tbuckley/cabot-search huggingface dataset:
Randomized phase 2 study of carboplatin plus irinotecan (CI) versus carboplatin plus amrubicin (CA) for extensive disease small-cell lung cancer (ED-SCLC): NJLCG0901.
Authors: Yosuke Kawashima, Naoto Morikawa, Shunichi Sugawara, Makoto Maemondo, Toshiyuki Harada, Masao Harada, Akira Inoue, Yuka Fujita, Terufumi Kato, Hiroshi Yokouchi, Hiroshi Watanabe, Kazuhiro Usui, Toshiro Suzuki, Satoshi Oizumi, Hiroki Nagai, Mariko Kanbe, Toshihiro Nukiwa
Journal: Journal of Clinical Oncology (2014)

7521 Background: Cisplatin-based regimens are standard first-line chemotherapy for ED-SCLC. In patients unfit for cisplatin due to advanced age or poor performance status (PS), carboplatin plus etoposide (CE) is as effective as cisplatin plus etoposide (JCOG9702 trial). Carboplatin plus irinotecan (CI) and carboplatin plus amrubicin (CA) are promising new carboplatin-based regimens identified in our previous studies (NJLCG0405 and NJCLG0701). Accordingly, we conducted this randomized phase 2 study to identify the appropriate regimen for comparison with CE in future phase 3 trials. Methods: Chemotherapy-naïve ED-SCLC patients were randomly assigned to receive 4–6 cycles of carboplatin (area under the curve [AUC] 5.0, day 1) plus irinotecan (70 mg/m2, days 1 and 8) every 3 weeks (CI arm) or carboplatin (AUC 4.0, day 1) plus amrubicin (35 mg/m2, days 1–3) every 3 weeks (CA arm). The primary endpoint was the overall response rate (ORR). Secondary endpoints were progression-free survival (PFS), overall survival(OS), and toxicity. Assuming that an ORR of 80% in eligible patients indicates potential usefulness and an ORR of 60% is the lower limit of interest, the target sample size was 35 patients in each arm (alpha, 0.05; beta, 0.20). Results: Between December 2009 and March 2013, 71 patients were enrolled. One patient in each arm did not receive any protocol treatment due to rapid disease progression. Characteristics of treated patients were as follows: median age, 70 years (range 51–84 years); proportion of males, 84%. The ORRs were 79% (95% confidence interval [CI]: 62–91) and 89% (95%CI: 73–97), median PFS were 5.1 and 6.3 months (hazard ratio [HR] = 0.51, 95%CI: 0.30–0.85, p = 0.01), and median OS were 14.9 and 15.9 months in the CI and CA arms, respectively. Toxicities of grade 3 or higher severity were neutropenia (CI, 53% and CA, 89%), anemia (CI, 26% and CA, 20%), thrombocytopenia (CI, 18% and CA, 14%), and febrile neutropenia (CI, 12% and CA, 29%). No treatment-related deaths were observed. Conclusions: CA was numerically effective than CI in chemo-naïve ED-SCLC patients, with acceptable toxicity. CA could be selected for future phase 3 trials. Clinical trial information: UMIN000008970.
Incidence of osteonecrosis of the jaw in patients receiving denosumab or zoledronic acid for bone metastases from solid tumors or multiple myeloma: Results from three phase III trials.
Authors: Allan Lipton, Fred Saad, Catherine H. Van Poznak, Janet Elizabeth Brown, Alison Stopeck, Karim Fizazi, David H. Henry, Neal D. Shore, Ingo J. Diel, Katia Sonia Tonkin, Richard H. De Boer, Huei Wang, Ada H. Braun
Journal: Journal of Clinical Oncology (2013)

