tbuckley/cabot-search huggingface dataset:
Safety and efficacy of the addition of simvastatin to cetuximab in <i>KRAS</i> mutant metastatic colorectal cancer patients.
Authors: Jara M Baas, Lisanne Krens, Albert J. Ten Tije, Frans Erdkamp, Henk-jan Guchelaar, Hans Gelderblom
Journal: Journal of Clinical Oncology (2013)

e14586 Background: Epithelial growth factor receptor (EGFR) inhibitors are not effective in KRAS mutant colorectal tumors. In these tumors the k-ras protein is activated by post-translational modification by binding farnesyl (C15) and geranylgeranyl (C17) moieties. Both are products of the mevalonate pathway, as is cholesterol. Statins (HMG-CoA-reductase inhibitors) not only inhibit synthesis of cholesterol, but also of C15 and C17 and thus may reduce post-translational activation of ras proteins. Therefore, statins may inhibit the expression of the mutant KRAS phenotype and normalize the phenotype into KRAS wild type. In a phase II study we investigated whether simvastatin treatment renders KRAS mutant colorectal tumors sensitive to cetuximab. Methods: Major eligibility criteria were metastatic colorectal cancer failing 5-FU, oxaliplatin and irinotecan containing regimens, with a mutation in codon 12, 13 or 61 of KRAS gene in a tumor sample. Patients were treated with simvastatin 80mg once daily and cetuximab 250mg/m 2 weekly (after a starting dose of 400mg/m 2 ). Primary objective was to investigate the percentage of patients free from progression and alive 12.5 weeks after the first administration of cetuximab, similar to the results of the KRAS wild type population of the phase III study. This phase II study was performed in a Simon two stage design, performing an interim analysis after enrolment of 15 patients. If at least 6 of these patients (i.e. 40%) were to be alive and free from progression at 12.5 weeks after the start of cetuximab, another 31 patients would be included during stage II. Results: Fifteen evaluable patients were enrolled at 3 study sites. Four patients (i.e. 27%) were free from progression at time of the primary endpoint. Three patients experienced serious adverse events; an allergic reaction during cetuximab infusion, rhabdomyolysis and intracranial haemorrhage due to cerebral metastases. Conclusions: Though 4 patients experienced stable disease at 12.5 weeks, the predefined efficacy boundary was not met in order to continue enrolment to stage II. Simvastatin 80mg once daily does not induce sensitivity to cetuximab in colorectal cancer patients with a mutation in the KRAS gene. Clinical trial information: NCT01190462.
From the authors
Authors: G. Zhang, P. N. Le Souëf
Journal: European Respiratory Journal (2008)

b 2 -adrenoceptor polymorphisms and lung function (maximal expiratory flow at functional residual capacity) was found at 1 month of age, probably before there could be any influence of the post-natal environment.In this small study, no influence of maternal smoking was detected.This association was not found at 10 yrs, but only 26% had a smoking parent.Were any associations between b 2 -adrenoceptor polymorphisms and lung function found at birth in the Australian cohort?If not, could population differences or even a more polluted intrauterine environment in the UK cohort explain why this association was only found in later childhood in Australia?
Reply
Authors: J. F. Dooley
Journal: British Journal of Sports Medicine (1991)

Characterizing the functional impact of novel mutations linked to autism spectrum disorder (ASD) provides a deeper mechanistic understanding of the underlying pathophysiological mechanisms. Here we show that a <i>de novo</i> Glu183 to Val (E183V) mutation in the CaMKIIα catalytic domain, identified in a proband diagnosed with ASD, decreases both CaMKIIα substrate phosphorylation and regulatory autophosphorylation, and that the mutated kinase acts in a dominant-negative manner to reduce CaMKIIα-WT autophosphorylation. The E183V mutation also reduces CaMKIIα binding to established ASD-linked proteins, such as Shank3 and subunits of l-type calcium channels and NMDA receptors, and increases CaMKIIα turnover in intact cells. In cultured neurons, the E183V mutation reduces CaMKIIα targeting to dendritic spines. Moreover, neuronal expression of CaMKIIα-E183V increases dendritic arborization and decreases both dendritic spine density and excitatory synaptic transmission. Mice with a knock-in CaMKIIα-E183V mutation have lower total forebrain CaMKIIα levels, with reduced targeting to synaptic subcellular fractions. The CaMKIIα-E183V mice also display aberrant behavioral phenotypes, including hyperactivity, social interaction deficits, and increased repetitive behaviors. Together, these data suggest that CaMKIIα plays a previously unappreciated role in ASD-related synaptic and behavioral phenotypes. <b>SIGNIFICANCE STATEMENT</b> Many autism spectrum disorder (ASD)-linked mutations disrupt the function of synaptic proteins, but no single gene accounts for &gt;1% of total ASD cases. The molecular networks and mechanisms that couple the primary deficits caused by these individual mutations to core behavioral symptoms of ASD remain poorly understood. Here, we provide the first characterization of a mutation in the gene encoding CaMKIIα linked to a specific neuropsychiatric disorder. Our findings demonstrate that this ASD-linked <i>de novo CAMK2A</i> mutation disrupts multiple CaMKII functions, induces synaptic deficits, and causes ASD-related behavioral alterations, providing novel insights into the synaptic mechanisms contributing to ASD.
JOINT SCIENTIFIC SESSIONS
Journal: JAMA (1962)

