tbuckley/cabot-search huggingface dataset:
Polyclonal Antithymocyte Globulin and Cardiovascular Disease in Kidney Transplant Recipients
Authors: Didier Ducloux, Cécile Courivaud, Jamal Bamoulid, Thomas Crepin, Jean-Marc Chalopin, Pierre Tiberghien, Philippe Saas
Journal: Journal of the American Society of Nephrology (2014)

T-lymphocyte activation may contribute to atherosclerosis, the prevalence of which is increased in transplant patients. However, the cardiovascular consequences of polyclonal antithymocyte globulin (ATG)-induced immune modifications, which include alterations in T-cell subsets, are unknown. We conducted a retrospective single-center study to assess whether ATG associates with an increased incidence of atherosclerotic events (CVEs) in kidney transplant patients. Propensity score analysis was performed to address potential confounding by indication. We also tested whether ATG use induces a proatherogenic immune status. Sixty-nine (12.2%) CVEs occurred during follow-up (87±31 months). The cumulative incidence of CVEs was higher in ATG-treated patients (14.7% versus 8.2%; P=0.03). Cox regression analysis revealed that ATG use was an independent risk factor for CVEs (hazard ratio [HR], 2.36; 95% confidence interval [95% CI], 1.35 to 4.13; P=0.003). Results obtained in the propensity score match analysis recapitulated those obtained from the overall cohort (HR, 2.09; 95% CI, 1.11 to 3.98; P=0.02). Late-stage differentiated CD8(+) T cells increased 1 year after transplantation only in ATG-treated patients. More generally, ATG associated with features of immune activation. These modifications increased markedly in patients exposed to cytomegalovirus (CMV). Subanalyses suggest that the effect of ATG on CVEs is restricted to CMV-exposed patients. However, CMV infection associated significantly with CVEs only in ATG-treated patients (HR, 2.07; 95% CI, 1.16 to 3.70; P=0.01). In conclusion, ATG associated with both immune activation and post-transplant CVEs in this cohort. Further studies should precisely determine whether ATG-induced immune activation is the causal link between ATG and CVEs.
Aplastic anemia after liver transplantation for fulminant liver failure
Authors: Mark S. Cattral, Alan N. Langnas, Rodney S. Markin, Dean L. Antonson, Thomas G. Heffron, Ira J. Fox, Michael F. Sorrell, Byers W. Shaw
Journal: Hepatology (1994)

We determined the incidence and outcome of aplastic anemia among 56 patients who underwent liver transplantation for fulminant liver failure at the University of Nebraska Medical Center between July 1985 and December 1993. Aplastic anemia developed in 6 of 18 (33%) children and 1 of 19 (5%) adults who had fulminant non–A, non–B hepatitis; no cases of aplastic anemia occurred among patients with other causes of fulminant liver failure. None of these patients had evidence of a preexisting hematological disorder or in fection with hepatitis C virus (as determined with a second–generation ELISA). Aplastic anemia was diagnosed at a median of 4 wk after the onset of hepatitis, with five cases seen before transplantation. Six patients received antithymocyte globulin to promote remission of aplastic anemia. Three children died (fungal infection in two, intracranial hemorrhage in one)—one at 43, one at 108 and one at 119 days after transplantation—without remission of aplastic anemia. Among the four surviving patients, with median follow–up of 25 mo, complete and partial remission of aplastic anemia have occurred in three and one, respectively. Liver allograft function is stable in all surviving patients. The data demonstrate that aplastic anemia is a common complication among children who undergo liver transplantation for fulminant non–A, non–B hepatitis. It is associated with a high rate of mortality, although most survivors appear to have full hematological recovery. (Hepatology 1994;20:813–818).
Involved field radiation therapy after surgical resection of solitary brain metastases—mature results
Authors: Eileen P. Connolly, Maya Mathew, Moses Tam, Josephine Vera King, Saroj D. Kunnakkat, Erik C. Parker, John G. Golfinos, Michael L. Gruber, Ashwatha Narayana
Journal: Neuro-Oncology (2013)

