tbuckley/cabot-search huggingface dataset:
Selective plasma filtration for treatment of fulminant hepatic failure induced by D-galactosamine in a pig model
Authors: D W Y Ho
Journal: Gut (2002)

<b>Background:</b> Plasma exchange may be useful for treating patients with fulminant hepatic failure but during the procedure growth factors that are important for hepatic regeneration are discarded. Addition of a selective plasma filter to the plasmapheresis circuit could eliminate protein bound toxic substances and retain growth factors for hepatic regeneration. This process is called selective plasma filtration. <b>Aims:</b> To determine if selective plasma filtration could be a useful treatment modality for fulminant hepatic failure. <b>Methods:</b> The system was tested in five groups of pigs with fulminant hepatic failure induced by galactosamine: group I, diseased control group (n=5); group II, sham control, (n=6); group III, plasma exchange (n=6); group IV, treatment with AC-1770 selective plasma filter (n=7); and group V, treatment with AC-1730 selective plasma filter which had a smaller pore size than AC-1770 (n=7). Fresh pig plasma was given to replace filtered plasma in pigs of groups III, IV, and V. Treatment was initiated 48 hours after administration of 0.75 g/kg galactosamine. The efficacy of selective plasma filtration was assessed by survival rate and improvement in haematological, biochemical, and immunohistological parameters. <b>Results:</b> Pigs treated with AC-1770 or AC-1730 selective plasma filters survived longer than the other groups (group I: 55 (10) hours; group II: 68 (7) hours; group III: 91 (10) hours; group IV: 269 (156) hours; group V: 950 (555) hours). One pig in group IV survived for 50 days; one pig in group V survived for 77 days and another pig in group V is still alive (&gt;150 days). After treatment, plasma levels of aspartate aminotransferase, bilirubin, bile acid, ammonia, lactate dehydrogenase, and α-glutathione-S-transferase decreased. Substantial amounts of tumour necrosis factor α (TNF-α) and endotoxin were found in the filtrate. The selective plasma filtration groups retained significantly higher amounts of hepatocyte growth factor than plasma exchange alone. Similar TNF-α clearance was observed in the selective plasma filtration groups and the plasma exchange group. On day 4, significant improvement in liver function, as measured by the indocyanine green clearance test, was observed in groups IV and V but not in the other groups. A higher regeneration index of hepatocytes was also observed in the groups treated with AC-1770 and AC-1730 selective plasma filters. <b>Conclusion:</b> Selective plasma filtration improved survival time and expedited liver regeneration in pigs with fulminant hepatic failure.
Optimizing Nutritional Health Through Behavioral Intervention in Young Children With Cystic Fibrosis
Authors: Marianna M. Sockrider
Journal: JAMA Pediatrics (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 Pediatrics 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 Pediatrics journal
Randomized, Double-Blind Phase II Trial With Prospective Classification by ATM Protein Level to Evaluate the Efficacy and Tolerability of Olaparib Plus Paclitaxel in Patients With Recurrent or Metastatic Gastric Cancer
Authors: Yung-Jue Bang, Seock-Ah Im, Keun-Wook Lee, Jae Yong Cho, Eun-Kee Song, Kyung Hee Lee, Yeul Hong Kim, Joon Oh Park, Hoo Geun Chun, Dae Young Zang, Anitra Fielding, Jacqui Rowbottom, Darren Hodgson, Mark J. O'Connor, Xiaolu Yin, Woo Ho Kim
Journal: Journal of Clinical Oncology (2015)