9640 Background: In patients with metastatic bone disease (MBD), the use of antiresorptive therapies such as denosumab or zoledronic acid (ZA) reduces the risk of skeletal-related events but is associated with a small risk of osteonecrosis of the jaw (ONJ). Two phase 3 clinical trials of denosumab vs ZA in patients with MBD showed overall cumulative ONJ incidences to be 3.8% to 4.7% at approximately 5 years of treatment with denosumab across blinded and open-label extension phases. ONJ associated with ZA was only assessed in the blinded treatment phases, as patients switched to denosumab once superior efficacy was demonstrated. Here we report incidence rates of ONJ by first vs subsequent years of exposure for the blinded treatment phase of all three phase III clinical trials. Methods: Patients (n = 5,677) with bone metastases from solid tumors or multiple myeloma received either SC denosumab 120 mg and IV placebo or IV ZA 4 mg (adjusted for renal function) and SC placebo Q4W in the double-blinded treatment phase of each trial. Patients who received ≥ 1 active dose during the blinded treatment phase were included in this analysis for up to 44.5 months of denosumab exposure and 41.3 months of ZA exposure. Oral assessments were conducted at baseline and every 6 months thereafter by the investigator or other qualified examiner. Potential ONJ events were independently adjudicated by a blinded committee of experts. Results: The median (Q1, Q3) time to onset of ONJ was similar in both treatment groups (15.6 [9.5, 20.0] months for denosumab, 15.8 [11.0, 23.6] months for ZA). Cumulative incidence rates of ONJ during the blinded treatment phases for all three trials by patient-years of follow-up are shown below (Table). Conclusions: The incidence of ONJ increased with longer duration of antiresorptive exposure. There were no significant differences between treatment groups in ONJ incidence at year 1 or beyond. Clinical trial information: NCT00321464; NCT00330759; NCT00321620. [Table: see text]
Discrepant mutational status between naevi and melanomas in naevus-associated melanomas: about mutation-specific immunohistochemistry: reply from the authors
Authors: D. Shitara, G. Tell-Martí, C. Badenas, M.M.S.S. Enokihara, L. Alós, A.B. Larque, N. Michalany, J.A. Puig-Butille, C. Carrera, J. Malvehy, S. Puig, E. Bagatin
Journal: British Journal of Dermatology (2016)
A Patient With Paroxysmal Nocturnal Hemoglobinuria Bearing Four Independent PIG-A Mutant Clones
Authors: Jun-ichi Nishimura, Norimitsu Inoue, Hiroshi Wada, Etsuko Ueda, Patcharin Pramoonjago, Toshiyuki Hirota, Takashi Machii, Takashi Kageyama, Akihisa Kanamaru, Junji Takeda, Taroh Kinoshita, Teruo Kitani
Journal: Blood (1997)
Kawasaki Disease
Authors: Ann R. Punnoose
Journal: JAMA (2012)

Diagnostic features of Kawasaki disease Red eyesRed, dry, cracked lips and inflamed tongue Fever (for more than 5 days) Swollen lymph nodesWidespread rash Changes in hands and feetSwelling and redness Peeling of skin around fingernails and toenails (after 1-2 weeks)
Rare and Common Germline Variants Contribute to Occurrence of Myelodysplastic Syndrome
Authors: Christopher N Hahn, Milena Babic, Andreas W Schreiber, Monika M Kutyna, L Amilia Wee, Anna L Brown, Michelle Perugini, Deepak Singhal, Smita Hiwase, Jinghua Feng, Wendy T Parker, Sarah Moore, Peter G Bardy, Russell Saal, Paula Marlton, Andrew S. Moore, Thomas J Gonda, Paul Leo, Susan Branford, Richard J D'Andrea, Ian D Lewis, Luen Bik To, Hamish S Scott, Devendra Hiwase
Journal: Blood (2015)
The persistent risk of chronicity in recurrent episodes of nonbipolar major depressive disorder: a prospective follow-up
Authors: M B Keller, P W Lavori, J Rice, W Coryell, R M Hirschfeld
Journal: American Journal of Psychiatry (1986)

The authors report on the course of illness in 101 patients who were in an episode (the "index episode") of major depressive disorder when they entered a clinical research study, recovered from that episode, and then relapsed into a new episode (the "first prospective episode") of the disorder. They found a 22% probability that these patients' first prospective episode would last at least 1 year, similar to the 21% rate of chronicity previously reported for the index episode. A long prior episode, older age, and low family income were found to predict chronicity in the first prospective episode.
Brief Communication: Induction of Epstein-Barr Virus-Associated Nuclear Antigen During In Vitro Transformation of Human Lymphoid Cells 2
Authors: W. Leibold, T. D. Flanagan, J. Menezes, G. Klein
Journal: JNCI Journal of the National Cancer Institute (1975)

