tbuckley/cabot-search huggingface dataset:
POSTOPERATIVE POTASSIUM DEFICIT AND METABOLIC ALKALOSIS. THE PATHOGENIC SIGNIFICANCE OF OPERATIVE TRAUMA AND OF POTASSIUM AND PHOSPHORUS DEPRIVATION 1
Authors: Leonard P. Eliel, Olof H. Pearson, Frederick C. White
Journal: Journal of Clinical Investigation (1952)

Patients maintained postoperatively on paren- teral fluids or a dietary intake low or lacking in potassium may develop a syndrome characterized by apathy, lethargy, muscular weakness, abdominal distension and ileus, cardiac arrhythmias and edema; and occasionally by confusion, delirium, muscular twitching and tetany.A clinical description of the syndrome as observed in 32 postopera- tive patients has appeared elsewhere (1).Evi- dence was found in these patients for the existence of potassium deficit, namely: 1) the presence of hypopotassemia, hypochloremia and metabolic al- kalosis, 2) electrocardiographic changes consistent with potassium deficit, 3) extensive expansion of the radiosodium space beyond the confines of the bromide space, suggesting that sodium had migrated into the cells to replace lost potassium, 4) lowering of erythrocyte potassium and increase of erythrocyte sodium concentrations in several patients, and 5) prompt reversal of the clinical and blood chem- ical abnormalities upon administration of adequate amounts of potassium.Two factors were thought to be of primary im- portance in the pathogenesis of the potassium deficit in the group studied: 1) adrenal cortical hyperfunction resulting from trauma ("alarm reaction") and leading to increased renal excretion of potas- sium and 2) a low potassium intake with poor re- nal conservation of potassium.The first factor
Nuclear DNA sequences from late Pleistocene megafauna
Authors: A. D. Greenwood, C. Capelli, G. Possnert, S. Paabo
Journal: Molecular Biology and Evolution (1999)

We report the retrieval and characterization of multi- and single-copy nuclear DNA sequences from Alaskan and Siberian mammoths (Mammuthus primigenius). In addition, a nuclear copy of a mitochondrial gene was recovered. Furthermore, a 13,000-year-old ground sloth and a 33,000-year-old cave bear yielded multicopy nuclear DNA sequences. Thus, multicopy and single-copy genes can be analyzed from Pleistocene faunal remains. The results also show that under some circumstances, nucleotide sequence differences between alleles found within one individual can be distinguished from DNA sequence variation caused by postmortem DNA damage. The nuclear sequences retrieved from the mammoths suggest that mammoths were more similar to Asian elephants than to African elephants.
Bcl-2–Mediated Drug Resistance
Authors: Rakesh K. Srivastava, Carl Y. Sasaki, J. Marie Hardwick, Dan L. Longo
Journal: The Journal of Experimental Medicine (1999)

Bcl-2 inhibits apoptosis induced by a variety of stimuli, including chemotherapy drugs and glucocorticoids. It is generally accepted that Bcl-2 exerts its antiapoptotic effects mainly by dimerizing with proapoptotic members of the Bcl-2 family such as Bax and Bad. However, the mechanism of the antiapoptotic effects is unclear. Paclitaxel and other drugs that disturb microtubule dynamics kill cells in a Fas/Fas ligand (FasL)-dependent manner; antibody to FasL inhibits paclitaxel-induced apoptosis. We have found that Bcl-2 overexpression leads to the prevention of chemotherapy (paclitaxel)-induced expression of FasL and blocks paclitaxel-induced apoptosis. The mechanism of this effect is that Bcl-2 prevents the nuclear translocation of NFAT (nuclear factor of activated T lymphocytes, a transcription factor activated by microtubule damage) by binding and sequestering calcineurin, a calcium-dependent phosphatase that must dephosphorylate NFAT to move to the nucleus. Without NFAT nuclear translocation, the FasL gene is not transcribed. Thus, it appears that paclitaxel and other drugs that disturb microtubule function kill cells at least in part through the induction of FasL. Furthermore, Bcl-2 antagonizes drug-induced apoptosis by inhibiting calcineurin activation, blocking NFAT nuclear translocation, and preventing FasL expression. The effects of Bcl-2 can be overcome, at least partially, through phosphorylation of Bcl-2. Phosphorylated Bcl-2 cannot bind calcineurin, and NFAT activation, FasL expression, and apoptosis can occur after Bcl-2 phosphorylation.
Fracture Management for Primary Care
Authors: Dilip R. Patel
Journal: JAMA (2012)

