tbuckley/cabot-search huggingface dataset:
Navigated transcranial magnetic stimulation improves the treatment outcome in patients with brain tumors in motor eloquent locations
Authors: D. Frey, S. Schilt, V. Strack, A. Zdunczyk, J. Rosler, B. Niraula, P. Vajkoczy, T. Picht
Journal: Neuro-Oncology (2014)

Neurological and oncological outcomes of motor eloquent brain-tumor patients depend upon the ability to localize functional areas and the respective proposed therapy. We set out to determine whether the use of navigated transcranial magnetic stimulation (nTMS) had an impact on treatment and outcome in patients with brain tumors in motor eloquent locations.We enrolled 250 consecutive patients and compared their functional and oncological outcomes to a matched pre-nTMS control group (n = 115).nTMS mapping results disproved suspected involvement of primary motor cortex in 25.1% of cases, expanded surgical indication in 14.8%, and led to planning of more extensive resection in 35.2% of cases and more restrictive resection in 3.5%. In comparison with the control group, the rate of gross total resections increased significantly from 42% to 59% (P < .05). Progression-free-survival for low grade glioma was significantly better in the nTMS group at 22.4 months than in control group at 15.4 months (P < .05). Integration of nTMS led to a nonsignificant change of postoperative deficits from 8.5% in the control group to 6.1% in the nTMS group.nTMS provides crucial data for preoperative planning and surgical resection of tumors involving essential motor areas. Expanding surgical indications and extent of resection based on nTMS enables more patients to undergo surgery and might lead to better neurological outcomes and higher survival rates in brain tumor patients. The impact of this study should go far beyond the neurosurgical community because it could fundamentally improve treatment and outcome, and its results will likely change clinical practice.
Clinic, Music City, 1985
Authors: Brenda Butka
Journal: Annals of Internal Medicine (2014)

Ad Libitum2 December 2014Clinic, Music City, 1985Brenda Butka, MDBrenda Butka, MDFrom Nashville, TennesseeSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M14-2444 Audio Reading - “Clinic, Music City, 1985” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "Clinic, Music City, 1985," by B. Butka. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail An army brat, born in Germany right down the streetfrom Roentgen's house, he always camewith his guitar in its tattered case dressed upwith a red plastic rose. His gentle fingerpickingsounded like a harp in the waiting room, floatingaround the coughs, the shuffling feet.Caught up in the epidemic of the young and lost,he knew he was going to die. When the time comes,he said, strumming his guitar, don't worryabout what to do. Just put me on the boat,just put me on the boat and push me up the riverto Valhalla. The gods will be waiting.His frayed jeans, his red ... Author, Article, and Disclosure InformationAffiliations: From Nashville, TennesseeCurrent Author Address: Brenda Butka, MD; e-mail, brenda.butk[email protected]edu. PreviousarticleNextarticle Advertisement Audio Reading - “Clinic, Music City, 1985” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "Clinic, Music City, 1985," by B. Butka. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics 2 December 2014Volume 161, Issue 11Page: 826KeywordsRivers ePublished: 2 December 2014 Issue Published: 2 December 2014 Copyright & PermissionsCopyright © 2014 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Physiologic response and lung distribution of lavage versus bolus Exosurf in piglets with acute lung injury.
Authors: V Balaraman, S L Sood, K C Finn, G Hashiro, C F Uyehara, D Easa
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Despite evidence of surfactant dysfunction in the acute respiratory distress syndrome (ARDS), treatment with exogenous surfactant remains experimental. Uneven pulmonary distribution is one factor that may limit response. We investigated whether exogenous surfactant administered by lavage, consisting of a 35 ml/kg volume instilled by gravity and followed immediately by passive drainage (LAVAGE), would result in better lung distribution and physiologic response than with surfactant administered as a 5 ml/kg bolus (BOLUS). Exosurf, an artificial surfactant, was administered after acute lung injury induced by saline lung lavage in neonatal piglets. In the LAVAGE group (n= 9), 10.1 +/- 0.4 ml/kg of surfactant was retained, corresponding to a phospholipid dose of 136 +/- 5 mg/kg. In the BOLUS group (n = 9), the dose administered was 203 mg/kg phospholipid. Piglets in the LAVAGE group demonstrated greater improvement in pulmonary function, including PaO2, PaCO2, ventilation efficiency index, functional residual capacity (FRC), and pressure-volume curves than piglets in the BOLUS group. Some differences were found in lung distribution of surfactant. We conclude that Exosurf is more effective when administered by lavage in this lung injury model. We speculate that the lavage method of administration holds promise as an alternative method of surfactant administration in patients with ARDS.
Complications of Multiple Myeloma Therapy, Part 2: Risk Reduction and Management of Venous Thromboembolism, Osteonecrosis of the Jaw, Renal Complications, and Anemia
Authors: Ruben Niesvizky, Ashraf Z. Badros
Journal: Journal of the National Comprehensive Cancer Network (2010)

