tbuckley/cabot-search huggingface dataset:
Results of a phase II trial of cetuximab + XELIRI as first-line therapy of patients with advanced and/or metastatic colorectal cancer
Authors: T. H. Cartwright, P. Kuefler, A. Cohn, W. Hyman, M. Yoffe, K. A. Boehm, D. Ilegbodu, L. Asmar
Journal: Journal of Clinical Oncology (2007)

4094 Background: We have previously shown that capecitabine/irinotecan (XELIRI) is effective and well-tolerated in metastatic colorectal cancer (mCRC). Cetuximab, a monoclonal IgG1 antibody that binds to the extracellular domain of EGFR, is active in mCRC alone or in combination with chemotherapy. This study was designed to evaluate if cetuximab (Erbitux®) added to XELIRI improves outcome in first-line treatment of mCRC. Methods: Subjects had histologically confirmed colorectal adenocarcinoma with T4 lesions that were unresectable after preoperative chemoradiation therapy and/or metastases. The study regimen was capecitabine 1700 mg/m 2 (850 mg/m 2 PO BID Days 1–14), irinotecan 200 mg/m 2 IV Day 1 every 3 weeks, and weekly cetuximab (initial dose 400 mg/m 2 IV over 120 minutes, subsequent doses 250 mg/m 2 over 30 minutes). Results: Between February and October 2005, 70 subjects enrolled. Baseline characteristics: 43 males (61%), median age 61.5 years, and ECOG PS 0/1= 66%/34%; 94% of subjects had adenocarcinoma. Prior therapy; surgery (91%), chemotherapy (20%), or radiotherapy (7%). Responses (pts &gt;2 cycles) were; CR (4%), PR (36%), SD (40%) and PD (20%); 15 patients failed treatment; (n=4 allergic reaction, n=2 MD request, n=2 withdrew consent, n=2 Grade 4 neutropenia, and n=5 other AEs). The overall response rate was 40% and the disease control rate was 80%. Median duration of response was 8.8 months (range, 2.6–15.1) and median time to response was 2.0 months (range, 1.2–8.3). 64% of patients remain alive; of the 25 deaths, 84% were due to PD. No death was drug related. The most frequent Grade 3 and 4 treatment-related adverse events (AEs) included: diarrhea (25%), neutropenia (18%), nausea/vomiting (12%), rash and dehydration (9%, each), HFS and fatigue (7%), and allergic reaction (6%). 54% of patients required dose reductions. To date, 64 patients (91%) have gone off study, primarily due to PD (39%) or AE (33%); 3 patients remain on treatment. Conclusions: The combination of cetuximab and XELIRI is feasible and tolerable in first line mCRC. Toxicities are expected and manageable with dose reductions/delay. Funded in part by Bristol-Myers Squibb, Plainsboro, NJ. No significant financial relationships to disclose.
Mortality in Lying-in Hospitals
Journal: BMJ (1879)

M.S., 1872.-"Describe fully the character of so-called soft and hard chancre, &c." " Second M.B., 1873.-"Give an account of the modes in which syphilis becomes propagated; the details by which the poison is diffused throughout the system, &c."First M.B., 1873.-"Describe the connexion of the lower four inches of the rectum in the male, the naked-eye c clia- racter of the coats of the gut for the same distance, &c."First M.B., 1875.-"Give an account of the genito-urinary organs of the human male."
Primary Plasma Cell Leukemia: Clinical, Immunophenotypic, DNA Ploidy, and Cytogenetic Characteristics
Authors: R. Garcı́a-Sanz, A. Orfão, M. González, M.D. Tabernero, J. Bladé, M.J. Moro, J. Fernández-Calvo, M.A. Sanz, J.A. Pérez-Simón, A. Rasillo, J.F. San Miguel
Journal: Blood (1999)
Clearance of bacteriuria on discontinuing oral contraception
Authors: D. Evans, L. Miao, C. H Hennekens, E. H Kass
Journal: BMJ (1980)

