tbuckley/cabot-search huggingface dataset:
Post-inflammatory elastolysis and cutis laxa
Authors: A.R. VERHAGEN, M.J. WOERDEMAN
Journal: British Journal of Dermatology (1975)

Post-inflammatory elastolysis and cutis laxa (Marshall, Heyl & Weber, 1966) is a skin disease in African infants which appears to be comparatively common in at least two countries. Destruction of elastic tissue and atrophy are preceded by urticarial or by annular erythematous-popular lesions and result in severe disfigurement. The clinical features are intermediate between anetoderma (macular atrophy) and acquired cutis laxa, but sufficiently typical and characteristic to constitute a distinctive syndrome, which might represent an abnormal reaction to the bite of an arthropod.
Consumption of a High-Fat Diet in Adulthood Ameliorates the Effects of Neonatal Parathion Exposure on Acetylcholine Systems in Rat Brain Regions
Authors: Theodore A. Slotkin, T. Leon Lassiter, Ian T. Ryde, Nicola Wrench, Edward D. Levin, Frederic J. Seidler
Journal: Environmental Health Perspectives (2009)

BackgroundDevelopmental exposure to a wide variety of developmental neurotoxicants, including organophosphate pesticides, evokes late-emerging and persistent abnormalities in acetylcholine (ACh) systems. We are seeking interventions that can ameliorate or reverse the effects later in life.ObjectivesWe administered parathion to neonatal rats and then evaluated whether a high-fat diet begun in adulthood could reverse the effects on ACh systems.MethodsNeonatal rats received parathion on postnatal days 1–4 at 0.1 or 0.2 mg/kg/day, straddling the cholinesterase inhibition threshold. In adulthood, half the animals were switched to a high-fat diet for 8 weeks. We assessed three indices of ACh synaptic function: nicotinic ACh receptor binding, choline acetyltransferase activity, and hemicholinium-3 binding. Determinations were performed in brain regions comprising all the major ACh projections and cell bodies.ResultsNeonatal parathion exposure evoked widespread abnormalities in ACh synaptic markers, encompassing effects in brain regions possessing ACh projections and ACh cell bodies. In general, males were affected more than females. Of 17 regional ACh marker abnormalities (10 male, 7 female), 15 were reversed by the high-fat diet.ConclusionsA high-fat diet reverses neurodevelopmental effects of neonatal parathion exposure on ACh systems. This points to the potential for nonpharmacologic interventions to offset the effects of developmental neurotoxicants. Further, cryptic neurodevelopmental deficits evoked by environmental exposures may thus engender a later preference for a high-fat diet to maintain normal ACh function, ultimately contributing to obesity.
Resuscitation experience in the Falkland Islands campaign.
Authors: J G Williams, T R Riley, R A Moody
Journal: BMJ (1983)

The recent campaign to retake the Falkland Islands was a novel military exercise from many points of view. This was particularly so for the medical support, which required much improvisation at all levels. Several surgical teams from the Royal Navy and the Royal Army Medical Corps were deployed in support of both the fleet and the troops on land. Two Royal Naval teams embarked in SS Canberra, and the journey south on board provided an opportunity to discuss and decide on a specific resuscitation policy for the casualties that might be encountered. We discuss the details of this policy and the results of using it.
A genome wide linkage analysis in Swedish families with hereditary non-familial adenomatous polyposis/non-hereditary non-polyposis colorectal cancer
Authors: T Djureinovic
Journal: Gut (2005)

