tbuckley/cabot-search huggingface dataset:
TREATMENT AND PREVENTION OF PELLAGRA BY A DAILY SUPPLEMENTAL MEAL
Journal: JAMA (1922)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
AMP-activated Protein Kinase Deficiency Blocks the Hypoxic Ventilatory Response and Thus Precipitates Hypoventilation and Apnea
Authors: Amira D. Mahmoud, Sophronia Lewis, Lara Juričić, Utibe-Abasi Udoh, Sandy Hartmann, Maurits A. Jansen, Oluseye A. Ogunbayo, Paolo Puggioni, Andrew P. Holmes, Prem Kumar, Jorge Navarro-Dorado, Marc Foretz, Benoit Viollet, Mayank B. Dutia, Ian Marshall, A. Mark Evans
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Modulation of breathing by hypoxia accommodates variations in oxygen demand and supply during, for example, sleep and ascent to altitude, but the precise molecular mechanisms of this phenomenon remain controversial. Among the genes influenced by natural selection in high-altitude populations is one for the adenosine monophosphate-activated protein kinase (AMPK) α1-catalytic subunit, which governs cell-autonomous adaptations during metabolic stress.We investigated whether AMPK-α1 and/or AMPK-α2 are required for the hypoxic ventilatory response and the mechanism of ventilatory dysfunctions arising from AMPK deficiency.We used plethysmography, electrophysiology, functional magnetic resonance imaging, and immediate early gene (c-fos) expression to assess the hypoxic ventilatory response of mice with conditional deletion of the AMPK-α1 and/or AMPK-α2 genes in catecholaminergic cells, which compose the hypoxia-responsive respiratory network from carotid body to brainstem.AMPK-α1 and AMPK-α2 deletion virtually abolished the hypoxic ventilatory response, and ventilatory depression during hypoxia was exacerbated under anesthesia. Rather than hyperventilating, mice lacking AMPK-α1 and AMPK-α2 exhibited hypoventilation and apnea during hypoxia, with the primary precipitant being loss of AMPK-α1 expression. However, the carotid bodies of AMPK-knockout mice remained exquisitely sensitive to hypoxia, contrary to the view that the hypoxic ventilatory response is determined solely by increased carotid body afferent input to the brainstem. Regardless, functional magnetic resonance imaging and c-fos expression revealed reduced activation by hypoxia of well-defined dorsal and ventral brainstem nuclei.AMPK is required to coordinate the activation by hypoxia of brainstem respiratory networks, and deficiencies in AMPK expression precipitate hypoventilation and apnea, even when carotid body afferent input is normal.
Safety and efficacy of pasireotide (SOM230) in patients with metastatic carcinoid tumors refractory or resistant to octreotide LAR: Results of a phase II study
Authors: L. Kvols, B. Wiedenmann, K. Oberg, J. E. Glusman, T. M. O’dorisio, W. De Herder, B. Gao, R. Arnold, L. Anthony
Journal: Journal of Clinical Oncology (2006)