the administration of intravenous sodium bicar- bonate, his urinary output rose to 50 ml/hour.However, by the next day blood urea had risen to 38 mmol/I (229 mg/100 ml) and the urate level was unchanged.Urgent haemodialysis was performed, with biochemical improvement; in particular, postdialysis urate was 0 50 mmol,l (8 40 mg/ 100 ml).Following a single haemodialysis his diuresis continued over the next three days and his recovery was otherwise uneventful, with no residual renal impairment.We agree that acute renal failure due to a nephrotoxic effect of alcohol is unlikely.In our case muscle damage was both apparent clinically and confirmed biochemically.How- ever, the uric acid level was also grossly ele- vated.The mechanism of acute renal failure as a consequence of myoglobinuria is uncertain although it has been suggested that other factors, including shock and acidosis, are important.'It is well recognised that hyperuricaemia occurs following muscle damage.'Additionally, hyperuricaemia may lead to acute renal failure in the absence of muscle damage.3Muscle damage may result from pressure necrosis following immobility during alcoholic stupor.4We suggest that the resulting hyperuricaemia is a major aetiological factor in the development of acute renal failure in this situation.In similar cases, priority should be given to the estimation of uric acid level and if it is grossly elevated then urgent alkalinisation to increase uric acid solubility and dialysis to reduce uric acid load is indicated.In such circumstances haemodialysis is to be greatly preferred to peritoneal dialysis, as urate clearance is significantly greater.3
Use of amphiregulin and epiregulin mRNA expression in primary tumors to predict outcome in metastatic colorectal cancer treated with cetuximab
Authors: H. Prenen, B. Jacobs, W. De Roock, R. Van Oirbeek, B. Biesmans, J. De Schutter, S. Fieuws, P. Laurent-Puig, E. Van Cutsem, S. Tejpar
Journal: Journal of Clinical Oncology (2009)

4019 Background: To study the power of two epidermal growth factor receptor (EGFR) ligands, epiregulin (EREG) and amphiregulin (AREG) expression in primary tumors to predict the outcome in patients with chemorefractory metastatic colorectal cancer (cmCRC) treated with the combination of cetuximab plus irinotecan. Methods: Gene expression measurements and KRAS mutation analysis were performed on archival formalin-fixed paraffin-embedded primary tumors of 220 cmCRC patients. Response was measured using RECIST criteria. The relation between ligand expression levels and outcome was evaluated using logistic regression for response and Cox regression for survival data. ROC analysis was performed for response and survival data. Confidence intervals (CI) for the performance indices were obtained with a non-parametric bootstrap procedure. Findings were externally validated on a series of 67 samples treated in a similar setting. Results: In KRAS wild-type (WT) patients, there was a significant association between log-transformed ligand expression and response (EREG: Odds ratio for objective response 1.90 (p=0.0005, 95%CI:1.27–2.83), c-index=0.681; AREG: Odds ratio for objective response: 1.82 (p=0.0017, 95%CI:1.22–2.72), c-index=0.673). In a Cox- regression model log-transformed ligand expression was significantly associated to progression-free survival (PFS) and overall survival (OS) (EREG: hazard ratio (HR) for PFS: 0.61 (p&lt;0.001, 95%CI:0.51–0.73), c τ -index=0.696; AREG: HR for PFS: 0.60 (95%CI:0.50–0.74), c τ -index=0.671; EREG: HR for OS: 0.61 (p&lt;0.001, 95%CI:0.50–0.73), c τ -index=0.667; AREG: HR for OS: 0.65 (p&lt;0.001, 95%CI:0.54–0.78), c τ -index=0.642). There was no predictive power of ligand expression in KRAS mutant patients. Conclusions: Expression of EGFR ligands in primary tumors significantly predicts favorable outcome in KRAS WT cmCRC treated with cetuximab and irinotecan. [Table: see text]
The Merck Manual of Geriatrics
Authors: Mark A. Rudberg
Journal: JAMA (1996)