Purpose Gastric cancer cell lines, particularly those with low levels of ataxia telangiectasia mutated (ATM), a key activator of DNA damage response, are sensitive to the poly (ADP-ribose) polymerase inhibitor olaparib. We compared the efficacy of olaparib plus paclitaxel (olaparib/paclitaxel) with paclitaxel alone in patients with recurrent or metastatic gastric cancer and assessed whether low ATM expression is predictive of improved clinical outcome for olaparib/paclitaxel. Patients and Methods In this phase II, double-blind study (Study 39; NCT01063517), patients were randomly assigned to oral olaparib 100 mg twice per day (tablets) plus paclitaxel (80 mg/m 2 per day intravenously on days 1, 8, and 15 of every 28-day cycle) or placebo plus paclitaxel (placebo/paclitaxel), followed by maintenance monotherapy with olaparib (200 mg twice per day) or placebo. The study population was enriched to 50% for patients with low or undetectable ATM levels (ATM low ). Primary end point was progression-free survival (PFS). Results One hundred twenty-three of 124 randomly assigned patients received treatment (olaparib/paclitaxel, n = 61; placebo/paclitaxel, n = 62). The screening prevalence of ATM low patients was 14%. Olaparib/paclitaxel did not lead to a significant improvement in PFS versus placebo/paclitaxel (overall population: hazard ratio [HR], 0.80; median PFS, 3.91 v 3.55 months, respectively; ATM low population: HR, 0.74; median PFS, 5.29 v 3.68 months, respectively). However, olaparib/paclitaxel significantly improved overall survival (OS) versus placebo/paclitaxel in both the overall population (HR, 0.56; 80% CI, 0.41 to 0.75; P = .005; median OS, 13.1 v 8.3 months, respectively) and the ATM low population (HR, 0.35; 80% CI, 0.22 to 0.56; P = .002; median OS, not reached v 8.2 months, respectively). Olaparib/paclitaxel was generally well tolerated, with no unexpected safety findings. Conclusion Olaparib/paclitaxel is active in the treatment of patients with metastatic gastric cancer, with a greater OS benefit in ATM low patients. A phase III trial in this setting is under way.
Alpha-Particle Emitting Atomic Generator (Actinium-225)-Labeled Trastuzumab (Herceptin) Targeting of Breast Cancer Spheroids
Authors: Åse M. Ballangrud, Wei-Hong Yang, Stig Palm, Richard Enmon, Paul E. Borchardt, Virginia A. Pellegrini, Michael R. McDevitt, David A. Scheinberg, George Sgouros
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The humanized monoclonal antibody, trastuzumab (Herceptin), directed against HER2/neu, has been effective in the treatment of breast cancer malignancies. However, clinical activity has depended on HER2/neu expression. Radiolabeled trastuzumab has been considered previously as a potential agent for radioimmunotherapy. The objective of this study was to investigate the efficacy of trastuzumab labeled with the α-particle emitting atomic generator, actinium-225 (225Ac), against breast cancer spheroids with different HER2/neu expression levels. 225Ac has a 10-day half-life and a decay scheme yielding four α-particles. Experimental Design: The breast carcinoma cell lines MCF7, MDA-MB-361 (MDA), and BT-474 (BT) with relative HER2/neu expression (by flow cytometry) of 1:4:18 were used. Spheroids of these cell lines were incubated with different concentrations of 225Ac-trastuzumab, and spheroid growth was measured by light microscopy over a 50-day period. Results: The activity concentration required to yield a 50% reduction in spheroid volume at day 35 was 18.1, 1.9, and 0.6 kBq/ml (490, 52, 14 nCi/ml) for MCF7, MDA, and BT spheroids, respectively. MCF7 spheroids continued growing but with a 20–30 day growth delay at 18.5 kBq/ml. MDA spheroid growth was delayed by 30–40 days at 3.7 kBq/ml; at 18.5 kBq/ml, 12 of 12 spheroids disaggregated after 70, days and cells remaining from each spheroid failed to form colonies within 2 weeks of being transferred to adherent dishes. Eight of 10 BT spheroids failed to regrow at 1.85 kBq/ml. All of the BT spheroids at activity concentrations 3.7 kBq/ml failed to regrow and to form colonies. The radiosensitivity of these three lines as spheroids was evaluated as the activity concentration required to reduce the treated to untreated spheroid volume ratio to 0.37, denoted DVR37. An external beam radiosensitivity of 2 Gy was found for spheroids of all three of the cell lines. After α-particle irradiation a DVR37 of 1.5, 3.0, and 2.0 kBq/ml was determined for MCF7, MDA, and BT, respectively. Conclusion: These studies suggest that 225Ac-labeled trastuzumab may be a potent therapeutic agent against metastatic breast cancer cells exhibiting intermediate to high HER2/neu expression.