Venous thromboembolism (VTE), osteonecrosis of the jaw, renal failure, and anemia are all common complications of multiple myeloma therapy. Many of these adverse events have been documented only in the past 5 to 10 years, in conjunction with the introduction of a series of the newer therapies thalidomide, bortezomib, and lenalidomide. This article discusses these complications in detail and provides strategies for health care providers to best prevent, identify, and manage them. Preventive measures, such as VTE prophylaxis and appropriate dental hygiene, as well as patient education, dose adjustments, limited duration of drug treatment, and consideration of therapies that are associated with less burdensome adverse-event profiles, can contribute to substantially improved outcomes and quality of life.
Treatment, prognostic factors, and outcomes in spinal cord astrocytomas
Authors: Mohamad H. Fakhreddine, Anita Mahajan, Marta Penas-Prado, Jeffrey Weinberg, Ian E. McCutcheon, Vinay Puduvalli, Paul D. Brown
Journal: Neuro-Oncology (2013)

Spinal astrocytomas are rare intramedullary CNS tumors for which there is limited consensus on treatment; the importance of the extent of resection (EOR), postoperative radiotherapy, and chemotherapy remains poorly understood. We report on outcomes associated with surgery, postoperative radiotherapy, and chemotherapy in a series of patients treated at M. D. Anderson Cancer Center (MDACC) with the aim of elucidating the role of these treatments in spinal astrocytomas.We retrospectively reviewed charts from a series of 83 patients with histologically confirmed spinal astrocytoma treated at MDACC during 1990-2011. Data collected included patient demographic characteristics, prognostic indicators, and treatment modality at diagnosis. We analyzed overall survival (OS) and progression-free survival (PFS) for pilocytic (World Health Organization [WHO] grade I) and infiltrative (WHO grades II, III, and IV) astrocytomas, separately. Multivariate analysis was performed for the infiltrative patients but not the pilocytic patients because of a limited number of cases.Higher WHO grade among all patients was associated with worse OS (P < .0001) and PFS (P = .0003). Among patients with infiltrative tumors, neither EOR nor radiotherapy was associated with a difference in outcomes in multivariate analysis; however, among patients with infiltrative astrocytomas, chemotherapy was significantly associated with improved PFS (hazard ratio = .22, P = .0075) but not OS (hazard ratio = .89, P = .83) in multivariate analysis.WHO grade was the strongest prognostic indicator in patients with spinal cord astrocytomas. Our results also show that chemotherapy improved PFS in infiltrative astrocytomas in multivariate analysis, but neither EOR nor radiation therapy influenced outcomes in this group.
Inward Rectification and Implications for Cardiac Excitability
Authors: C.G. Nichols, E.N. Makhina, W.L. Pearson, Q. Sha, A.N. Lopatin
Journal: Circulation Research (1996)

Abstract Since the cloning of the first inwardly rectifying K + channel in 1993, a family of related clones has been isolated, with many members being expressed in the heart. Exogenous expression of different clones has demonstrated that between them they encode channels with the essential functional properties of classic inward rectifier channels, ATP-sensitive K + channels, and muscarinic receptor–activated inward rectifier channels. High-level expression of cloned channels has led to the discovery that classic strong inward, or anomalous, rectification is caused by very steeply voltage-dependent block of the channel by polyamines, with an additional contribution by Mg 2+ ions. Knowledge of the primary structures of inward rectifying channels and the ability to mutate them have led to the determination of many of the structural requirements of inward rectification. The implications of these advances for basic understanding and pharmacological manipulation of cardiac excitability may be significant. For example, cellular concentrations of polyamines are altered under different conditions and can be manipulated pharmacologically. Simulations predict that changes in polyamine concentrations or changes in the relative proportions of each polyamine species could have profound effects on cardiac excitability.
Gain-of-function mutant of angiotensin II receptor, type 1A, causes hypertension and cardiovascular fibrosis in mice
Authors: Sandrine Billet, Sabine Bardin, Sonia Verp, Véronique Baudrie, Annie Michaud, Sophie Conchon, Martine Muffat-Joly, Brigitte Escoubet, Evelyne Souil, Ghislaine Hamard, Kenneth E. Bernstein, Jean Marie Gasc, Jean-Luc Elghozi, Pierre Corvol, Eric Clauser
Journal: Journal of Clinical Investigation (2007)