Since the first edition of<i>The Merck Manual of Geriatrics</i>was published in 1990, the field of geriatrics has evolved. In large part, the results of basic and clinical research have increased the depth and breadth of knowledge available to practitioners. As examples, new treatments for osteoporosis and the effects of specific exercise prescriptions have been published since the first edition. At the same time, practitioners are increasingly asked to care for older persons with a multitude of challenging issues in a variety of settings. For instance, such care includes effectively evaluating older impaired patients who drive and efficiently caring for nursing home residents with complex multiple problems. Such issues have been increasingly defined, explored, and evaluated in the literature. These and the many other new concepts, diagnostics, and therapeutics have been well incorporated into the second edition of<i>The Merck Manual of Geriatrics</i>. In the tradition of<i>The Merck</i>
Interactions of Aniline with Soil and Groundwater at an Industrial Spill Site
Authors: David S. Kosson, Stephen V. Byrne
Journal: Environmental Health Perspectives (1995)

The interactions of aniline with soil at an industrial spill site were investigated.Sorption of aniline to the soil was observed to occur through a two- step mechanism.The first step was an ion exchange process with the protonated amine serving as an organic cation.This step was influenced by solution pH and ionic composition.The second step was covalent bonding most likely with quinone moieties and oxidation with polymerization of aniline.The extent of covalent bonding was influenced by the presence of oxygen and redox potential.The majority of aniline that was bound to the soil did not readily desorb under a variety of abiotic conditions.However, aniline was released to a significant extent in the presence of denitrifying and methanogenic microbial activity.Aniline in aqueous solution was readily biodegradable under aerobic and denitrifying conditions.Soil-bound ani- line was observed not to be biodegradable.This paper provides an overview of results.
Antiproliferative effects of ?-interferon in carbon tetrachloride (CCl4)-induced cirrhosis . Dept of Medicine, Scott/White &amp; Texas A&amp;M University COM, Temple TX 76504
Journal: Hepatology (1995)

Gut hormone receptors are over-expressed in human cancer and allow receptor-targeted tumor imaging and therapy. A novel promising receptor for these purposes is the secretin receptor. The secretin receptor expression was investigated in the human liver because the liver is a physiological secretin target and because novel diagnostic and treatment modalities are needed for liver cancer.Nineteen normal livers, 10 cirrhotic livers, 35 cholangiocarcinomas, and 45 hepatocellular carcinomas were investigated for secretin receptor expression by in vitro receptor autoradiography using 125I-[Tyr10] rat secretin and, in selected cases, for secretin receptor mRNA by RT-PCR.Secretin receptors were present in normal bile ducts and ductules, but not in hepatocytes. A significant receptor up-regulation was observed in ductular reaction in liver cirrhosis. Twenty-two (63%) cholangiocarcinomas were positive for secretin receptors, while hepatocellular carcinomas were negative. RT-PCR revealed wild-type receptor mRNA in the non-neoplastic liver, wild-type and spliced variant receptor mRNAs in cholangiocarcinomas found receptor positive in autoradiography experiments, and no receptor transcripts in autoradiographically negative cholangiocarcinomas.The expression of secretin receptors in the biliary tract is the molecular basis of the secretin-induced bicarbonate-rich choleresis in man. The high receptor expression in cholangiocarcinomas may be used for in vivo secretin receptor-targeting of these tumors and for the differential diagnosis with hepatocellular carcinoma.
CEREBRAL LOCALIZATION.
Authors: SYDNEY KUH
Journal: JAMA (1900)

Fifty years after Gall had published his doctrine of cerebral localization, the scientific medical world still believed with Flourens that "not only did all perceptions, all volitions, all intellectual faculties, reside exclusively in the brain, but that all faculties occupied the same place in it. That as soon as one of them disappeared from a lesion of any one point of the brain proper, they all disappeared; that as soon as one returned after the healing of that lesion, all returned. That the ability to perceive and to will, therefore, constituted essentially but one faculty; and that that faculty resided essentially in a single organ." Again fifty years had elapsed and a chart of the surface of a brain could be fitly compared to "a political map of Germany at the end of the seventeenth century." So greatly has our knowledge of cerebral localization advanced in those years that it
<i>Medical Jurisprudence of Insanity, or Forensic Psychiatry.</i>By S. V. Clevenger, M. D., with an exhaustive presentation of the<i>Judicial Decisions upon the Subject</i>by F. H. Bowlby. Published by the Lawyers' Co-operative Publishing Company, Rochester, New York, in two volumes, LXVII, 1356 pp., 1898
Journal: American Journal of Psychiatry (1898)
Dietary and Environmental Determinants of Blood and Bone Lead Levels in Lactating Postpartum Women Living in Mexico City
Authors: Mauricio Hernandez-Avila, Teresita Gonzalez-Cossio, Eduardo Palazuelos, Isabelle Romieu, Antonio Aro, Eugenia Fishbein, Karen E. Peterson, Howard Hu
Journal: Environmental Health Perspectives (1996)