Whole brain radiation therapy (WBRT) reduces local recurrence in patients after surgical resection of brain metastases without improving overall survival. Involved field radiation therapy (IFRT) has been used at our center to avoid delayed neurotoxicity associated with WBRT in well-selected patients with surgically resected single brain metastases. The purpose of this study was to evaluate the long-term outcomes of these patients.Thirty-three consecutive patients with single brain metastases from a known primary tumor were treated with gross total resection followed by IFRT between 2006 and 2011. The postoperative surgical bed was treated to 40.05 Gy in 15 fractions of 2.67 Gy with conformal radiation therapy. Patients received serial MRIs and neurological exams in follow-up. Surgery, WBRT, or stereotactic radiosurgery was performed as salvage treatment when necessary.The median follow-up was 16 months (range: 2-65 months). Local control, distant brain recurrence-free survival, and overall survival at 12 and 24 months were 90.3% and 85.8%, 60.7% and 51.4%, and 65.6% and 61.5%, respectively. Overall, 5 (15%) patients developed recurrence at the resection cavity, and 13 (39%) patients experienced recurrence at a new intracranial site. Two patients received WBRT, 8 stereotactic radiosurgery, 2 surgery, and 2 both chemotherapy and IFRT as salvage. Four patients died from CNS disease progression.For patients with newly diagnosed single brain metastases treated with surgical resection, postoperative IFRT to the resection cavity achieves reasonable rates of local control and is an excellent alternative to WBRT.
Pagetoid reticulosis, epidermotropic mycosis fungoides and mycosis fungoides: a disease spectrum
Authors: R.S-H. TAN, T.I.F. MACLEOD, S.G. DEAN
Journal: British Journal of Dermatology (1987)

Journal Article Pagetoid reticulosis, epidermotropic mycosis fungoides and mycosis fungoides: a disease spectrum Get access R.S‐H. TAN, R.S‐H. TAN Departments of Dermatology and Histopathology, Royal United Hospital, Bath, U.K. Dr R.S‐H.Tan, Department of Dermatology, Royal United Hospital, Combe Park, Bath, U.K. Search for other works by this author on: Oxford Academic Google Scholar T.I.F. MACLEOD, T.I.F. MACLEOD Departments of Dermatology and Histopathology, Royal United Hospital, Bath, U.K. Search for other works by this author on: Oxford Academic Google Scholar S.G. DEAN S.G. DEAN Departments of Dermatology and Histopathology, Royal United Hospital, Bath, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 116, Issue 1, 1 January 1987, Pages 67–77, https://doi.org/10.1111/j.1365-2133.1987.tb05792.x Published: 01 January 1987
Destabilization of natriuretic peptide C-receptor mRNA by phorbol myristate acetate.
Authors: R V Paul, P S Wackym, M N Budisavljevic
Journal: Journal of the American Society of Nephrology (1998)

Natriuretic peptide C receptor (NPR-C) expression in rat mesangial cells is downregulated by platelet-derived growth factor (PDGF) and the protein kinase C agonist phorbol myristate acetate (PMA). This study shows that PDGF and PMA diminish NPR-C mRNA abundance and that PMA does so by accelerating the degradation of the transcript. Exposure to PMA (0.1 microM) decreased mesangial cell NPR-C mRNA levels by more than 50% within 3 h and 125I-atrial natriuretic peptide binding by approximately 50% within 6 h. Disappearance of NPR-C transcripts after PMA treatment was more than twice as rapid as that seen after inhibition of RNA transcription with actinomycin D. Treatment with PDGF A/B (10 ng/ml) also produced downregulation of NPR-C mRNA, but the rate of transcript disappearance was similar to that seen after actinomycin D. Coincubation with actinomycin D inhibited the rapid disappearance of NPR-C mRNA with PMA. NPR-C mRNA levels increased four- to eightfold within 6 h after treatment with the protein synthesis inhibitor cycloheximide, but simultaneous treatment with PMA or PDGF still decreased the level of NPR-C mRNA despite the presence of cycloheximide. These results indicate that NPR-C expression is rapidly regulated by changes in the rate of catabolism of its mRNA through a protein kinase C-activated mechanism that depends on transcription. Treatment with cycloheximide induces NPR-C mRNA, but downregulation of this mRNA by either PDGF or PMA does not depend on synthesis of new protein.
High fluorescence in situ hybridization percentage of deletion 11q in patients with chronic lymphocytic leukemia is an independent predictor of adverse outcome
Authors: Preetesh Jain, Michael Keating, Phillip A. Thompson, Long Trinh, Xuemei Wang, William Wierda, Alessandra Ferrajoli, Jan Burger, Hagop Kantarjian, Zeev Estrov, Lynne Abruzzo, Susan O'Brien
Journal: American Journal of Hematology (2015)

