tbuckley/cabot-search huggingface dataset:
Skin cancer chemoprophylaxis in renal transplant recipients: 5 years of experience using low-dose acitretin
Authors: None McKENNA, None MURPHY
Journal: British Journal of Dermatology (1999)

Renal transplant recipients have an increased risk of developing skin cancers, which are often multiple and aggressive. Frequently, these tumours develop on a background of widespread epidermal dysplasia. Systemic retinoids are known inhibitors of skin cancer but reports of their use in renal transplant patients are limited. We describe our experience using 0.3 mg/kg daily of acitretin in 16 patients over a 5‐year period. Overall, there was a significant reduction in the number of new tumours excised in 12 of 16 patients during treatment compared with the same pretreatment interval. A significant chemoprophylactic effect was shown for up to 4 years of treatment. Patients with five or more tumours prior to acitretin benefited most. Two patients discontinued treatment because of side‐effects and two patients developed hyperlipidaemia. Two patients with end‐stage graft failure proceeded to haemodialysis. The introduction of low‐dose acitretin proved to be a useful strategy in the long‐term reduction of skin cancer in renal transplant recipients with multiple skin cancers and extensive epidermal dysplasia.
Activation, Self-management, Engagement, and Retention in Behavioral Health Care
Authors: Margarita Alegría, Nicholas Carson, Michael Flores, Xinliang Li, Ping Shi, Anna Sophia Lessios, Antonio Polo, Michele Allen, Mary Fierro, Alejandro Interian, Aida Jimenez, Martin La Roche, Catherine Lee, Roberto Lewis-Fernández, Gabriela Livas-Stein, Laura Safar, Catherine Schuman, Joan Storey, Patrick E. Shrout
Journal: JAMA Psychiatry (2014)

Given minority patients' unequal access to quality care, patient activation and self-management strategies have been suggested as a promising approach to improving mental health care. To determine whether the DECIDE (Decide the problem; Explore the questions; Closed or open-ended questions; Identify the who, why, or how of the problem; Direct questions to your health care professional; Enjoy a shared solution) intervention, an educational strategy that teaches patients to ask questions and make collaborative decisions with their health care professional, improves patient activation and self-management, as well as engagement and retention in behavioral health care. In this multisite randomized clinical trial performed from February 1, 2009, through October 9, 2011 (date of last follow-up interview), we recruited 647 English- or Spanish-speaking patients 18 to 70 years old from 13 outpatient community mental health clinics across 5 states and 1 US territory. A total of 722 patients were included in analyses of secondary outcomes. Three DECIDE training sessions delivered by a care manager vs giving patients a brochure on management of behavioral health. Primary outcomes were patient assessment of activation (Patient Activation Scale) and self-management (Perceived Efficacy in Patient-Physician Interactions). Secondary outcomes included patient engagement (proportion of visits attended of those scheduled) and retention (attending at least 4 visits in the 6 months after the baseline research assessment), collected through medical record review or electronic records. Patients assigned to DECIDE reported significant increases in activation (mean β = 1.74, SD = 0.58; P = .003) and self-management (mean β = 2.42, SD = 0.90; P = .008) relative to control patients, but there was no evidence of an effect on engagement or retention in care. The DECIDE intervention appears to help patients learn to effectively ask questions and participate in decisions about their behavioral health care, but a health care professional component might be needed to augment engagement in care. DECIDE appears to have promise as a strategy for changing the role of minority patients in behavioral health care. clinicaltrials.gov Identifier: NCT01226329
Left Ventricular Diastolic Dysfunction and Diastolic Heart Failure
Authors: William H. Gaasch, Michael R. Zile
Journal: Annual Review of Medicine (2004)

Thirty to fifty percent of patients presenting with signs and symptoms of heart failure have a normal left ventricular (LV) systolic ejection fraction. The clinical examination cannot distinguish these patients (diastolic heart failure) from those with a depressed ejection fraction (systolic heart failure), but echocardiography can. The management of diastolic heart failure has two major objectives. The first is to reverse the consequences of diastolic dysfunction (e.g., venous congestion), and the second is to eliminate or reduce the factors responsible for diastolic dysfunction (e.g., myocardial hypertrophy, fibrosis, and ischemia).
Two doses of NGR-hTNF in combination with capecitabine plus oxaliplatin in colorectal cancer patients failing standard therapies
Authors: S. Mammoliti, V. Andretta, E. Bennicelli, F. Caprioni, D. Comandini, G. Fornarini, A. Guglielmi, A. Pessino, S. Sciallero, A.F. Sobrero, G. Mazzola, A. Lambiase, C. Bordignon
Journal: Annals of Oncology (2010)

asparagine-glycine-arginine-human tumour necrosis factor (NGR-hTNF), an agent selectively damaging the tumour vasculature, showed a biphasic dose-response curve in preclinical models. Previous phase I trials of NGR-hTNF indicated 0.8 and 45 μg/m(2) as optimal biological and maximum-tolerated dose, respectively.Two sequential cohorts of 12 colorectal cancer (CRC) patients who had failed standard therapies received NGR-hTNF 0.8 or 45 μg/m(2) in combination with capecitabine-oxaliplatin (XELOX).Median number of prior treatment lines was 3 in the low-dose and 2 in the high-dose cohort. Overall, 21 patients had been pretreated with oxaliplatin-based regimens. No grade 3-4 NGR-hTNF-related toxicities were observed. Grade 1-2 chills were reported in 43% and 40% of cycles in the low-dose and high-dose cohorts, respectively. In the low-dose cohort, one patient achieved a partial response and five had stable disease for a median of 4.6 months. In the high-dose cohort, six patients had stable disease for a median of 3.6 months. Three-month progression-free survival (PFS) rates were 50% and 33% in the low-dose and high-dose cohort, respectively. Three patients in low-dose cohort experienced PFS longer than PFS on last prior therapy.Both NGR-hTNF doses were safely combined with XELOX in pretreated CRC patients. Hint of activity was apparent only with low-dose NGR-hTNF.
Evaluation of Universal Antenatal Screening for Group B Streptococcus
Authors: Melissa K. Van Dyke, Christina R. Phares, Ruth Lynfield, Ann R. Thomas, Kathryn E. Arnold, Allen S. Craig, Janet Mohle-Boetani, Ken Gershman, William Schaffner, Susan Petit, Shelley M. Zansky, Craig A. Morin, Nancy L. Spina, Kathryn Wymore, Lee H. Harrison, Kathleen A. Shutt, Joseph Bareta, Sandra N. Bulens, Elizabeth R. Zell, Anne Schuchat, Stephanie J. Schrag
Journal: New England Journal of Medicine (2009)

Group B streptococcal disease is one of the most common infections in the first week after birth. In 2002, national guidelines recommended universal late antenatal screening of pregnant women for colonization with group B streptococcus to identify candidates for intrapartum chemoprophylaxis.
Genomic Analysis of Metastatic Cutaneous Squamous Cell Carcinoma
Authors: Yvonne Y. Li, Glenn J. Hanna, Alvaro C. Laga, Robert I. Haddad, Jochen H. Lorch, Peter S. Hammerman
Journal: Clinical Cancer Research (2015)

A rare 5% of cutaneous squamous cell carcinomas (cSCC) metastasize, lack FDA-approved therapies, and carry a poor prognosis. Our aim was to identify recurrent genomic alterations in this little-studied population of metastatic cSCCs.We performed targeted sequencing of 504 cancer-associated genes on lymph node metastases in 29 patients with cSCC and identified mutations and somatic copy-number alterations associated with metastatic cSCC. We determined significantly mutated, deleted, and amplified genes and associated genomic alterations with clinical variables.The cSCC genome is heterogeneous with widely varying numbers of genomic alterations and does not appear to be associated with human papillomavirus. We found previously identified recurrently altered genes (TP53, CDKN2A, NOTCH1/2) but also a wide spectrum of oncogenic mutations affecting RAS/RTK/PI3K, squamous differentiation, cell cycle, and chromatin remodeling pathway genes. Specific mutations in known oncogenic drivers and pathways were correlated with inferior patient outcomes. Our results suggest potential therapeutic targets in metastatic cSCC, including PIK3CA, FGFR3, BRAF, and EGFR, similar to those reported in SCCs of the lung and head and neck, suggesting that clinical trials could be developed to accrue patients with SCCs from multiple sites of origin.We have genomically characterized a rare cohort of 29 metastatic cSCCs and identified a diverse array of oncogenic alterations that can guide future studies of this disease.
Multiple immuno-regulatory defects in type-1 diabetes
Authors: Anjli Kukreja, Giulia Cost, John Marker, Chenhui Zhang, Zhong Sun, Karen Lin-Su, Svetlana Ten, Maureen Sanz, Mark Exley, Brian Wilson, Steven Porcelli, Noel Maclaren
Journal: Journal of Clinical Investigation (2002)

Susceptibility to immune-mediated diabetes (IMD) in humans and NOD mice involves their inherently defective T cell immunoregulatory abilities. We have followed natural killer (NK) T cell numbers in patients with IMD, both by flow cytometry using mAbs to the characteristic junctions found in the T cell receptors of this cell subtype, and by semiquantitative RT-PCR for the corresponding transcripts. Both before and after clinical onset, the representation of these cells in patients’ PBMCs is reduced. We also report low numbers of resting CD4+ CD25+ T cells in IMD patients, a subset of T cells shown to have important immunoregulatory functions in abrogating autoimmunities in 3-day thymectomized experimental mice. Whereas a biased Th1 to Th2 cytokine profile has been suggested to underlie the pathogenesis of IMD in both species, we found defective production of IFN-γ in our patients after in vitro stimulation of their PBMCs by phorbol-myristate acetate and ionomycin and both IFN-γ and IL-4 deficiencies in Vα24+ NK T–enriched cells. These data suggest that multiple immunoregulatory T (Treg) cell defects underlie islet cell autoimmunity leading to IMD in humans and that these lesions may be part of a broad T cell defect.
Cognitive Function After the Initiation of Adjuvant Endocrine Therapy in Early-Stage Breast Cancer: An Observational Cohort Study
Authors: Patricia A. Ganz, Laura Petersen, Steven A. Castellon, Julienne E. Bower, Daniel H.S. Silverman, Steven W. Cole, Michael R. Irwin, Thomas R. Belin
Journal: Journal of Clinical Oncology (2014)

This report examines cognitive complaints and neuropsychological (NP) testing outcomes in patients with early-stage breast cancer after the initiation of endocrine therapy (ET) to determine whether this therapy plays any role in post-treatment cognitive complaints.One hundred seventy-three participants from the Mind Body Study (MBS) observational cohort provided data from self-report questionnaires and NP testing obtained at enrollment (T1, before initiation of ET), and 6 months later (T2). Bivariate analyses compared demographic and treatment variables, cognitive complaints, depressive symptoms, quality of life, and NP functioning between those who received ET versus not. Multivariable linear regression models examined predictors of cognitive complaints at T2, including selected demographic variables, depressive symptoms, ET use, and other medical variables, along with NP domains that were identified in bivariate analyses.Seventy percent of the 173 MBS participants initiated ET, evenly distributed between tamoxifen or aromatase inhibitors. ET-treated participants reported significantly increased language and communication (LC) cognitive complaints at T2 (P = .003), but no significant differences in NP test performance. Multivariable regression on LC at T2 found higher LC complaints significantly associated with T1 LC score (P < .001), ET at T2 (P = .004), interaction between ET and past hormone therapy (HT) (P < .001), and diminished improvement in NP psychomotor function (P = .05). Depressive symptoms were not significant (P = .10).Higher LC complaints are significantly associated with ET 6 months after starting treatment and reflect diminished improvements in some NP tests. Past HT is a significant predictor of higher LC complaints after initiation of ET.
A Genome-Scale RNA Interference Screen Implicates NF1 Loss in Resistance to RAF Inhibition
Authors: Steven R. Whittaker, Jean-Philippe Theurillat, Eliezer Van Allen, Nikhil Wagle, Jessica Hsiao, Glenn S. Cowley, Dirk Schadendorf, David E. Root, Levi A. Garraway
Journal: Cancer Discovery (2013)

RAF inhibitors such as vemurafenib and dabrafenib block BRAF-mediated cell proliferation and achieve meaningful clinical benefit in the vast majority of patients with BRAF(V600E)-mutant melanoma. However, some patients do not respond to this regimen, and nearly all progress to therapeutic resistance. We used a pooled RNA interference screen targeting more than 16,500 genes to discover loss-of-function events that could drive resistance to RAF inhibition. The highest ranking gene was NF1, which encodes neurofibromin, a tumor suppressor that inhibits RAS activity. NF1 loss mediates resistance to RAF and mitogen-activated protein kinase (MAPK) kinase kinase (MEK) inhibitors through sustained MAPK pathway activation. However, cells lacking NF1 retained sensitivity to the irreversible RAF inhibitor AZ628 and an ERK inhibitor. NF1 mutations were observed in BRAF-mutant tumor cells that are intrinsically resistant to RAF inhibition and in melanoma tumors obtained from patients exhibiting resistance to vemurafenib, thus showing the clinical potential for NF1-driven resistance to RAF/MEK-targeted therapies.
Increased sputum and bronchial biopsy IL-13 expression in severe asthma
Authors: Shironjit K. Saha, Mike A. Berry, Deborah Parker, Salman Siddiqui, Angela Morgan, Richard May, Phillip Monk, Peter Bradding, Andrew J. Wardlaw, Ian D. Pavord, Christopher E. Brightling
Journal: Journal of Allergy and Clinical Immunology (2008)
Double-blind trial of cholestyramine in post-vagotomy diarrhoea.
Authors: V M Duncombe, T D Bolin, A E Davis
Journal: Gut (1977)