Known colorectal cancer syndromes, such as familial adenomatous polyposis and hereditary non-polyposis colorectal cancer, have been identified in only a small proportion of cases with a family history of disease. In an attempt to identify loci harbouring novel predisposing genes, we have performed a genome wide linkage analysis in 18 colorectal cancer families recruited from the Department of Clinical Genetics at Karolinska Hospital, Sweden.Multipoint parametric and non-parametric linkage analyses were performed using two affected status criteria, stringent and less stringent. Parametric analysis was performed under the assumption of locus homogeneity and locus heterogeneity.The initial scan performed using the less stringent affected status criteria revealed regions of interest on chromosome 11 (marker D11S1314: heterogeneity logarithm of odds (HLOD) score 1.96, non-parametric LOD (NPL) score 1.28; and marker D11S908: HLOD score 2.10, NPL score 2.16) and chromosome 14 (marker D14S258: HLOD score 2.61, NPL score 2.88). Using the stringent affected status criteria, a locus on chromosome 22 was suggested in the parametric analysis (marker D22S315: HLOD score 1.26). After finemapping of the regions on chromosomes 11 and 14, HLOD and NPL scores were reduced but still within the range of suggestive linkage. Haplotype analysis revealed overlapping regions between D11S987 and D11S4207 (proximal region), D11S4120 and D11S4090 (distal region), on chromosome 11, and between D14S1038 and D14S1069 on chromosome 14.Our study provides evidence of genetic heterogeneity among Swedish colorectal cancer families. Three novel regions were suggested to be of interest in a proportion of families analysed. Further studies are needed to confirm this result.
Caring for the Whole Patient: The Science of Psychosocial Care
Authors: Paul B. Jacobsen, Jimmie C. Holland, David P. Steensma
Journal: Journal of Clinical Oncology (2012)

Special Series relates to thescienceofpsychosocialcare.Thisseriesisdesignedtoprovideoncol-ogyprofessionalswiththemostrecentinformationaboutthepsycho-logical,psychiatric,andsocialaspectsofcancercare.Theemergenceoftheﬁeldofpsychosocialcarereﬂectsgrowingpublicandprofessionalawareness of the potential for cancer and its treatment to have pro-foundeffectsonmanyaspectsoflife.Aprincipalgoalofpsychosocialcareistorecognizeandaddresstheeffectsthatcanceranditstreatmenthaveonthementalstatusandemotionalwell-beingofpatients,theirfamily members, and their professional caregivers. In addition toimproving emotional well-being and mental health,
Signal transduction of eNOS activation
Authors: I Fleming
Journal: Cardiovascular Research (1999)

Consistent with its classification as a Ca2+/calmodulin-dependent enzyme the constitutive endothelial nitric oxide (NO) synthase (eNOS) can be activated by receptor-dependent and -independent agonists as a consequence of an increase in the intracellular concentration of free Ca2+ ([Ca2+]i) and the association of the Ca2+/calmodulin complex with eNOS. Additional post-translational mechanisms regulate the activity of eNOS, including the interaction of eNOS with caveolin-1, heat shock protein 90 (Hsp90), or membrane phospholipids, as well as enzyme translocation and phosphorylation. In response to fluid shear stress the maintained production of NO by native and cultured endothelial cells is associated with only a transient increase in [Ca2+]i. In the absence of extracellular Ca2+ and in the presence of calmodulin antagonists, shear stress stimulates a maintained production of NO which is insensitive to the removal of extracellular Ca2+, but sensitive to tyrosine kinase inhibitors, Hsp90-binding proteins and phosphatidylinositol 3-kinase inhibitors. A pharmacologically identical activation of eNOS can be induced by protein tyrosine phosphatase inhibitors suggesting that the phosphorylation of eNOS, and possibly that of an associated regulatory protein(s), is crucial for its Ca2+-independent activation.
Does Cognitive Recovery After Treatment of Poststroke Depression Last? A 2-Year Follow-Up of Cognitive Function Associated With Poststroke Depression
Authors: Kenji Narushima, Keen-Loong Chan, James T. Kosier, Robert G. Robinson
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: Cognitive impairment is common after stroke and may be caused by poststroke depression. Remission of poststroke major depression after treatment has been associated with improvement in cognitive function. The current study was designed to examine how long that cognitive improvement lasts and to compare depressed patients' cognitive status with that of nondepressed patients with comparable lesions. METHOD: Seventeen patients with poststroke depression and cognitive impairment who had early and sustained remission of their depression during a double-blind treatment study were compared with 42 nondepressed stroke patients who remained nondepressed throughout the follow-up. Mood and cognitive function were followed-up over 2 years with the Hamilton Depression Rating Scale and Mini-Mental State Examination (MMSE). RESULTS: In the patients with early and sustained remission of depression, there was rapid improvement of cognitive function, which was maintained over 2 years. Their initial MMSE score of 23.3 (SD=4.2) improved to 26.6 (SD=3.5) at 3 months and was 26.1 (SD=3.6) at 2 years. The nondepressed patients showed essentially no change in cognitive function over 2 years (initial MMSE score: mean=26.3, SD=3.1; score at 2-year follow-up: mean=25.7, SD=4.1). CONCLUSIONS: Cognitive function, once improved after remission of poststroke depression, is likely to remain stable over the next 2 years in the absence of subsequent reinjury to the central nervous system. Cognitive impairment due to poststroke depression is reversible and can be quantified separately from cognitive impairment on the basis of the location and extent of ischemic brain damage.
Peripheral airway involvement in asthma assessed by single-breath SF<sub>6</sub>and He washout
Authors: P.M. Gustafsson, H.K. Ljungberg, B. Kjellman
Journal: European Respiratory Journal (2003)