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
487 PROLONGED ANTIVIRAL TREATMENT FOR RECURRENT HEPATITIS C AFTER LIVER TRANSPLANTATION IN PATIENTS WITHOUT RAPID VIROLOGICAL RESPONSE REDUCES RELAPSES AND ENHANCES SUSTAINED VIROLOGICAL RESPONSE
Authors: J.M. Pascasio, J.M. Sousa, M.T. Ferrer, F. Gavilan, M. Sayago, J. Serrano-Diez Canedo, A. Giraldez, L. Barrera, J.M. Alamo, M.A. Gomez-Bravo
Journal: Journal of Hepatology (2010)
Incidence and Risk Factors for New-Onset Diabetes in HIV-Infected Patients
Authors: Stephane De Wit, Caroline A. Sabin, Rainer Weber, Signe Westring Worm, Peter Reiss, Charles Cazanave, Wafaa El-Sadr, Antonella d'Arminio Monforte, Eric Fontas, Matthew G. Law, Nina Friis-Møller, Andrew Phillips
Journal: Diabetes Care (2008)

The aims of this study were to determine the incidence of diabetes among HIV-infected patients in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) cohort, to identify demographic, HIV-related, and combination antiretroviral therapy (cART)-related factors associated with the onset of diabetes, and to identify possible mechanisms for any relationships found.
Diagnosis of acute myocardial infarction in a community hospital: significance of CPK-MB determination.
Authors: S F Roark, G S Wagner, H L Izlar, C R Roe
Journal: Circulation (1976)

Twice-daily CPK-MB determinations were performed but not made availabe to the physicians of 179 consecutive patients with precordial pain admitted to a community hospital to evaluate the diagnostic importance of this isoenzyme. Physician decision was based upon history and once-daily ECG and total enzymes (CPK, SGOT, LDH). Following hospital discharge, each patient's clinical record was reviewed to determine the physician diagnostic decision. The patients were subdivided into three groups. The first group consisted of 46 patients with diagnostic QRS changes and elevated total enzymes. All 46 had physician diagnosis of acute myocardial infarction and CPK-MB was present in 44 (96%). The second group included 55 patients with nondiagnostic QRS but elevated total enzymes. Physician diagnosis was acute myocardial infarction in 28 (51%) but 16 (57%) of these had no CPK-MB. The third group contained 50 patients with nondiagnostic QRS and normal enzyme levels. Six (12%) had physician diagnosis of acute myocardial infarction but none had CPK-MB. Thus, absence of CPK-MB failed to confirm physician diagnosis of acute myocardial infarction when based upon history and total enzymes in the absence of QRS changes in 22 of 34 (65%) patients.
Preschool exposure to traffic-related air pollution and small airway involvement in adolescence
Authors: Erica Sofia Schultz, Jenny Hallberg, Tom Bellander, Anna Bergström, Matteo Bottai, Flaminia Chiesa, Per M. Gustafsson, Olena Gruzieva, Per Thunqvist, Göran Pershagen, Erik Melén
Journal: European Respiratory Journal (2014)

Introduction:  Air pollution exposure early in life has been related to lung function decrements in 8-year old children (Schultz et al AJRCCM 186(12):1286-91.), but whether the negative effect persists into adolescence is unknown.   Aims and objectives:  To analyze the relationship between long-term exposure to air pollution and small airway involvement measured with impulse oscillometry (IOS) at 16 years of age.   Methods:  2416 children in the Swedish birth cohort BAMSE performed IOS at 16 years of age. Exposure to air pollution from road traffic was estimated (as nitrogen oxides (NO x )) for residential, daycare and school addresses from birth up to 16 years of age using an emission inventory and dispersion modelling. The relationship between a time-weighted average traffic-NO x  exposure over different time windows and frequency dependence resistance (fdR; R5Hz-R20Hz) as well as square root of reactance area (AX) were analyzed by quantile regression on the median.   Results: A 10 ɥg/m³ increase in first year of life exposure to traffic-NO x  was associated with impaired lung function in all subjects (0.002 kP/L/s 95% CI: 0.0002 to 0.0036 p=0.025 for fdR and 0.005 (kP/L) 1/2  95% CI: 0.0002 to 0.0106p=0.041 for AX) and in males separately (p=0.001 and p=0.057, respectively). Exposure during year 1 to 8 showed significant association with AX, but not with fdR. Later exposures showed no clear effects.   Conclusions  Our data indicate that exposure to traffic-related air pollution in preschool age is associated with impaired small airway function at 16 years of age.
Decreased Absolute Counts of T Lymphocyte Subsets and Their Relation to Disease in Squamous Cell Carcinoma of the Head and Neck
Authors: Iris Kuss, Bridget Hathaway, Robert L. Ferris, William Gooding, Theresa L. Whiteside
Journal: Clinical Cancer Research (2004)

