tbuckley/cabot-search huggingface dataset:
Acetaminophen Use During Pregnancy, Behavioral Problems, and Hyperkinetic Disorders
Authors: Zeyan Liew, Beate Ritz, Cristina Rebordosa, Pei-Chen Lee, Jørn Olsen
Journal: JAMA Pediatrics (2014)

Acetaminophen (paracetamol) is the most commonly used medication for pain and fever during pregnancy in many countries. Research data suggest that acetaminophen is a hormone disruptor, and abnormal hormonal exposures in pregnancy may influence fetal brain development.To evaluate whether prenatal exposure to acetaminophen increases the risk for developing attention-deficit/hyperactivity disorder (ADHD)-like behavioral problems or hyperkinetic disorders (HKDs) in children.We studied 64,322 live-born children and mothers enrolled in the Danish National Birth Cohort during 1996-2002.Acetaminophen use during pregnancy was assessed prospectively via 3 computer-assisted telephone interviews during pregnancy and 6 months after child birth.To ascertain outcome information we used (1) parental reports of behavioral problems in children 7 years of age using the Strengths and Difficulties Questionnaire; (2) retrieved HKD diagnoses from the Danish National Hospital Registry or the Danish Psychiatric Central Registry prior to 2011; and (3) identified ADHD prescriptions (mainly Ritalin) for children from the Danish Prescription Registry. We estimated hazard ratios for receiving an HKD diagnosis or using ADHD medications and risk ratios for behavioral problems in children after prenatal exposure to acetaminophen.More than half of all mothers reported acetaminophen use while pregnant. Children whose mothers used acetaminophen during pregnancy were at higher risk for receiving a hospital diagnosis of HKD (hazard ratio = 1.37; 95% CI, 1.19-1.59), use of ADHD medications (hazard ratio = 1.29; 95% CI, 1.15-1.44), or having ADHD-like behaviors at age 7 years (risk ratio = 1.13; 95% CI, 1.01-1.27). Stronger associations were observed with use in more than 1 trimester during pregnancy, and exposure response trends were found with increasing frequency of acetaminophen use during gestation for all outcomes (ie, HKD diagnosis, ADHD medication use, and ADHD-like behaviors; P trend < .001). Results did not appear to be confounded by maternal inflammation, infection during pregnancy, the mother's mental health problems, or other potential confounders we evaluated.Maternal acetaminophen use during pregnancy is associated with a higher risk for HKDs and ADHD-like behaviors in children. Because the exposure and outcome are frequent, these results are of public health relevance but further investigations are needed.
Dermoscopic patterns of naevi in fifth grade children of the Framingham school system
Authors: A. Scope, A.A. Marghoob, S.W. Dusza, J.M. Satagopan, A.L.C. Agero, C. Benvenuto-Andrade, J.A. Lieb, M.A. Weinstock, S.A. Oliveria, A.C. Geller, A.C. Halpern
Journal: British Journal of Dermatology (2008)

Childhood is a critical period for naevogenesis.To describe the prevalence of dermoscopic patterns of naevi using cross-sectional data from a population-based cohort of children.We obtained overview digital photography of the back of fifth graders (age 10-11 years) from all 10 schools in Framingham, MA, U.S.A. From each participant, dermoscopic images of up to four naevi were obtained, including the largest and one randomly selected naevus on the upper back and a corresponding pair from the lower back.The study included 443 children, 61% boys, with 1181 back naevi analysed. Globular pattern was seen in 37% of naevi, reticular pattern in 13%, homogeneous pattern in 44% and complex (reticular-globular) dermoscopic pattern in 5%. Globular naevi were significantly more frequent and larger on the upper than the lower back. There was a significant hierarchic trend in naevus diameter by dermoscopic pattern: complex naevi (4.3 mm)>globular (3.3 mm)>reticular (3.0 mm)>homogeneous (2.8 mm). Reticular naevi were more prevalent in children with darker pigment phenotype (P<0.0001). There was a decrease in the size of naevi in children with darker pigmentation (P<0.0001).An interrelationship was observed in childhood between dermoscopic pattern, naevus size, anatomical location on the back and pigment phenotype.
Vaccine-Acquired Rotavirus in Infants with Severe Combined Immunodeficiency
Authors: Niraj C. Patel, Paula M. Hertel, Mary K. Estes, Maite de la Morena, Ann M. Petru, Lenora M. Noroski, Paula A. Revell, I. Celine Hanson, Mary E. Paul, Howard M. Rosenblatt, Stuart L. Abramson
Journal: New England Journal of Medicine (2010)