The aim of the study was to assess how deep into the acinar region the airway response to cold dry-air hyperventilation challenge (CACh) reaches in subjects with asthma of different severity. Peripheral airway function was measured using a single-breath sulphur hexafluoride (SF 6 ) and helium (He) washout test and overall airway function by forced expiratory volume in one second (FEV 1 ) at rest, after CACh and β 2 -therapy in 55 adults with a history of asthma. The normalised phase-III slopes (Sn III ) for SF 6 and He were used to assess peripheral airway obstruction and the (SF 6 -He) Sn III difference to indicate where obstruction occurred. While a greater He versus SF 6 slope increase indicates a response close to the acinar entrance, the reverse indicates a response deeper into the acinar airspaces. Twelve subjects had a major fall in FEV 1 (≥20%) after CACh, 16 a minor fall (10–19%), and 27 did not react. Resting He and SF 6 Sn III were significantly greater in major responders with respect to minor and nonresponders, while resting FEV 1 did not differ between the three groups. The major responders showed marked increases of He and SF 6 Sn III after CACh, with greater increase for He resulting in a negative (SF 6 -He) Sn III difference. To conclude, airways close to the acinar entrance participate in the overall airway response to cold-air challenge in asthmatic adults with marked airway hyperresponsiveness to cold, dry air.
Fraternal concordance of types of abnormal hepatocellular mitochondria in Wilson's disease
Authors: Irmin Sternlieb
Journal: Hepatology (1992)

Three distinct patterns of structural abnormalities of mitochondria, indicated as types I, II and III and associated with steatosis, were identified in the hepatocytes of 40 of 42 asymptomatic and 8 of 22 symptomatic patients with documented Wilson's disease before treatment. No correlation was seen between the type of mitochondrial abnormality and the patient's age, hepatic copper concentration, degree of hepatic steatosis or serum aminotransferase level. However, comparison of the types of abnormal hepatocellular mitochondria displayed by five pairs and one trio of asymptomatic siblings revealed remarkably similar types of abnormalities in each family. The variety of mitochondrial types encountered in different families and the high degree of type identity in sibling relationships indicate that the structural changes are genetically determined. (Hepatology 1992;16:728-732).
The SDF-1/CXCR4 axis in stem cell preconditioning
Authors: C. Cencioni, M. C. Capogrossi, M. Napolitano
Journal: Cardiovascular Research (2012)