Apoptosis of circulating CD8+ T cells seen in patients with squamous cell carcinoma of the head and neck [SCCHN (Hoffmann T, et al. Clin Cancer Res 2002;8:2553-62)] suggested a possibility of lymphocyte imbalance. Therefore, absolute numbers and percentages of lymphocyte subsets were examined in the peripheral blood of SCCHN patients and controls.Venous blood was obtained from 146 patients with SCCHN and 54 normal volunteers. Absolute numbers of CD3+, CD4+, and CD8+ T lymphocytes were determined using fluorobeads in a flow cytometry-based technique. Percentages of T lymphocyte subsets were also evaluated by flow cytometry. The patients were grouped at the time of blood draw [active versus no evidence of disease (NED), type of therapy administered, and the length of follow-up].Patients with SCCHN had significantly lower absolute numbers of CD3+ CD4+, and CD8+ T cells than normal controls. However, no differences in the percentages of T-cell subsets between patients and normal controls were observed. Patients with active disease had significantly lower CD3+ and CD4+ T-cell counts than those with NED. Patients who had NED after surgery and radiotherapy had the lowest T-cell counts among the NED cohort. Patients who had NED for >2 years did not recover their T-cell counts, and the T-cell imbalance was evident many years after curative surgery. The tumor-node-metastasis (TNM) stage or site of the disease was not related to the absolute T-cell count. Patients with recurrent disease at the time of blood draw tended to have the lowest CD4+ T-cell counts.Patients with SCCHN have altered lymphocyte homeostasis, which persists for months or years after curative therapies.
Preirradiation paclitaxel in glioblastoma multiforme: efficacy, pharmacology, and drug interactions. New Approaches to Brain Tumor Therapy Central Nervous System Consortium.
Authors: M R Fetell, S A Grossman, J D Fisher, B Erlanger, E Rowinsky, J Stockel, S Piantadosi
Journal: Journal of Clinical Oncology (1997)

PURPOSE The purpose of this study was to determine the response rate of paclitaxel administered at maximal tolerated doses (MTD) in patients with newly diagnosed glioblastoma multiform. PATIENTS AND METHODS All patients in this multicenter study were 45 years or older and had measurable residual tumor on postoperative MRI scans. Up to 3 cycles of paclitaxel were administered as a continuous 96-hour intravenous infusion prior to radiation, provided that the tumor did not enlarge on serial MRIs. The initial 10 patients were treated with the previously recommended phase II dose of 140 mg/m2. Less than anticipated toxicity led to the development of a phase I/II study in 24 patients in which paclitaxel doses were escalated separately in patients receiving (+EIAED) or not receiving (-EIAED), concomitant enzyme-inducing antiepileptic drugs. Paclitaxel plasma steady-state concentrations (Css) were measured during the first cycle of chemotherapy. Response was the primary efficacy endpoint for this study, although survival was also assessed. RESULTS The MTD was 140 mg/m2 in the -EIAED, and 200 mg/m2 in the +EIAED patient groups. The mean Css for the -EIAED patients treated at 140 mg/m2 was 38 nM, whereas the mean Css for +EIAED patients were 17 nm at 140 mg/m2, 27 nM at 175 mg/m2, 46 nM at 200 mg/m2, and 51 nM at 230 mg/m2. One patient, who had a verified partial response, had his diagnosis changed to an anaplastic oligodendroglioma on subsequent central neuropathologic review. None of the 15 assessable glioblastoma patients treated at or above the MTD doses showed a radiographic response to paclitaxel. The median survival of eligible patients on this protocol was 355 days (95% CI, 255 to 485 days), which is similar to the survival of comparable patients treated with conventional therapy. CONCLUSIONS These results suggest that (1) paclitaxel given as a 96-hour infusion at the MTD has minimal activity in patients with untreated glioblastoma, (2) the concomitant administration of EIAEDs alters the pharmacology of paclitaxel, resulting in a lower Css, reduced systemic toxicity, and higher dose requirements, (3) this study design, in which a new agent is given prior to radiation therapy (with serial monitoring of MRI), did not adversely affect survival in this patient population.
SJG-136 (NSC 694501), A Novel Rationally Designed DNA Minor Groove Interstrand Cross-Linking Agent with Potent and Broad Spectrum Antitumor Activity
Authors: Michael C. Alley, Melinda G. Hollingshead, Christine M. Pacula-Cox, William R. Waud, John A. Hartley, Philip W. Howard, Stephen J. Gregson, David E. Thurston, Edward A. Sausville
Journal: Cancer Research (2004)