Live pentavalent human-bovine reassortant rotavirus vaccine is recommended in the United States for routine immunization of infants. We describe three infants, two with failure to thrive, who had dehydration and diarrhea within 1 month after their first or second rotavirus immunization and subsequently received a diagnosis of severe combined immunodeficiency. Rotavirus was detected, by means of reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay, in stool specimens obtained from all three infants, and gene-sequence analysis revealed the presence of vaccine rotavirus. These infections raise concerns regarding the safety of rotavirus vaccine in severely immunocompromised patients.
Diseases of the Reticuloendothelial System and Hematology: Hemorrhagic and Leukocytic Diseases
Authors: Clement A. Finch
Journal: Annual Review of Medicine (1951)

Postpartum depression (PPD) is common, disabling, and treatable. The strongest risk factor is a history of mood or anxiety disorder, especially having active symptoms during pregnancy. As PPD is one of the most common complications of childbirth, it is ...Read More
Oral airway resistance during wakefulness in patients with obstructive sleep apnoea
Authors: T C Amis, N O'Neill, J R Wheatley
Journal: Thorax (1999)

<h3>BACKGROUND</h3> Patients with obstructive sleep apnoea (OSA) have a number of upper airway structural abnormalities which may influence the resistance of the oral airway to airflow. There have been no systematic studies of the flow dynamics of the oral cavity in such patients. <h3>METHODS</h3> Inspiratory oral airway resistance to airflow (R<sub>O</sub>) was measured in 13 awake patients with OSA in both the upright and supine positions (neck position constant). Each subject breathed via a mouthpiece while the nasal airway was occluded with a nasal mask. <h3>RESULTS</h3> In the upright position the mean (SE) R<sub>O</sub> was 1.26 (0.19) cm H<sub>2</sub>O/l/s (at 0.4 l/s) which increased to 2.01 (0.43) cm H<sub>2</sub>O/l/s when supine (p&lt;0.05, paired<i>t</i> test). The magnitude of this change correlated negatively with the respiratory disturbance index (<i>r</i> = –0.60, p = 0.03). <h3>CONCLUSION</h3> In awake patients with OSA R<sub>O</sub> is normal when upright but abnormally raised when in the supine position.
How to Use the New DSM-5 Somatic Symptom Disorder Diagnosis in Research and Practice: A Critical Evaluation and a Proposal for Modifications
Authors: Winfried Rief, Alexandra Martin
Journal: Annual Review of Clinical Psychology (2014)

The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) changed the term "somatoform disorders" to "somatic symptom and related disorders" and further modified diagnostic labels and criteria. We review evidence for the validity of the new criteria, specifically of somatic symptom disorder (SSD), and present a critical discussion of unsolved and new problems. We also provide an update of mechanisms and interventions that have been empirically evaluated in somatoform disorders. For many mechanisms, it is unclear whether their role can be easily transposed to SSD. Therefore more research is needed on the similarities and differences between medically unexplained and medically explained conditions. To overcome the obvious shortcomings of the current classification, we offer a modification of this DSM-5 section as well as a crossover system to apply these criteria for somatic symptom and related disorders. This proposal allows working with DSM-5 but also continuing successful lines of research with concepts such as hypochondriasis/illness anxiety, chronic pain, and medically unexplained versus medically explained syndromes.
Lymphedema: current issues in research and management
Authors: J. A. Petrek, P. I. Pressman, R. A. Smith
Journal: CA A Cancer Journal for Clinicians (2000)

Lymphedema is a common and troublesome problem that can develop following breast cancer treatment. As with other quality-of-life and nonlethal conditions, it receives less research funding and attention than do many other areas of study. In 1998, an invited workshop sponsored by the American Cancer Society reviewed and evaluated the current state of knowledge about lymphedema. Recommendations and research initiatives proposed by the 60 international participants are presented in the conclusion section of the article, following a summary of current knowledge of the anatomy, physiology, detection, and current treatment of lymphedema. The etiology of lymphedema is multifaceted; all of the factors that contribute to the condition and the nature of their interaction have not yet been identified. To compound the problem, methods of assessing the degree of arm and hand swelling vary and are not agreed upon, and reliable methods of assessing the functional impact of lymphedema have not yet been developed. In the absence of a cure for lymphedema, precautions and prevention are emphasized. Current treatments include elevation, elastic garments, pneumatic compression pumps, and complete decongestive therapy; surgical and medical techniques remain controversial. Elements and details of these treatments are described.
Weekly Fluconazole for the Prevention of Mucosal Candidiasis in Women with HIV Infection
Authors: Paula Schuman, Linnea Capps, Grace Peng, Jose Antonio Vazquez, Wafaa El-Sadr, Anne I. Goldman, Beverly Alston, C. Lynn Besch, Anita Vaughn, Melanie A. Thompson, Malik N. Cobb, Thomas Kerkering, Jack D. Sobel
Journal: Annals of Internal Medicine (1997)