4082 Background: Pasireotide is a novel multiligand somatostatin analogue that exhibits high binding affinity to 4 of 5 somatostatin receptor subtypes: sst 1,2,3 and sst 5 . Compared with octreotide, pasireotide has 30, 5 and 40 times greater affinity for sst 1,3 and sst 5 receptors respectively and a comparable affinity for sst 2 . Methods: This was a Phase II, open-label, multicenter study in patients with metastatic carcinoid tumors whose symptoms (diarrhea and flushing) were inadequately controlled by octreotide LAR. Patients had histopathologically confirmed disease, elevated 5-HIAA and/or CgA levels and at least one measurable lesion (excluding bone). Patients initially received pasireotide 300 μg sc bid and escalated to a maximum dose of 1200 μg sc bid every 3 days until clinical response was achieved. Partial response (PR) was defined as a mean of &lt;4 bowel movements (BM)/day with no more than 6 BM on any given day, and a mean of &lt;2 flushing episodes/day for 15 consecutive days on a fixed dose of pasireotide. Complete response (CR) was defined as a mean of ≤3 BM/day, with no more than 3 BM on any given day, and no flushing episodes. Results: Safety data are reported from 45 patients as of September 2005; 44 patients (mean age 61 years) qualified for efficacy assessment. Carcinoid tumors were predominantly of midgut origin. Preliminary efficacy data in controlling symptoms of carcinoid syndrome showed PR in 9 patients (20%) at 600–1200 μg sc bid doses and CR in 2 patients (5%) at the 600 and 900 μg sc bid doses. Objective tumor response in 11 patients showed 9 with stable disease and 2 with progressive disease at 6 months. Adverse events (AEs) were primarily gastrointestinal (GI): abdominal pain (31%) and nausea (27%). Weight loss (22%) and fatigue (22%) were also reported. Most AEs were mild or moderate. Glucose-related AEs (predominantly CTC grade 1–2) were observed in 24% of patients. Most discontinuations were due to GI AEs (n = 6) or lack of therapeutic response. Conclusions: Pasireotide 600–1200 μg sc bid was effective in controlling symptoms of diarrhea and flushing in 25% of patients with metastatic carcinoid tumors inadequately controlled by octreotide LAR. The safety profile of pasireotide is similar to octreotide LAR. [Table: see text]
Efficient Capture and Isolation of Tumor-Related Circulating Cell-Free DNA from Cancer Patients Using Electroactive Conducting Polymer Nanowire Platforms
Authors: SeungHyun Jeon, HyungJae Lee, Kieun Bae, Kyong-Ah Yoon, Eun Sook Lee, Youngnam Cho
Journal: Theranostics (2016)

Circulating cell-free DNA (cfDNA) is currently recognized as a key non-invasive biomarker for cancer diagnosis and progression and therapeutic efficacy monitoring.Because cfDNA has been detected in patients with diverse types of cancers, the use of efficient strategies to isolate cfDNA not only provides valuable insights into tumour biology, but also offers the potential for developing new cancer-specific targets.However, the challenges associated with conventional cfDNA extraction methods prevent their further clinical applications.Here, we developed a nanostructured conductive polymer platform for the efficient capture and release of circulating cfDNA and demonstrated its potential clinical utility using unprocessed plasma samples from patients with breast and lung cancers.Our results confirmed that the platform's enhanced efficiency allows tumor-specific circulating cfDNA to be recovered at high yield and purity.
Benefit of treatment of latent tuberculosis infection in individual patients
Authors: Kyle Fluegge
Journal: European Respiratory Journal (2016)

In their recent article, Dobler et al. [1] described a decision aid that estimates a net benefit of treatment for latent tuberculosis infection (LTBI) in a low tuberculosis incidence environment. While the aid probably confers some clinical utility as described, its dynamic robustness could be strengthened in some important respects. In a series of previous articles [2–4] using primary longitudinal data from an urban American tuberculosis clinic that would be likely to benefit from use in some form of these authors' decision aid, I showed empirically a number of outcomes relevant to LTBI treatment in a low-incidence, mostly immigrant setting. First, nonadherent patients are likely to experience more adverse and expensive LTBI treatment outcomes (had they completed therapy) [2, 4], and potentially, greater likelihood of TB re-activation [3]; second, a transitional approach to treatment improves the net benefit received over any isoniazid (H) monotherapy (6 months (6H) or 9H) [4]; and third, ethnic heterogeneity in an immigrant clinic population may provide clinicians with guidance on tolerability to isoniazid [4]. LTBI treatment should consider risk of progression and ethnicity in immigrant populations in low-incidence settings <http://ow.ly/X6Irg>
Abstract 1232: Regulation of Mitochondria membrane Potential by Shear Stress: Implication of NO Signaling
Authors: Mahsa Rouhanizadeh, Ryan Hamilton, Enrique Cadenas, Tzung Hsiai
Journal: Circulation (2007)