The role of the renin-angiotensin system has been investigated by overexpression or inactivation of its different genes in animals. However, there is no data concerning the effect of the constitutive activation of any component of the system. A knockin mouse model has been constructed with a gain-of-function mutant of the Ang II receptor, type 1A (AT(1A)), associating a constitutively activating mutation (N111S) with a C-terminal deletion, which impairs receptor internalization and desensitization. In vivo consequences of this mutant receptor expression in homozygous mice recapitulate its in vitro characteristics: the pressor response is more sensitive to Ang II and longer lasting. These mice present with a moderate (~20 mmHg) and stable increase in BP. They also develop early and progressive renal fibrosis and cardiac fibrosis and diastolic dysfunction. However, there was no overt cardiac hypertrophy. The hormonal parameters (low-renin and inappropriately normal aldosterone productions) mimic those of low-renin human hypertension. This new model reveals that a constitutive activation of AT(1A) leads to cardiac and renal fibrosis in spite of a modest effect on BP and will be useful for investigating the role of Ang II in target organs in a model similar to some forms of human hypertension.
<i>CDC4</i> Mutations Occur in a Subset of Colorectal Cancers but Are Not Predicted to Cause Loss of Function and Are Not Associated with Chromosomal Instability
Authors: Zoe Kemp, Andrew Rowan, William Chambers, Noel Wortham, Sarah Halford, Oliver Sieber, Neil Mortensen, Axel von Herbay, Thomas Gunther, Mohammad Ilyas, Ian Tomlinson
Journal: Cancer Research (2005)

CDC4/FBXW7 is part of a ubiquitin ligase complex which targets molecules such as cyclin E, c-myc, and c-jun for destruction. CDC4 mutations occur in several cancer types and are best described in colorectal tumors. Knockout of CDC4 in vitro in colorectal cancer cells causes changes suggestive of chromosomal instability (CIN). In p53(+/-) mice, radiation-induced lymphomas show deletion or mutation of one copy of CDC4 and knockdown of CDC4 leads to increased aneuploidy in mouse fibroblasts. We screened 244 colorectal tumors and 40 cell lines for CDC4 mutations and allelic loss. Six percent (18 of 284) of tumors, including near-diploid (CIN-) lesions, harbored CDC4 mutations and there was no association between mutation and CIN (polyploidy). The CDC4 mutation spectrum in colorectal tumors was heavily biased towards C:G > T:A changes, either missense mutations at critical arginine residues or nonsense changes in the 5' half of the gene. The reasons for this odd mutation spectrum were unclear but C:G > T:A changes were not found more often than expected at APC, K-ras, or p53 in the same tumors and we found no specific defects in DNA repair to account for the observations. No colorectal tumor was found to carry two CDC4 mutations predicted to abolish protein function; partial loss of CDC4 function may therefore cause tumorigenesis. The in vitro studies, therefore, did not assess the functional effects of mutant alleles which are found in vivo. CDC4 mutations may be selected primarily to drive progression through the cell cycle although CIN might be an important secondary effect in some cancers.
Elevated Ornithine Decarboxylase Levels Activate Ataxia Telangiectasia Mutated–DNA Damage Signaling in Normal Keratinocytes
Authors: Gang Wei, Karen DeFeo, Candace S. Hayes, Patrick M. Woster, Laura Mandik-Nayak, Susan K. Gilmour
Journal: Cancer Research (2008)