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
Livingston-Wheeler therapy
Journal: CA A Cancer Journal for Clinicians (1990)

Livingston-Wheeler's cancer treatment is based on the belief that cancer is caused by a bacterium she has named Progenitor cryptocides. Careful research using modern techniques, however, has shown that there is no such organism and that Livingston-Wheeler has apparently mistaken several different types of bacteria, both rare and common, for a unique microbe. In spite of diligent research to isolate a cancer-causing microorganism, none has been found. Similarly, Livingston-Wheeler's autologous vaccine cannot be considered an effective treatment for cancer. While many oncologists have expressed the hope that someday a vaccine will be developed against cancer, the cause(s) of cancer must be determined before research can be directed toward developing a vaccine. The rationale for other facets of the Livingston-Wheeler cancer therapy is similarly faulty. No evidence supports her contention that cancer results from a defective immune system, that a whole-foods diet restores immune system deficiencies, that abscisic acid slows tumor growth, or that cancer is transmitted to humans by chickens.
Physicians' utilization and charges for outpatient diagnostic imaging in a Medicare population
Authors: B. J. Hillman
Journal: JAMA (1992)

<h3>Objectives and Rationale.</h3> —For 10 common clinical presentations, we assessed differences in physicians' utilization of and charges for diagnostic imaging, depending on whether they performed imaging examinations in their offices (self-referral) or referred their patients to radiologists (radiologist-referral). <h3>Methods.</h3> —Using previously developed methodologies, we generated episodes of medical care from an insurance claims database. Within each episode, we determined whether diagnostic imaging had been performed, and if so, whether by a self-referring physician or a radiologist. For each of the 10 clinical presentations, we compared the mean imaging frequency, mean imaging charges per episode of care, and mean imaging charges for diagnostic imaging attributable to self- and radiologist-referral. <h3>Results.</h3> —Depending on the clinical presentation, self-referral resulted in 1.7 to 7.7 times more frequent performance of imaging examinations than radiologistreferral (<i>P</i>&lt;.01, all presentations). Within all physician specialties, self-referral uniformly led to significantly greater utilization of diagnostic imaging than radiologistreferral. Mean imaging charges per episode of medical care (calculated as the product of the frequency of utilization and mean imaging charges) were 1.6 to 6.2 times greater for self-referral than for radiologist-referral (<i>P</i>&lt;.01, all presentations). When imaging examinations were performed—including those performed in both physicians' offices and hospital outpatient departments—mean imaging charges were significantly greater for radiologists than for self-referring physicians in seven of the clinical presentations (<i>P</i>&lt;.01). This result is related to the high technical charges of hospital outpatient departments; in office practice, radiologists' mean charges for imaging examinations were significantly less than those of self-referring physicians for seven clinical presentations (<i>P</i>&lt;.01). <h3>Conclusions.</h3> —Nonradiologist physicians who operate diagnostic imaging equipment in their offices perform imaging examinations more frequently, resulting in higher imaging charges per episode of medical care. These results extend our previous research on this subject by their focus on a broader range of clinical presentations; a mostly elderly, retired population; and the inclusion of highertechnology imaging examinations. (<i>JAMA</i>. 1992;268:2050-2054)
Prevalence and consequences of second opinions from medical oncologists for early-stage breast cancer: Results from the iCanCare study.
Authors: Allison W. Kurian, Christopher Ryan Friese, Irina Bondarenko, Reshma Jagsi, Steven J. Katz
Journal: Journal of Clinical Oncology (2015)

6508 Background: A second medical oncology opinion (SMO) may facilitate increasingly complex decision-making about use of chemotherapy. However, little is known about use of SMOs in the community or the interplay between SMOs and the quality of decision-making or chemotherapy use. Methods: We surveyed women newly diagnosed with early-stage invasive breast cancer in 2013-2014, accrued approximately 5 months after diagnosis through two population-based SEER registries (Georgia and Los Angeles), about their experiences with medical oncologists, their decision-making, and their use of chemotherapy. We evaluated demographic, clinical and decisional factors associated with SMO using logistic regression. Results: Among 1350 surveyed patients with invasive disease who consulted with a medical oncologist and answered questions about second opinions, 9.5% had SMO and 3.3% received chemotherapy from the SMO provider. On multivariable analysis that included an extensive list of demographic covariates and clinical factors, younger age (odds ratio, OR = 0.96, 95% confidence interval, CI 0.92-0.99), usage of a web-based support group (OR = 1.32, 95% CI 1.05-1.67) and education (p-value = 0.03) were significant predictors of SMO. On univariate analysis, compared to non-recipients, SMO recipients less strongly wanted their doctor to tell them what to do (none or little of the time: 27.0% vs. 18%, p-value = 0.008). Patient ratings of satisfaction with chemotherapy decision-making were high and did not differ between those who did versus did not receive an SMO (86.3% quite or totally satisfied vs 85.8%, p-value = 0.87). Chemotherapy use did not differ between SMO recipients vs. non-recipients (p-value = 0.7). Conclusions: SMO use and treatment by SMO clinicians was remarkably low among early-stage breast cancer patients. High decision satisfaction and no difference between SMO receipt groups suggest little unmet demand. While chemotherapy use did not vary between SMO recipients vs. non-recipients, additional measures of treatment quality will be presented. Funding: P01-CA-163233
In Reply:
Authors: Beth N. Peshkin, Claudine Isaacs, Shawna Willey, Marc D. Schwartz
Journal: Journal of Clinical Oncology (2005)