Introduction : Mitochondria are the most important source of intracellular reactive oxygen species (ROS) in vascular endothelial cells (EC). Mitochondrial membrane potential (ΔΨm) is an indicator of mitochondrial energy state and mtROS production. Shear stress is known to induce eNOS and produce nitric oxide (NO). Hypothesis: We assessed whether NO is implicated in shear stress-induced ΔΨm and mtROS generation. Methods : Confluent HAEC were subjected to three conditions: static control (τ ave = 0 dyn.cm −2 at ∂τ/∂t = 0); pulsatile shear stress (PSS) at a mean shear stress (τ ave ) of 23 dyn.cm −2 with a temporal variation (∂τ/∂t) at 71 dyn.cm −2 .s −1 ; and oscillatory shear stress (OSS) at τ ave = 0.02 with ∂τ/∂t at ±3 dyn.cm − 2.s −1 . Tetramethyl rhodamine methyl ester (TMRM) and Mitosox red fluorescent dyes were used to assess mitochondrial ΔΨm and O 2 ·− production respectively. Intracellular H 2 O 2 production was assessed by carboxy-H 2 DCFDA. HAEC were treated with DETA-NO (NO donor) and L-NAME (eNOS inhibitor) to assess how shear stress-induced NO production regulates ΔΨm. Results: Delta;Ψm was increased by 12±5.3 mV in response to OSS, and by 33.5±8.9 mV in response to PSS (n=3, P &lt;0.05) relative to static control. DETA-NO at 0.21mM and 0.94mM was used to simulate PSS-induced NO production during 1 hour and 4 hours of flow and it increased Delta;Ψm by 9.6±4.9 mV and 18.9 ±3.2 mV, respectively (n=3, P&lt;0.05). L-NAME reduced Delta;Ψm (n=3, P&lt;0.05) suggesting that NO is involved in Delta;Ψm regulation. PSS-induced Delta;Ψm was accompanied by a 1.4 fold increase in mtROS production (n=3, P&lt;0.05) and a concomitant 10 fold upregulation in mitochondrial manganese superoxide dismutase (MnSOD) mRNA expression (n=6, P&lt;0.05). Conclusion: Nitric oxide modulates Delta;Ψm and mtROS production. PSS, which upregulates eNOS, is more potent than OSS at increasing Delta;Ψm and mtROS, implicating NO as a signaling molecule in mitochondrial and endothelial function.
Does Metformin Really Increase Height or Is There Some Problem With the Controls?
Authors: Alison Poulton
Journal: JAMA Pediatrics (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 Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Pediatrics journal
Investigations and control measures following a non-travel-associated case of toxigenic Cornyebacterium diphtheriae, London, United Kingdom, December 2009-January 2010
Authors: S Perkins, R Cordery, G Nixon, A Abrahams, J Andrews, J White, A Efstratiou, S Anaraki
Journal: Eurosurveillance (2010)

This article reports the investigation and control measures undertaken following the identification of a toxigenic strain of Cornyebacterium diphtheriae var gravis, designated ribotype Minsk , in a partially vaccinated teenager born in the United Kingdom with no recent history of travel or known contact with a case of diphtheria or a carrier. This case highlights the need for ongoing work to improve vaccine uptake rates to ensure children receive all scheduled vaccinations.
Prevention of mother‐to‐child transmission of hepatitis B virus by treating mothers with high viral loads
Authors: Yi‐Hua Zhou
Journal: Hepatology (2016)

I read with interest the meta-analysis by Brown et al.1 on oral antivirals in preventing mother-to-child transmission of hepatitis B virus (HBV) based on 26 studies (92% from China). Here, I would like to comment on some studies cited in this meta-analysis. First, many cited articles are overlapping publications. References 29 and 34 have same author groups and the patient recruitment periods were overlapped. Some authors of these two references and one author of reference 28 are the cocontributors of reference 27. Reference 31 might also overlap with references 29 and 34, given that some authors are same. Moreover, six articles (references 39, 41-44, and 51) are published by the same group; the contents in these articles are significantly redundant. Second, the meta-analysis included 10 randomized, controlled trials (references 26-35); however, these studies were not all randomized. Reference 30 clearly stated grouping patients by their willing. References 29, 32, 33, and 35 were less likely randomized because of the different patient number in each group. Furthermore, the date of last patients enrollment in reference 35 was September 2010 and the infants were followed up at 1 year old; it required at least 14 months completing infant follow-up; however, the article was submitted for publication in August 2011. The time conflict is hard to interpret. Third, the infection rates in infants of control mothers were as high as 15.9%-45% in references 27, 30, 32, 35, and 46. Interpretation of high infection rate is difficult, because it is usually <10% in children of hepatitis B e antigen (HBeAg)-positive mothers after combined immunoprophylaxis.2-4 Even in daily practice with suboptimal immunoprophylaxis between 2002 and 2004, only 12.2% of the children of HBeAg-positive mothers were infected.5 Last, almost no adverse event was reported in the references by mainland Chinese authors, which is unusual. Actually, others (references 37 and 50) documented congenital abnormalities in infants of treated mothers. Therefore, more high-quality studies are required before anti-HBV therapy is routinely recommended in women with high viral loads to prevent mother-to-child transmission of HBV. Yi-Hua Zhou, M.D., Ph.D. Departments of Experimental Medicine and Infectious Diseases Nanjing Drum Tower Hospital and Jiangsu Key Laboratory for Molecular Medicine Nanjing University Medical School Nanjing, China Author names in bold designate shared co-first authorship.
Preclinical analyses of a new gamma-secretase inhibitor targeting notch signaling in melanoma.
Authors: L. Poliseno, C. T. Huynh, M. F. Segura, R. Medicherla, S. Menendez, A. E. Rose, A. C. Pavlick, J. Boylan, I. Osman, E. Hernando
Journal: Journal of Clinical Oncology (2010)