We examined the effect of increased expression of ornithine decarboxylase (ODC), a key rate-limiting enzyme in polyamine biosynthesis, on cell survival in primary cultures of keratinocytes isolated from the skin of K6/ODC transgenic mice (Ker/ODC) and their normal littermates (Ker/Norm). Although elevated levels of ODC and polyamines stimulate proliferation of keratinocytes, Ker/ODC undergo apoptotic cell death within days of primary culture unlike Ker/Norm that continue to proliferate. Phosphorylation of ataxia telangiectasia mutated (ATM) and its substrate p53 are significantly induced both in Ker/ODC and in K6/ODC transgenic skin. Chromatin immunoprecipitation analyses show that the increased level of p53 in Ker/ODC is accompanied by increased recruitment of p53 to the Bax proximal promoter. ATM activation is polyamine dependent because alpha-difluoromethylornithine, a specific inhibitor of ODC activity, blocks its phosphorylation. Ker/ODC also displays increased generation of H(2)O(2), acrolein-lysine conjugates, and protein oxidation products as well as polyamine-dependent DNA damage, as measured by the comet assay and the expression of the phosphorylated form of the histone variant gamma H2AX. Both reactive oxygen species generation and apoptotic cell death of Ker/ODC may, at least in part, be due to induction of a polyamine catabolic pathway that generates both H(2)O(2) and cytotoxic aldehydes, because spermine oxidase (SMO) levels are induced in Ker/ODC. In addition, treatment with MDL 72,527, an inhibitor of SMO, blocks the production of H(2)O(2) and increases the survival of Ker/ODC. These results show a novel activation of the ATM-DNA damage signaling pathway in response to increased ODC activity in nontumorigenic keratinocytes.
The association between pulmonary arterial hypertension secondary to chronic lung disease and serum asymmetric dimethylarginine levels
Authors: Baris Açikmese, Güngör Çamsari, Aygün Gür, Nur Dilek Bakan, Gülcihan Özkan, Pinar Güven
Journal: European Respiratory Journal (2012)

Asymmetric dimethylarginin (ADMA) is an endogenous molecule that prevents nitric oxide synthesis enzyme inhibition. It has been shown that serum ADMA levels increase in COPD patients as well as idiopathic pulmonary hypertension patients. In this study, association between serum ADMA levels and pulmonary hypertensionsecondary to COPD and interstitial lung disease (ILD) was evaluated.  Fifty-six COPD and 20 ILD patients who have no documented additional disease were included into the study. Echocardiography was used to evaluate pulmonary arterial pressure (PAP). Serum ADMA levels were measured by ELISA.  Association between OPAP and serum ADMA levels were evaluated by Pearson correlation test. Mean ADMA levels of patients have normal and high OPAP were compared by student-t test. Mean serum ADMA levels of patients have increased OPAP was found significantly higher than that of patients have normal OPAP (p  Serum ADMA levels measurement may be an indicator for PH secondary to COPD and ILD but it is not enough sensitive test according to the ROC analysis.
Laser hair reduction in the hirsute patient: a critical assessment
Authors: L. A. Sanchez
Journal: Human Reproduction Update (2002)

Hirsutism affects 5–10% of unselected women, depending on ethnicity and definition. The past two decades have seen the development of lasers for the removal of unwanted hair, using selective destruction of the hair follicle without damage to adjacent tissues. Selective photothermolysis relies on the absorption of a brief radiation pulse by specific pigmented targets, which generates and confines the heat to that selected target. In general, laser hair removal is most successful in patients with lighter skin colours and dark coloured hairs. Some studies have documented the results of laser hair removal in a controlled setting, although few have extended their observations beyond 1 year. In general, treatment with the ruby, alexandrite or diode lasers, or the use of intense pulsed light results in similar success rates, although these are somewhat lower for the neodymium:Yttrium–Aluminum–Garnet (nd:YAG) laser. Overall, laser hair removal should not be considered 'permanent', at least when considering the current data available. Repeated therapies are necessary, although complete alopoecia is rarely achieved and it is unclear at what point the maximum benefit is achieved from multiple therapies. While larger prospective, controlled, blinded and uniform studies are still needed, laser hair removal appears to be a useful adjuvant in the treatment of the hirsute patient.
Regulatory Challenges for the Resuscitation Outcomes Consortium
Authors: Samuel A. Tisherman, Judy L. Powell, Terri A. Schmidt, Tom P. Aufderheide, Peter J. Kudenchuk, Julie Spence, Dixie Climer, Donna Kelly, Angela Marcantonio, Todd Brown, George Sopko, Richard Kerber, Jeremy Sugarman, David Hoyt
Journal: Circulation (2008)
Clinical Course of Patients with Non–Small Cell Lung Cancer and Epidermal Growth Factor Receptor Exon 19 and Exon 21 Mutations Treated with Gefitinib or Erlotinib
Authors: Gregory J. Riely, William Pao, DuyKhanh Pham, Allan R. Li, Naiyer Rizvi, Ennapadam S. Venkatraman, Maureen F. Zakowski, Mark G. Kris, Marc Ladanyi, Vincent A. Miller
Journal: Clinical Cancer Research (2006)