Human lymphoid cells isolated from the peripheral blood of adults, from cord blood, and from fetal liver, spleen, bone marrow, and thymus were cultivated with or without a cell-free preparation of Epstein-Barr virus (EBV) with demonstrated transforming activity. The cultures were examined for the EBV-associated nuclear antigen (EBNA) and for transfromation into permanent lymphoblastoid cell lines (LCL). EBNA, seen only in cultures that had received exogenous EBV, was detected between days 1 and 6 after addition of EBV, most frequently on day 3. EBNA-positive cells had a lymphoblastoid appearance. Transformation into established LCL became apparent between days 12 and 19. The addition of pokeweed mitogen to cultures containing EBV enhanced the development of EBNA, whereas phytohemagglutinin or concanavalin A had no such effect. Neither EBNA nor transfomration was observed in lymphoid cells from fetal thymus. In fetal spleen, bone marrow, and liver cells, EBV regularly induced EBNA and LCL transformation.
Use of Diazoxide With Trichlormethiazide for Hypertension
Authors: R OKUN, R P RUSSELL, W R WILSON
Journal: JAMA (1963)

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
Mode of Inheritance and Variation of Mitochondrial DNA in Hybridogenetic Fishes of the Genus Poeciliopsis
Journal: Molecular Biology and Evolution (1987)

A genetic survey of mitochondrial DNA (mtDNA) in a hybridogenetic complex of fishes (genus Poeciliopsis) was conducted to assess the possibility of low-level paternal transmission of mtDNA to progeny. In this reproductive system, females of the unisexual hybrid biotype between P. monacha and P. lucida effectively participate in a perpetual backcross to males of a sexual species, P. lucida. As judged on the basis of numerous restriction digests, the mtDNAs of the bisexual parental species (P. monacha and P. lucida) were highly distinct, yet the mtDNA of the natural hybridogens was not different from that of P. monacha from the same river system. Since the hybridogens are probably thousands of generations old, the present results demonstrate that paternal leakage of mtDNA must be extremely low or absent in these fishes. MtDNA genotypic differences among hybridogenetic strains were also present and corresponded to geographic locale. These differences provide a foundation for estimation of both origins and phylogeny of the unisexual forms.
Diagnosis of major depression in cancer patients according to four sets of criteria
Authors: R G Kathol, A Mutgi, J Williams, G Clamon, R Noyes
Journal: American Journal of Psychiatry (1990)

Diagnoses of major depression in 152 cancer patients differed as much as 13% depending on the diagnostic system used. The Beck Depression Inventory and the Hamilton Rating Scale for Depression were useful tools for screening patients with depressive symptoms but frequently misclassified those who had no major depression according to one or more of the criteria-based diagnostic systems.
Shared genetic effects between hepatic steatosis and fibrosis: A prospective twin study
Authors: Jeffrey Cui, Chi‐Hua Chen, Min‐Tzu Lo, Nicholas Schork, Ricki Bettencourt, Monica P. Gonzalez, Archana Bhatt, Jonathan Hooker, Katherine Shaffer, Karen E. Nelson, Michelle T. Long, David A. Brenner, Claude B. Sirlin, Rohit Loomba, None for the Genetics of NAFLD in Twins Consortium
Journal: Hepatology (2016)

Nonalcoholic fatty liver disease is associated with metabolic risk factors including hypertension and dyslipidemia and may progress to liver fibrosis. Studies have shown that hepatic steatosis and fibrosis are heritable, but whether they have a significant shared gene effect is unknown. This study examined the shared gene effects between hepatic steatosis and fibrosis and their associations with metabolic risk factors. This was a cross-sectional analysis of a prospective cohort of well-characterized, community-dwelling twins (45 monozygotic, 20 dizygotic twin pairs, 130 total subjects) from southern California. Hepatic steatosis was assessed with magnetic resonance imaging-proton density fat fraction and hepatic fibrosis with magnetic resonance elastography. A standard bivariate twin additive genetics and unique environment effects model was used to estimate the proportion of phenotypic variance between two phenotypes accounted for by additive genetic effects and individual-specific environmental effects. Genetic correlations estimated from this model represent the degree to which the genetic determinants of two phenotypes overlap. Mean (± standard deviation) age and body mass index were 47.1 (±21.9) years and 26.2 (±5.8) kg/m2 , respectively. Among the cohort, 20% (26/130) had hepatic steatosis (magnetic resonance imaging-proton density fat fraction ≥5%), and 8.2% (10/122) had hepatic fibrosis (magnetic resonance elastography ≥3 kPa). Blood pressure (systolic and diastolic), triglycerides, glucose, homeostatic model assessment of insulin resistance, insulin, hemoglobin A1c, and low high-density lipoprotein had significant shared gene effects with hepatic steatosis. Triglycerides, glucose, homeostatic model assessment of insulin resistance, insulin, hemoglobin A1c, and low high-density lipoprotein had significant shared gene effects with hepatic fibrosis. Hepatic steatosis and fibrosis had a highly significant shared gene effect of 0.756 (95% confidence interval 0.716-1, P < 0.0001).Genes involved with steatosis pathogenesis may also be involved with fibrosis pathogenesis. (Hepatology 2016;64:1547-1558).
Case 46-1964
Authors: Marian W. Ropes, Benjamin Castleman
Journal: New England Journal of Medicine (1964)