Superiority of the Triple Combination of Bortezomib-Thalidomide-Dexamethasone Over the Dual Combination of Thalidomide-Dexamethasone in Patients With Multiple Myeloma Progressing or Relapsing After Autologous Transplantation: The MMVAR/IFM 2005-04 Randomized Phase III Trial From the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation
Authors: Laurent Garderet, Simona Iacobelli, Philippe Moreau, Mamoun Dib, Ingrid Lafon, Dietger Niederwieser, Tamas Masszi, Jean Fontan, Mauricette Michallet, Alois Gratwohl, Giuseppe Milone, Chantal Doyen, Brigitte Pegourie, Roman Hajek, Philippe Casassus, Brigitte Kolb, Carine Chaleteix, Bernd Hertenstein, Francesco Onida, Heinz Ludwig, Nicolas Ketterer, Christian Koenecke, Marleen van Os, Mohamad Mohty, Andrew Cakana, Norbert Claude Gorin, Theo de Witte, Jean Luc Harousseau, Curly Morris, Gösta Gahrton
Journal: Journal of Clinical Oncology (2012)

This prospective multicenter phase III study compared the efficacy and safety of a triple combination (bortezomib-thalidomide-dexamethasone [VTD]) versus a dual combination (thalidomide-dexamethasone [TD]) in patients with multiple myeloma (MM) progressing or relapsing after autologous stem-cell transplantation (ASCT).Overall, 269 patients were randomly assigned to receive bortezomib (1.3 mg/m(2) intravenous bolus) or no bortezomib for 1 year, in combination with thalidomide (200 mg per day orally) and dexamethasone (40 mg orally once a day on 4 days once every 3 weeks). Bortezomib was administered on days 1, 4, 8, and 11 with a 10-day rest period (day 12 to day 21) for eight cycles (6 months), and then on days 1, 8, 15, and 22 with a 20-day rest period (day 23 to day 42) for four cycles (6 months).Median time to progression (primary end point) was significantly longer with VTD than TD (19.5 v13.8 months; hazard ratio, 0.59; 95% CI, 0.44 to 0.80; P = .001), the complete response plus near-complete response rate was higher (45% v 21%; P 0.001), and the median duration of response was longer (17.9 v 13.4 months; P.04) [corrected].The 24-month survival rate was in favor of VTD (71% v 65%; P = .093). Grade 3 peripheral neuropathy was more frequent with VTD (29% v 12%; P = .001) as were the rates of grades 3 and 4 infection and thrombocytopenia.VTD was more effective than TD in the treatment of patients with MM with progressive or relapsing disease post-ASCT but was associated with a higher incidence of grade 3 neurotoxicity.