Despite the recent declines in environmental lead exposure in the United States and Mexico, the potential for delayed toxicity from bone lead stores remains a significant public health concern. Some evidence indicates that mobilization of lead from bone may be markedly enhanced during the increased bone turnover of pregnancy and lactation, resulting in lead exposure to the fetus and the breast-fed infant. We conducted a cross-sectional investigation of the interrelationships between environmental, dietary, and lifestyle histories, blood lead levels, and bone lead levels among 98 recently postpartum women living in Mexico City. Lead levels in the patella (representing trabecular bone) and tibia (representing cortical bone) were measured by K X-ray fluorescence (KXRF). Multivariate linear regression models showed that significant predictors of higher blood lead included a history of preparing or storing food in lead-glazed ceramic ware, lower milk consumption, and higher levels of lead in patella bone. A 34 micrograms/g increase in patella lead (from the medians of the lowest to the highest quartiles) was associated with an increase in blood lead of 2.4 micrograms/dl. Given the measurement error associated with KXRF and the extrapolation of lead burden from a single bone site, this contribution probably represents an underestimate of the influence of trabecular bone on blood lead. Significant predictors of bone lead in multivariate models included years living in Mexico City, lower consumption of high calcium content foods, and nonuse of calcium supplements for the patella and years living in Mexico City, older age, and lower calcium intake for tibia bone. Low consumption of milk and cheese, as compared to the highest consumption category (every day), was associated with an increase in tibia bone lead of 9.7 micrograms Pb/g bone mineral. The findings of this cross-sectional study suggest that patella bone is a significant contributor to blood lead during lactation and that consumption of high calcium content foods may protect against the accumulation of lead in bone.
Nicotine and Tobacco
Journal: JAMA (2001)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
THU0123 Statins do not influence clinical response and B cell depletion after rituximab treatment in rheumatoid arthritis:
Authors: S. Das, M. Fernandez Matilla, S. Dass, E. Vital, P. Emery
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> B cell depletion by rituximab requires cross linking of CD20, which induces redistribution of CD20 to lipid rafts. This redistribution is correlated with efficiency of CDC and ADCC in previous studies. The integrity of the lipid rafts may also be important in induction of apoptosis. Statins interfere with the formation of cholesterol-rich micro domains within the plasma membrane- the lipid rafts<sup>1</sup>. Statins were recently reported to inhibit rituximab's clinical efficacy in rheumatoid arthritis (RA)<sup>2</sup>. <h3>Objectives</h3> To study the effect of statin on rituximab's clinical efficacy and B cell depletion in RA. <h3>Methods</h3> 119 patients pooled from three clinical trials were treated with 2×1000mg of rituximab. DAS28 and EULAR response were calculated at baseline and 6 months. B cell naïve, memory and plasmablast subsets were measured by flow cytometry. <h3>Results</h3> Among 119 patients, 26 patients received a statin. Baseline characteristics are summarised in table 1. At baseline, mean (SEM) DAS28-CRP were; 5.84 (0.23) and 5.52 (0.12) for SG and NSG respectively. At 6 months this improved to 3.92 (0.31) and 3.99 (0.14). Delta DAS28 was 1.92 (0.33) for SG vs. 1.52 (0.16) for NSG, p=0.590. EULAR response rates were as follows. SG: NON 23.1% (6), MOD 42.3% (11), GOOD 34.6% (9); in NSG: NON 34.4% (32), MOD 38.7% (36), GOOD 26.9% (25). There was no difference in the complete B cell depletion data at 2 weeks timepoint among the groups (SG-60% (15), NSG-52.9% (42), p=0.650). No difference in B cell subsets before or after rituximab was observed according to statin use. <h3>Conclusions</h3> We found no evidence that clinical response to rituximab or degree of B cell depletion was influenced by use of statins. <h3>References</h3> Winiarska M, PLoS Med 2008;5:e64 EEA Arts, Ann Rheum Dis 2011; 70(5) <h3>Disclosure of Interest</h3> S. Das: None Declared, M. Fernandez Matilla: None Declared, S. Dass Grant/Research support from: Honorarium Roche, Speakers Bureau: Roche, E. Vital Grant/Research support from: Honararium Roche, P. Emery Grant/Research support from: Roche, Consultant for: Roche, Speakers Bureau: Roche
Nivolumab + ipilimumab combination therapy in patients with advanced hepatocellular carcinoma: subgroup analyses from CheckMate 040
Authors: Bruno Sangro, Aiwu Ruth He, Thomas Yau, Chiun Hsu, Yoon-Koo Kang, Tae-You Kim, Armando Santoro, Ignacio Melero, Masatoshi Kudo, Ming-Mo Ho, Ana Matilla, Francesco Tovoli, Jennifer Knox, Bassel El-Rayes, Mirelis Rivera Acosta, Jaclyn Neely, Yun Shen, Marina Tschaika, Anthony El-Khoureiry
Journal: Journal of Hepatology (2020)
Regulation of seizure spreading by neuroserpin and tissue-type plasminogen activator is plasminogen-independent
Authors: Manuel Yepes, Maria Sandkvist, Timothy A. Coleman, Elizabeth Moore, Jiang-Young Wu, David Mitola, Thomas H. Bugge, Daniel A. Lawrence
Journal: Journal of Clinical Investigation (2002)