We review the pivotal role of the stromal derived factor (SDF)-1 chemokine in tissue ischaemia and how it orchestrates the rapid revascularization of injured, ischaemic, and regenerating tissues via the CXC chemokine receptors CXCR4 and CXCR7. Furthermore, we discuss the effects of preconditioning (PC), which is a well-known protective phenomenon for tissue ischaemia. The positive effect of both hypoxic and acidic PC on progenitor cell therapeutic potential is reviewed, while stressing the role of the SDF-1/CXCR4 axis in this process.
Thrombospondins deployed by thrombopoietic cells determine angiogenic switch and extent of revascularization
Authors: Hans-Georg Kopp, Andrea T. Hooper, M. Johan Broekman, Scott T. Avecilla, Isabelle Petit, Min Luo, Till Milde, Carlos A. Ramos, Fan Zhang, Tabitha Kopp, Paul Bornstein, David K. Jin, Aaron J. Marcus, Shahin Rafii
Journal: Journal of Clinical Investigation (2006)

Thrombopoietic cells may differentially promote or inhibit tissue vascularization by releasing both pro- and antiangiogenic factors. However, the molecular determinants controlling the angiogenic phenotype of thrombopoietic cells remain unknown. Here, we show that expression and release of thrombospondins (TSPs) by megakaryocytes and platelets function as a major antiangiogenic switch. TSPs inhibited thrombopoiesis, diminished bone marrow microvascular reconstruction following myelosuppression, and limited the extent of revascularization in a model of hind limb ischemia. We demonstrate that thrombopoietic recovery following myelosuppression was significantly enhanced in mice deficient in both TSP1 and TSP2 (TSP-DKO mice) in comparison with WT mice. Megakaryocyte and platelet levels in TSP-DKO mice were rapidly restored, thereby accelerating revascularization of myelosuppressed bone marrow and ischemic hind limbs. In addition, thrombopoietic cells derived from TSP-DKO mice were more effective in supporting neoangiogenesis in Matrigel plugs. The proangiogenic activity of TSP-DKO thrombopoietic cells was mediated through activation of MMP-9 and enhanced release of stromal cell–derived factor 1. Thus, TSP-deficient thrombopoietic cells function as proangiogenic agents, accelerating hemangiogenesis within the marrow and revascularization of ischemic hind limbs. As such, interference with the release of cellular stores of TSPs may be clinically effective in augmenting neoangiogenesis.
Connexin40 Imparts Conduction Heterogeneity to Atrial Tissue
Authors: David E. Leaf, Jonathan E. Feig, Carolina Vasquez, Pamela L. Riva, Cindy Yu, Joshua M. Lader, Andrianos Kontogeorgis, Elvera L. Baron, Nicholas S. Peters, Edward A. Fisher, David E. Gutstein, Gregory E. Morley
Journal: Circulation Research (2008)

Impulse propagation in cardiac tissue is a complex process in which intercellular coupling through gap junction channels is a critical component. Connexin40 (Cx40) is an abundant gap junction protein that is expressed in atrial myocytes. Alterations in the expression of Cx40 have been implicated in atrial arrhythmogenesis. The purpose of the current study was to assess the role of Cx40 in atrial impulse propagation. High-resolution optical mapping was used to study conduction in the right and left atrial appendages of isolated Langendorff-perfused murine hearts. Wild-type (Cx40 +/+ ), heterozygous (Cx40 +/− ), and knockout (Cx40 −/− ) mice, both adult and embryonic, were studied to assess the effects of reduced Cx40 expression on sinus node function and conduction velocity at different pacing cycle lengths (100 and 60 ms). In both adult and late-stage embryonic Cx40 +/+ mice, heterogeneity in CV was found between the right and left atrial appendages. Either partial (Cx40 +/− ) or complete (Cx40 −/− ) deletion of Cx40 was associated with the loss of conduction heterogeneity in both adult and embryonic mice. Additionally, sinus node impulse initiation was found to be ectopic in Cx40 −/− mice at 15.5 days postcoitus, whereas Cx40 +/+ mice showed normal activation occurring near the crista terminalis. Our findings suggest that Cx40 plays an essential role in establishing interatrial conduction velocity heterogeneity in the murine model. Additionally, we describe for the first time a developmental requirement for Cx40 in normal sinus node impulse initiation at 15.5 days postcoitus.
Effectiveness of a Letter Notification Program for Women With Early-Stage Breast Cancer Eligible for Extended Adjuvant Letrozole
Authors: Heather L. McArthur, Karen A. Gelmon, Ivo A. Olivotto, Caroline H. Speers, Susan L. Ellard, Susan E. O'Reilly, Hagen F. Kennecke
Journal: Journal of Clinical Oncology (2009)