Cisplatin and Etoposide Regimen Is Superior to Cyclophosphamide, Epirubicin, and Vincristine Regimen in Small-Cell Lung Cancer: Results From a Randomized Phase III Trial With 5 Years’ Follow-Up
Authors: Stein Sundstrøm, Roy M. Bremnes, Stein Kaasa, Ulf Aasebø, Reidulv Hatlevoll, Ragnar Dahle, Nils Boye, Mari Wang, Tor Vigander, Jan Vilsvik, Eva Skovlund, Einar Hannisdal, Steinar Aamdal
Journal: Journal of Clinical Oncology (2002)

To investigate whether chemotherapy with etoposide and cisplatin (EP) is superior to cyclophosphamide, epirubicin, and vincristine (CEV) in small-cell lung cancer (SCLC).A total of 436 eligible patients were randomized to chemotherapy with EP (n = 218) or CEV (n = 218). Patients were stratified according to extent of disease (limited disease [LD], n = 214; extensive disease [ED], n = 222). The EP group received five courses of etoposide 100 mg/m(2) intravenously (IV) and cisplatin 75 mg/m(2) IV on day 1, followed by oral etoposide 200 mg/m(2) daily on days 2 to 4. The CEV group received five courses of epirubicin 50 mg/m(2), cyclophosphamide 1,000 mg/m(2), and vincristine 2 mg, all IV on day 1. In addition, LD patients received thoracic radiotherapy concurrent with chemotherapy cycle 3, and those achieving complete remission during the treatment period received prophylactic cranial irradiation.The treatment groups were well balanced with regard to age, sex, and prognostic factors such as weight loss, and performance status. The 2- and 5-year survival rates in the EP arm (14% and 5%, P =.0004) were significantly higher compared with those in the CEV arm (6% and 2%). Among LD patients, median survival time was 14.5 months versus 9.7 months in the EP and CEV arms, respectively (P =.001). The 2- and 5-year survival rates of 25% and 10% in the EP arm compared with 8% and 3% in the CEV arm (P =.0001). For ED patients, there was no significant survival difference between the treatment arms. Quality-of-life assessments revealed no major differences between the randomized groups.EP is superior to CEV in LD-SCLC patients. In ED-SCLC patients, the benefits of EP and CEV chemotherapy seem equivalent, with similar survival time and quality of life.
Proximal Neuropathic Lesions in Distal Symmetric Diabetic Polyneuropathy
Authors: Mirko Pham, Dimitrios Oikonomou, Philipp Bäumer, Angelika Bierhaus, Sabine Heiland, Per M. Humpert, Peter P. Nawroth, Martin Bendszus
Journal: Diabetes Care (2011)

OBJECTIVE This study investigated high-resolution magnetic resonance neurography (MRN) in distal symmetric diabetic polyneuropathy (dPNP). RESEARCH DESIGN AND METHODS MRN comprised high-resolution transaxial imaging of peripheral nerves of the lower limbs in 20 patients with type 2 diabetes (10 with dPNP, type 2/dPNP[+], and 10 without dPNP, type 2/dPNP[−]), seven patients with type 1 diabetes (two with dPNP, type 1/dPNP[+], five without dPNP, type 1/dPNP[−]), and 10 nondiabetic control subjects. Intraneural T2 lesions, as the main diagnostic criterion of MRN, were detected visually by two independent observers and quantitatively by analysis of T2 contrast ratios. RESULTS Multifocal fascicular, symmetric intraneural T2 lesions occurred in the proximal trunks of sciatic nerves in four patients (three with type 2/dPNP[+] and one with type 1/dPNP[+]) but not in control subjects (type 2/dPNP[−], type 1/dPNP[−], nondiabetic control subjects), which was confirmed by quantitative analysis. Clinical severity was higher in patients with T2 lesions (neuropathy deficit score: 10 vs. 7.8; P = 0.05). CONCLUSIONS For the first time, proximal neuropathic lesions of dPNP are reported in vivo. This supports that accumulation of proximal, multifocal fascicular injury may be important in disease progression.
Is Radiotherapy Needed for Pediatric Hodgkin Lymphoma?