Abstract Pyrrolo[2,1-c][1,4]benzodiazepine dimer SJG-136 (NSC 694501) selectively cross-links guanine residues located on opposite strands of DNA, and exhibits potent in vitro cytotoxicity. In addition, SJG-136 is highly active in vivo in hollow fiber assays. In the current investigation, SJG-136 was evaluated for in vivo efficacy in 10 tumor models selected on the basis of sensitivity of cells grown in the hollow fiber and in vitro time course assays: LOX IMVI and UACC-62 (melanomas); OVCAR-3 and OVCAR-5 (ovarian carcinomas); MDA-MB-435 (breast carcinoma); SF-295 and C-6 (gliomas); LS-174T (colon carcinoma); HL-60 TB (promyelocytic leukemia); and NCI-H522 (lung carcinoma). SJG-136 was active against small (150 mg) and large (250–400 mg) xenografts with tumor mass reductions in all 10 models. In addition, significant growth delays occurred in nine models, cell kill in six models ranged between 1.9 and 7.2 logs, and there were 1 to 4/6 tumor-free responses in six models. SJG-136 is active following i.v. bolus injections, as well as by 5-day continuous infusions. Of all of the schedules tested, bolus administrations for 5 consecutive days (qd×5) conferred the greatest efficacy. SJG-136 is active over a wide dosage range in athymic mouse xenografts: on a qd×5 schedule, the maximum-tolerated dose was ∼120 μg/kg/dose (total dose: 0.6 mg/kg = 1.8 mg/m2) and the minimum effective dose in the most sensitive model (SF-295) was ∼16 μg/kg/dose (total dose: 0.08 mg/kg = 0.24 mg/m2). Results of this study extend the initial in vivo observations reported in the reference above and confirm the importance of expediting more detailed preclinical evaluations on this novel agent in support of phase I clinical trials in the United Kingdom and the United States, which are planned to commence shortly.
Aggregated Low-Density Lipoprotein Uptake Induces Membrane Tissue Factor Procoagulant Activity and Microparticle Release in Human Vascular Smooth Muscle Cells
Authors: Vicenta Llorente-Cortés, Marta Otero-Viñas, Sandra Camino-López, Oriol Llampayas, Lina Badimon
Journal: Circulation (2004)

Tissue factor (TF) is the main initiator of the arterial blood coagulation system, and aggregated LDL (agLDL) are found in the arterial intima. Our hypothesis is that agLDL internalization by vascular smooth muscle cells (VSMCs) may trigger TF-procoagulant activity.Cultured human VSMCs were obtained from human coronary arteries of explanted hearts during transplant operations. VSMCs were incubated with native LDL (nLDL) or agLDL. TF mRNA was analyzed by real-time polymerase chain reaction, and cellular and released TF protein antigen were analyzed by Western blot. TF microparticle (MP) content was analyzed by flow cytometry and TF activity by a factor Xa generation test. Both nLDL and agLDL strongly and equally increased TF mRNA and cell membrane protein expression, by approximately 5- and 9-fold, respectively. A sustained TF procoagulant activity was induced by agLDL but not by nLDL (agLDL 2.46+/-0.22 versus nLDL 0.72+/-0.12 mU/mg protein at 12 hours). AgLDL increased TF antigen release (agLDL 5.64+/-0.4 versus nLDL 3.28+/-0.22 AU) and TF MP release (agLDL 89.85+/-8.51 versus nLDL 19.69+/-4.59 TF MP/10(3) cells). TF activation and release induced by agLDL is not related to apoptosis. Blockade of LDL receptor-related protein, a receptor for agLDL, prevented the agLDL-induced release of TF protein and TF MP.VSMC-TF expression is upregulated by both nLDL and agLDL. However, only agLDL engagement to LDL receptor-related protein induced cellular TF procoagulant activity and TF release by human VSMCs.
TRANSIENT TOXICITY WITH CARPHENAZINE HYDROCHLORIDE
Authors: J. MENDELS
Journal: American Journal of Psychiatry (1964)

