tbuckley/cabot-search huggingface dataset:
Hodgkin lymphoma treatment with ABVD in the US and the EU: neutropenia occurrence and impaired chemotherapy delivery
Authors: Matthias Schwenkglenks, Ruth Pettengell, Thomas D Szucs, Eva Culakova, Gary H Lyman
Journal: Journal of Hematology & Oncology (2010)

In newly diagnosed patients with Hodgkin lymphoma (HL) the effect of doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD)-related neutropenia on chemotherapy delivery is poorly documented. The aim of this analysis was to assess the impact of chemotherapy-induced neutropenia (CIN) on ABVD chemotherapy delivery in HL patients.Data from two similarly designed, prospective, observational studies conducted in the US and the EU were analysed. One hundred and fifteen HL patients who started a new course of ABVD during 2002-2005 were included. The primary objective was to document the effect of neutropenic complications on delivery of ABVD chemotherapy in HL patients. Secondary objectives were to investigate the incidence of CIN and febrile neutropenia (FN) and to compare US and EU practice with ABVD therapy in HL. Pooled data were analysed to explore univariate associations with neutropenic events.Chemotherapy delivery was suboptimal (with a relative dose intensity < or = 85%) in 18-22% of patients. The incidence of grade 4 CIN in cycles 1-4 was lower in US patients (US 24% vs. EU 32%). Patients in both the US and the EU experienced similar rates of FN across cycles 1-4 (US 12% vs. EU 11%). Use of primary colony-stimulating factor (CSF) prophylaxis and of any CSF was more common in the US than the EU (37% vs. 4% and 78% vs. 38%, respectively). The relative risk (RR) of dose delays was 1.54 (95% confidence interval [CI] 1.08-2.23, p = 0.036) for patients with vs. without grade 4 CIN and the RR of grade 4 CIN was 0.35 (95% CI 0.12-1.06, p = 0.046) for patients with vs. without primary CSF prophylaxis.In this population of HL patients, CIN was frequent and FN occurrence clinically relevant. Chemotherapy delivery was suboptimal. CSF prophylaxis appeared to reduce CIN rates.
DERMATOLOGICAL MANIFESTATIONS OF THE IMMUNITY DEFICIENCY SYNDROMES
Authors: N. R. Rowell
Journal: British Journal of Dermatology (1968)

Journal Article DERMATOLOGICAL MANIFESTATIONS OF THE IMMUNITY DEFICIENCY SYNDROMES Get access N. R. Rowell N. R. Rowell Department of Dermatology, General Infirmary, Leeds Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 80, Issue 9, 1 September 1968, Pages 618–620, https://doi.org/10.1111/j.1365-2133.1968.tb12363.x Published: 01 September 1968
Sensitivity of routine system for reporting patient safety incidents in an NHS hospital: retrospective patient case note review
Authors: Ali Baba-Akbari Sari, Trevor A Sheldon, Alison Cracknell, Alastair Turnbull
Journal: BMJ (2006)

Background/Objective Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized for the selective death of motor neurons; nevertheless its pathogenesis remains incompletely understood. Recent evidence suggest that microglial activation, as well as certain proinflammatory cytokines may play a critical role in the pathogenesis of the disease. In this study, we analyze the levels of macrophage inflammatory protein (MIP1 β) in cerebral spinal fluid (CSF) of ALS patients and compare it to control subjects. Material and Methods 77 ALS subjects and 13 control patients with tension headache were included. In the ALS group, disease progression and the ALS functional rating scale-revised (ALSFRS-R) were assessed by registered neurologists. CSF levels of MIP1β were measured with a multiplex fluorescent bead based system (Bioplex Human). We performed a Mann-Whitney-U test and Bonferroni correction to compare MIP1β levels in both groups. Results ALS patients presented higher levels of MIP1β compared to control subjects (p=0.000) with an estimated shift of 5.11 pg/dl (range 2.84 - 8.06) (Figure 1). Conclusion The higher levels of MIP1β in our cohort suggest that this chemokine might participate in the neuroinflammatory pathophysiology of ALS. Further analysis are needed in order to clarify the specific role of this cytokine in ALS progression. Key Words: ALS, neuroinflammation, CSF, cytokines, MIP1β. <b>Disclosure:</b> Dr. Escamilla Ocanas has nothing to disclose. Dr. Martinez has nothing to disclose. Dr. González-Garza has nothing to disclose. Dr. Moreno-Cuevas has nothing to disclose. Dr. Tenorio-Pedraza has nothing to disclose.
G Protein-Coupled Receptor Trafficking in Health and Disease: Lessons Learned to Prepare for Therapeutic Mutant Rescue in Vivo
Authors: P. Michael Conn, Alfredo Ulloa-Aguirre, Joel Ito, Jo Ann Janovick
Journal: Pharmacological Reviews (2007)

G protein-coupled receptors (GPCR) comprise the largest family of drug targets. This is not surprising as many signaling systems rely on this class of receptor to convert external and internal stimuli to intracellular responses. As is the case with other membrane proteins, GPCRs are subjected to a stringentquality control mechanism at the endoplasmic reticulum, which ensures that only correctly folded proteins enter the secretory pathway. Because of this quality control system, point mutations resulting in protein sequence variations may result in the production of misfolded and disease-causing proteins that are unable to reach their functional destinations in the cell. There is now a wealth of information demonstrating the functional rescue of misfolded mutant receptors by small nonpeptide molecules originally designed to serve as receptor antagonists; these small molecules ("pharmacoperones") serve as molecular templates, promoting correct folding and allowing the mutants to pass the scrutiny of the cellular quality control system and be expressed at the cell surface membrane. Two of these systems are especially well characterized: the gonadotropin-releasing hormone and the vasopressin type 2 receptors, which play important roles in regulating reproduction and water homeostasis, respectively. Mutations in these receptors can lead to well defined diseases that are recognized as being caused by receptor misfolding that may potentially be amenable to treatment with pharmacoperones. This review is focused on protein misfolding and misrouting related to various disease states, with special emphasis on these two receptors, which have proved to be of value for development of drugs potentially useful in regulating GPCR trafficking in healthy and disease states.
Pharmacological Management of Lewy Body Dementia: A Systematic Review and Meta-Analysis
Authors: Chris Stinton, Ian McKeith, John-Paul Taylor, Louise Lafortune, Eneida Mioshi, Elijah Mak, Victoria Cambridge, James Mason, Alan Thomas, John T. O’Brien
Journal: American Journal of Psychiatry (2015)

Objective: The authors examined research on effects, costs, and patient and caregiver views of pharmacological management strategies for Lewy body dementia. Method: Studies were identified through bibliographic databases, trials registers, gray literature, reference lists, and experts. The authors used the search terms "Lewy or parkinson" and "dementia" through March 2015 and used the following inclusion criteria: participants with diagnoses of Lewy body dementia, dementia with Lewy bodies, or Parkinson's disease dementia (or participants' caregivers); investigation of pharmacological management strategies; outcome measures and test scores reported. Data extraction and quality assessment were conducted by at least two authors. Meta-analyses were conducted, and when studies could not be combined, summaries were provided. Results: Forty-four studies examining 22 strategies were included in the review. Meta-analysis indicated beneficial effects of donepezil and rivastigmine for cognitive and psychiatric symptoms. Rivastigmine, but not donepezil, was associated with greater risk of adverse events. Meta-analysis of memantine suggested that it is well tolerated but with few benefits. Descriptive summaries provide some evidence of benefits for galantamine, modafinil, levodopa, rotigotine, clozapine, duloxetine, clonazepam, ramelteon, gabapentin, zonisamide, and yokukansan. Piracetam, amantadine, selegiline, olanzapine, quetiapine, risperidone, and citalopram do not appear to be effective. Conclusions: High-level evidence related to pharmacological strategies for managing Lewy body dementia is rare. Strategies for important areas of need in Lewy body dementia, such as autonomic symptoms and caregiver burden, have not been investigated, nor have the views of patients and caregivers about pharmacological strategies.
Aberrant expression and function of gap junctions during carcinogenesis.
Authors: H Yamasaki
Journal: Environmental Health Perspectives (1991)

Gap junctional intercellular communication plays a key role in the maintenance of homeostasis in multicellular organisms. Reflecting deranged homeostasis in cancer cells, most transformed or cancerous cells show aberrant gap junctional intercellular communication; they have decreased junctional communication between each other and/or with surrounding normal cells. Studies with in vitro cell transformation and animal carcinogenesis models suggest an involvement of blocked intercellular communication in later stages of carcinogenesis. Analysis of expression of gap junction proteins (connexins) and corresponding mRNA indicates that a number of regulation sites are involved in aberrant function of gap junctions during carcinogenesis. Suppression of transformed phenotypes is often seen when transformed cells are physically in contact with their normal counterparts. Some studies suggest that gap junctional intercellular communication is involved in such tumor suppression.
MEK-Independent Survival of B-RAFV600E Melanoma Cells Selected for Resistance to Apoptosis Induced by the RAF Inhibitor PLX4720
Authors: Chen Chen Jiang, Fritz Lai, Rick F. Thorne, Fan Yang, Hao Liu, Peter Hersey, Xu Dong Zhang
Journal: Clinical Cancer Research (2010)

To examine mechanisms that determine long-term responses of B-RAF(V600E) melanoma cells to B-RAF inhibitors.B-RAF(V600E) melanoma cells were exposed to the B-RAF inhibitor PLX4720 for prolonged periods to select for cells resistant to apoptosis induced by the inhibitor. The resultant cells were analyzed for activation of extracellular signal regulated kinase (ERK), MAP/ERK kinase (MEK), and Akt, and related signals. Their roles in survival of the cells were also examined.B-RAF(V600E) melanoma cells selected for resistant to PLX4720-induced apoptosis retained the V600E mutation in B-RAF, and proliferated steadily in the presence of the inhibitor, albeit with slow growth rate. These cells displayed high levels of ERK activation, that is, at least in part, independent of the conventional RAF/MEK/ERK pathway, as MEK activation was low and inhibition of MEK did not significantly block activation of ERK. In contrast, extracellular signals appeared involved. This was associated with elevated activation of the phosphoinositide 3-kinase (PI3k)/Akt pathway and could be inhibited by serum starvation and inhibition of PI3k/Akt. Inhibition of MEK did not impact on survival of these cells, whereas serum starvation, inhibition of PI3K/Akt, and inhibition of ERK1/2 reduced their viability.These results indicate that sensitivity to induction of apoptosis may be a major determinant of long-term responses of B-RAF(V600E) melanomas to specific inhibitors and suggest that rebound melanoma growth after initial treatment with the inhibitors may not be responsive to MEK inhibitors, but may be susceptible to inhibition of the PI3k/Akt pathway.
Prevalence and prognostic significance of exercise-induced silent myocardial ischemia detected by thallium scintigraphy and electrocardiography in asymptomatic volunteers.
Authors: J L Fleg, G Gerstenblith, A B Zonderman, L C Becker, M L Weisfeldt, P T Costa, E G Lakatta
Journal: Circulation (1990)

Although a silent ischemic electrocardiographic response to treadmill exercise in clinically healthy populations is associated with an increased likelihood of future coronary events (i.e., angina pectoris, myocardial infarction, or cardiac death), such a response has a low predictive value for future events because of the low prevalence of disease in asymptomatic populations. To examine whether detection of reduced regional perfusion by thallium scintigraphy improved the predictive value of exercise-induced ST segment depression, we performed maximal treadmill exercise electrocardiography (ECG) and thallium scintigraphy (201Tl) in 407 asymptomatic volunteers 40-96 years of age (mean = 60) from the Baltimore Longitudinal Study on Aging. The prevalence of exercise-induced silent ischemia, defined by concordant ST segment depression and a thallium perfusion defect, increased more than sevenfold from 2% in the fifth and sixth decades to 15% in the ninth decade. Over a mean follow-up period of 4.6 years, cardiac events developed in 9.8% of subjects and consisted of 20 cases of new angina pectoris, 13 myocardial infarctions, and seven deaths. Events occurred in 7% of individuals with both negative 201Tl and ECG, 8% of those with either test positive, and 48% of those in whom both tests were positive (p less than 0.001). By proportional hazards analysis, age, hypertension, exercise duration, and a concordant positive ECG and 201Tl result were independent predictors of coronary events. Furthermore, those with positive ECG and 201Tl had a 3.6-fold relative risk for subsequent coronary events, independent of conventional risk factors.(ABSTRACT TRUNCATED AT 250 WORDS)
Activation of NAD(P)H:quinone oxidoreductase ameliorates spontaneous hypertension in an animal model via modulation of eNOS activity
Authors: Yong-Hoon Kim, Jung Hwan Hwang, Jung-Ran Noh, Gil-Tae Gang, Do Hyung Kim, Hwa-Young Son, Tae Hwan Kwak, Minho Shong, In-Kyu Lee, Chul-Ho Lee
Journal: Cardiovascular Research (2011)

Hypertension is one of the most common human diseases worldwide, and extensive research efforts are focused upon the identification and utilizing of novel therapeutic drug targets. Nitric oxide (NO) produced by endothelial NO synthase (eNOS) is an important regulator of blood pressure (BP). β-Lapachone (βL), a well-known substrate of NAD(P)H:quinone oxidoreductase (NQO1), increases the cellular NAD(+)/NADH ratio via the activation of NQO1. In this study, we evaluated whether βL-induced activation of NQO1 modulates BP in an animal model of hypertension.Spontaneously hypertensive rats (SHR), primary human aortic endothelial cells (HAEC), and endothelial cell lines were used to investigate the hypotensive effect of βL and its mode of action. βL treatment stimulated endothelium-dependent vascular relaxation in response to acetylcholine in aorta of SHR and dramatically lowered BP in SHR, but the hypotensive effect was completely blocked by eNOS inhibition with ω-nitro-l-arginine methyl ester. Aortic eNOS phosphorylation and eNOS protein expression were significantly increased in βL-treated SHR. In vitro studies revealed that βL treatment elevated the intracellular NAD(+)/NADH ratio and concentration of free Ca(2+) ([Ca(2+)]i), and resulted in Akt/AMP-activated protein kinase/eNOS activation. These effects were abolished by NQO1 siRNA and [Ca(2+)]i inhibition through a ryanodine receptor blockade.This study is the first to demonstrate that NQO1 activation has a hypotensive effect mediated by eNOS activation via cellular NAD(+)/NADH ratio modulation in an animal model. These results provide strong evidence suggesting NQO1 might be a new therapeutic target for hypertension.
The A3 Adenosine Receptor Is Highly Expressed in Tumor <b> <i>versus</i> </b> Normal Cells
Authors: Lea Madi, Avivit Ochaion, Lea Rath-Wolfson, Sara Bar-Yehuda, Abigail Erlanger, Gil Ohana, Arie Harish, Ofer Merimski, Faina Barer, Pnina Fishman
Journal: Clinical Cancer Research (2004)

A(3) adenosine receptor (A(3)AR) activation was shown to inhibit the growth of various tumor cells via the down-regulation of nuclear factor kappaB and cyclin D1. To additionally elucidate whether A(3)AR is a specific target, a survey of its expression in tumor versus adjacent normal cells was conducted.A(3)AR mRNA expression in various tumor tissues was tested in paraffin-embedded slides using reverse transcription-PCR analysis. A comparison with A(3)AR expression in the relevant adjacent normal tissue or regional lymph node metastasis was performed. In addition, A(3)AR protein expression was studied in fresh tumors and was correlated with that of the adjacent normal tissue.Reverse transcription-PCR analysis of colon and breast carcinoma tissues showed higher A(3)AR expression in the tumor versus adjacent non-neoplastic tissue or normal tissue. Additional analysis revealed that the lymph node metastasis expressed even more A(3)AR mRNA than the primary tumor tissue. Protein analysis of A(3)AR expression in fresh tumors derived from colon (n = 40) or breast (n = 17) revealed that 61% and 78% had higher A(3)AR expression in the tumor versus normal adjacent tissue, respectively. The high A(3)AR expression level in the tumor tissues was associated with elevated nuclear factor kappaB and cyclin D1 levels. High A(3)AR mRNA expression was also demonstrated in other solid tumor types.Primary and metastatic tumor tissues highly express A(3)AR indicating that high receptor expression is a characteristic of solid tumors. These findings and our previous data suggest A(3)AR as a potential target for tumor growth inhibition.
Effect of interpregnancy interval on outcomes of pregnancy after miscarriage: retrospective analysis of hospital episode statistics in Scotland
Authors: E. R. Love, S. Bhattacharya, N. C. Smith, S. Bhattacharya
Journal: BMJ (2010)

<b>Objective</b> To determine the optimum interpregnancy interval after miscarriage in a first recorded pregnancy. <b>Design</b> Population based retrospective cohort study. <b>Setting</b> Scottish hospitals between 1981 and 2000. <b>Participants</b> 30 937 women who had a miscarriage in their first recorded pregnancy and subsequently became pregnant. <b>Main outcome measures</b> The primary end point was miscarriage, live birth, termination, stillbirth, or ectopic pregnancy in the second pregnancy. Secondary outcomes were rates of caesarean section and preterm delivery, low birthweight infants, pre-eclampsia, placenta praevia, placental abruption, and induced labour in the second pregnancy. <b>Results</b> Compared with women with an interpregnancy interval of 6-12 months, those who conceived again within six months were less likely to have another miscarriage (adjusted odds ratio 0.66, 95% confidence interval 0.57 to 0.77), termination (0.43, 0.33 to 0.57), or ectopic pregnancy (0.48, 0.34 to 0.69). Women with an interpregnancy interval of more than 24 months were more likely to have an ectopic second pregnancy (1.97, 1.42 to 2.72) or termination (2.40, 1.91 to 3.01). Compared with women with an interpregnancy interval of 6-12 months, women who conceived again within six months and went on to have a live birth in the second pregnancy were less likely to have a caesarean section (0.90, 0.83 to 0.98), preterm delivery (0.89, 0.81 to 0.98), or infant of low birth weight (0.84, 0.71 to 0.89) but were more likely to have an induced labour (1.08, 1.02 to 1.23). <b>Conclusions</b> Women who conceive within six months of an initial miscarriage have the best reproductive outcomes and lowest complication rates in a subsequent pregnancy.
Critically Ill Patients and Acute Renal Failure
Authors: D. O. d'Avila
Journal: JAMA (2006)

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ESCMID guideline for the diagnosis and management of Candida diseases 2012: diagnostic procedures
Authors: M. Cuenca-Estrella, P. E Verweij, M. C Arendrup, S. Arikan-Akdagli, J. Bille, J. P Donnelly, H. E Jensen, C. Lass-Flörl, M. D Richardson, M. Akova, M. Bassetti, T. Calandra, E. Castagnola, O. A Cornely, J. Garbino, A. H Groll, R. Herbrecht, W. W Hope, B. J Kullberg, O. Lortholary, W. Meersseman, G. Petrikkos, E. Roilides, C. Viscoli, A. J Ullmann
Journal: Clinical Microbiology and Infection (2012)
Epirubicin sequential natural killer cells enhanced the cytotoxicity to breast cancer cells in vitro
Authors: Yanqiu Song, Qian Wang, Hui Feng, Ying Dong, Jingtao Chen
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Anthracycline-based chemotherapy is a conventional therapy for breast cancer patients, but also negatively affects host immune function. When the host immune system does not work, chemotherapy and radiotherapy cannot kill the cancer cells efficiently. Therefore, improve the host
Human leukocyte antigen class II and III alleles and severity of hepatitis C virus-related chronic liver disease
Authors: Margherita Asti, Miryam Martinetti, Claudo Zavaglia, Maria Clara Cuccia, Laura Gusberti, Carmine Tinelli, Agostino Cividini, Savino Bruno, Laura Salvaneschi, Gaetano Ideo, Mario U. Mondelli, Enrico M. Silini
Journal: Hepatology (1999)

Hepatitis C outcome is likely related both to viral factors and host's immune responses. We correlated the severity of liver disease with human leukocyte antigen (HLA) genes (C4A, C4B, TNFA, TNFB, DRB1, DRB3, DRB4, DRB5, DQA1, DQB1, TAP1, and TAP2) in three groups of subjects: 99 patients with chronic hepatitis, 41 asymptomatic carriers, and 179 uninfected controls. Patients with grade/stage 3 to 4 hepatitis significantly differentiated for their low frequency of alleles TNFB*1, DRB1*1104, and DRB3*03, which had a protective role, and high frequency of allele DRB1*1001, which was associated with disease severity. HLA-DRB*11 subtypes were differentially distributed: DRB1*1104 was most frequent in carriers, whereas DRB1*1101 was more frequent in patients. The TAP1C,2A haplotype was also underrepresented in patients with respect to controls. Finally, a decrease of heterozygous subjects was observed in patients with respect to carriers at the DQB1 locus. Multivariate analysis by correspondence analysis and multiple logistic regression indicated that age, sex, and hepatitis C virus (HCV) type were the strongest risk factors; however, some immunogenetic variables (TNFB*1, DRB1*1104, and DRB3*03) showed an independent contribution, especially in comparing patients with extreme manifestations of disease. The involvement of different genes in various HLA subregions suggests that anti-HCV responses are modulated by a complex gene interplay rather than by single alleles.
Poor prognosis nonseminomatous germ-cell tumours (NSGCTs): should chemotherapy doses be reduced at first cycle to prevent acute respiratory distress syndrome in patients with multiple lung metastases?
Authors: C. Massard, A. Plantade, M. Gross-Goupil, Y. Loriot, B. Besse, B. Raynard, F. Blot, S. Antoun, G. Nitenberg, B. Escudier, K. Fizazi
Journal: Annals of Oncology (2010)