Authors: Adam S. Reese
Journal: Journal of Clinical Oncology (2013)

TO THE EDITOR: Dorffel et al recently reported results from the nonrandomized phase II German Society of Pediatric Oncology and Hematology–Hodgkin’s Disease 95 (GPOH-HD95) trial involving the omission of radiotherapy for children and adolescents with Hodgkin lymphoma. They conclude that radiotherapy can be safely omitted in early-stage Hodgkin lymphoma in patients with a complete response. This statement does not seem justified. Compared with their historical standard, Deutschen Arbeitsgemeinschaft fur Leukamieforschung–Hodgkin’s Disease 90 (DALHD90), radiotherapy significantly improved 10-year progression-free survival (PFS; 92% v 84%; P .004) for all 165 patients. In the patient subset with early-stage disease (n 66), radiotherapy did not improve PFS. Can the omission of radiotherapy be based on 66 patients compared with a historical control? More than 10 times as many patients are needed to show noninferiority. For example, Hodgkin’s Disease 11 (HD11) was a noninferiority trial that involved 1,395 adult patients, and found that 20 Gy of radiotherapy was inferior to 30 Gy. Dorffel et al claim that their results are consistent with those of previous randomized trials. The Children’s Cancer Group (CCG) conducted a phase III trial evaluating whether radiotherapy could be omitted with a complete response after chemotherapy. The trial met early stopping rules because the event-free survival (EFS) was inferior in children who did not receive radiotherapy. The EFS difference of 91.2% versus 82.9% (P .004) in favor of radiotherapy persisted at 10 years, although the 10-year overall survival difference did not reach statistical significance. Overall survival requires more power than EFS because the event rate is lower. Thus, because the CCG trial closed early as a result of inferior results without radiotherapy, it lacked power to show an overall survival benefit. In my opinion, both trials indicate that radiotherapy is required in Hodgkin lymphoma, whereas the authors conclude the opposite. The combination of chemotherapy and radiotherapy should continue to be the standard of care for patients with pediatric Hodgkin lymphoma.
Folate and Cardiovascular Disease
Authors: Meir J. Stampfer
Journal: JAMA (1996)

In this issue ofThe Journal, Morrison and colleagues<sup>1</sup>provide important new information that fits neatly with the rapidly emerging area of homocysteine, folate, and cardiovascular disease. As comprehensively reviewed last year in<i>JAMA</i>,<sup>2</sup>strong and remarkably consistent data have linked elevated levels of homocysteine with increased risk of cardiovascular diseases. The risk appears to be graded across the whole distribution of homocysteine levels and, if causal, would account for a substantial fraction of the incidence of these diseases. Elevated homocysteine levels can be reduced by even modest amounts of folate,<sup>3,4</sup>providing a plausible mechanism for the remarkable findings of Morrison et al of a 69% increased risk of coronary mortality among those in the lowest quartile, as compared with highest quartile of serum folate. The findings are similar to previous studies using intermediate end points,<sup>5</sup>as well as case-control data<sup>5</sup>and preliminary prospective data
Tumor-Associated Macrophages as the Primary Source of Lysozyme in the Urine of Mice Bearing GPC-11, a Transplantable Reticulum Cell Sarcoma2
Authors: Sandra Bordin, Elton T. Young
Journal: JNCI Journal of the National Cancer Institute (1976)

Large amounts of lysozyme accumulated In the serum and urine of (NZB × BALB/c)F1 mice with GPC-11, a transplantable reticulum cell sarcoma, type A. We separated GPC-11 cell suspensions on 20% Ludox HS gradients. (HS Is one of the nine general grades of Ludox offered by du Pont de Nemours & Co., Wilmington, Del.) We did morphologic, functional, and biochemical experiments to detect oncogenic and enzymatic activity in each fraction. Oncogenic cells did not produce lysozyme. In contrast, macrophages associated with the solid tumor did produce lysozyme. The lysozyme purified from the GPC-11-associated macrophages resembled in size, electrophoretic mobility, and antigenicity the lysozyme purified from the urine of mice with the GPC-11 tumor.