Tissue-type plasminogen activator (tPA) is a highly specific serine proteinase expressed in the CNS during events that require neuronal plasticity. In this study we demonstrate that endogenous tPA mediates the progression of kainic acid–induced (KA-induced) seizures by promoting the synchronization of neuronal activity required for seizure spreading, and that, unlike KA-induced cell death, this activity is plasminogen-independent. Specifically, seizure induction by KA injection into the amygdala induces tPA activity and cell death in both hippocampi, and unilateral treatment of rats with neuroserpin, a natural inhibitor of tPA in the brain, enhances neuronal survival in both hippocampi. Inhibition of tPA within the hippocampus by neuroserpin treatment does not prevent seizure onset but instead markedly delays the progression of seizure activity in both rats and wild-type mice. In tPA-deficient mice, seizure progression is significantly delayed, and neuroserpin treatment does not further delay seizure spreading. In contrast, plasminogen-deficient mice show a pattern of seizure spreading and a response to neuroserpin that is similar to that of wild-type animals. These findings indicate that tPA acts on a substrate other than plasminogen and that the effects of neuroserpin on seizure progression and neuronal cell survival are mediated through the inhibition of tPA.
Occupational risks for child-care providers and teachers
Authors: L. K. Pickering
Journal: JAMA (1990)

Exposure to large numbers of preschool children in out-ofhome child-care settings is associated with an increased frequency of acquiring a variety of communicable diseases.<sup>1,2</sup>This increase in frequency exists not only for the children but also for their parents and for their adult care givers.<sup>3</sup>Although one might assume such exposure merely accelerates the process of acquiring natural immunity to a variety of unavoidable communicable diseases, an increased risk for significant morbidity due to several infectious agents has been identified among both preschool children and adults in the day-care setting. Infants and toddlers attending day care are at greater risk for chronic or recurrent otitis media, for bacterial meningitis, for dehydration due to diarrheal disease, and for serious lower respiratory tract infection.<sup>4-6</sup>Parents and care givers exposed to children attending day care are at increased risk for illness due to shigellosis and hepatitis A, which is usually
Commentary
Authors: Lester S. King
Journal: JAMA (1977)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal