tbuckley/cabot-search huggingface dataset:
Abstract 62: Cardiac Troponin T Isoform Switching in Early Childhood Tropomyosin-linked Dilated Cardiomyopathy
Authors: Melissa Lynn, Lauren Tal-Grinspan, J.-P. Jin, Jil Tardiff
Journal: Circulation Research (2015)

An oft-noted component of sarcomeric DCM is the observation that patients within families carrying the same primary mutation exhibit significant phenotypic variability. This lack of a distinct link between genotype and phenotype has complicated clinical management. In a recent study of two unrelated multigenerational families with the tropomyosin (Tm) mutation Asp230Asn (D230N), a striking “bimodal” distribution of severity was observed. In these families, many children (&lt;1 year) with the mutation presented with a severe form of DCM that led to sudden, often fatal CHF while adults developed a mild to moderate DCM in mid-life. Of note, children who survived the initial presentation often recovered significant systolic function into young adulthood. A potential hypothesis to explain this improvement despite the continued presence of the mutant Tm, is that the phenotype is modified by other thin filament isoforms. Thus we propose that the age-dependent remodeling seen in children with D230N Tm is a result of temporal isoform switches involving a closely linked Tm binding partner cardiac Troponin T (cTnT). Our initial biophysical studies (Regulated-IVM) revealed a decreased Ca2+ sensitivity in filaments containing D230N Tm that is more severe in the presence of fetal TnT (cTnT1), suggesting a modulatory role for cTnT1. Cardiac performance, assessed via 2D echo, in our novel D230N Tm x cTnT1 double transgenic (DTg) mouse model found a significantly reduced % FS for DTg (17%) mice as compared to D230N Tm (21%) littermates. This reduction in %FS was seen at 4 months but not 2 suggesting a progressive cardiomyopathy. Current efforts aim to model the early phase of this “bimodal” phenotype and assess the potential for disease reversibility using a cardiac specific inducible cTnT1 transgenic mouse model. Furthermore, we propose that modulation by cTnT1 could represent a more general mechanism for the progressive remodeling seen in human heart failure. Preliminary in vitro studies with human tissue found that RNA levels of cTnT1 are significantly higher in failing hearts as compared to non-failing. Thus these data suggest an isoform dependent mechanism for the “bimodal” phenotype in patients carrying D230N Tm that could translate to other sarcomeric cardiomyopathies.
Dose modifications, dose-effect relationship, and adverse effects in patients with advanced non-small cell lung cancer treated with erlotinib.
Authors: D. Binder, T. Beinert, R. Hübner, B. Temmesfeld-Wollbrück, N. Suttorp
Journal: Journal of Clinical Oncology (2010)

e18113 Background: Erlotinib is a valuable treatment option in some patients (pts.) with non-small cell lung cancer. In sensitive patients the treatment allows long-lasting disease control. However, many patients suffer from adverse effects leading to dose reductions or termination of treatment. Up to now there is only sparse knowledge about the dose-effect relationship with erlotinib. Methods: We retrospectively reviewed the files of all pts. treated with erlotinib. We assessed dose reductions, adverse event management and efficacy. Results: From November, 2005 to December, 2009 fifty-one pts. with advanced non-small cell lung cancer were treated with erlotinib. There were 10 never-smokers, 21 ex-smokers and 20 smokers. 28 pts. were female and 23 male. In 32 pts. erlotinib was the second-line treatment, while in 9/9/1 it was third/fourth/fifth line. Of the 40 pts. initially on 150 mg daily dose 14 (35%) required dose reductions. After adjustment of the doses, most of the pts. reached a “stable dose” where toxicity was tolerable. In 9 pts. the stable dose was 100 mg daily and in 9 pts. 75 or 50 mg daily. We observed two female pts. whose stable dose was 50 mg/day and whose disease was controlled for 31 mo. (EGFR exon 21 mutation) and 50+ months (exon 18/19/21 wildtype). One female patient under 75 mg daily had disease controlled for 18 mo. (exon 18/19/21 wildtype). The treatment was discontinued due to adverse effects in 4/51 pts. (8%) (painful oral ulcerations, severe kerato-conjunctivitis, severe mucositis in a patient with Sjögren's syndrome, nausea/weakness). Conclusions: Numerous patients require dose reductions under treatment with erlotinib. However, in tumors with sensitivity to erlotinib, even daily doses of 50-75 mg can result in sustained disease control. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Payment of travel expenses
Herpes Simplex Virus Type 2 and Human Cervical Cancer: Relationship Between Cellular and Humoral Immune Assays for the Detection of Previous Infection2, 3
Authors: Jerry W. Smith, Jose E. Torres, Nelson D. Holmquist
Journal: JNCI Journal of the National Cancer Institute (1981)

Journal Article Herpes Simplex Virus Type 2 and Human Cervical Cancer: Relationship Between Cellular and Humoral Immune Assays for the Detection of Previous Infection, Get access Jerry W. Smith, Jerry W. Smith Search for other works by this author on: Oxford Academic PubMed Google Scholar Jose E. Torres, Jose E. Torres Search for other works by this author on: Oxford Academic PubMed Google Scholar Nelson D. Holmquist Nelson D. Holmquist Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 66, Issue 6, June 1981, Pages 1031–1036, https://doi.org/10.1093/jnci/66.6.1031 Published: 01 June 1981 Article history Received: 04 August 1980 Accepted: 17 December 1980 Published: 01 June 1981
Abstract 15053: Directing Stem Cells to the Infarcted Heart Using StemBells™: Introducing a Novel Technique Using Targeted Microbubbles
Authors: Benno Naaijkens, Paul Krijnen, Sylvia Bogaards, Elisa Meinster, Otto Kamp, Rene Musters, Tom Kokhuis, Nico de Jong, Annemieke van Dijk, Hans Niessen, Lynda Juffermans
Journal: Circulation (2013)
Not all women with dense breasts need further imaging after normal mammogram, study shows
Authors: S. Mayor
Journal: BMJ (2015)

Women who are found to have dense breasts on an apparently normal mammogram sometimes undergo further imaging to check their risk of breast cancer, but a new US study shows that more than half of these women are at low risk and recommends that other risk factors should be considered before further investigation.

High breast density, with a higher proportion of breast and connective tissue than of fat, increases the risk of breast cancer and can mask tumours, reducing the sensitivity of mammography. As a result, …
Analysis of hormonal receptor status in tissue from prostate cancer that developed 26 years after bilateral orchiectomy and following 41 years of estrogen therapy
Authors: R. A. Miksad, G. Bubley, P. Church, A. Cooper, N. Rofsky, I. Kaplan, M. Sanda
Journal: Journal of Clinical Oncology (2006)

14610 Background: The development of prostate cancer in the absence of normal male testosterone levels and in the presence of elevated estrogen levels is rare and poorly understood. Methods: The androgen, estrogen and progesterone receptors were evaluated in prostate cancer tissue from a 60-year-old, long-term transgender woman. Her serum hormone levels were assessed and the prostate specific antigen (PSA) level was followed during hormonal and radiation treatment. This patient began estrogen therapy at age 19 and underwent bilateral orchiectomy at age 34 during gender re-assignment surgery. Work-up for gross hematuria revealed a Gleason 8, locally advanced prostate cancer. Results: The tumor showed abundant staining for androgen receptors (AR), with a nuclear pattern consistent with hormone refractory prostate cancer. The tumor did not stain for estrogen receptors (ER) or progesterone receptors (PR). Compared to reference values for men, this transgender woman had low serum testosterone (44 ng/dl) and free testosterone (0.9 pg/mL) levels and elevated estradiol (53 pg/mL) and estrone (377 pg/mL) levels. Prior to the initiation of radiation, treatment with bicalutamide and dutasteride reduced her PSA from 240 ng/ml to 77 ng/ml at week 6 (see Table). After treatment with external beam radiation her PSA fell to 4.6 ng/mL. At week 24, her PSA was 0.8 ng/mL. Conclusions: This high-grade, locally advanced prostate cancer in a transgender woman represents the longest reported duration of a castrate state preceding the development of prostate cancer, exceeding prior reports by several decades. The AR positive and ER/PR negative status of this tumor in the setting of low testosterone and elevated estrogen levels challenge long-standing paradigms regarding the testosterone requirement for prostatic carcinogenesis. In addition, these findings raise questions about the role of estrogens in prostate cancer. [Table: see text] [Table: see text]
Value of Personalized Medicine—Reply
Authors: Michael J. Joyner, Nigel Paneth
Journal: JAMA (2016)

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
Bevacizumab and irinotecan for recurrent oligodendroglial tumors
Authors: S. Taillibert, L. A. Vincent, B. Granger, Y. Marie, C. Carpentier, R. Guillevin, A. Bellanger, D. Psimaras, M. Sanson, J. Delattre
Journal: Journal of Clinical Oncology (2009)

2054 Background: Treatment with a regimen of bevacizumab/irinotecan has been shown to be effective in recurrent grade 3 and 4 gliomas, but the effect of this regimen against recurrent oligodendroglial tumors has not been specifically studied. Methods: The bevacizumab/irinotecan regimen was retrospectively evaluated in a consecutive series of 25 patients with recurrent oligodendroglial tumors. All patients had failed previous treatment with radiation therapy and at least one line of temozolomide chemotherapy. Bevacizumab (10 mg/kg) and irinotecan (125 or 340 mg/m 2 according to the antiepileptic regimen) were delivered every 14 days. Response was measured clinically and on monthly MRI. Results: The objective response rate was 72% (20% complete response, 52% partial response). After a median follow-up (from the first cycle) of 310 days (95% CI, 47–499), the median progression-free survival was 174 days (95% CI, 116–342), and the median overall survival was 328 days (95%CI, 217-not reached). The 6-month progression-free survival was 42 % (95 % CI, 26% to 67%). Among the 20 patients who progressed at the time of the analysis, the radiological pattern of progression was atypical in seven patients with an isolated multifocal or diffuse spread of the FLAIR signal, or an isolated meningeal spread or FLAIR abnormalities preceding contrast-enhancement recurrence. Among the 10 patients who are still alive, two are still on follow-up since 6 months with a complete response after, respectively, 10 and 12 months of treatment. Among the 17 patients in whom the status of the main molecular alterations of gliomas could be evaluated (search for deletions of chromosomes 1p, 19q, 9p, 10q, and amplification of EGFR, MDM2, CDK4), no relation could be found between the response rate and the type of genetic change (including 1p-19q co-deletion). The profile of tolerance was fair, with treatment discontinuation in 20% of patients. Intratumoral hemorrhages occurred in six patients (24%), but the treatment had to be discontinued because of symptomatic bleeding in only one patient (4%). Conclusions: This regimen is effective in recurrent oligodendrogliomas, and the overall tolerance is acceptable. [Table: see text]
Quality of surgical margins and local recurrence in primary extremity soft tissue sarcoma (STS).
Authors: S. Bonvalot, A. Dunant, C. le Pechoux, P. Terrier, F. Rimareix, B. Boulet, L. Medjoub, A. Cioffi, J. Domont, A. Le Cesne
Journal: Journal of Clinical Oncology (2010)

10068 Background: In previous studies, quality of margins after resection of primary STS of extremity was only defined by their size. Methods: We analyzed all patients (pts) with primary limbs STS addressed for surgery in our institution from 1997 to 2008 in a prospective data base. All histological specimens were reviewed and quality of margins prospectively evaluated. The minimum margin (in mm) and the type of surrounding tissue (muscle, aponevrosis, fat, periosteum) were registered on fixed specimen. The endpoints were mortality, local recurrence (LR) and distant metastasis analyzed by Cox multivariate models. Results: There were 450 pts: 50% were operated at first after pre-operative biopsy (Group A) and 50% had a second extended resection after unplanned surgery (Group B). 81% were deep. Mean tumor size was 12cm in group A and 7cm in group B (p<.0001). Grades were: 1 (21%), 2 (33%), 3 (47%). 99% had limb sparing surgery with 14% flap reconstruction. Margins (mm) were 0 in 14%, [0 – 1]: 28%, [1 – 5]: 37%, [5 – 10]: 11%, >10: 10%. Clear median minimum margin was 2mm (0.5 – 35). Tissue type varied according to width, with higher proportion of aponevrosis and periosteum below 2mm (61%) than above (29%) (p<.0001). In group B, residual tumor was found in 61% of pts. 36% of pts received chemotherapy (neo-adjuvant 88%, adjuvant 12%), 18% had neo-adjuvant isolated limb perfusion. 74% of pts received radiotherapy (post op 93%, pre op 6%) with a median dose of 50Gy (30 to 70Gy). Among pts who had neo adjuvant ILP/CT/RX, the mean% of viable cells was 36, 44 and 46 respectively. With a median follow up of 4.2 yrs, the 5-yr OS, LR and metastatic rates were 79%, 8% and 22% respectively. In the multivariate analysis, high grade (p<.0001) and large tumor size (p<.002) were the only predictive factors for shorter OS. Absence of clear margins (0mm) was significantly predictive of LR (p<.001). Conclusions: In this high risk series, a very low rate of local recurrence was observed despite a small median minimum margin. This suggests that the quality of margins should integrate the quality of the tissue involved. A planned extended surgery associated with combined treatments guarantees a very low risk of amputation or re intervention. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis, Pfizer, PharmaMar Novartis, Pfizer, PharmaMar
Long-term results of cyclosporin A therapy in children.
Authors: J Brodehl, A Bökenkamp, P F Hoyer, G Offner
Journal: Journal of the American Society of Nephrology (1992)

In order to assess the long-term effectiveness and tolerability of cyclosporin A (CsA) treatment in children with renal transplantation (Tx), the follow-ups of 32 children (17 boys, 15 girls; age at Tx = 12.2 yr; range, 5.1 to 16.9) with a functioning graft of greater than or equal to 5 yr and continuous treatment with CsA and low-dose prednisolone are analyzed retrospectively. For comparison, data of 34 children (19 boys, 15 girls; age at Tx, 11.0; range, 3.2 to 17.1) are collected who had received a graft before the introduction of CsA, had at least 5 yr of graft function, and were continuously treated with azathioprine (AZA) plus high-dose prednisolone. The mean observation period in the CsA group was 6.5 (range, 5.0 to 8.0) yr, and in the AZA group was 10.4 yr (range, 5.7 to 15.8). CsA dosage remained unchanged in the range of 200 mg/m2/day; CsA whole blood trough level was 120 to 130 ng/mL throughout the years. One patient died in each group. Four more grafts were lost in the CsA group by chronic rejection, which was associated with noncompliance in three, and two grafts were lost in the AZA group by chronic rejection. Late acute reversible rejection episodes occurred more frequent in the CsA (six) than in the AZA group (two). The overall survival rates for patients and grafts were significantly better with CsA. The graft function in CsA-treated recipients was significantly lower than that in AZA patients, but there was no progressive loss over the years.(ABSTRACT TRUNCATED AT 250 WORDS)
Pharmacokinetic (PK) analysis of a phase I trial investigating continuous treatment with the angiokinase inhibitor BIBF 1120 combined with pemetrexed in previously treated patients with non-small cell lung cancer (NSCLC)
Authors: N. H. Hanna, Y. Zhao, R. Kaiser, P. Stopfer, S. Gyorffy, P. M. Ellis
Journal: Journal of Clinical Oncology (2008)