Four patients who developed signs of hepatic and haematological toxicity while being treated with carphenazine hydrochloride are reported. The drug was stopped in one patient and continued in 3. All signs of toxicity disappeared in 12-16 weeks, without any reduction in dosage.
Therapeutic efficacy of intravenous immunoglobulin preparations depends on the immunoglobulin G dimers: studies in experimental immune thrombocytopenia
Authors: Jessica L. Teeling, Theo Jansen-Hendriks, Taco W. Kuijpers, Masja de Haas, Jan G. J. van de Winkel, C. Erik Hack, Wim K. Bleeker
Journal: Blood (2001)
Distinct Macrophage Phenotypes Contribute to Kidney Injury and Repair
Authors: Sik Lee, Sarah Huen, Hitoshi Nishio, Saori Nishio, Heung Kyu Lee, Bum-Soon Choi, Christiana Ruhrberg, Lloyd G. Cantley
Journal: Journal of the American Society of Nephrology (2011)

The ischemically injured kidney undergoes tubular cell necrosis and apoptosis, accompanied by an interstitial inflammatory cell infiltrate. In this study, we show that iNos-positive proinflammatory (M1) macrophages are recruited into the kidney in the first 48 hours after ischemia/reperfusion injury, whereas arginase 1– and mannose receptor–positive, noninflammatory (M2) macrophages predominate at later time points. Furthermore, depletion of macrophages before ischemia/reperfusion diminishes kidney injury, whereas depletion at 3 to 5 days after injury slows tubular cell proliferation and repair. Infusion of Ifnγ-stimulated, bone marrow–derived macrophages into macrophage-depleted mice at the time of kidney reperfusion restored injury to the level seen without macrophage depletion, suggesting that proinflammatory macrophages worsen kidney damage. In contrast, the appearance of macrophages with the M2 phenotype correlated with the proliferative phase of kidney repair. In vitro studies showed that IFNγ-stimulated, proinflammatory macrophages begin to express markers of M2 macrophages when cocultured with renal tubular cells. Moreover, IL-4–stimulated macrophages with an M2 phenotype, but not IFNγ-stimulated proinflammatory macrophages, promoted renal tubular cell proliferation. Finally, tracking fluorescently labeled, IFNγ-stimulated macrophages that were injected after injury showed that inflammatory macrophages can switch to an M2 phenotype in the kidney at the onset of kidney repair. Taken together, these studies show that macrophages undergo a switch from a proinflammatory to a trophic phenotype that supports the transition from tubule injury to tubule repair.
HORMONE-LIKE ACTIVITY OF A THYMUS HUMORAL FACTOR ON THE INDUCTION OF IMMUNE COMPETENCE IN LYMPHOID CELLS
Authors: Abraham I. Kook, Nathan Trainin
Journal: The Journal of Experimental Medicine (1974)

Experiments reported here were performed to understand the mechanism by which THF increases the immunocompetence of spleen cells from NTx mice. Dibutyryl cAMP or substances which increase intracellular levels of cAMP in lymphocytes such as Poly(A:U), theophylline, or PGE(2) were shown to mimic the effect of THF and confer reactivity in an in vitro GvH response to spleen cells from NTx mice. Flufenamic acid, an antagonist to PGE(2), was shown to inhibit the induction of competence by this substance. It was found that THF induces competence by activating membranal adenyl cyclase which leads to a rise in intracellular cAMP in thymus-derived cells only. These biochemical changes occur before antigenic stimulation and are unrelated to antigenic challenge. These findings indicate that THF exerts its effect via cAMP and are in agreement with the concepts which permit to classify THF as a thymus hormone.