The effect of cholestyramine in post-vagotomy diarrhoea has been assessed under double-blind conditions. Cholestyramine produced a significant improvement in frequency, urgency, and consistency of stool as well as episodic diarrhoea. Faecal bile acid excretion was significantly higher in the post-vagotomy group when compared with normal controls. These findings confirm the effectiveness of cholestyramine and support the concept of a bile acid mediated aetiology in post-vagotomy diarrhoea.
Pseudomembranous Colitis Associated with<i>Clostridium difficile</i>
Authors: Paul L Wolf, Armen Kasyan
Journal: New England Journal of Medicine (2005)

A 75-year-old man with peripheral vascular disease, chronic obstructive pulmonary disease, and diabetes mellitus presented with gangrene of the right fourth toe and underwent tarsal–metatarsal amputation to manage the progression of gangrene, followed by amputation of the right leg below the knee. His hospital course was complicated by a myocardial infarction and pneumonia. During hospitalization, he was treated with multiple antimicrobial agents, including imipenem, vancomycin, piperacillin, tazobactam, and gatifloxacin. During the sixth week of hospitalization, abdominal pain, nausea, diarrhea, fever, and leukocytosis characterized by 48,000 leukocytes per microliter developed. A stool culture and toxin screen were both positive for Clostridium . . .
Glucose homeostasis during the perinatal period in normal rats and rats with a glycogen storage disorder.
Authors: K R Gain, R Malthus, C Watts
Journal: Journal of Clinical Investigation (1981)

The fetal rat mobilizes liver glycogen during parturition for use as a glucose source until the onset of gluconeogenesis at 2 h after birth. A rat strain (NZR/Mh) unable to mobilize liver glycogen because of a phosphorylase b kinase deficiency has been used to assess the importance of liver glycogen in glucose homeostasis of the newborn. In normal rats the mean blood glucose concentration of the fetus measured at various times up to 24 h after natural birth ranged between 3.7 and 5.4 mM. In contrast, fetuses of the affected rats were hypoglycemic before birth (2.02 +/- 0.15 mM), and by 1 h after birth the blood glucose had decreased to 0.74 +/- 0.14 mM. Concentrations increased by 4 h to 1.48 +/- 0.17 mM and by 24 h reached values not significantly different from the normal newborn rats. Changes in plasma insulin over the perinatal period were similar in both groups although concentrations were always significantly lower in the affected rts. The findings demonstrate the crucial role of the fetal liver glycogen store in the maintenance of normoglycemia in the newborn. The normal rat does not develop hypoglycemia when born naturally and left with the mother after birth (in contrast to other studies in which the newborn were taken by cesarian delivery 1 d prematurely and kept in an artificial environment without food). The rats with the glycogen storage disorder experienced severe hypoglycemia without any apparent effects, which raises questions concerning alternative fuels available to and utilized by the newborn.
THE PSYCHIATRIC MANPOWER OF NEW JERSEY
Authors: HENRY A. DAVIDSON
Journal: American Journal of Psychiatry (1948)