Background: Candidiasis is a frequent complication of infection with the human immunodeficiency virus (HIV); however, few data exist about the natural history, prevention, and treatment of mucosal candidiasis in women. Objective: To evaluate the safety and effectiveness of weekly fluconazole prophylaxis for mucosal candidiasis in women infected with HIV. Design: Randomized, double-blind, placebo-controlled trial. Setting: 14 sites participating in the Community Programs for Clinical Research on AIDS (CPCRA). Patients: 323 women with HIV infection and CD4+ cell counts of 300 cells/mm3 or less. Intervention: 200 mg of fluconazole per week or placebo. Open-label fluconazole for candidiasis prophylaxis was permitted after two oropharyngeal or vaginal episodes or one esophageal episode. Measurements: Development of mucosal candidiasis, clinical and in vitro resistance of Candida species to fluconazole, survival, and adverse events. Results: After a median follow-up of 29 months, 72 of 162 patients receiving fluconazole and 93 of 161 patients receiving placebo had at least one episode of candidiasis (relative risk [RR], 0.56 [95% CI, 0.41 to 0.77]; P < 0.001). Weekly fluconazole was effective in preventing oropharyngeal candidiasis (RR, 0.50 [CI, 0.33 to 0.74]; P < 0.001) and vaginal candidiasis (RR, 0.64 [CI, 0.40 to 1.00]; P = 0.05) but not esophageal candidiasis (RR, 0.91 [CI, 0.48 to 1.72]; P > 0.2). Relative risks were similar for women who had a history of mucosal candidiasis (RR, 0.51 [CI, 0.35 to 0.75]) and those who did not (RR, 0.69 [CI, 0.35 to 1.34]). Absolute risk reduction for patients with a history of infection was 25.6 per 100 person-years, which is more than twice the reduction of 11.2 per 100 person-years seen in patients with no history of infection. This difference reflects the higher risk of patients who previously had an infection. Candida albicans was not usually resistant to fluconazole in vaginal specimens in clinical or in vitro settings; such resistance occurred in less than 5% of patients in each group. Conclusions: Weekly fluconazole (200 mg) seems to be safe and effective in preventing oropharyngeal and vaginal candidiasis. This regimen has a useful role in the management of HIV-infected women who are at risk for recurrent mucosal candidiasis.
Imaging and Modulating Antisense Microdistribution in Solid Human Xenograft Tumor Models
Authors: Joseph D. Mocanu, Kenneth W. Yip, Julia Skliarenko, Wei Shi, Pierre Busson, Kwok-Wai Lo, Carlo Bastianutto, Fei-Fei Liu
Journal: Clinical Cancer Research (2007)

Abstract Purpose: The tumor microenvironment is complex and heterogeneous, populated by tortuous irregular vasculature, hypoxic cells, and necrotic regions. These factors can all contribute to the biodistribution difficulties encountered by most cancer therapeutic agents. Antisense oligodeoxynucleotides (ASO) are a class of therapeutics where limited information is available about their distribution within a solid tumor environment. Experimental Design: To assess ASO distribution, a fluorescein-labeled phosphorothionated ASO based on the G3139 mismatch control was injected systemically (i.v.) into tumor-bearing severe combined immunodeficient mice. Hoechst 33342 was injected i.v. to visualize active vasculature. Unstained sections were imaged through tiled fluorescence stereomicroscopy and then quantitated using novel algorithms. Tumor sections from four human tumor models were examined (CaSki, DU-145, C666-1, and C15) for hypoxia, apoptosis/necrosis, and morphology. Results: For all four tumors, ASO accumulated within regions of hypoxia, necrosis, and apoptosis. Scatter plots of ASO versus active vasculature generated for each individual tumor revealed a consistent pattern of distribution of the ASO within each model. In C666-1 xenografts, the slopes of these scatter plots were significantly reduced from 0.41 to 0.16 when pretreated with the antivascular agent ZD6126 48 h before ASO injection. This was accompanied by the formation of large disseminated necrotic regions in the tumor, along with a 13.1 mmHg reduction in interstitial fluid pressure. Conclusions: These data suggest the possibility that these algorithms might offer a generalizable and objective methodology to describe the distribution of molecular therapeutic agents within a tumor microenvironment and to quantitatively assess distribution changes in response to combination therapies.
Alveolar rhabdomyosarcoma–associated PAX3-FOXO1 promotes tumorigenesis via Hippo pathway suppression
Authors: Lisa E.S. Crose, Kathleen A. Galindo, Julie Grondin Kephart, Candy Chen, Julien Fitamant, Nabeel Bardeesy, Rex C. Bentley, Rene L. Galindo, Jen-Tsan Ashley Chi, Corinne M. Linardic
Journal: Journal of Clinical Investigation (2013)