Presentation of CaseA sixty-seven-year-old man entered the hospital because of pain in the back.Eight months before admission pain in the lumbar region developed, and x-ray films of the spine revealed compression fractures of the bodies of the twelfth dorsal and first lumbar vertebras. The pain was not relieved by a corset. During the four weeks before entry he experienced pain in the upper portion of the back that was exaggerated by coughing and by movement.Nineteen years earlier a fall from a ladder had resulted in fracture of several spinous processes. A diagnosis of diabetes was made five . . .
'Chlamydia Monday' in Sweden
Authors: F Hansdotter, A Blaxhult
Journal: Eurosurveillance (2008)

The number of reported cases of Chlamydia trachomatis infections has increased in Sweden in the last decade, as in many other European countries [1]. After a temporary fall in the number of cases reported in Sweden in 2006, due to the spread of a new variant that was not detectable with some of the test methods used at the time, 2007 showed a record high of over 47,000 reported cases [2].
ClinicalTrials.gov and Drugs@FDA: A Comparison of Results Reporting for New Drug Approval Trials
Authors: Lisa M. Schwartz, Steven Woloshin, Eugene Zheng, Tony Tse, Deborah A. Zarin
Journal: Annals of Internal Medicine (2016)

Background: Pharmaceutical companies and other trial sponsors must submit certain trial results to ClinicalTrials.gov. The validity of these results is unclear. Purpose: To validate results posted on ClinicalTrials.gov against publicly available U.S. Food and Drug Administration (FDA) reviews on Drugs@FDA. Data Sources: ClinicalTrials.gov (registry and results database) and Drugs@FDA (medical and statistical reviews). Study Selection: 100 parallel-group, randomized trials for new drug approvals (January 2013 to July 2014) with results posted on ClinicalTrials.gov (15 March 2015). Data Extraction: 2 assessors extracted, and another verified, the trial design, primary and secondary outcomes, adverse events, and deaths. Results: Most trials were phase 3 (90%), double-blind (92%), and placebo-controlled (73%) and involved 32 drugs from 24 companies. Of 137 primary outcomes identified from ClinicalTrials.gov, 134 (98%) had corresponding data at Drugs@FDA, 130 (95%) had concordant definitions, and 107 (78%) had concordant results. Most differences were nominal (that is, relative difference <10%). Primary outcome results in 14 trials could not be validated. Of 1927 secondary outcomes from ClinicalTrials.gov, Drugs@FDA mentioned 1061 (55%) and included results data for 367 (19%). Of 96 trials with 1 or more serious adverse events in either source, 14 could be compared and 7 had discordant numbers of persons experiencing the adverse events. Of 62 trials with 1 or more deaths in either source, 25 could be compared and 17 were discordant. Limitation: Unknown generalizability to uncontrolled or crossover trial results. Conclusion: Primary outcome definitions and results were largely concordant between ClinicalTrials.gov and Drugs@FDA. Half the secondary outcomes, as well as serious events and deaths, could not be validated because Drugs@FDA includes only "key outcomes" for regulatory decision making and frequently includes only adverse event results aggregated across multiple trials. Primary Funding Source: National Library of Medicine.
Hormonal contraceptives: pharmacology tailored to women's health
Authors: Vincenzo De Leo, Maria Concetta Musacchio, Valentina Cappelli, Paola Piomboni, Giuseppe Morgante
Journal: Human Reproduction Update (2016)