1. New Jersey, a state with a population of 4¼ million, has about 5,000 physicians; of these 262 are doing psychiatry, either fulltime or part-time, in institutions or in private practice. 2. Of the 262 physicians doing psychiatry in New Jersey, 75 are board diplomates; 101 additional doctors are members of a recognized psychiatric association; and there are 73 physicians doing psychiatry in hospitals, clinics, or other agencies, who are neither diplomates nor society members. The remaining 13 physicians devote much of their office time to psychiatry but do not have hospital, board, or society recognition in the specialty. 3. Of the 262 physicians doing psychiatry in New Jersey, 112 are in private practice; of these, all but 13 devote their full professional time to the specialty. Ninety-three (of the 262 psychiatrists) are employed by state or county hospitals or clinics and 45 by the Veterans Administration. 4. In addition to the 112 doctors in private practice, there are 35 others who, though engaged in institutional work, do accept private patients so that, in all, some 147 psychiatrists of varying grade are privately available to the people of New Jersey. 5. Of the 147 psychiatrists available to private patients, 40 are Board diplomates, and 66 others belong to recognized psychiatric associations. 6. Of private practitioners, 32% are Board diplomates; of Veterans Administration psychiatrists, 29% are Board diplomates. For psychiatrists in state hospitals, the figure is 27%. 7. Of the 75 Board diplomates in New Jersey, about one-half (actually 36) are primarily engaged in private practice, while the other half (actually 39) are in hospital, agency, or institutional practice. 8. Some 2.1% of all New Jersey physicians belong to the American Psychiatric Association. The national figure is 2.2%. The states nearest to New Jersey in population are Michigan, Missouri, North Carolina, and Massachusetts. In Massachusetts 3.0% of physicians belong to the A. P. A. but in the other states the figure is the same as (or lower than) that in New Jersey. 9. Using as an index the number of Board diplomates per thousand physicians, the ratio nationally is 14; in New Jersey it is 13, in Missouri 8, in North Carolina 1, and in Massachusetts 26. 10. Psychiatrists are available for private consultation in every county of New Jersey except the 4 smallest. Each of these 4 counties (Salem, Ocean, Hunterdon, Cape May) is adjacent to a county in which private psychiatrists are available. 11. Private psychiatrists are available at a ratio of 29,000 persons per practitioner, which is considered an average though not an ideal figure. In terms of referring physicians, the state has 31 privately available psychiatrists per thousand physicians, which is also an average figure.
The Safety of the Hepatitis B Vaccine
Authors: Donald P. Francis
Journal: JAMA (1986)

In the United States, one hepatitis B vaccine (Heptavax-B) has been licensed for the prevention of hepatitis B virus infections. Even though this vaccine has been shown to be highly effective and well tolerated in controlled trials and has been recommended for use in those at risk for acquiring infection by hepatitis B virus, many individuals have been reluctant to be immunized for fear of contracting acquired immunodeficiency syndrome (AIDS). In this study, we demonstrate that each of the three inactivation steps used in the manufacture of Heptavax-B independently will inactivate the infectivity of high-titered preparations of the AIDS virus; recipients of the hepatitis B vaccine do not develop antibodies to the AIDS virus; the hepatitis B vaccine does not contain detectable levels of nucleic acids related to the AIDS virus. These observations clearly demonstrate that vaccination with the currently available hepatitis B vaccine poses no demonstrable risk for acquiring AIDS.
Effect of laquinimod on MRI-monitored disease activity in patients with relapsing-remitting multiple sclerosis: a multicentre, randomised, double-blind, placebo-controlled phase IIb study
Authors: G Comi, A Pulizzi, M Rovaris, O Abramsky, T Arbizu, A Boiko, R Gold, E Havrdova, S Komoly, KW Selmaj, B Sharrack, M Filippi
Journal: The Lancet (2008)
Myocardial Blood Flow in Man: Effects of Coronary Collateral Circulation and Coronary Artery Bypass Surgery
Authors: Sidney C. Smith, Richard Gorlin, Michael V. Herman, Warren J. Taylor, John J. Collins
Journal: Journal of Clinical Investigation (1972)

The effects of coronary artery bypass graft (CAB) and coronary collaterals (CC) on myocardial blood flow (MBF) were studied in 24 patients undergoing 29 CAB's. MBF after CAB was compared to preexisting MBF by intraoperatively injecting (133)xenon via distal CAB with proximal CAB first occluded then open. Pressure gradients across bypassed obstructions were measured. The results were correlated with preoperative coronary arteriograms to determine the effects of CC on MBF and postobstructive perfusion pressures. Mean MBF was increased by CAB from 32+/-6 (se) ml/min per 100 g (CAB occluded) to 118+/-13 ml/min per 100 g (CAB open). The (133)Xe clearance curves with CAB open were resolved into slow (19+/-2 ml/min per 100 g) and rapid (133+/-12 ml/min per 100 g) phases, suggesting that MBF remained heterogeneous after CAB. Vessels with less than 80% stenosis by angiography had pressure gradients less than 20 mm Hg across obstructions, high postobstructive perfusion pressures (75+/-7 mm Hg), and normal MBF (87+/-6 ml/min per 100 g) even with CAB occluded. Vessels with greater than 80% stenosis or total occlusion by angiography had significant pressure gradients with marked reduction of postobstructive MBF. No significant difference in postobstructive MBF was found when vessels with CC (21+/-4 ml/min per 100 g) were compared to those without CC (17+/-4 ml/min per 100 g) (P > 0.4). These studies demonstrate that (a) mean MBF increased 268% after CAB, (b) heterogeneous MBF persisted after CAB, (c) CC were not associated with significant increases in MBF, and (d) vessels with less than 80% stenosis had less than 20 mm Hg gradient with minimal effect on resting MBF.