MHC class II, tumour necrosis factor , and lymphotoxin gene haplotype associations with serological subsets of systemic lupus erythematosus
Authors: N J McHugh
Journal: Annals of the Rheumatic Diseases (2005)

<b>Objective:</b> To conduct a case–control study to investigate whether there are independent tumour necrosis factor α (TNFα) or lymphotoxin α (LTα) haplotype associations with SLE or with any of the major serological subsets of SLE. <b>Methods:</b> 157 patients with SLE were genotyped for HLA-DRB1, HLA-DQB1, TNFα, and LTα alleles by polymerase chain reaction and compared with 245 normal white controls. For TNFα, six single nucleotide polymorphisms (SNPs) at positions −1031, −863, −857, −308, −238, and +488 and for LTα three SNPs at positions +720, +365, and +249 were studied to assign six TNFα haplotypes (TNF1-6) and four LTα haplotypes (LTA1-4). All SLE patients had full serological profiles on serial samples. <b>Results:</b> The most significant association with SLE overall was with HLA-DR3 (p&lt;0.001; odds ratio (OR) = 2.5 (95% confidence interval, 1.6 to 3.8)) and the extended haplotype HLA-DQB1*0201;DRB1*0301;TNF2;LTA2 (p&lt;0.001; OR = 2.3 (1.4 to 3.7)). Associations were strongest in the anti-La positive group (13%) of SLE patients (HLA-DR3, OR = 71 (9 to 539); HLA-DQB1*0201, OR = 35 (5 to 267); TNF2, OR = 10 (2.8 to 36), and LTA2, OR = 4.9 (1.1 to 21)). There was an increase in the HLA-DR2 associated extended haplotype (HLA-DQB1*0602;DRB1*1501;TNF1;LTA1) in patients with anti-Ro in the absence of anti-La (p&lt;0.005; OR = 3.9 (1.5 to 10)). The HLA-DR7 extended haplotype (HLA-DQB1*0303; DRB1*0701/2; TNF5;LTA3) was decreased in SLE overall (p&lt;0.02; OR = 0.2 (0.05 to 0.8)). <b>Conclusions:</b> The strongest association in this predominantly white population with SLE was between HLA-DR3 and anti-La, which seemed to account for any associations with TNFα alleles on an extended DR3 haplotype.
Primary glioblastoma with oligodendroglial differentiation has better clinical outcome but no difference in common biological markers compared with other types of glioblastoma
Authors: R. C. Laxton, S. Popov, L. Doey, A. Jury, R. Bhangoo, R. Gullan, C. Chandler, L. Brazil, G. Sadler, R. Beaney, N. Sibtain, A. King, I. Bodi, C. Jones, K. Ashkan, S. Al-Sarraj
Journal: Neuro-Oncology (2013)

Glioblastoma multiforme with an oligodendroglial component (GBMO) has been recognized in the World Health Organization classification—however, the diagnostic criteria, molecular biology, and clinical outcome of primary GBMO remain unclear. Our aim was to investigate whether primary GBMO is a distinct clinicopathological subgroup of GBM and to determine the relative frequency of prognostic markers such as loss of heterozygosity (LOH) on 1p and/or 19q, O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation, and isocitrate dehydrogenase 1 (IDH1) mutation. We examined 288 cases of primary GBM and assessed the molecular markers in 57 GBMO and 50 cases of other primary GBM, correlating the data with clinical parameters and outcome. GBMO comprised 21.5% of our GBM specimens and showed significantly longer survival compared with our other GBM (12 mo vs 5.8 mo, P = .006); there was also a strong correlation with younger age at diagnosis (56.4 y vs 60.6 y, P = .005). Singular LOH of 19q (P = .04) conferred a 1.9-fold increased hazard of shorter survival. There was no difference in the frequencies of 1p or 19q deletion, MGMT promoter methylation, or IDH1 mutation (P = .8, P = 1.0, P = 1.0, respectively). Primary GBMO is a subgroup of GBM associated with longer survival and a younger age group but shows no difference in the frequency of LOH of 1p/19q, MGMT, and IDH1 mutation compared with other primary GBM.