Alveolar rhabdomyosarcoma (aRMS) is an aggressive sarcoma of skeletal muscle characterized by expression of the paired box 3-forkhead box protein O1 (PAX3-FOXO1) fusion oncogene. Despite its discovery nearly two decades ago, the mechanisms by which PAX3-FOXO1 drives tumor development are not well characterized. Previously, we reported that PAX3-FOXO1 supports aRMS initiation by enabling bypass of cellular senescence checkpoints. We have now found that this bypass occurs in part through PAX3-FOXO1-mediated upregulation of RASSF4, a Ras-association domain family (RASSF) member. RASSF4 expression was upregulated in PAX3-FOXO1-positive aRMS cell lines and tumors. Enhanced RASSF4 expression promoted cell cycle progression, senescence evasion, and tumorigenesis through inhibition of the Hippo pathway tumor suppressor MST1. We also found that the downstream Hippo pathway target Yes-associated protein 1 (YAP), which is ordinarily restrained by Hippo signaling, was upregulated in RMS tumors. These data suggest that Hippo pathway dysfunction promotes RMS. This work provides evidence for Hippo pathway suppression in aRMS and demonstrates a progrowth role for RASSF4. Additionally, we identify a mechanism used by PAX3-FOXO1 to inhibit MST1 signaling and promote tumorigenesis in aRMS.
Mature CD8+ T lymphocyte response to viral infection during fetal life
Authors: Arnaud Marchant, Victor Appay, Marianne van der Sande, Nicolas Dulphy, Corinne Liesnard, Michael Kidd, Steve Kaye, Olubukola Ojuola, Geraldine M.A. Gillespie, Ana L. Vargas Cuero, Vincenzo Cerundolo, Margaret Callan, Keith P.W.J. McAdam, Sarah L. Rowland-Jones, Catherine Donner, Andrew J. McMichael, Hilton Whittle
Journal: Journal of Clinical Investigation (2003)

Immunization of newborns against viral infections may be hampered by ineffective CD8(+) T cell responses. To characterize the function of CD8(+) T lymphocytes in early life, we studied newborns with congenital human cytomegalovirus (HCMV) infection. We demonstrate that HCMV infection in utero leads to the expansion and the differentiation of mature HCMV-specific CD8(+) T cells, which have similar characteristics to those detected in adults. High frequencies of HCMV-specific CD8(+) T cells were detected by ex vivo tetramer staining as early as after 28 weeks of gestation. During the acute phase of infection, these cells had an early differentiation phenotype (CD28(-)CD27(+)CD45RO(+), perforin(low)), and they acquired a late differentiation phenotype (CD28(-)CD27(-)CD45RA(+), perforin(high)) during the course of the infection. The differentiated cells showed potent perforin-dependent cytolytic activity and produced antiviral cytokines. The finding of a mature and functional CD8(+) T cell response to HCMV suggests that the machinery required to prime such responses is in place during fetal life and could be used to immunize newborns against viral pathogens.
Serotypes and clones causing invasive pneumococcal disease before the use of new conjugate vaccines in Catalonia, Spain
Authors: Carmen Muñoz-Almagro, Pilar Ciruela, Cristina Esteva, Francesc Marco, Marian Navarro, Rosa Bartolome, Goretti Sauca, Carmen Gallés, Montse Morta, Frederic Ballester, Xavier Raga, Laura Selva
Journal: Journal of Infection (2011)
Exon 15 <b> <i>BRAF</i> </b> Mutations Are Uncommon in Melanomas Arising in Nonsun-Exposed Sites
Authors: Yoram Cohen, Eli Rosenbaum, Shahnaz Begum, David Goldenberg, Clemens Esche, Ofer Lavie, David Sidransky, William H. Westra
Journal: Clinical Cancer Research (2004)