and post-test counseling was apparently administered via telephone by the genetic counselor. 1This suggests the need for direct physician involvement in the post-test counseling and prospective assessment of phenotype in BRCA-negative cases to provide a firm basis for recommendations.Our study shows that even with the real life circumstances of requirements for insurance preauthorization for both testing and genetic counseling and standard turnaround times associated with nonexpedited BRCA-mutation testing (3 to 4 weeks), it is feasible to integrate GCRA into the management of women with newly diagnosed breast cancer.Analysis of long-term outcomes including quality of life is ongoing.Furthermore, it is possible that timely GCRA may actually decrease the rate of inappropriate bilateral mastectomy for young newly diagnosed breast cancer patients.
Carbenicillin-induced acidosis and seizures
Authors: A. Whelton
Journal: JAMA (1971)

A patient with chronic, active pyelonephritis was treated with carbenicillin disodium, a drug that is generally accepted as having low toxicity to the central nervous system. While receiving a high dose of the drug the patient developed a combination of acute metabolic acidosis and grand mal seizures. The seizures, and in large part the acute acidosis, were the results of excessively high blood levels of carbenicillin which accumulated in the presence of nonoliguric renal impairment.
Risks to surgeons and patients from HIV and hepatitis: guidelines on precautions and management of exposure to blood or body fluids. Joint Working Party of the Hospital Infection Society and the Surgical Infection Study Group.
Authors: D Shanson
Journal: BMJ (1992)

Concern is increasing among surgeons and operating theatre staff about the risks of occupational exposure to HIV and hepatitis viruses.'-6There has also been much public debate about the risk of patients who undergo invasive procedures acquiring these viruses from in- fected surgeons.7 Eminent bodies have published reports on the topic, yet views vary about the risk of transmission of HIV8-'4 and the level of precautions appropriate to British hospitals.'59It was against this background that in October 1991 the Hospital Infection Society and the Surgical Infection Study Group convened a one day workshop at the Royal Society of Medicine, London, to review the degree of risk and prepare practical guidelines for surgeons, anaesthetists, and health care workers working in operating theatres.Its report forms the basis of the recommendations presented below.The incidence of nosocomially acquired hepatitis far exceeds that of HIV infection.Hepatitis B is preventable with immunisation and hence is discussed first.TRANSMISSION FROM HEALTH WORKERS TO PATIENTS Outbreaks of hepatitis among patients where an infected surgeon was the source continue to be re-
Re-establishing abstinence after alcohol relapse after early transplant (LT) for alcoholic hepatitis (AH) provides survival advantage
Authors: George Therapondos, Brian Lee, Gene Im, John Rice, Ann Lazar, Michael R. Lucey, Ethan Weinberg, Hyosun Han, Haripriya Maddur, R. Mark Ghobrial, Christine Hsu, Oren Fix, Sheila Eswaran, Kirti Shetty, Neha Jakhete, David Victor, David Foley, Neil Mehta, Mary Rinella, Thomas Schiano, Constance Mobley, Norah Terrault
Journal: Journal of Hepatology (2020)
Effect of dialysate temperature and flow rate on peritoneal clearance
Authors: M. Gross
Journal: JAMA (1967)

Intermittent peritoneal dialysis was performed to observe the effect of dialysate temperature and flow rate on peritoneal clearance. At the same hourly flow rates, the dialysate heated to 37 C had a 35% greater clearance than the dialysate at 20 C. The most efficient method of dialysis with commercially available equipment is a repeated 2-liter exchange of dialysate at 37 C with no pause between inflow and outflow. This method in an average dialysate volume of 3.3 liters/hr and an average urea nitrogen clearance of 20.8 ml/min.
Report of Multiple Periodic Anniversary Reactions in one Individual
Journal: JAMA (1963)

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
Cardiovascular Effects of D-Tubocurarine During Fluothane Anesthesia
Journal: JAMA (1963)

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
In Clinical Trials of Anticoagulants, Correlate Conclusions With Treatment
Journal: JAMA (1964)

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
THE OLD-TIME TREATMENT OF STRICTURE OF THE URETHRA BY CAUSTICS.
Journal: JAMA (1894)

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Literature and Medicine
Authors: Samuel A. Banks
Journal: JAMA (1989)

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