In patients with non-small cell lung cancer (NSCLC), mutations in the epidermal growth factor receptor (EGFR) tyrosine kinase domain have been associated with sensitivity to erlotinib and gefitinib. We undertook this study to explore the relationship between EGFR mutation type and clinical variables, including treatment with gefitinib and erlotinib.In patients with NSCLC, EGFR exon 19 deletion mutations and EGFR L858R point mutations were analyzed by nonsequencing PCR-based methods from paraffin blocks of tissue obtained before treatment. The results were correlated with clinical information (sex, pathologic subtype, race/ethnicity, treatment, and overall survival).The two most common EGFR mutations were identified in 24% (70 of 291; 95% confidence interval, 26%-38%) of tumors from patients with NSCLC. EGFR mutation was associated with Asian ethnicity (P = 0.0023) and being a "never smoker" (P = 0.0001). Among patients with EGFR mutations, 39% (27 of 70) had EGFR L858R, whereas 61% (43 of 70) had an EGFR exon 19 deletion. After treatment with erlotinib (n = 12) or gefitinib (n = 22), patients with EGFR mutations had a median overall survival of 20 months. After treatment with erlotinib or gefitinib, patients with EGFR exon 19 deletions had significantly longer median survival than patients with EGFR L858R (34 versus 8 months; log-rank P = 0.01).EGFR mutations in exons 19 or 21 are correlated with clinical factors predictive of response to gefitinib and erlotinib. Those with EGFR exon 19 deletion mutations had a longer median survival than patients with EGFR L858R point mutation. These observations warrant confirmation in a prospective study and exploration of the biological mechanisms of the differences between the two major EGFR mutations.
Akt Inhibitors MK-2206 and Nelfinavir Overcome mTOR Inhibitor Resistance in Diffuse Large B-cell Lymphoma
Authors: Adam M. Petrich, Violetta Leshchenko, Pei-Yu Kuo, Bing Xia, Venu K. Thirukonda, Netha Ulahannan, Shanisha Gordon, Melissa J. Fazzari, B. Hilda Ye, Joseph A. Sparano, Samir Parekh
Journal: Clinical Cancer Research (2012)

The mTOR pathway is constitutively activated in diffuse large B-cell lymphoma (DLBCL). mTOR inhibitors have activity in DLBCL, although response rates remain low. We evaluated DLBCL cell lines with differential resistance to the mTOR inhibitor rapamycin: (i) to identify gene expression profile(s) (GEP) associated with resistance to rapamycin, (ii) to understand mechanisms of rapamycin resistance, and (iii) to identify compounds likely to synergize with mTOR inhibitor.We sought to identify a GEP of mTOR inhibitor resistance by stratification of eight DLBCL cell lines with respect to response to rapamycin. Then, using pathway analysis and connectivity mapping, we sought targets likely accounting for this resistance and compounds likely to overcome it. We then evaluated two compounds thus identified for their potential to synergize with rapamycin in DLBCL and confirmed mechanisms of activity with standard immunoassays.We identified a GEP capable of reliably distinguishing rapamycin-resistant from rapamycin-sensitive DLBCL cell lines. Pathway analysis identified Akt as central to the differentially expressed gene network. Connectivity mapping identified compounds targeting Akt as having a high likelihood of reversing the GEP associated with mTOR inhibitor resistance. Nelfinavir and MK-2206, chosen for their Akt-inhibitory properties, yielded synergistic inhibition of cell viability in combination with rapamycin in DLBCL cell lines, and potently inhibited phosphorylation of Akt and downstream targets of activated mTOR.GEP identifies DLBCL subsets resistant to mTOR inhibitor therapy. Combined targeting of mTOR and Akt suppresses activation of key components of the Akt/mTOR pathway and results in synergistic cytotoxicity. These findings are readily adaptable to clinical trials.