Abstract Purpose: An activating point mutation of the BRAF oncogene has been identified in a high proportion of cutaneous nevi and cutaneous melanomas, but its frequency in melanomas arising from the mucosa of head and neck is unknown. Experimental Design: We tested 17 malignant mucosal melanomas of the head and neck for the thymine (T)→adenine (A) missense mutation at nucleotide 1796 in the BRAF gene using direct sequencing and a newly developed assay that uses a novel primer extension method (Mutector assay). We also tested 21 cutaneous melanomas, including 13 arising from sun-exposed sites and 8 from a nonsun-exposed site, the vulvar skin. Results: The 1796T→A mutation was detected in only 1 (6%) of the sinonasal melanomas. As for cutaneous melanomas, a BRAF mutation was detected in 8 (62%) of the tumors arising in sun-exposed sites but in none (0%) of vulvar melanomas. Conclusions: In contrast to cutaneous melanomas arising in sun-exposed sites, mucosal melanomas of the head and neck do not frequently harbor an activating mutation of BRAF. This finding additionally supports the view that the various subtypes of melanoma are not equivalent and that distinct genetic alterations may underlie well recognized differences in risk factors and behavioral patterns. Accordingly, patients with melanomas should not be collectively regarded as a uniform group as new strategies are developed that target specific genetic alterations.
Inhibition of leucocyte migration by tumour-associated antigens of the colon and rectum
Authors: P. J. Guillou, G. R. Giles
Journal: Gut (1973)

The test of leucocyte migration inhibition has been used to detect lymphocyte sensitization to tumour-associated antigens of the colon and rectum. The procedure for the isolation of antigens from colorectal adenocarcinomata and normal colonic mucosa is described. The circulating lymphocytes of 22 patients suffering from colorectal adenocarcinomata of various stages have been examined and compared with the results obtained for identical studies performed on the peripheral lymphocytes of 15 control subjects. Sensitization of lymphocytes to tumour antigen was demonstrated in 15 of the 22 patients when culture was performed in homologous AB serum. Of these 15 patients only six showed inhibition of leucocyte migration in the presence of tumour extract when culture was performed in autologous serum. These observations would suggest the presence of factors in the serum of such patients which may prevent the expression of cellular immunity to tumour antigens.
Lead-In Phase to Randomized Trial of Motexafin Gadolinium and Whole-Brain Radiation for Patients With Brain Metastases: Centralized Assessment of Magnetic Resonance Imaging, Neurocognitive, and Neurologic End Points
Authors: Minesh P. Mehta, William R. Shapiro, Michael J. Glantz, Roy A. Patchell, Michael A. Weitzner, Christina A. Meyers, Christopher J. Schultz, Wilson H. Roa, Mark Leibenhaut, Judith Ford, Walter Curran, See Phan, Jennifer A. Smith, Richard A. Miller, Markus F. Renschler
Journal: Journal of Clinical Oncology (2002)

PURPOSE: Motexafin gadolinium is a redox mediator that selectively targets tumor cells, is detectable by magnetic resonance imaging (MRI), and enhances the effect of radiation therapy. This lead-in phase to a randomized trial served to evaluate radiologic, neurocognitive, and neurologic progression end points and to evaluate the safety and radiologic response of motexafin gadolinium administered concurrently with 30 Gy in 10-fraction whole-brain radiation therapy for the treatment of brain metastases. PATIENTS AND METHODS: Motexafin gadolinium (5.0 mg/kg/d for 10 days) was administered before each radiation treatment in this prospective international trial. Patients were evaluated by MRI, neurologic examinations, and neurocognitive tests. Prospective criteria and centralized review procedures were established for radiologic, neurocognitive, and neurologic progression end points. RESULTS: Twenty-five patients with brain metastases from lung (52%) and breast (24%) cancer, recursive partitioning analysis class 2 (96%), and an average of 11 brain metastases were enrolled. Neurocognitive function was highly impaired at presentation. Motexafin gadolinium was well tolerated. Freedom from neurologic progression was 77% at 1 year. Median survival was 5.0 months. In 29% of patients, the cause of death was brain metastasis progression. The radiologic response rate was 68%. Motexafin gadolinium’s tumor selectivity was established with MRI. CONCLUSION: (1) Centralized neurologic progression scoring that incorporated neurocognitive tests was implemented successfully. (2) Motexafin gadolinium was well tolerated. (3) Local control, measured by radiologic response rate, neurologic progression, and death caused by progression of brain metastasis, seemed to be improved compared with historical results. A randomized phase III trial using these methods for evaluation of efficacy has just been completed.