute to ulcerative colitis susceptibility
Authors: Andre Franke, Tobias Balschun, Tom H Karlsen, Jurgita Sventoraityte, Susanna Nikolaus, Gabriele Mayr, Francisco S Domingues, Mario Albrecht, Michael Nothnagel, David Ellinghaus, Christian Sina, Clive M Onnie, Rinse K Weersma, Pieter C F Stokkers, Cisca Wijmenga, Maria Gazouli, David Strachan, Wendy L McArdle, Séverine Vermeire, Paul Rutgeerts, Philip Rosenstiel, Michael Krawczak, Morten H Vatn, Christopher G Mathew, Stefan Schreiber
Journal: Nature Genetics (2008)
Primary care in the United States: Profiling performance in primary care in the United States
Authors: N. Goldfield
Journal: BMJ (2003)

Purchasers of health care in both the United States (governments, employers, health plans) and the United Kingdom (government) need to be able to measure the quality of services they are paying for. 1 Moreover, public concerns about the variable quality of health services have increased in both countries.Measuring the performance of primary care physicians and healthcare providers is one method of meeting these challenges. 2 3 We review the development of this approach (commonly termed "profiling") in the United States.
Thermal pants may reduce the risk of recurrent hamstring injuries in rugby players.
Authors: P A Upton, T D Noakes, J M Juritz
Journal: British Journal of Sports Medicine (1996)

OBJECTIVE--To determine whether the use of thermal pants might reduce the risk of hamstring injury in rugby players. METHODS--44 male rugby players from the Cape Province, South Africa, who had previously suffered a hamstring injury were given the choice of wearing thermal warming pants or not, and were then monitored for the development of hamstring injuries during the 1992 season. RESULTS--In the group who wore warmers some of the time, the injury rate was significantly lower when using the warmers (3 injuries/1000 playing hours) than when not (57/1000 playing hours). There was no difference in injury rates between groups who either wore warmers all the time or none of the time, probably because the number who wore the warmers all the time was small (n = 5). Eighteen percent of the injuries recurred at exactly the same site in the muscle and within 12 d of returning to rugby after the initial injury. The incidence of injury was high in the first three weeks of the season and again in the same period after the mid-season break. More than 80% of all match and practice time lost by these players during the study was a direct result of their hamstring injuries. CONCLUSIONS--Thermal pants may have a role in preventing recurrent hamstring injuries but other factors such as inadequate preseason training and incomplete rehabilitation after injury are likely to be more significant risk factors for injury.
The gene encoding the transcriptional regulator Yin Yang 1 (YY1) is a myeloid transforming gene interfering with neutrophilic differentiation
Authors: Stefan J. Erkeland, Marijke Valkhof, Claudia Heijmans-Antonissen, Ruud Delwel, Peter J. M. Valk, Mirjam H. A. Hermans, Ivo P. Touw
Journal: Blood (2003)
The Risk of Death by Age, Sex, and Smoking Status in the United States: Putting Health Risks in Context
Authors: Steven Woloshin, Lisa M. Schwartz, H. Gilbert Welch
Journal: JNCI Journal of the National Cancer Institute (2008)

BackgroundTo make sense of the disease risks they face, people need basic facts about the magnitude of a particular risk and how one risk compares with other risks. Unfortunately, this fundamental information is not readily available to patients or physicians. We created simple one-page charts that present the 10-year chance of dying from various causes according to age, sex, and smoking status.