We have analyzed patients with previously untreated chronic lymphocytic leukemia with del11q fluorescence in situ hybridization (FISH) abnormality ( n = 196) in this study. Detection of the 11q22.3 used a multicolor FISH technique. Patients with del11q fell into two major FISH subsets—sole del11q ( n = 64) and del11q with del13q ( n = 132). FISH subsets were compared using the median del11q FISH% (&gt;58%, high vs. ≤58%, low). Overall survival (OS) and time to first treatment (TTFT) were estimated using Kaplan–Meier plots (log rank). Multivariate analysis was performed to assess the association between FISH% of del11q and outcomes. Patients with sole del11q were similar to del11q with del13q in terms of TTFT and OS. Patients with high FISH% of del11q had significantly shorter OS and TTFT as compared with patients with low FISH%, particularly in sole del11q; this negative impact of high FISH% of del11q on OS and TTFT was diminished with coexistent del13q. In multivariate analysis, high FISH% of del11q was a significant predictor for shorter OS and TTFT. A comparison of these del11q subsets with a separate cohort of ( n = 673) previously untreated patients with sole del13q showed that the high FISH% del11q cohort had a significantly shorter TTFT and OS. In addition, bulky disease by physical examination or computed tomography imaging was infrequent at presentation in patients with del11q. High FISH% of del11q can reliably discriminate higher risk patients with chronic lymphocytic leukemia. Presence of coexistent del13q should be accounted for while prognosticating patients with del11q. Am. J. Hematol. 90:471–477, 2015. © 2015 Wiley Periodicals, Inc.
Psychological Well-Being and Ill-Being: Do They Have Distinct or Mirrored Biological Correlates?
Authors: Carol D. Ryff, Gayle Dienberg Love, Heather L. Urry, Daniel Muller, Melissa A. Rosenkranz, Elliot M. Friedman, Richard J. Davidson, Burton Singer
Journal: Psychotherapy and Psychosomatics (2006)

&lt;i&gt;Background: &lt;/i&gt;Increasingly, researchers attend to both positive and negative aspects of mental health. Such distinctions call for clarification of whether psychological well-being and ill-being comprise opposite ends of a bipolar continuum, or are best construed as separate, independent dimensions of mental health. Biology can help resolve this query – bipolarity predicts ‘mirrored’ biological correlates (i.e. well-being and ill-being correlate similarly with biomarkers, but show opposite directional signs), whereas independence predicts ‘distinct’ biological correlates (i.e. well-being and ill-being have different biological signatures). &lt;i&gt;Methods:&lt;/i&gt; Multiple aspects of psychological well-being (eudaimonic, hedonic) and ill-being (depression, anxiety, anger) were assessed in a sample of aging women (n = 135, mean age = 74) on whom diverse neuroendocrine (salivary cortisol, epinephrine, norepinephrine, DHEA-S) and cardiovascular factors (weight, waist-hip ratio, systolic and diastolic blood pressure, HDL cholesterol, total/HDL cholesterol, glycosylated hemoglobin) were also measured. &lt;i&gt;Results: &lt;/i&gt;Measures of psychological well-being and ill-being were significantly linked with numerous biomarkers, with some associations being more strongly evident for respondents aged 75+. Outcomes for seven biomarkers supported the distinct hypothesis, while findings for only two biomarkers supported the mirrored hypothesis. &lt;i&gt;Conclusion&lt;/i&gt;: This research adds to the growing literature on how psychological well-being and mental maladjustment are instantiated in biology. Population-based inquiries and challenge studies constitute important future directions.
Injury incidence and injury patterns in professional football: the UEFA injury study
Authors: J Ekstrand, M Hägglund, M Waldén
Journal: British Journal of Sports Medicine (2009)

Objective To study the injury characteristics in professional football and to follow the variation of injury incidence during a match, during a season and over consecutive seasons. Design Prospective cohort study where teams were followed for seven consecutive seasons. Team medical staff recorded individual player exposure and time-loss injuries from 2001 to 2008. Setting European professional men's football. Participants The first team squads of 23 teams selected by the Union of European Football Associations as belonging to the 50 best European teams. Main outcome measurement Injury incidence. Results 4483 injuries occurred during 566 000 h of exposure, giving an injury incidence of 8.0 injuries/1000 h. The injury incidence during matches was higher than in training (27.5 vs 4.1, p&lt;0.0001). A player sustained on average 2.0 injuries per season, and a team with typically 25 players can thus expect about 50 injuries each season. The single most common injury subtype was thigh strain, representing 17% of all injuries. Re-injuries constituted 12% of all injuries, and they caused longer absences than non re-injuries (24 vs 18 days, p&lt;0.0001). The incidence of match injuries showed an increasing injury tendency over time in both the first and second halves (p&lt;0.0001). Traumatic injuries and hamstring strains were more frequent during the competitive season, while overuse injuries were common during the preseason. Training and match injury incidences were stable over the period with no significant differences between seasons. Conclusions The training and match injury incidences were stable over seven seasons. The risk of injury increased with time in each half of matches.
BRCA-1 in Sporadic Epithelial Ovarian Cancer: Lessons Learned from the Genetics of Hereditary Disease
Authors: Stephen A. Cannistra
Journal: Clinical Cancer Research (2007)