8546 Background: Treatment of metastatic melanoma remains a challenge because most cases are refractory to chemotherapy. The lack of effective treatment and the propensity for rapid disease progression warrant further investigations into cellular pathways that may provide melanoma cells with a survival benefit. Several reports have demonstrated a role for aberrant Notch signaling in melanoma genesis or progression, prompting us to explore if targeting this pathway is a valid therapeutic approach against melanoma. Methods: To investigate the potential benefits of Notch inhibition in melanoma, we are using RO4929097, a novel inhibitor of gamma secretase, a key component of the enzymatic complex that cleaves and activates Notch. RO4929097 is completing phase I dose escalation in cancer patients and a CTEP-sponsored phase II clinical trial in melanoma is currently under review. We assessed the effects of RO4929097 on human melanoma cell lines both in vitro (proliferation assays, colony formation assay, sphere formation assay) and in vivo (xenograft tumor growth). Results: Our in vitro assays revealed a dose-dependent effect of RO4929097 on the levels of Notch targets Hes1 and Hey1, measured by qPCR. Moreover, sensitive cells displayed phenotypic and functional changes in response to treatment, including reduced proliferation and impaired ability to organize in tridimensional spheroids and to form colonies in soft agar. In vivo studies using human melanoma xenografts in NOD/SCID mice showed delayed tumor growth following daily RO4929097 oral administration at 10 mg/kg of mouse. Tumors developed by RO4929097-treated mice displayed extensive necrosis and significantly lower proliferative index. Strikingly, RO4929097 administration interfered also with the growth of preexisting tumors, blunting their invasive potential. As opposed to other gamma-secretase inhibitors, RO4929097 did not produce overt toxicity. Conclusions: Our data support Notch inhibition as a targeted therapy against melanoma. Ongoing studies aimed at identifying the molecular bases of response or resistance to RO4929097 might be used for patient selection in future clinical trials. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche Roche
Long-Term Effects of Neonatal Estrogen Treatment on Mitogen Responsiveness of Mouse Spleen Lymphocytes&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: T Kalland, O Strand, J G Forsberg
Journal: JNCI Journal of the National Cancer Institute (1979)

Neonatal female NMRI mice were given injections of olive oil (controls) or daily doses of corticosterone (10 µ9) 17β-estradiol (10 µ9). or diethylstilbestrol (DES) (0.01, 0.1,1, or 5 µg) for the first 5 days after birth. The 5-µg dose of DES resulted in a persistently reduced in vitro mitogen response to concana-valin A or bacterial lipopolysaccharide of spleen lymphocytes from 6-, 10-, and 18-week-old or 17-month-old females. DES injections from day 6 through day 10 did not influence the later mitogen response. Treatment of ovariectomized 10-week-old females with 5 µg DES for 5 days resulted in a tendency to a reduced mitogen response (not statistically significant) 24 hours after the last DES injection. Four weeks later, the mitogen response was the same in experimental and control females. Different possible mechanisms for the persistent effect on the mitogen response are discussed. Neonatal DES treatment not only resulted in persistent changes in the cervicovaginal epithelium and in the hypothalamic-pituitary gland control system but also in the spleen lymphocyte mitogen response. The altered mitogen response should be a stimulus for a detailed analysis of the immune system in women exposed to DES during fetal life, some of whom develop later in life clear cell adenocarcinoma of the uterine cervix and vagina.
Cisplatin plus irinotecan (PI) alternating with a three-drug combination of doxorubicin, cyclophosphamide and etoposide (ACE) in patients with extensive-stage small-cell lung cancer (ED-SCLC): A phase II study of Okayama Lung Cancer Study Group (OLCSG)
Authors: T. Yonei, H. Ueoka, T. Sato, K. Kiura, M. Tabata, S. Kuyama, Y. Segawa, S. Harita, S. Hiraki, M. Tanimoto
Journal: Journal of Clinical Oncology (2004)