14511 Background: BIBF 1120 is a novel, oral, potent angiokinase inhibitor blocking the VEGFR 1/2/3, FGFR 1/3, and PDGFR α/β tyrosine kinases. The potential additive antitumour effects of an angiokinase inhibitor in combination with pemetrexed may result in more effective treatment of recurrent NSCLC compared to a single agent alone. Methods: The objectives of this Phase I trial were to determine safety, tolerability, maximum tolerated dose (MTD) and PK of BIBF 1120 in combination with standard dose of pemetrexed. The BIBF 1120 dose was increased by 50 mg/cohort until the MTD was determined. PK samples were taken on Days 1 and 2 of treatment cycle (TC) 2. PK parameters were calculated by non-compartmental techniques. Results: A total of 26 patients (pts) (13 male, 13 female, median age: 61.5 years, range 36–81, ECOG performance status of 0–1) with recurrent NSCLC and one prior platinum based chemotherapy regimen received pemetrexed (500 mg/m2) on Day 1 of each 21-day TC and BIBF 1120 starting at 100 mg bid on Days 2–21. The MTD of BIBF 1120 was 200 mg bid. At 250 mg bid of BIBF 1120, 1 pt had a Grade 3 ALT-increase, fatigue and esophageal pain and 1 had Grade 2 AST-elevation. For pemetrexed, main exposure occurred during 24 hours after i.v. administration (geometric mean [gMean] AUC0–24=200 μg·h/mL on Day 1 of TC2; median tmax values ≈0.28 hours [range 0.016–0.5 hours]; gMean terminal half-life [t1/2] ≈3.71 hours on Day 1 of TC2). gMean total body clearance (CL) on Day 1 of TC 2 = 4.78 L/hour. At the MTD of BIBF 1120, maximum plasma concentrations (Cmax) of BIBF 1120 were reached ∼2 hours after dosing on Day 2 of TC 2 (range 0–3 hours); gMean Cmax = 50.4 ng/mL. The gMean exposure (AUC0–24) to BIBF 1120 = 308 ng·h/mL; t1/2 ≈12.1 on Day 2 of TC 2. The apparent volume of distribution (8,580 L) and clearance (8,180 mL/min) during the terminal phase were relatively high. No systematic change in trough plasma concentrations or deviation from dose proportionality of BIBF 1120 was observed in combination with pemetrexed. Conclusions: There was no clinically relevant PK interaction between BIBF 1120 and pemetrexed in pts with advanced NSCLC, showing that this combination is viable for future studies. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Boehringer Ingelheim Pharma GmbH & Co. KG, Boehringer Ingelheim Pharmaceuticals, Inc. Boehringer Ingelheim, Eli Lilly Boehringer Ingelheim, Eli Lilly
Abstract 13892: Early as Compared to Late Development of Acute Kidney Injury is a Strong Predictor of In-Hospital Mortality in Patients With Acute Myocardial Infarction
Authors: Noriaki Moriyama, Masaharu Ishihara, Teruo Noguchi, Hiroki Sakamoto, Michio Nakanishi, Tetsuo Arakawa, Yasuhide Asaumi, Leon Kumasaka, Tomoaki Kanaya, Tadayoshi Miyagi, Toshiyuki Nagai, Takafumi Yamane, Masashi Fujino, Satoshi Honda, Reiko Fujiwara, Toshihisa Anzai, Atsushi Kusano, Yoichi Goto, Satoshi Yasuda, Hisao Ogawa
Journal: Circulation (2013)

Background: Acute kidney injury (AKI) often occurs in patients with acute myocardial infarction (AMI) and is associated with unfavorable outcomes. However, the impact of timing of AKI development o...
Characteristics of women at risk for psychosocial distress in the year after breast cancer.
Authors: C A Schag, P A Ganz, M L Polinsky, C Fred, K Hirji, L Petersen
Journal: Journal of Clinical Oncology (1993)

PURPOSE To provide a detailed description of rehabilitation problems of women, considered to be low risk and at risk for psychosocial morbidity, diagnosed with stage I and II breast cancer 1 month and 1 year after primary treatment. PATIENTS AND METHODS A sample of 227 newly diagnosed breast cancer patients were systematically interviewed by a clinical social worker and classified for risk of psychosocial distress in the year after diagnosis. They completed a battery of standardized instruments to assess quality of life (QL), rehabilitation needs, and psychologic distress. The primary QL instrument, the Cancer Rehabilitation Evaluation System (CARES), provides a detailed listing of rehabilitation needs. Descriptive CARES data are presented with comparisons between the two groups. RESULTS The at-risk women had significantly more problems with greater severity than the low-risk women in all areas (physical, psychosocial, medical interaction, sexual, and marital). While both groups showed improvement over the year following diagnosis, the at-risk group had significantly more problems 1 year later. Many physical problems subside, but problems at the local surgical site, psychologic distress, communication with marital partners, and negative body image are more persistent in the at-risk group 1 year later, while half of both groups continue to have sexual dysfunction. CONCLUSION The detailed listing of problems provided by the CARES may be helpful to clinicians in their interactions with patients. The need for preventive and early intervention for the at-risk patients is underscored.
CHAPTER 2: Management of Blood Pressure in Hemodialysis Patients
Authors: Kailash Jindal, Christopher T. Chan, Clement Deziel, David Hirsch, Steven D. Soroka, Marcello Tonelli, Bruce F. Culleton
Journal: Journal of the American Society of Nephrology (2006)

### Recommendations



1.  Use predialysis blood pressure to guide therapy. (Grade C) 

2.  Target predialysis blood pressure to be <140/90 (Grade C); optimal blood pressure is unknown. 

3.  Ambulatory recording devices or home self-measurement should be applied to patients where difficulty occurs