tbuckley/cabot-search huggingface dataset:
Effect of Five Antineoplastic Agents on Tumor Xenografts With Different Growth Rates&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Jürgen Mattern, Klaus Wayss, Manfred Volm
Journal: JNCI Journal of the National Cancer Institute (1984)

The effects of cyclophosphamide (Cy), doxorubicin (Dx), cisplatin (DDP), melphalan (L-PAM), and vincristine (VCR) on various human and animal tumor lines with different growth rates, growing as xenografts in NMRI (nu/nu) mice, were studied. Two types of response were observed: For Cy and Dx, the response of the xenografts was negatively correlated with tumor volume doubling time (TD), indicating that rapidly growing tumors were more sensitive to these drugs than were slowly growing tumors. For DDP, L-PAM, and VCR, the effects were positively correlated with the TD, indicating that slowly growing tumors were more sensitive to these drugs than rapidly growing tumors. The data are discussed in relation to the effects of the drugs on proliferating and nonproliferating cells obtained with other cell lines.
Inhibition of benzalkonium chloride-induced skin inflammation in mice by an indol-1-ylpropan-2-one inhibitor of cytosolic phospholipase A2α
Authors: K. Roebrock, M. Wolf, S. Bovens, M. Lehr, C. Sunderkötter
Journal: British Journal of Dermatology (2011)

Irritant contact dermatitis (ICD) is a frequent and often underrated problem for which the major efficacious therapy is still local glucocorticoids, although they have known adverse effects due to their wide spectrum of action. A more focused therapeutic strategy would be the inhibition of a key enzyme for biosynthesis of the lipid mediators, cytosolic phospholipase A(2) α (cPLA(2) α), in ICD. We are analysing the pharmacological and biological effects of a selective cPLA(2) α inhibitor.To examine the usefulness of the potent and selective cPLA(2) α inhibitor 3-(5-carboxypentanoyl)-1-[3-(4-octylphenoxy)-2-oxopropyl]indole-5-carboxylic acid (compound 1) for therapy of inflammatory skin disorders.We examined clinical and cellular effects of a selective cPLA(2) α inhibitor (compound 1) on ICD in mice.Topical application of the compound significantly reduced ear swelling after induction by the irritant benzalkonium chloride. Concomitantly, compound 1 inhibited the accumulation of granulocytes as well as the expression of inflammatory proteins such as tumour necrosis factor-α, interleukin-1β and macrophage inflammatory proteins 1α and 1β in the ear tissue. In primary murine keratinocytes, the benzalkonium chloride-induced expression of these proteins was also downregulated after treatment with compound 1 in vitro.Compound 1 is a well-aimed agent for the treatment of nonspecific skin inflammation as it selectively inhibits cPLA(2) α and as it acts on an early stage of skin inflammation after its elicitation.
Review: Immediate vs deferred antiepileptics reduce recurrence at 1 to 2 y after an unprovoked first seizure
Authors: Richard J. Davenport
Journal: Annals of Internal Medicine (2015)

Source Citation Krumholz A, Wiebe S, Gronseth GS, et al. Evidence-based guideline: management of an unprovoked first seizure in adults: report of the guideline development subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology. 2015;84:1705-13. 25901057
Phase I and Pharmacokinetic Trial of Weekly Oral Fluorouracil Given With Eniluracil and Low-Dose Leucovorin to Patients With Solid Tumors
Authors: Jean L. Grem, Nancy Harold, Jeremy Shapiro, Dao-Qin Bi, Mary G. Quinn, Suzanne Zentko, Bruce Keith, J. Michael Hamilton, Brian P. Monahan, Sean Donavan, Frank Grollman, Geraldine Morrison, Chris H. Takimoto
Journal: Journal of Clinical Oncology (2000)