7313 Background: ACE regimen is considered to be one of the standard regimens for ED-SCLC. Recent JCOG study (JCOG 9511) demonstrated a significant superiority of PI regimen to cisplatin plus etoposide which is also a current standard regimen in the treatment of ED-SCLC. Based on these results, we designed this phase II study to determine the effectiveness and safety of an alternating chemotherapy consisting of PI and ACE in patients with ED-SCLC. Methods: Eligibility criteria included age under 76 years, presence of measurable disease, adequate organ function, no prior chemotherapy, ECOG performance status (PS) of 0–1 and written informed consent. In the 1st, 3rd and 5th cycles of chemotherapy, PI (cisplatin: 60 mg/m2 on day 1 and irinotecan: 60 mg/m2 on days 1, 8, 15) was given, and ACE (doxorubicin: 50 mg/m2 on day 1, cyclophosphamide: 750 mg/m2 on day 1 and etoposide: 80 mg/m2 on days 1, 2, 3) was administered in the 2nd, 4th and 6th cycles. Both regimens were repeated every 3 to 4 weeks unless intolerable toxicity or disease progression occurred. G-CSF was administered when patients encountered grade 4 neutropenia or grade 3 febrile neutropenia. Between November 1999 and November 2002, twenty-eight patients were enrolled. Characteristics of the eligible patients were as follows; male/female: 22/5; median age: 67 (range 47–75); PS 0/1: 9/18. Results: Among the 27 evaluable patients, 4 had CR and 21 had PR for an overall response rate of 92.6%. Median survival time was 13.8 months with survival rates of 51.6% at 1-year and 9.0% at 2-year. Grade 3 or 4 toxicities included neutropenia (96.3%), febrile neutropenia (37.0%) and thrombocytopenia (25.9%). There was no treatment-related death. Conclusions: These results indicate that this alternating chemotherapy is effective and well tolerable in patients with ED-SCLC. No significant financial relationships to disclose.
Use of L-Dopa in the Detection of Presymptomatic Huntington's Chorea
Authors: Harold L. Klawans, George W. Paulson, Steven P. Ringel, Andre Barbeau
Journal: New England Journal of Medicine (1972)

Abstract There is evidence that choreiform movements are related to an action of dopamine within the brain. In an attempt to identify subjects in whom Huntington's chorea will develop, L-dopa was given to 28 subjects genetically at risk for this disease. Similar regimens of L-dopa or L-dopa in conjunction with a dopa decarboxylase inhibitor were given to 24 control subjects. Of the 28 subjects at risk, chorea developed in 10 (35.7 percent) while they were receiving L-dopa. The chorea always disappeared on discontinuation of the L-dopa. None of 24 control subjects manifested chorea. It is suggested that patients in whom signs of chorea appeared during this procedure will later have Huntington's chorea. The failure of L-dopa to elicit abnormal movements in the controls suggests that there would be few false-positive results among the subjects at risk for Huntington's chorea. The failure to manifest chorea is less important, and in subjects in this group chorea may still develop.
TCT-382 Percutaneous Coronary Intervention vs. Coronary Artery Bypass Graft for Multi-Vessel Coronary Artery Disease in Patients with Chronic Renal Failure and Renal Replacement Therapy
Authors: Se Hun Kang, Yu Na Kim, Cheol Hyun Lee, Hee-Soon Park, Jae-Hyung Roh, Pil Hyung Lee, Mineok Chang, Sung-Han Yoon, Jung-Min Ahn, Soo-Jin Kang, Duk-Woo Park, Seung-Whan Lee, Young-Hak Kim, Cheol Whan Lee, Seong-Wook Park, Seung-Jung Park
Journal: Journal of the American College of Cardiology (2015)