Individuals with familial breast or ovarian cancer typically inherit a germ-line mutation in either the BRCA-1 or BRCA-2 genes, whose protein products are involved in the repair of double-stranded DNA breaks through homologous recombination ([1][1]). Tumors that arise in the setting of a BRCA-1 or
Peter Agre, 2003 Nobel Prize Winner in Chemistry
Authors: Mark A. Knepper, Soren Nielsen
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. Peter C. Agre, an American Society of Nephrology member, is the recipient of the 2003 Nobel Prize in Chemistry for his discovery of the aquaporin water channels. The function of many cells requires that water move rapidly into and out of them. There was only indirect evidence that proteinaceous channels provide this vital activity until Agre and colleagues purified aquaporin-1 from human erythrocytes and reported its cDNA sequence. They proved that aquaporin-1 is a specific water channel by cRNA expression studies in <i>Xenopus</i> oocytes and by functional reconstitution of transport activity in liposomes after the incorporation of the purified protein. These findings sparked a veritable explosion of work that affects several long-standing areas of investigation such as the biophysics of water permeation across cell membranes, the structural biology of integral membrane proteins, the physiology of fluid transport in the kidney and other organs, and the pathophysiological basis of inherited and acquired disorders of water balance. Agre's discovery of the first water channel has spurred a revolution in animal and plant physiology and in medicine.
Alcoholic "Blackouts": A Review and Clinical Study of 100 Alcoholics
Authors: DONALD W. GOODWIN, J. BRUCE CRANE, SAMUEL B. GUZE
Journal: American Journal of Psychiatry (1969)

In the past 25 years, numerous publications have cited "blackouts" as a major prodromal symptom of alcoholism. In contrast, this study, based on a structured interview with 100 hospitalized alcoholics, revealed that more than one-third of the subjects had never experienced a blackout and that, among those who did report the experience, blackouts generally began well along in the course of alcoholism rather than at an early stage. Blackouts were positively associated with severity and duration of alcoholism, extent and duration of alcohol consumption per drinking episode, capacity for drinking large amounts, "loss of control," neglect of meals, gulping drinks, and a history of head trauma. Only one patient had experienced blackouts after moderate drinking.
Aspergillus fumigatus: re-invention of the wheel
Authors: A. SEATON;, T. MURAYAMA, R. AMITANI
Journal: Thorax (1999)

An 11 year old boy with cystic fibrosis suffered a stroke, producing right sided weakness.Four years previously a totally implantable venous access device (Port-a-Cath) had been inserted.Magnetic resonance angiography revealed a filling defect in the left middle cerebral artery.Transoesophageal echocardiography demonstrated a thrombus attached to the tip of the Port-a-Cath and also the presence of a patent foramen ovale.After an initial period of anticoagulation the defect was closed using a septal occlusion device introduced via a cardiac catheter.The boy's neurological signs completely resolved and he remains free from further thromboembolic episodes.Whilst pulmonary embolism has been described before in relation to a totally implantable venous access device, this is believed to be the first description of a paradoxical embolism in relation to such a device.
Correlation of Kinase Genotype and Clinical Outcome in the North American Intergroup Phase III Trial of Imatinib Mesylate for Treatment of Advanced Gastrointestinal Stromal Tumor: CALGB 150105 Study by Cancer and Leukemia Group B and Southwest Oncology Group
Authors: Michael C. Heinrich, Kouros Owzar, Christopher L. Corless, Donna Hollis, Ernest C. Borden, Christopher D.M. Fletcher, Christopher W. Ryan, Margaret von Mehren, Charles D. Blanke, Cathryn Rankin, Robert S. Benjamin, Vivien H. Bramwell, George D. Demetri, Monica M. Bertagnolli, Jonathan A. Fletcher
Journal: Journal of Clinical Oncology (2008)