In recent years, several new oral contraceptives have become available. In some ways, they represent an evolution in terms of individualization and compliance on the part of women. The new formulations make it increasingly possible to prescribe a specific hormonal contraceptive on an individual basis. A systematic literature search of PubMed was performed using the following combination of terms: 'oral contraceptives', 'estroprogestins' and 'combined oral contraceptive'. Only English-language papers published between January 2000 and July 2014 were included in our analysis. The present review analyzes all aspects of the choice of oral contraceptives in the different phases of a woman's life in detail. Regarding the estrogen component, lowering the dose of ethinylestradiol (EE) helped reduce associated side effects. Natural estradiol is now available and represents a valid alternative to EE. And regarding progestins, the dose has changed over time, as well as the endocrine and metabolic characteristics. These are the fruit of much research into improvement of old products (19-nor-progesterone-derived progestins) with androgenic effects and testing of new molecules with improved metabolic neutrality in terms of insulin sensitivity and lipid parameters. New progestins were a genuine turning point because they greatly reduced major side effects, such as water retention, and their anti-androgenic properties made them indicated for all forms of hyperandrogenism associated with acne and mild hirsutism. The associations of estradiol/dienogest and estradiol/nomegestrol acetate are the most suitable contraceptives for women with abundant menstrual bleeding and can increase the number of potential users of hormonal contraception. Progress in the provision of new oral contraceptives has improved the risk/benefit ratio, by increasing benefits and reducing risks. The present challenge is to tailor contraceptives to individual needs in terms of efficacy and protection of reproductive health.
Screening and Breast Cancer
Authors: Michael W Retsky, Romano Demicheli, William J M Hrushesky
Journal: New England Journal of Medicine (2006)

control cancer pain.I,L However, we later encountered advanced morphine tolerance.3Since intrathecal alpha-adrenergic agonists produce analgesia in animal models4 we began to study such agents (clonidine) to see if they could be used to initiate intrathecal analgesia when advanced systemic and spinal narcotic tolerance had developed in terminal cancer patients.The first step, since we knew of no prior use intrathecally in man, was to evaluate neurotoxicity in a chronic animal model.5 With this reassurance, we proceeded with trials of bolus intrathecal clonidine in cancer patients,6 followed by chronic intrathecal infusion in patients with advanced morphine tolerance.A similar approach was taken by Yaksh et al, using the intrathecal delta agonist D-ala2-D-leu5 -enkephalin (DADLE).8The knowledge gained from these studies on neurotoxicity and efficacy justified further careful study of both a2-agonists (such as clonidine)and DADLE in the setting of cancer pain.Since the earliest reports of successful intraspinal narcotic analgesia, a host of agents have been tried intraspinally, often in non-cancer patients.Most of this work has been done without studies to check on the absence of spinal cord neurotoxicity.Clonidine and related Q'2-agonists theoretically have the potential to affect adversely regional spinal cord blood flow, systemic vascular resistance, and heart rate.6,9It might have been practically acceptable, though ethically debatable, for clonidine to have been tried in terminally ill,patients before studies of neurotoxicity had been complete but our desire to help in difficult pain cases, such as those reported by Tamsen and Gordh, should not lead us to sacrifice a measured, scientific approach to the study of new intraspinal agents.Such agents must be free of serious neurotoxicity and deliverable in the long term without serious side-effects, addiction, or tolerance.These limitations are illustrated in a detailed report of observations during chronic intrathecal clonidine use in a cancer pain patient.
d-Amphetamine-induced heterogeneous changes in psychotic behavior in schizophrenia
Authors: D P van Kammen, W E Bunney, J P Docherty, S R Marder, M H Ebert, J E Rosenblatt, J N Rayner
Journal: American Journal of Psychiatry (1982)

In this placebo-paired, double-blind study, 13 of 45 schizophrenic patients showed an acute improvement in schizophrenic symptoms following d-amphetamine infusion (20 mg). The 18 patients who worsened tended to have higher CSF 3-methoxy-4-hydroxyphenylglycol levels than did those who improved. d-Amphetamine blood levels and clinical descriptors of schizophrenic subgroups did not differentiate patients who improved from those who worsened; however, patients who improved had been significantly more psychotic before the infusion. Patients who worsened had been more psychotic than those who did not change. The authors suggest that those who did not change. The authors suggest that sensitivity to dopamine stimulation in schizophrenia is state-dependent rather than trait-dependent and that the simple, undirectional hypothesis of schizophrenia needs to be reformulated.
HG-94TOXICITY AND EFFICACY OF CONVECTION-ENHANCED DELIVERY WITH LIPOSOMAL DOXORUBICIN IN DIPG AND THALAMIC PEDIATRIC HIGH GRADE GLIOMA MODELS
Authors: A. Charlotte P. Sewing, Tonny Lagerweij, Dannis G. van Vuurden, Susanna JE Veringa, W. Pieter Vandertop, David P. Noske, Pieter Wesseling, Gertjan J.L. Kaspers, Esther Hulleman
Journal: Neuro-Oncology (2016)