After National Cancer Institute of Canada trial MA.17 demonstrated benefits with letrozole after 5 years of tamoxifen, oncologists needed to identify and offer therapy to patients in community follow-up who were eligible for extended adjuvant hormone therapy. In British Columbia (BC), letters about extended letrozole therapy were sent to eligible BC women, their primary care physicians (PCPs), and their oncologists. We evaluated the effectiveness of this communication strategy.Eight hundred eighty-five women with stage I-III breast cancer who completed 4 to 6 years of tamoxifen in 2004 with no documented recurrence were sent letters describing extended adjuvant letrozole in February 2005. Treatment uptake and characteristics for women who did or did not receive a subsequent letrozole prescription were described.Among 838 eligible women, 305 (36%) received a letrozole prescription before April 2006. More women in the letrozole cohort had tumors larger than 2.0 cm (44.2% v 30.8%); node-positive disease (52.5% v 22.5%); prior radiotherapy (71.1% v 58.5%); and prior chemotherapy (51.5% v 20.8%; all P <or= .001). Among women younger than 70 years with node-positive disease, 65% received letrozole (122 of 188). Most prescribing physicians were oncologists (57.0%) or PCPs (30.8%). A significant increase in letrozole prescriptions was observed after the letter mail-out.In this population-based setting, extended adjuvant letrozole was more common among younger women with higher risk disease and more prior therapy but underutilized overall. The reasons for extended therapy underutilization and the role of the letter mail-out strategy in informing breast cancer survivors of new available treatments in other health systems warrant further study.
Efficacy and Tolerability of Citalopram in the Treatment of Late-Life Anxiety Disorders: Results From an 8-Week Randomized, Placebo-Controlled Trial
Authors: Eric J. Lenze, Benoit H. Mulsant, M. Katherine Shear, Mary Amanda Dew, Mark D. Miller, Bruce G. Pollock, Patricia Houck, Barbara Tracey, Charles F. Reynolds
Journal: American Journal of Psychiatry (2004)

Anxiety disorders are highly prevalent in elderly persons. However, to date, the efficacy of selective serotonin reuptake inhibitors (SSRIs) for the treatment of anxiety disorders in this age group has not been established.Thirty-four participants age 60 and older with a DSM-IV anxiety disorder (mainly generalized anxiety disorder) and a Hamilton Anxiety Rating Scale score of 17 or higher were randomly assigned under double-blind conditions to either citalopram or placebo. Response was defined as a score of 1 (very much improved) or 2 (much improved) on the Clinical Global Improvement scale or a 50% reduction in the Hamilton anxiety scale score. Response and side effects with citalopram and placebo were compared by using chi-square tests and linear modeling.Eleven (65%) of the 17 citalopram-treated participants responded by 8 weeks, versus four (24%) of the 17 placebo-treated participants. The most common and problematic side effect in the citalopram group was sedation.The authors believe this to be the first prospective controlled study to test the efficacy of an SSRI in the management of anxiety disorders among the elderly. These results support the efficacy of citalopram in late-life anxiety disorders. They need to be replicated in a larger study group.
Hemodynamic Effects of Fenofibrate and Coenzyme Q10 in Type 2 Diabetic Subjects With Left Ventricular Diastolic Dysfunction
Authors: Gerard T. Chew, Gerald F. Watts, Timothy M.E. Davis, Bronwyn G.A. Stuckey, Lawrence J. Beilin, Peter L. Thompson, Valerie Burke, Philip J. Currie
Journal: Diabetes Care (2008)