Imatinib mesylate is standard treatment for patients who have advanced gastrointestinal stromal tumor (GIST), but not all patients benefit equally. In previous studies, GIST genotype correlated with treatment outcome and optimal imatinib dosing.We examined the relationship between kinase genotype and treatment outcome for 428 patients enrolled on the North American phase III study SWOG S0033/CALGB 150105 and treated with either 400 mg or 800 mg daily doses of imatinib.The presence of KIT exon 11-mutant genotype (n = 283) correlated with improved treatment outcome when compared with KIT exon 9-mutant (n = 32) and wild-type (WT; n = 67) genotypes for objective response (complete response [CR]/partial response [PR], 71.7% v 44.4% [P = .007]; and 44.6% [P = .0002], respectively); time to tumor progression (TTP; median 24.7 months v 16.7 and 12.8 months, respectively); and overall survival (OS; median 60.0 months v 38.4 and 49.0 months, respectively). The survival outcomes for patients with exon 9-mutant, exon 11-mutant or WT GIST were not affected by imatinib dose. However, there was evidence of improved response rates for patients with exon 9-mutant tumors treated with imatinib 800 mg versus 400 mg (CR/PR, 67% v 17%; P = .02). Patients who had CD117-negative GIST had similar TTP but inferior OS compared with patients who had CD117-positive disease, which suggests that patients who have CD117-negative GIST may benefit from imatinib treatment. In addition, we identified novel but rare mutations of the KIT extracellular domain (exons 8 and 9).We confirmed the favorable impact of KIT exon 11 genotype when compared with KIT exon 9 and wild-type genotype for patients with advanced GIST who are treated with imatinib.
Prostaglandin-E2 is a potent inhibitor of human interleukin 12 production.
Authors: T C van der Pouw Kraan, L C Boeije, R J Smeenk, J Wijdenes, L A Aarden
Journal: The Journal of Experimental Medicine (1995)

During human immunodeficiency virus infection and allergic diseases, characterized by a dominant T helper (Th) 2 response, overproduction of prostaglandin E2 (PGE2) is observed. In this paper we studied the effect of PGE2 on interleukin (IL)-12 synthesis, because this cytokine has been described to be essential in induction of Th1 responses. IL-12 synthesis was induced in monocytes that were stimulated with Neisseria meningitidis-derived lipopolysaccharide in whole blood cultures. PGE2 almost completely inhibited lipopolysaccharide induced IL-12 production, whereas IL-6 production was only partially inhibited by PGE2. In contrast, the production of IL-10 was approximately twofold enhanced at these conditions. The effects of PGE2 were due to its cAMP-inducing capacity, since they could be mimicked by other cAMP inducers. Recombinant human IL-10 also inhibited IL-12 and IL-6 production. However, the inhibitory effect of PGE2 on IL-12 production was independent of IL-10 since neutralizing anti-IL-10 antibodies were unable to reverse this inhibition. These results suggest that the capacity of an antigen to induce PGE2 synthesis may play a crucial role in the development of either a Th1 or Th2 response.
Medical lessons from the Falklands.
Authors: T Richards
Journal: BMJ (1983)

Whether you regard the battle for the Falkland Islands as a victorious fight for right or a folly of mammoth proportions is your own affair. Nevertheless, it would be churlish to deny the armed services credit for conducting a successful campaign under extremely difficult circumstances. Just how difficult becomes apparent on reflection that those remote outposts of our erstwhile empire lie some 8000 miles away. The logistics of conducting Operation Corporate to reclaim the occupied islands were therefore complex and compounded by the problem that it was impossible to know exactly what measures would be necessary to achieve this objective. A disbelieving world saw last ditch diplomacy fail, but it was still hard to foresee the scale of the Argentine resistance. Our forces, and among them the medical teams, had to be capable of meeting an unpredictable challenge. In the event the number of casualties was thankfully less than anticipated (255 of the task force were killed and 777 wounded), and the medical care provided was of a high calibre. A two day meeting organised by the United Service section of the Royal Society of Medicine reviewed the medical aspects of the crisis. The meeting was held at the Royal College of Surgeons, and an impressive number of doctors from the services, and those who had seen active service in previous wars, were in attendance. Most of the speakers had taken an active role in the conflict, and collectively their short papers gave a vivid impression of the medical problems. In a few there was also a glimpse of the psychological trauma which such an experience can engender. If at times the meeting hit a justifiably self congratulatory note, it was toned down by an attempt to consider what medical lessons could be learnt from the conflict.