Fluorouracil (5-FU) given as a weekly, high-dose 24-hour infusion is active and tolerable. We evaluated an oral regimen of eniluracil (which inactivates dihydropyrimidine dehydrogenase [DPD]), 5-FU, and leucovorin to simulate this schedule.Patients received a single 24-hour infusion of 5-FU (2,300 mg/m(2) on day 2) with leucovorin (15 mg orally [PO] bid on days 1 through 3) to provide reference pharmacokinetic data. Two weeks later, patients began treatment with eniluracil (20 mg) and leucovorin (15 mg) (PO bid on days 1 through 3) and 5-FU (10 to 15 mg/m(2) PO bid on day 2).Dose-limiting toxicity (diarrhea, neutropenia, and fatigue) was seen with 5-FU 15 mg/m(2) PO bid on day 2 given weekly for either 6 of 8 weeks or 3 of 4 weeks, whereas five of seven patients tolerated 5-FU 10 mg/m(2) PO bid given weekly for 3 of 4 weeks. Eniluracil led to a 35-fold reduction in 5-FU clearance. Fluoro-beta-alanine, a 5-FU catabolite, was not detected in plasma during oral 5-FU-eniluracil therapy. DPD activity was markedly suppressed in all patients during eniluracil therapy; the inactivation persisted after the last eniluracil dose; percentages of baseline values were 1.8% on day 5, 4.5% on day 12, and 23.6% on day 19.The recommended oral dosage of 5-FU (10 mg/m(2) PO bid) given with eniluracil and leucovorin is approximately 115-fold lower than the reference dosage for 24-hour infusional 5-FU. This difference is greater than expected given the reduction in 5-FU clearance. DPD inactivation persisted for several weeks after completion of eniluracil therapy.
Low catalase activity contributes to oxidative stress in patients with alpha-1 antitrypsin deficiency
Authors: Amparo Escribano, Mónica Amor, Silvia Castillo, Francisco Sanz, Sara Pastor, Pilar Codoñer-Franch, Francisco Dasí
Journal: European Respiratory Journal (2014)

Background: Alpha-1 antitrypsin deficiency (AATD) is a hereditary condition that leads to decreased circulating AAT levels, significantly increasing the risk of serious lung and liver disease in children and adults. Oxidative stress has been shown to be a contributing factor in the development of liver and lung damage in animal models of AAT deficiency.   Rationale and aims : We have previously demonstrated that oxidative stress is increased in serum of children with AATD. However, the mechanisms leading to the oxidative stress observed in these patients are currently unknown.   Methods : Fifty-one children diagnosed with AATD were prospectively included in the study. Patients were classified in three risk groups of developing lung disease: low (MM; MS; SS phenotypes), intermediate (MZ; SZ) and high risk (ZZ). The activity of enzymes involved in oxidative stress metabolism, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GRd), were determined in serum of AATD patients and controls using ELISA.   Results : Our results show that, when compared to the control group, intermediate and high-risk groups showed significantly increased GPx activity and decreased CAT activity whereas no differences were observed with the low-risk group. No significant differences were observed in SOD and GRd activities.   Conclusions : Low CAT activity is responsible for the oxidative stress observed in these patients.   Funding Sources : Supported by SVN, GVA AP-096/11, ISCIII PI11/02884 grants.
Gender Difference in the Prevalence of Clinical Depression: The Role Played by Depression Associated With Somatic Symptoms
Authors: Brett Silverstein
Journal: American Journal of Psychiatry (1999)

This study tested the hypothesis that female subjects may exhibit a higher prevalence than male subjects of depression associated with somatic symptoms but not a higher prevalence of depression not associated with these other symptoms.The author reanalyzed research interview data on major depression from the National Comorbidity Survey, dividing respondents into those who met overall criteria for major depression and exhibited fatigue and appetite and sleep disturbance ("somatic depression") and those who met overall criteria but did not exhibit these somatic criteria ("pure depression").Female subjects exhibited a higher prevalence than male subjects of somatic depression but not a higher prevalence of pure depression. Somatic depression was associated with a high prevalence of anxiety disorder and, among female subjects, with body aches and onset of depression during early adolescence.The gender difference in depression may result from a difference in a specific subtype of anxious somatic depression.
Hema e-Chart Registry of invasive fungal infections in haematological patients: improved outcome in recent years in mould infections
Authors: A.M. Nosari, M. Caira, M.L. Pioltelli, R. Fanci, A. Bonini, C. Cattaneo, C. Castagnola, S.F. Capalbo, P. De Fabritiis, V. Mettivier, M. Morselli, D. Pastore, F. Aversa, G. Rossi, L. Pagano
Journal: Clinical Microbiology and Infection (2012)
Bundles of Care for Patients With Ruptured Abdominal Aortic Aneurysms
Authors: Peyman Benharash, William Toppen
Journal: JAMA Surgery (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Studies on the transposition rates of mobile genetic elements in a natural population of Drosophila melanogaster.
Authors: D S Suh, E H Choi, T Yamazaki, K Harada
Journal: Molecular Biology and Evolution (1995)

In an isolated population of Drosophila melanogaster on Ishigaki Island the chromosomal distribution of several retrotransposons, including copia, 412, 297, 17.6, I, and jockey elements, was examined by in situ hybridization. In this population the cosmopolitan inversion, In(2L)t, is known to exist in high frequency. One major haplotype concerning the occupied sites of the transposable elements was identified in the In(2L)t-carrying chromosomes. This haplotype is suggested to be the ancestral one. The age of the inversion in this local population was estimated to be 1,400 generations. The transposition rates of these elements were estimated based on the age of the inversion and the number of the elements lost and gained. The excision rates were in the range from 9.13 x 10(-5) to 2.25 x 10(-4) per site per generation. They were similar each other in the copia-like elements as well as in the LINE-like elements. The rate was higher in the copia-like elements than in the LINE-like elements. Insertions occurred in the range from 6.79 x 10(-4) to 9.05 x 10(-4) per element per generation. It is herein shown that both insertions and excisions occurred at a significantly higher rate in this population than in the laboratory.
Serum Trimethylamine-N-Oxide is Elevated in CKD and Correlates with Coronary Atherosclerosis Burden
Authors: Jason R Stubbs, John A House, A Jacob Ocque, Shiqin Zhang, Cassandra Johnson, Cassandra Kimber, Kyle Schmidt, Aditi Gupta, James B Wetmore, Thomas D Nolin, John A Spertus, Alan S Yu
Journal: Journal of the American Society of Nephrology (2015)

Trimethlyamine-N-oxide (TMAO) was recently identified as a promoter of atherosclerosis. Patients with CKD exhibit accelerated development of atherosclerosis; however, no studies have explored the relationship between TMAO and atherosclerosis formation in this group. This study measured serum concentrations and urinary excretion of TMAO in a CKD cohort (n=104), identified the effect of renal transplant on serum TMAO concentration in a subset of these patients (n=6), and explored the cross-sectional relationship between serum TMAO and coronary atherosclerosis burden in a separate CKD cohort (n=220) undergoing coronary angiography. Additional exploratory analyses examined the relationship between baseline serum TMAO and long-term survival after coronary angiography. Serum TMAO concentrations demonstrated a strong inverse association with eGFR (r2=0.31, P<0.001). TMAO concentrations were markedly higher in patients receiving dialysis (median [interquartile range], 94.4 μM [54.8–133.0 μM] for dialysis-dependent patients versus 3.3 μM [3.1–6.0 μM] for healthy controls; P<0.001); whereas renal transplantation resulted in substantial reductions in TMAO concentrations (median [min–max] 71.2 μM [29.2–189.7 μM] pretransplant versus 11.4 μM [8.9–20.2 μM] post-transplant; P=0.03). TMAO concentration was an independent predictor for coronary atherosclerosis burden (P=0.02) and predicted long-term mortality independent of traditional cardiac risk factors (hazard ratio, 1.26 per 10 μM increment in TMAO concentration; 95% confidence interval, 1.13 to 1.40; P<0.001). In conclusion, serum TMAO concentrations substantially increase with decrements in kidney function, and this effect is reversed by renal transplantation. Increased TMAO concentrations correlate with coronary atherosclerosis burden and may associate with long-term mortality in patients with CKD undergoing coronary angiography.
Prevalence of OSAS in a cohort of 1112 patients hospitalized for hypertension exploration
Authors: Kamila Sedkaoui, Bernard Chamontin, Jacques Amar, Béatrice Duly, Ludivine Leseux, Alain Didier
Journal: European Respiratory Journal (2014)

Introduction. The direct link between systemic hypertension (AHT) and OSAS (Obstructive Sleep Apnea Syndrome) is well documented. 30% of AHT patients presented an OSAS associated and this prevalence is higher, about 80% for resistant AHT patients. However the interest of systematic sleep exploration of all hypertensive patients is not established.

Objective / Methods.The objective of the study was to determine the prevalence of OSAS in a cohort of patients hospitalized between 2003 and 2012 for AHT exploration in a specialized unit, in Toulouse (France). All these patients, with or whithout suspected symptoms of OSAS, have been explored by a polygraphy ventilation.The diagnosis of OSAS was based on an apnea / hypopnea index (IAH) < 5 by hour.

Results: 1112 hypertensive patients were evaluated, including 311 (28%) with resistant AHT. In this cohort, 679 patients (61%) presented an OSAS. 165 patients (14.8%) had a severe OSAS with an AHI > 30 / h. All patients with severe OSAS (165/165) presented a resistant AHT.

Conclusion. Severe OSAS represents nearly 15% of cases in this population and have to be treated by Continuous Positive Airway Pressure. This result underlines the interest of a systematic search for sleep disordered breathing in AHT patients hospitalized in a specialized unit.
Clinical features and prognosis of follicular large-cell lymphoma: a report from the Nebraska Lymphoma Study Group.
Authors: J R Anderson, J M Vose, P J Bierman, D D Weisenberger, W G Sanger, J Pierson, M Bast, J O Armitage
Journal: Journal of Clinical Oncology (1993)

Our purpose was to describe the treatment outcome of patients with follicular large-cell lymphoma (FLCL) and to identify prognostic factors that affect the treatment outcome.Between 1980 and 1991, 107 newly diagnosed, previously untreated patients with FLCL were prospectively treated using treatment plans of the Nebraska Lymphoma Study Group (NLSG). Most stage I/II patients received two to three cycles of one of four closely related six-drug combination chemotherapy regimens (cyclophosphamide, doxorubicin or mitoxantrone, and procarbazine, plus bleomycin, vincristine, and prednisone or dexamethasone [CAP/BOP I-IV]) plus involved-field radiotherapy; 10 patients received involved-field irradiation only. Stage III/IV patients received six to eight cycles of CAP/BOP.Forty-four percent of patients had stage I/II disease. Stage I/II patients were older and more often female than stage III/IV patients. Cytogenetic studies were available on 35 patients: seven were normal; the most common abnormality was a translocation involving 14q32. Abnormalities of 1p or 1q were also common, often secondary to a 14q32 abnormality. The median follow-up of surviving patients is 2 years. The complete response rates observed were stage I/II, 88%; stage III/IV, 49%. Complete response rates were affected by both age and tumor bulk. Failure-free survival (FFS; time to first occurrence of progression, relapse after response, or death from any cause) at 3 years was estimated to be 61% for stage I/II patients and 34% for stage III/IV patients. Survival at 3 years was estimated to be 76% and 61%, respectively. FFS of stage III/IV patients was poorer for stage IV patients and those with composite lymphomas. Significantly poorer survival was only seen in patients older than 70 years of age.A proportion of stage I/II FLCL patients may obtain long-term disease control with combination chemotherapy plus radiotherapy. Results for patients with stage III/IV FLCL are similar to those seen for other follicular lymphomas.
P-042 Institutional experience in induction chemotherapy and neoadjuvant IMRT for borderline resectable and locally advanced pancreatic adenocarcinoma
Authors: M.V. de Torres Olombrada, T. Garcia Cañibano, I. Juez Martel, D. Gutierrez Abad, F. Pereira Perez, B. Ludeña Martinez
Journal: Annals of Oncology (2015)
Cytarabine and neurologic toxicity.
Authors: W J Baker, G L Royer, R B Weiss
Journal: Journal of Clinical Oncology (1991)

Cytarabine is an effective drug in the treatment of certain hematologic malignancies and its common toxicities are myelosuppression and gastrointestinal disturbance. In the past decade, neurotoxicity has been an increasingly recognized cytarabine effect. Intrathecal (IT) cytarabine may result in myelopathy that is incompletely reversible. Combined IT drug and cranial irradiation may lead to necrotizing leukoencephalopathy. Intravenous (IV) therapy may cause a peripheral neuropathy that varies greatly in its severity. The high IV cytarabine doses now commonly used can cause seizures, cerebral dysfunction, or an acute cerebellar syndrome with an incidence up to 14%. Patient age (greater than 60 years) appears to be the most important risk factor, but drug dose/schedule, cumulative drug dose, renal and hepatic dysfunction, and concomitant use of neurotropic antiemetic agents may also influence the risk of neurotoxicity. A better understanding of the pathophysiology and pharmacology of such cytarabine-induced neuronal injury will allow this drug to be used with greater efficacy and safety.
Intranasally administered peptidic viral fusion inhibitor protected hDPP4 transgenic mice from MERS-CoV infection
Authors: Shibo Jiang, Xinrong Tao, Shuai Xia, Tania Garron, Fei Yu, Lanying Du, Lu Lu, Chien-Te K Tseng
Journal: The Lancet (2015)

BackgroundMiddle East respiratory syndrome coronavirus (MERS-CoV), a new coronavirus that emerged in 2012, causes severe and fatal acute respiratory illness in man. Its high mortality (roughly 38%) has raised public fear worldwide, calling for the development of effective and safe therapeutics to combat MERS-CoV infection. On the basis of our previous work in development of peptide fusion inhibitors against HIV and SARS-CoV, and the crystal structure of the six-helix-bundle core of the MERS-CoV spike protein, we identified a peptide derived from the MERS-CoV S protein S2 subunit HR2 domain (HR2P) with a potent inhibitory activity against S-protein-mediated cell–cell fusion. Here, we tested an HR2P analogue with improved pharmaceutical properties, HR2P-M2, for its inhibitory activity against MERS-CoV infection in vitro and in vivo (appendix).MethodsWe assessed the anti-MERS-CoV activities of HR2P-M2 in vitro with pseudotyped MERS-CoVs in cell culture and in vivo with live MERS-CoVs in hDPP4-transgenic mice. The activities of HR2P-M2 to form six-helix bundles with HR1 peptides and to block fusion core formation between HR1 and HR2 peptides were studied using methods such as circular dichroism, N-PAGE, and FN-PAGE.FindingsHR2P-M2 was highly effective in blockade of cell–cell fusion mediated by MERS-CoV S proteins and inhibition of infection by MERS pseudoviruses expressing MERS-CoV S protein with or without mutation in the HR1 region, with IC50 (the concentration causing 50% inhibition) less than 0·7 μM. HR2P-M2 bound to the HR1 peptide to form stable six-helix bundles and blocked fusion core formation between the HR1 and HR2 peptides. Intranasal administration of HR2P-M2 before viral challenge fully protected hDPP4-transgenic mice (n=5) from MERS-CoV infection, whereas all the untreated mice (n=5) died 8 days after viral challenge.InterpretationOur findings suggest that the HR2P-M2 peptide merits further development as an effective and safe anti-MERS-CoV drug, alone or in combination with other antiviral drugs, to treat MERS-CoV-infected patients and to prevent the disease in high-risk populations, including health-care workers and family members of patients.FundingThis work was supported by grants from the National Science Fund of China (81173098 and 81361120378 to SJ, 81373456 to LL), the National 973 Program of China (2012CB519001 to SJ), and the US National Biocontainment Laboratories Operations Support (5UC7AI094660-05 to C-TKT). The funders had no role in interpretation of the findings and writing of this abstract.
Biological monitoring of cellular effects of omalizumab with basophil degranulation test (BAT) in severe asthma
Authors: Anna Stanziola, Francesco Perna, Diana Radicella, Carolina Vitale, Emanuela Carpentieri, Christian Russo, Matteo Sofia
Journal: European Respiratory Journal (2011)

The use of anti-IgE antibodies (Omalizumab) for the treatment of severe asthma is the first approach with biological drugs in this setting. IgE bound to receptor on responsive cells induce both mast cell and basophil degranulation with release of new mediators responsible of clinical features. There aren9t objective tests to dimonstrate the biological effects to this treatment. We evaluated basophil degranulation during treatment with Omalizumab using a basophil degranulation test based on a one-step method of basophil staining after exposure to a specific allergen with flow citometry that shows basophilic reactivity in vitro and their degranulation after contact with specific allergens. This method is based on recognition of peripheric blood cells positive to marking with monoclonal antibody CD123 that together with citophluorimetric caratheristic by Forward and Side Scatter and the contemporary negativity of expression of superficial antigen HLA-DR,identify basophil granocyte subset. In these cells after specific stimulation in vitro, is possible to identify IgE degranulation for the expression on the citoplasmatic surface of the antigen with monoclonal antibody CD63.  Seven patients were examined with the test baseline and after 12 and 24 months of OMA treatment. After 24 months of treatment degranulated basophil cells were 0.7% in comparison 53.9%at 12 months and 53.5% at baseline and this decrease was associated both to clinical improvements and reduction in oral corticosteroid daily dosage.Basophil degranulation test may be an appropriate method to evaluate Omalizumab biologic therapy in severe asthma where response and treatment duration are important aims.