OBJECTIVE—To investigate the effects of fenofibrate and coenzyme Q10 (CoQ) on diastolic function, ambulatory blood pressure (ABP), and heart rate (HR) in type 2 diabetic subjects with left ventricular diastolic dysfunction (LVDD). RESEARCH DESIGN AND METHODS—We randomized, double-blind, 74 subjects to fenofibrate 160 mg daily, CoQ 200 mg daily, fenofibrate 160 mg plus CoQ 200 mg daily, or matching placebo for 6 months. Echocardiography (including tissue Doppler imaging) and 24-h ABP and HR monitoring were performed pre- and postintervention. RESULTS—Neither fenofibrate nor CoQ, alone or in combination, altered early diastolic mitral annular myocardial relaxation velocity (E′), early-to-late mitral inflow velocity ratio (E/A), deceleration time, isovolumic relaxation time, or the ratio of early mitral flow velocity to early diastolic mitral annular myocardial relaxation velocity (E/E′) compared with placebo (P &amp;gt; 0.05). Fenofibrate and CoQ interactively (P = 0.001) lowered 24-h systolic blood pressure (−3.4 ± 0.09 mmHg, P = 0.010), with a prominent nocturnal effect (−5.7 ± 1.5 mmHg, P = 0.006). Fenofibrate (−1.3 ± 0.5 mmHg, P = 0.013) and CoQ (−2.2 ± 0.5 mmHg, P &amp;lt; 0.001) independently lowered 24-h diastolic blood pressure. Fenofibrate reduced 24-h HR (−3.3 ± 0.5 beats/min, P &amp;lt; 0.001), but CoQ had no effect on HR. CONCLUSIONS—In type 2 diabetic subjects with LVDD, neither fenofibrate nor CoQ, alone or in combination, improved diastolic function significantly. However, fenofibrate and CoQ independently and interactively lowered 24-h blood pressure, and fenofibrate alone reduced 24-h HR.
Aggressive Variants of Castration-Resistant Prostate Cancer
Authors: Himisha Beltran, Scott Tomlins, Ana Aparicio, Vivek Arora, David Rickman, Gustavo Ayala, Jiaoti Huang, Lawrence True, Martin E. Gleave, Howard Soule, Christopher Logothetis, Mark A. Rubin
Journal: Clinical Cancer Research (2014)

Abstract A subset of patients with advanced castration-resistant prostate cancer may eventually evolve into an androgen receptor (AR)–independent phenotype, with a clinical picture associated with the development of rapidly progressive disease involving visceral sites and hormone refractoriness, often in the setting of a low or modestly rising serum prostate-specific antigen level. Biopsies performed in such patients may vary, ranging from poorly differentiated carcinomas to mixed adenocarcinoma-small cell carcinomas to pure small cell carcinomas. These aggressive tumors often demonstrate low or absent AR protein expression and, in some cases, express markers of neuroendocrine differentiation. Because tumor morphology is not always predicted by clinical behavior, the terms “anaplastic prostate cancer” or “neuroendocrine prostate cancer” have been used descriptively to describe these rapidly growing clinical features. Patients meeting clinical criteria of anaplastic prostate cancer have been shown to predict for poor prognosis, and these patients may be considered for platinum-based chemotherapy treatment regimens. Therefore, understanding variants within the spectrum of advanced prostate cancer has important diagnostic and treatment implications. Clin Cancer Res; 20(11); 2846–50. ©2014 AACR.